Efficacy of the traction method for gastric endoscopic submucosal dissection: a randomized controlled trial (with videos).

BACKGROUND AND AIMS: To overcome the technical difficulties associated with gastric endoscopic submucosal dissection (ESD), a novel traction device that can alter the direction of traction was developed. This study compared the efficacy and safety of conventional ESD versus those of traction-assisted gastric ESD. METHODS: Patients with a single gastric epithelial neoplasm were randomized to receive conventional (n = 75) or traction-assisted (n = 73) gastric ESD. The primary outcome was ESD procedure time. RESULTS: There were no differences between the conventional and traction-assisted groups with respect to treatment results or adverse events. The mean procedure time was similar for both groups (78.9 vs 88.3 minutes, respectively; P = .3); however, times for the traction device tended to be shorter for lesions in the lesser curvature of the upper or middle stomach (84.6 vs 123.2 minutes; P = .057). CONCLUSIONS: Traction-assisted ESD for lesions in the lesser curvature of the upper or middle stomach were shorter, thereby reducing the procedure time of conventional ESD. (Clinical trial registration: University Hospital Medial Information Network Clinical Trials Registry, identifier 000044450.).

Lusutrombopag Reduces the Risk of Hemoperitoneum Caused by Percutaneous Radiofrequency Ablation for Hepatocellular Carcinoma Compared with Platelet Transfusion.

INTRODUCTION: Patients with liver cirrhosis develop thrombocytopenia and an increased risk of bleeding events after invasive procedures. Lusutrombopag, a thrombopoietin receptor agonist, can increase the platelet count. This study assessed whether lusutrombopag reduces the risk of hemoperitoneum following percutaneous radiofrequency ablation for hepatocellular carcinoma, compared with platelet transfusion. METHODS: Participants in the present study comprised patients with severe thrombocytopenia (platelet count <50,000/µL) enrolled between November 2012 and March 2020, excluding patients with idiopathic thrombocytopenia or anticoagulant use. Hemoperitoneum rate, hemostasis rate, hemoglobin reduction rate, rate of achieving a platelet count ≥50,000/µL, and increases in platelet count and factors contributing to hemoperitoneum were retrospectively analyzed. RESULTS: This study enrolled 41 patients, comprising 18 patients administered lusutrombopag and 23 patients who received platelet transfusion. The major hemoperitoneum rate after RFA was tend to be lower in the lusutrombopag group (0%) than in the platelet transfusion group (21.7%). All of the major hemoperitoneum was observed in the platelet transfusion group. Hemoglobin reduction rate was lower in the lusutrombopag group (-0.17%) than in the platelet transfusion group (6.79%, p = 0.013). Hemostasis rate was lower in the lusutrombopag group (0%) than in the platelet transfusion group (21.7%, p = 0.045). The rate of achievement of platelet counts ≥50,000/µL the day after RFA was higher in the lusutrombopag group (100%) than in the platelet transfusion group (60.9%, p = 0.005). CONCLUSION: Lusutrombopag may be able to perform RFA more safely with respect to the hemoperitoneum caused by percutaneous radiofrequency ablation compared with platelet transfusion.

The methylation level of a single cancer risk marker gene reflects methylation burden in gastric mucosa.

BACKGROUND: Gastric cancer risk can be accurately predicted by measuring the methylation level of a single marker gene in gastric mucosa. However, the mechanism is still uncertain. We hypothesized that the methylation level measured reflects methylation alterations in the entire genome (methylation burden), induced by Helicobacter pylori (H. pylori) infection, and thus cancer risk. METHODS: Gastric mucosa of 15 healthy volunteers without H. pylori infection (G1), 98 people with atrophic gastritis (G2), and 133 patients with gastric cancer (G3) after H. pylori eradication were collected. Methylation burden of an individual was obtained by microarray analysis as an inverse of the correlation coefficient between the methylation levels of 265,552 genomic regions in the person's gastric mucosa and those in an entirely healthy mucosa. RESULTS: The methylation burden significantly increased in the order of G1 (n = 4), G2 (n = 18), and G3 (n = 19) and was well correlated with the methylation level of a single marker gene (r = 0.91 for miR124a-3). The average methylation levels of nine driver genes tended to increase according to the risk levels (P = 0.08 between G2 vs G3) and was also correlated with the methylation level of a single marker gene (r = 0.94). Analysis of more samples (14 G1, 97 G2, and 131 G3 samples) yielded significant increases of the average methylation levels between risk groups. CONCLUSIONS: The methylation level of a single marker gene reflects the methylation burden, which includes driver gene methylation, and thus accurately predicts cancer risk.

Endoscopic N-butyl-2-cyanoacrylate and ethanolamine oleate injection is equivalent to balloon-occluded retrograde transvenous obliteration for preventing gastric variceal bleeding.

OBJECTIVES: Endoscopic injection sclerotherapy (EIS) is effective for temporary hemostasis, but EIS and balloon-occluded retrograde transvenous obliteration (BRTO) have been reported as effective for secondary prophylaxis of gastric varices (GV) bleeding. This study retrospectively compared EIS and BRTO in patients with GV in terms of the efficacy for secondary prevention of GV bleeding and effects on liver function. METHODS: From our database of patients with GV who underwent EIS or BRTO between February 2011 and April 2020, a total of 42 patients with GV were retrospectively enrolled. The primary endpoint was the bleeding rate from GV, which was compared between EIS and BRTO groups. Secondary endpoints were liver function after treatment and rebleeding rate from EV, compared between EIS and BRTO groups. Rebleeding rates from GV and EV and liver function after treatment were also compared between EIS-ethanolamine oleate (EO)/histoacryl (HA) and EIS-HA groups. RESULTS: Technical success was achieved for all EIS cases, but two cases were unsuccessful in the BRTO group and underwent additional EIS. No significant differences in bleeding rates or endoscopic findings for GV improvement were seen between EIS and BRTO groups. Liver function also showed no significant difference in the amount of change after treatment between groups. CONCLUSION: EIS therapy appears effective for GV in terms of preventing GV rebleeding and effects on liver function after treatment. EIS appears to represent an effective treatment for GV.

Pivotal trial of a biodegradable stent for patients with refractory benign esophageal stricture.

OBJECTIVE: Benign esophageal strictures (BES) cause dysphagia and decrease patients' quality of life. Although mechanical dilation is the standard of care for BES, in some patients, dysphagia is unrelieved despite repeated procedures. The biodegradable stent was developed to resolve refractory BES, with reported favorable outcomes, but it is unapproved in Japan. Thus, we evaluated the safety and efficacy of the biodegradable stent (BDS) for patients with refractory BES for regulatory approval. METHODS: This was a nonrandomized single-arm prospective trial conducted at eight institutions. We included patients with BES after ≥ 5 times of dilation or ≥ one time of radial incision and cutting whose dysphagia score (DS) was 2 or worse and an endoscope could not admit. The primary endpoint was the proportion of patients whose DS improvement of ≤ 1 was maintained at 3 months. RESULTS: Thirty patients (median age: 69 years, male/female: 27:3) were enrolled and treated; BDS placement failed in 1 patient. Fourteen patients maintained their DS improvement until 3 months after placement (proportion of DS improvement at 3 months 46.7% [95% CI: 28.3-65.7]), and the median dysphagia-free survival was 98 days [95% CI: 68-123]. Most adverse events could be managed conservatively; however, a patient with BES after chemoradiotherapy (CRT) developed an esophago-left atrium fistula and died approximately 4 months after stent placement. CONCLUSION: The BDS was effective for refractory BES and the safety was acceptable. However, the indication for this procedure in patients RECEIVING CRT for esophageal cancer should be carefully considered.

Oral indigo carmine for the detection of colon adenoma.

OBJECTIVES: Colonoscopy is currently considered the optimal method to detect colorectal neoplasia; however, some adenomas remain undetected. While indigo carmine staining with a dye-spray catheter has demonstrated promising results for reducing the miss rate, we investigated the oral indigo carmine method. The aim of this study was to determine whether oral indigo carmine intake before standard colonoscopy increases the adenoma (and adenocarcinoma) detection rate (ADR) or the mean number of adenomas per patient (MAP). MATERIALS AND METHODS: The oral indigo carmine method was performed from April 2018 to July 2020 in two hospitals. Data were collected in a prospective manner and compared to the conventional group whose data were collected retrospectively and consecutively from January 2016 to March 2018. All data were anonymized. RESULTS: Among the 704 patients included, colonoscopies were completely performed in 693 patients (347 in the indigo group). The ADR did not significantly differ between the groups: 42.3% vs. 40.3% (indigo vs. conventional group; odds ratio: 1.13; 95% confidence interval: 0.9-1.33, p = .33). The MAP was significantly greater in the indigo group (1.15) than that in the conventional group (0.82; p = .009). The cecal intubation rate and time to cecal intubation did not differ between the indigo and conventional group (98.6% vs. 98.3%, p = .83, and 6.2 min vs. 5.9 min, p = .39, respectively). CONCLUSION: The routine use of oral indigo carmine does not lead to a higher ADR despite the higher MAP.

Endoscopic ultrasonography shear wave as a predictive factor of endocrine/exocrine dysfunction in chronic pancreatitis.

BACKGROUND AND AIM: Chronic pancreatitis (CP) leads to permanent impairment of exocrine and endocrine functions. The endoscopic ultrasonography (EUS)-based Rosemont classification plays an important role in diagnosing CP. However, it is based on subjective judgment. In contrast, EUS shear wave measurement (EUS-SWM) has been established to be a precise method for evaluating tissue hardness. This study aimed to evaluate the utility of EUS-SWM in diagnosing CP and determining exocrine and endocrine dysfunctions. METHODS: We evaluated 40 patients who underwent EUS-SWM between January 2019 and January 2020. They were classified into the normal pancreas and early, probable, and definite CP groups following the Japan Pancreatic Society criteria. EUS-SWM value was compared between the normal pancreas group and the early, probable, and definite CP groups. The relationship between EUS-SWM value and exocrine/endocrine dysfunctions was also assessed. The cut-off value of EUS-SWM for diagnosing CP and exocrine/endocrine dysfunctions was investigated. RESULTS: The EUS-SWM value was positively correlated with the Japan Pancreatic Society criteria stages. The probable and definite CP groups had significantly higher EUS-SWM values than the normal group. The areas under the receiver operating characteristic curve for the diagnostic accuracy of EUS-SWM for CP, exocrine dysfunction, and endocrine dysfunction were 0.92, 0.78, and 0.63, respectively. The cut-off values of 1.96, 1.96, and 2.34 for diagnosing CP, exocrine dysfunction, and endocrine dysfunctions had 83%, 90%, and 75% sensitivity, respectively, and 100%, 65%, and 64% specificity, respectively. CONCLUSIONS: Endoscopic ultrasonography shear wave measurement provides objective assessment and can thus be an alternative diagnostic tool for diagnosing CP and exocrine/endocrine dysfunctions.

Novel endoscopic ultrasonography imaging technique for visualizing microcirculation without contrast enhancement in subepithelial lesions: Prospective study.

OBJECTIVES: Detective flow imaging for endoscopic ultrasonography (DFI?EUS) is a new imaging modality developed for detecting fine vessels without using ultrasound contrast agents. This study aimed to evaluate its utility by comparing it with a type of directional power Doppler (eFLOW) for subepithelial lesions (SELs). METHODS: Between January 2019 and January 2020, 28 patients with SELs undergoing DFI?EUS and eFLOW?EUS were enrolled. DFI?EUS and eFLOW?EUS assessing the vascularity in SELs were compared in terms of the rates of identification of intratumoral vessels. We also investigated how large vessels were depicted in both modalities based on surgical specimens as well as the detection rates of intratumoral vessels in gastrointestinal stromal tumors (GISTs) and non?GISTs using either DFI?EUS or eFLOW?EUS. RESULTS: Among 28 patients, 23 with pathological confirmation by EUS?guided fine?needle aspiration biopsy (EUS?FNAB) specimens were included. Of those 23 patients, the 10 who underwent surgical resection were selected for analysis. The rate of detection of intratumoral vessels in SELs was significantly higher on DFI?EUS (80%) than on eFLOW?EUS (30%) (P\xA0=\xA00.03). Comparison with surgical specimens revealed that detection rate for vessels with maximum size of less 1000\xA0µm was higher in DFI?EUS (66%) than that in eFLOW?EUS (0%). GIST patients had significantly higher positive rates (90%) of intratumoral vessels than non?GIST patients (31%) on DFI in 23 cases including EUS?FNAB specimens (P\xA0=\xA00.045). CONCLUSIONS: Detective flow imaging?EUS is more sensitive for depicting intratumoral vessels than eFLOW?EUS. Evaluation of intratumoral vessels on DFI?EUS is useful for identifying GISTs without contrast agents.

Radical treatment for walled-off necrosis: Transmural nasocyst continuous irrigation.

BACKGROUND AND AIM: Treatment efficiency of walled-off necrosis (WON) using endoscopic ultrasound-guided drainage (EUS-D) with a double pigtail stent (DPS) is limited. Endoscopic necrosectomy is often carried out if EUS-D fails. However, endoscopic necrosectomy is associated with significant morbidity and mortality. Thus, we developed transmural nasocyst continuous irrigation (TNCCI) as an alternative therapeutic option for WON. This study aimed to evaluate the usefulness of TNCCI therapy for WON. METHODS: Between April 2009 and March 2018, 19 of 39 patients admitted with WON underwent EUS-D. Ten consecutive patients also received TNCCI therapy (TNCCI group) between May 2015 and March 2018. TNCCI was carried out by inserting an external tube from the gastroduodenal lumen into the WON under endoscopic ultrasonography guidance and then continuously irrigating the WON with saline at a rate of 40 ml/h. Nine consecutive patients who underwent EUS-D without TNCCI therapy between April 2009 and April 2015 were used for comparison (control group). Various parameters were compared between the TNCCI and control groups. RESULTS: Time taken to reduce WON (6 vs 32 days, P = 0.001), implementation rate of endoscopic necrosectomy (0% vs 55.6%, P = 0.01), and number of endoscopic necrosectomy sessions per patient (0 vs 0.8 ± 1.0, P = 0.008) were significantly lower in the TNCCI group than in the control group. CONCLUSIONS: Walled-off necrosis can be effectively and safely treated by endoscopic drainage with a DPS and TNCCI. This technique can be an alternative therapeutic option before carrying out endoscopic necrosectomy.

Autophagy impairment by Helicobacter pylori-induced methylation silencing of MAP1LC3Av1 promotes gastric carcinogenesis.

Helicobacter pylori (H. pylori) infection induces methylation silencing of tumor suppressor genes causing gastric carcinogenesis. Impairment of autophagy induces DNA damage leading to genetic instability and carcinogenesis. We aimed to identify whether H. pylori infection induced methylation silencing of host autophagy-related (Atg) genes, impairing autophagy and enhancing gastric carcinogenesis. Gastric mucosae were obtained from 41 gastric cancer patients and 11 healthy volunteers (8 H. pylori-uninfected and 3 H. pylori-infected). Methylation status of Atg genes was analyzed by a methylation microarray and quantitative methylation-specific PCR (qMSP); mRNA expression was assessed by quantitative reverse transcription PCR (qRT-PCR). Cell proliferation, migration and invasion were assessed in normal rat gastric epithelial cells. Gene knock-down was performed by siRNA. Autophagy was assessed by western blotting. Of 34 Atg genes, MAP1LC3A variant 1 (MAP1LC3Av1) and ULK2 were identified by methylation microarray analysis as exhibiting specific methylation in H. pylori-infected mucosae and gastric cancer tissues. Methylation silencing of MAP1LC3Av1 was confirmed by qMSP, qRT-PCR and de-methylation treatment in two gastric cancer cell lines. Knock-down of map1lc3a, the rat homolog of the human MAP1LC3Av1, inhibited autophagy response and increased cell proliferation, migration and invasion in normal rat gastric epithelial cells, despite the presence of map1lc3b, the rat homolog of the human MAP1LC3B gene important for autophagy. Furthermore, MAP1LC3Av1 was methylation-silenced in 23.3% of gastric cancerous mucosae and 40% of non-cancerous mucosae with H. pylori infection. MAP1LC3Av1 is essential for autophagy and H. pylori-induced methylation silencing of MAP1LC3Av1 may impair autophagy, facilitating gastric carcinogenesis.

Serum pepsinogen levels can quantify the risk of development of metachronous gastric cancer after endoscopic resection.

We have previously reported that serum pepsinogen (PG) can quantify the level of gastric mucosal atrophy, and that H. pylori eradication reduces cancer development in subjects with mild atrophy identified by serum PG levels. The aim of this study was to elucidate the predictive ability of serum PG levels for the development of metachronous gastric cancer (MGC) after endoscopic resection (ER) of primary cancer in association with H. pylori eradication. A retrospective chart review was performed, and 330 patients who underwent ER for initial early gastric cancer were enrolled. Presence or absence of H. pylori, serum PG levels, and endoscopic atrophy at ER were evaluated. H. pylori eradication was performed at the patient's request after ER. The incidence of MGC in these patients was analyzed. Of 330 patients, 47 developed MGC. Endoscopic extensive atrophy was observed more frequently in patients with MGC (p = 0.001). Although PG I or PG II alone did not significantly differ according to development of MGC, the proportion of PG I/II ≤ 3.0, which is one of the criteria of PG test-positive, was significantly higher in patients with MGC (83 vs. 69%, p = 0.04). H. pylori eradication after ER did not affect MGC development (p = 0.2). On multivariate analysis, serum PG I/II ratio ≤ 3.3 was significantly associated with the development of MGC (hazard ratio: 3.66, 95% confidence interval: 1.47-12.25, p = 0.004). The risk of MGC after ER could be quantitatively predicted by the PG I/II ratio regardless of H. pylori status.

Incidence of and risk factors for metachronous gastric cancer after endoscopic resection and successful Helicobacter pylori eradication: results of a large-scale, multicenter cohort study in Japan.

BACKGROUND: A previous multicenter prospective randomized study from Japan showed that Helicobacter pylori eradication reduced the development of metachronous gastric cancer (MGC) after endoscopic resection for early gastric cancer. MGC risk, however, is not eliminated; yet few studies have evaluated its long-term incidence and risk factors. In this study, we investigated the incidence of and risk factors for MGC in patients who underwent endoscopic resection for early gastric cancer with successful H. pylori eradication. METHODS: A total of 594 patients who underwent endoscopic resection for early gastric cancer and successful H. pylori eradication at three institutions (National Cancer Center Hospital, University of Tokyo Hospital, and Wakayama Medical University Hospital) were analyzed retrospectively. Annual endoscopic surveillance was performed after initial endoscopic resection. MGC was defined as a gastric cancer newly detected at least 1 year after successful H. pylori eradication. RESULTS: Ninety-four MGCs were detected in 79 patients during the 4.5-year median follow-up period. Kaplan-Meier analysis showed the cumulative incidence of MGC 5 years after successful H. pylori eradication was 15.0 %; the incidence of MGC calculated by use of the person-year method was 29.9 cases per 1000 person-years. Multivariate analysis using the Cox proportional hazards model revealed that male sex, severe gastric mucosal atrophy, and multiple gastric cancers before successful H. pylori eradication were independent risk factors for MGC. Eleven percent of MGCs (10 of 94) were detected more than 5 years after successful H. pylori eradication. CONCLUSION: Surveillance endoscopy for MGC in patients who have undergone endoscopic resection for early gastric cancer should be performed even after successful H. pylori eradication.

Hypointense hepatocellular carcinomas on apparent diffusion coefficient mapping: Pathological features and metastatic recurrence after hepatectomy.

AIM: The present study aimed to evaluate pathological features of hepatocellular carcinomas (HCC) appearing hypointense on the apparent diffusion coefficient (ADC) map, and to elucidate the association between the signal intensity on the ADC map and metastatic recurrences after hepatectomy. METHODS: In total, 52 consecutive patients with initial hypervascular HCC (solitary lesion ≤5 cm in diameter) without vascular invasion on imaging were examined by diffusion-weighted magnetic resonance imaging before hepatectomy. The signal intensities of HCC on the ADC map were visually compared with the surrounding liver and categorized as hypointense or non-hypointense. Intrahepatic metastatic recurrence was defined as more than three intrahepatic recurrences. RESULTS: The 52 HCC were evaluated as 26 hypointense and 26 non-hypointense tumors. No significant differences between the hypointense and non-hypointense groups were seen for age, sex, etiology, tumor size and tumor marker levels. However, in resected specimens, significant differences between the two groups were noted for histological grade and microscopic portal invasion. The percentages of poorly differentiated HCC and microscopic portal invasion in the hypointense group were significantly higher than those in the non-hypointense group. The cumulative 3-year metastatic recurrence rates of the hypointense and non-hypointense groups on the ADC map were 56% and 13% (P = 0.001), respectively. Multivariate analyses indicated that hypointensity on the ADC map was the only independent factor related to metastatic recurrence. CONCLUSION: Hypointense HCC on ADC mapping are characterized by poor histological differentiation and more frequent microscopic portal invasion, and are significantly associated with metastatic recurrences after hepatectomy.

Contribution of Contrast-Enhanced Sonography With Perfluorobutane Microbubbles for Diagnosis of Recurrent Hepatocellular Carcinoma.

OBJECTIVES: The role of contrast-enhanced sonography in the diagnosis of recurrent hepatocellular carcinoma is still unclear. This study aimed to clarify the usefulness and limitations of contrast-enhanced sonography with a perfluorobutane microbubble contrast agent (Sonazoid; Daiichi-Sankyo, Tokyo, Japan) after contrast-enhanced computed tomography (CT) for diagnosis of recurrent hepatocellular carcinoma and to establish its optimal use. METHODS: A total of 514 patients, who were suspected to have recurrent hepatocellular carcinoma on contrast-enhanced CT, underwent contrast-enhanced sonography. Of 514 suspicious lesions, 484 were diagnosed as recurrent hepatocellular carcinomas, including 142 recurrent hepatocellular carcinomas measuring 1 cm or smaller in diameter. The largest lesion was evaluated in each patient. A final diagnosis of recurrent hepatocellular carcinoma after contrast-enhanced CT was reached on the basis of the typical hallmarks of hepatocellular carcinoma on any of the other contrast imaging modalities or by resected tissue or tumor enlargement during follow-up. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of contrast-enhanced CT were 68%, 93%, 99%, 15%, and 70%, respectively, and the values of contrast-enhanced sonography were 91%, 100%, 100%, 31%, and 91%, excluding 60 unassessable lesions on contrast-enhanced sonography. The diagnostic rate for recurrent hepatocellular carcinoma on contrast-enhanced sonography for lesions with an atypical enhancement pattern on contrast-enhanced CT was 71%. On multivariate analysis of factors contributing to the unassessability of contrast-enhanced sonography, lesion size, location, and abdominal wall thickness were independent factors. CONCLUSIONS: Although the assessability of contrast-enhanced sonography depends on lesion size, location, and abdominal wall thickness, contrast-enhanced sonography after contrast-enhanced CT is useful for confirmative diagnosis of small recurrent hepatocellular carcinoma with an atypical enhancement pattern on contrast-enhanced CT, even for lesions measuring 1 cm or smaller in diameter.

Kupffer Imaging by Contrast-Enhanced Sonography With Perfluorobutane Microbubbles Is Associated With Outcomes After Radiofrequency Ablation of Hepatocellular Carcinoma.

OBJECTIVES: An ultrasound contrast agent consisting of perfluorobutane microbubbles (Sonazoid; Daiichi Sankyo, Tokyo, Japan) accumulates in Kupffer cells, which thus enables Kupffer imaging. This study aimed to elucidate the association of defect patterns of hepatocellular carcinoma during the Kupffer phase of Sonazoid contrast-enhanced sonography with outcomes after radiofrequency ablation (RFA). METHODS: For this study, 226 patients with initial hypervascular hepatocellular carcinoma, who could be evaluated by contrast-enhanced sonography with Sonazoid before RFA, were analyzed. Patients were divided into 2 groups according to the tumor defect pattern during the Kupffer phase. The irregular-defect group was defined as patients with hepatocellular carcinoma that had a defect with an irregular margin, and the no-irregular-defect group was defined as patients with hepatocellular carcinoma that had either a defect with a smooth margin or no defect. Critical recurrence was defined as more than 3 intrahepatic recurrences, vascular invasion, dissemination, or metastasis. RESULTS: The irregular-defect and no-irregular-defect groups included 86 and 140 patients, respectively, and had cumulative 5-year critical recurrence rates of 49% and 17% (P < .01). Multivariate analysis indicated that the tumor diameter, lens culinaris agglutinin- reactive α-fetoprotein level, and defect pattern were independent factors related to critical recurrence. The cumulative 5-year overall survival rates for the irregular-defect and no-irregular-defect groups were 46% and 61% (P< .01). Multivariate analysis indicated that the Child-Pugh class, tumor diameter, lens culinaris agglutinin-reactive α-fetoprotein level, and defect pattern were independent factors related to survival. CONCLUSIONS: The defect pattern of hepatocellular carcinoma during the Kupffer phase of Sonazoid contrast-enhanced sonography is associated with critical recurrence and survival after RFA.

Endoscopic features associated with development of metachronous gastric cancer in patients who underwent endoscopic resection followed by Helicobacter pylori eradication.

OBJECTIVES: The preventive effect of Helicobacter pylori (HP) eradication on metachronous gastric cancer development after endoscopic resection remains controversial. The aim of this study was to identify specific endoscopic features that correlated with the risk of metachronous gastric cancer development after endoscopic submucosal dissection (ESD) using both endoscopic findings before ESD and changes of findings after HP eradication. METHODS: This retrospective study investigated 122 consecutive patients who underwent ESD for early gastric cancer and successful HP eradication after ESD. Endoscopic findings linked with HP before ESD and changes after HP eradication were evaluated according to the development of metachronous cancer. RESULTS: Most patients showed severe atrophy and intestinal metaplasia (IM) before ESD (97% and 83%, respectively). Improvement of spotty redness, improvement of diffuse redness, emergence of patchy redness, and emergence of map-like redness were frequent findings after HP eradication (52%, 50%, 54%, and 32%, respectively). Kaplan-Meier curves indicated that patients without IM before ESD never developed metachronous cancer, while patients with emergence of map-like redness after HP eradication were significantly more likely to develop metachronous cancer (log-rank test, p = 0.031 and p < 0.001, respectively). Multivariate analysis indicated that emergence of map-like redness after HP eradication was the only predictive factor for development of metachronous cancer (hazard ratio, 3.61; 95% confidence interval, 1.41-9.21; p = 0.007). CONCLUSIONS: Absence of IM before ESD and emergence of map-like redness after HP eradication were useful endoscopic findings in the negative and positive prediction of metachronous gastric cancer developing after ESD.

Argon plasma coagulation is effective for prevention of recurrent esophageal varices after endoscopic injection sclerotherapy: Single-center case-control study.

BACKGROUND AND AIM: Esophageal varices are usually treated with endoscopic injection sclerotherapy (EIS) or endoscopic band ligation (EBL). However, frequent recurrences of varices after those procedures have been problematic. Argon plasma coagulation (APC) after EIS may be effective for preventing varix recurrence and, in recent years, we have routinely carried out APC after EIS. The aim of the present study was to verify the effectiveness of APC for preventing recurrence of varices after EIS. METHODS: A case-control study was carried out using a historical control cohort in a single center. The varix recurrence rate in 62 patients (34 men and 28 women, median age; 69 years) who underwent APC after EIS for hemorrhagic or risky esophageal varices (APC group) was compared with that of control patients who did not undergo APC after EIS (control group). Age-, sex-, and liver function-matched two control subjects were selected for one case subject (control group). Recurrence of varices was defined as rupture of varices or reappearance of risky varices. RESULTS: The 1-year and 2-year recurrence rates of the APC group were 9.7% and 11.3%, respectively. In contrast, the rates of the control group were 29.0% and 34.7%, respectively. Kaplan-Meier curves showed a significantly lower recurrence rate in the APC group (P = 0.013, log-rank test). No APC-related severe adverse events were observed. CONCLUSION: APC after EIS was safe and could significantly prevent recurrence of esophageal varices. Therefore, the addition of APC should be routinely carried out after EIS.

Demonstration of the usefulness of epigenetic cancer risk prediction by a multicentre prospective cohort study.

BACKGROUND: Epigenetic alterations accumulate in normal-appearing tissues of patients with cancer, producing an epigenetic field defect. Cross-sectional studies show that the degree of the defect may be associated with risk in some types of cancer, especially cancers associated with chronic inflammation. OBJECTIVE: To demonstrate, by a multicentre prospective cohort study, that the risk of metachronous gastric cancer after endoscopic resection (ER) can be predicted by assessment of the epigenetic field defect using methylation levels. DESIGN: Patients with early gastric cancer, aged 40-80 years, who planned to have, or had undergone, ER, were enrolled at least 6 months after Helicobacter pylori infection discontinued. Methylation levels of three preselected genes (miR-124a-3, EMX1 and NKX6-1) were measured by quantitative methylation-specific PCR. Patients were followed up annually by endoscopy, and the primary endpoint was defined as detection of a metachronous gastric cancer. Authentic metachronous gastric cancers were defined as cancers excluding those detected within 1 year after the enrolment. RESULTS: Among 826 patients enrolled, 782 patients had at least one follow-up, with a median follow-up of 2.97 years. Authentic metachronous gastric cancers developed in 66 patients: 29, 16 and 21 patients at 1-2, 2-3 and ≥3 years after the enrolment, respectively. The highest quartile of the miR-124a-3 methylation level had a significant univariate HR (95% CI) (2.17 (1.07 to 4.41); p=0.032) and a multivariate-adjusted HR (2.30 (1.03 to 5.10); p=0.042) of developing authentic metachronous gastric cancers. Similar trends were seen for EMX1 and NKX6-1. CONCLUSIONS: Assessment of the degree of an epigenetic field defect is a promising cancer risk marker that takes account of life history.

Video capsule endoscopy as the initial examination for overt obscure gastrointestinal bleeding can efficiently identify patients who require double-balloon enteroscopy.

BACKGROUND: Both double-balloon enteroscopy (DBE) and video capsule endoscopy (VCE) have similar diagnostic yields for patients with overt obscure gastrointestinal bleeding (OGIB). However, the choice of initial modality is still controversial. The aim of this study was to show the clinical outcome of the strategy of initial VCE, followed by DBE. METHODS: Eighty-nine consecutive overt OGIB patients who had undergone VCE as the initial examination were analyzed. The interpreters of VCE evaluated the necessity of performing DBE, and the antegrade or retrograde route was chosen, depending on the transit time of the capsule. RESULTS: Thirty-seven patients (42 %) underwent DBE depending on the findings of VCE. Of these, bleeding sites in the small bowel were identified in 29 patients with the initially selected route (21 antegrade and 8 retrograde). The remaining 8 later underwent DBE by the other route, but 7 had no bleeding lesion, which was confirmed by second-look VCE. One remaining patient had a jejunal varix found by VCE, but DBE from either side could not reach the lesion. The sensitivity and negative predictive value of VCE were 100 %, both for the presence of small bowel lesions and the requirement of hemostasis in the small bowel; this indicated that VCE never misses relevant findings in the small bowel, and that negative VCE findings correspond to the lack of necessity for further examination. CONCLUSIONS: VCE as the initial examination can efficiently identify overt OGIB patients who require DBE. The strategy of initial VCE for overt OGIB appears to be reasonable.