Comparison of metronidazole versus clarithromycin in first-line vonoprazan-based triple therapy for Helicobacter pylori: A multicenter randomized trial in Japan.

Background and Aim: To date, no randomized trials have compared the efficacy of 7-day vonoprazan, amoxicillin, and metronidazole triple therapy (VAM) versus 7-day vonoprazan, amoxicillin, and clarithromycin triple therapy (VAC) as a first-line treatment for Helicobacter pylori eradication. This study was performed to compare the efficacy of VAM and VAC as first-line treatments. Methods: This prospective multicenter randomized trial was performed in Japan and involved 124 H. pylori-positive patients without a history of eradication. Patients without antibiotic resistance testing of H. pylori were eligible. The patients were randomized to receive either VAC (vonoprazan 20 mg + amoxicillin 750 mg + clarithromycin 200 or 400 mg twice a day) or VAM (vonoprazan 20 mg + amoxicillin 750 mg + metronidazole 250 mg twice a day) for 7 days, with stratification by age and sex. Eradication success was evaluated using the 13C-urea breath test. We evaluated safety using patient questionnaires (UMIN000025773). Results: The intention-to-treat and per-protocol eradication rates of VAM were 91.3% (95% confidence interval [CI], 82.0-96.7%) and 92.6% (95% CI, 83.7-97.6%), respectively, and those of VAC were 89.1% (95% CI, 77.8-95.9%) and 96.1% (95% CI, 86.5-99.5%), respectively. No significant difference was observed between VAM and VAC in either analysis (P = 0.76 and P = 0.70, respectively). Abdominal fullness was more frequent in patients who received VAM than VAC. Conclusions: These findings suggest that VAM as a first-line treatment in Japan can be categorized as grade B (intention-to-treat cure rate of 90-95%) and have potential as a first-line national insurance -approved regimen.

The Complex Interaction between Proton Pump Inhibitors and Cancer Treatment.

We have read the article authored by Rizzo et al [...].

Vonoprazan and high-dose amoxicillin dual therapy for Helicobacter pylori first-line eradication: A single-arm, interventional study.

Background: To date, no interventional trial has assessed the efficacy and safety of vonoprazan and high-dose (500 mg four times daily, 2000 mg/day) amoxicillin dual therapy in terms of Helicobacter pylori eradication. We explored whether this was an appropriate first-line treatment. Methods: This prospective, dual-center, single-arm interventional study was performed in Japan. Twenty H. pylori-positive patients lacking any eradication history were treated with vonoprazan 20 mg twice daily and amoxicillin 500 mg four times daily (qid) for 7 days. Eradication was evaluated using a stool H. pylori antigen test. We evaluated safety using patient questionnaires. This study was registered in the jRCT database (jRCT031200128). Results: The intention-to-treat and per-protocol eradication rates were 90% (95% confidence interval [CI] 68.3-98.8%, n = 20) and 94.4% (95% CI 72.7-99.9%, n = 18) respectively. No significant adverse event was recorded. Conclusion: Vonoprazan/high-dose amoxicillin dual therapy can be a safe standard first-line therapy. We are now undergoing a randomized controlled trial comparing dual therapy and vonoprazan-based triple therapy.

The Origin of Epithelium with Low-Grade Atypia in Early Gastric Cancer.

INTRODUCTION: Helicobacter pylori (HP) infection causes chronic inflammation and atrophy of the gastric mucosa and thus a high risk of gastric cancer (GC). With the increasing success of HP infection treatment, a larger number of GCs that develop after eradication can be assessed. Several studies have shown that epithelium with low-grade atypia (ELA) is a frequent characteristic of these GCs, but the origin of this condition is unknown. In this study, we compared the mucin phenotype, cellular proliferation, and p53 staining in ELA and cancerous tissues obtained from patients with GC with and without HP eradication. METHODS: The study population consisted of 23 patients with GC that developed after successful HP eradication therapy (eradicated group) and 24 patients with GC and HP infection (infected group). The prevalence of ELA was determined by hematoxylin and eosin staining. Tumor tissue and ELA samples were further analyzed by immunohistochemical staining for Muc5AC, Muc2, p53, and Ki-67. RESULTS: The ELA coverage rate was significantly higher in the eradicated group than in the infected group. Gastric-type mucin was frequently expressed by the ELA, and the mucin phenotypes of ELA and cancerous areas differed in 75% of cases. The Ki-67 labeling index was consistently lower in ELA than in the cancerous mucosa. Fourteen of 21 (66.7%) cancerous lesions, but only 3 ELA samples, were p53-positive. CONCLUSION: In most cases, ELA on the surfaces of GCs seems to have originated from normal gastric cells, not from cancer cells.

Sofosbuvir-based therapies associated with regression of liver fibrosis in patients with hepatitis C virus infection: A prospective observational study.

ABSTRACT: Oral direct-acting antiviral (DAA) treatment leads to >95% sustained virological response (SVR) and could be clinically useful in regression of liver fibrosis in chronic hepatitis C virus (HCV) infection. We evaluated if ledipasvir/sofosbuvir or sofosbuvir + ribavirin is associated with regression of fibrosis in HCV patients who achieved SVR.In this prospective cohort study performed at 3 sites in Japan, patients with genotype 1 and genotype 2 were given standard treatment of ledipasvir 90 mg/sofosbuvir 400 mg and sofosbuvir 400 mg + 200-1000 mg/day ribavirin, respectively, for 12 weeks. Liver fibrosis was assessed using Mac-2-binding protein glycosylation isomer (M2BPGi) and other fibrosis markers (platelet count, Fib-4 index, liver stiffness measurement [LSM]) in patients who achieved SVR.A total of 98.1% of (n = 101/103) patients in genotype 1 cohort and 100% (n = 16/16) in the genotype 2 cohort achieved SVR12. Based on per-protocol analysis, M2BPGi levels showed a significant decrease (-2.2  cut-off index [COI], P < .0001) at week 48 after treatment initiation. Forty-three patients showed a significant decrease in Fib-4 index (-1.2, P < .0001), and 44 patients showed improvement in LSM (-5.9 kPa, P < .0001).Achievement of SVR after antiviral therapy was associated with fibrosis regression. M2BPGi correlated well with LSM at week 48 after treatment initiation, supporting the sustainable benefit of HCV therapy.

Helicobacter pylori rescue treatment with vonoprazan, metronidazole, and sitafloxacin in the presence of penicillin allergy.

BACKGROUND AND AIM: To assess the efficacy and safety of 7-day Helicobacter pylori rescue treatment consisting of a vonoprazan (VPZ), metronidazole (MNZ), and sitafloxacin (STFX) regimen (VPZ-MNZ-STFX therapy) in patients with penicillin allergy. METHODS: This was a registered prospective intervention study. Patients with penicillin allergy who were diagnosed with H. pylori infection and had a history of H. pylori eradication were eligible for inclusion. Seventeen patients were prospectively treated with VPZ 20 mg bid, MNZ 250 mg bid, and STFX 100 mg bid for 7 days. Safety was evaluated using a questionnaire on adverse effects. RESULTS: The eradication rate of 7-day VPZ-MNZ-SFTX therapy was 88.2% (95% confidence interval: 63.6-98.5%; n = 17) in both intention-to-treat and per-protocol analyses. On the questionnaire, 25% of patients reported experiencing diarrhea, with a score of 2 or 3. All patients undergoing VPZ-MNZ-STFX therapy completed 100% of their medication course. CONCLUSION: Rescue H. pylori eradication with VPZ-MNZ-STFX therapy is effective and well tolerated in patients with penicillin allergy (UMIN000016335, jRCTs031180133).

Influence of NOS3 rs2070744 genotypes on hepatocellular carcinoma patients treated with lenvatinib.

We investigated whether or not nitric oxide synthase 3 (NOS3) rs2070744 genotypes can affect the response for lenvatinib treatment in patients with hepatocellular carcinoma (HCC). We evaluated the relation of the NOS3 rs2070744 genotypes to the tumor response, progression-free survival (PFS), and overall survival (OS) as the response for lenvatinib. We also examined the association between fibroblast growth factor receptor (FGFR) gene polymorphisms, a potential feature of lenvatinib, and the response. There were no significant differences between the studies for either PFS or OS, even though patients with the TT genotype had a longer mean PFS (hazard ratio [HR] 0.60; p = 0.069) and mean OS (HR 0.46; p = 0.075) than those with the TC/CC genotypes. However, patients with a single-nucleotide polymorphism (SNP) combination pattern of the NOS3 rs2070744 TC/CC and FGFR4 rs351855 CT/TT genotypes had a significantly shorter mean PFS (HR 2.56; p = 0.006) and mean OS (HR 3.36; p = 0.013) than those with the other genotypes. The NOS3 rs2070744 genotypes did not influence the clinical response. However, the SNP combination pattern of the NOS3 rs2070744 and FGFR4 rs351855 genotypes may be helpful as treatment effect predictors and prognostic factors for HCC patients treated with lenvatinib.

Loss of Pancreatic E-Cadherin Causes Pancreatitis-Like Changes and Contributes to Carcinogenesis.

BACKGROUND & AIMS: E-cadherin (Cdh1) is a key molecule for adherence required for maintenance of structural homeostasis. Loss of E-cadherin leads to poor prognosis and the development of resistance to chemotherapy in pancreatic cancer. Here, we evaluated the physiological and pathologic roles of E-cadherin in the pancreas. METHODS: We crossbred Ptf1a-Cre mice with Cdh1f/f mice to examine the physiological roles of E-cadherin in the pancreas. In addition, we crossbred these mice with LSL-KrasG12D/+ mice (PKC) to investigate the pathologic roles of E-cadherin. We also generated a tamoxifen-inducible system (Ptf1a-CreERT model). Organoids derived from these models using lentiviral transduction were analyzed for immunohistochemical features. Established cell lines from these organoids were analyzed for migratory and invasive activities as well as gene expression by complementary DNA microarray analyses. RESULTS: None of the Ptf1a-Cre mice crossbred with Cdh1f/f mice survived for more than 28 days. We observed aberrant epithelial tubules that resembled the structure of acinar-to-ductal metaplasia after postnatal day 6, showing features of pancreatitis. All of the PKC mice died within 10 days. We observed tumorigenicity with increasing stroma-like aggressive tumors. Ptf1a-CreERT models showed that deletion of E-cadherin led to earlier pancreatic intraepithelial neoplasm formation. Cells established from PKC organoids had greater migratory and invasive activities, and these allograft tumors showed a poorly differentiated phenotype. Gene expression analysis indicated that Hdac1 was up-regulated in PKC cell lines and a histone deacetylase 1 inhibitor suppressed PKC cell proliferation. CONCLUSIONS: Under physiological conditions, E-cadherin is important for maintaining the tissue homeostasis of the pancreas. Under pathologic conditions with mutational Kras activation, E-cadherin plays an important role in tumor formation via the acquisition of tumorigenic activity.

Randomized, phase II trial of sequential hepatic arterial infusion chemotherapy and sorafenib versus sorafenib alone as initial therapy for advanced hepatocellular carcinoma: SCOOP-2 trial.

BACKGROUND: The efficacy of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) remains unclear. We conducted a multi-center randomized phase II study comparing a sequential HAIC-sorafenib regimen versus sorafenib alone as an initial therapy for HCC. METHODS: Patients were randomly assigned (ratio, 1:1) to receive sequential HAIC with cisplatin followed by sorafenib (HAIC group, n = 35) or sorafenib alone (sorafenib group, n = 33) as an initial therapy. The primary endpoint was the one-year survival rate. Secondary endpoint included overall survival (OS), the 2-year survival rate, the time-to-progression (TTP), the objective response rate (ORR), the disease control rate (DCR), and safety. RESULTS: For the primary endpoint, the one-year survival rates were 46% in the HAIC group and 58% in the sorafenib group. The median OS period was 10.0 months (95% CI, 7.0-18.8) in the HAIC group and 15.2 months (95% CI, 8.2-19.7) in the sorafenib group (hazard ratio [HR], 1.08; 95% CI, 0.63 to 1.86, P = 0.78). The median TTP, ORR and DCR in the HAIC group were 2.8 months (95% CI, 1.7-5.5), 14.3, and 45.7%, respectively, while those in the sorafenib group were 3.9 months (95% CI, 2.3-6.8), 9.1, and 45.5%, respectively. No unexpected adverse events related to HAIC or sorafenib were observed in either group. CONCLUSIONS: Sequential HAIC with cisplatin and sorafenib does not improve the survival benefit, compared with sorafenib alone, when used as an initial therapy for advanced HCC. However, this study was underpowered in regard to its primary and secondary endpoints, so the results should be interpreted with caution. TRIAL REGISTRATION: UMIN ID 000006147 , registration data: August 11, 2011.

Circulating microRNA-1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma.

AIMS: Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. METHODS: We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real-time quantitative reverse transcription-polymerase chain reaction (PCR). RESULTS: Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA-1246 (miR-1246). Quantitative PCR confirmed that miR-1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P < 0.001). Serum miR-1246 showed a receiver operating characteristic curve area of 0.762, with 77.4% specificity and 54.1% sensitivity in discriminating HCC patients with ETR from HCC patients without ETR. Altered expression of miR-1246 was associated with aggressive tumor characteristics, including tumor-node-metastasis classification (P = 0.0413), tumor differentiation (P = 0.0419), and portal vein invasion (P = 0.0394). Moreover, multivariate Cox regression analysis identified serum miR-1246 level as an independent risk factor for overall survival (hazard ratio, 2.784; 95% confidence interval, 1.528-5.071; P = 0.0008). CONCLUSION: Circulating miR-1246 in serum has strong potential as a novel ETR and prognostic biomarker for HCC.

Comparison Between Low Mechanical Index and High Mechanical Index Contrast Modes of Contrast-Enhanced Ultrasonography: Evaluation of Perfusion Defects of Hypervascular Hepatocellular Carcinomas During the Post-Vascular Phase.

OBJECTIVES: We evaluated the detection rates for perfusion defects in hypervascular hepatocellular carcinomas comparing the low mechanical index (MI) and high MI contrast modes during the post-vascular phase (PVP) of contrast-enhanced ultrasonography. METHODS: Seventy-eight patients with 84 hypervascular hepatocellular carcinomas (mean diameter, 23.4 ± 11.2 mm) were selected for this retrospective study. All the patients underwent whole-liver scanning using conventional ultrasonography before injection of a perflubutane-based contrast agent (Sonazoid), and all the detected nodules were classified as either hypoechoic or hyperechoic nodules. Next, hypoechoic and hyperechoic nodules were evaluated using contrast-enhanced ultrasonography, and the presence of a perfusion defect was assessed for each nodule using both the low MI (0.2-0.3) and the high MI (0.7-1.2) contrast modes during the PVP (10 minutes after injection). The data were analyzed using the McNemar test. RESULTS: Forty-four nodules were classified as hypoechoic nodules, and the remaining 40 nodules were classified as hyperechoic nodules using conventional ultrasonography. The detection rate for perfusion defects determined using the high MI contrast mode was higher than that determined using the low MI contrast mode in hyperechoic nodules during the PVP (low MI, 58% [23 of 40]; high MI, 90% [36 of 40]; P < .0001). However, no significant difference was observed between the low MI and the high MI contrast modes in hypoechoic nodules (low MI, 80% [35 of 44]; high MI, 89% [39 of 44]; P = .125). CONCLUSION: Compared with the low MI contrast mode, the high MI contrast mode was more sensitive for detecting perfusion defects in hypervascular hepatocellular carcinomas in patients with hyperechoic nodules during the PVP.

Randomized trial of vonoprazan-based versus proton-pump inhibitor-based third-line triple therapy with sitafloxacin for Helicobacter pylori.

BACKGROUND AND AIM: This was a prospective, randomized trial of the efficacy of vonoprazan-based and proton-pump inhibitor-based 7-day triple regimens with amoxicillin and sitafloxacin as a third-line therapy for eradicating Helicobacter pylori after failure of clarithromycin-based and metronidazole-based first-line and second-line therapy. METHODS: We enrolled 63 patients positive for H. pylori in whom first-line and second-line regimens for eradicating failed. Patients were randomized to the V-AS group (vonoprazan 20-mg bid, amoxicillin 750-mg bid, and sitafloxacin 100-mg bid for 7 days) or PPI-AS group (esomeprazole 20-mg bid, rabeprazole 10-mg bid, or lansoprazole 30-mg bid; amoxicillin 750-mg bid; and sitafloxacin 100-mg bid for 7 days). We assessed the outcome of eradication therapy using the 13 C-urea breath test. We evaluated safety using patient questionnaires. This study was registered in the UMIN Clinical Trials Registry (UMIN000016336). RESULTS: The intention-to-treat and per-protocol eradication rates of V-AS were 75.8% (95% confidence interval [CI]: 57.7-88.9%) and 83.3% (95% CI: 65.3-94.4%), respectively. The respective eradication rates of PPI-AS were 53.3% (95% CI: 34.3-71.7%) and 57.1% (95% CI: 37.2-75.5%). In per-protocol analyses, the eradication rate of the V-AS group was significantly higher than that of the PPI-AS group (P = 0.043); however, no significant differences were observed in intention-to-treat analyses (P = 0.071). Questionnaire scores did not differ significantly between the groups. CONCLUSIONS: The findings suggest that 7-day triple therapy with vonoprazan, amoxicillin, and sitafloxacin is more effective than proton-pump inhibitor, amoxicillin, and sitafloxacin as a third-line regimen for eradicating H. pylori.

Comparison of vascularity observed using contrast-enhanced 3D ultrasonography and pathological changes in patients with hepatocellular carcinoma after sorafenib treatment.

Aim: The aim of this study was to compare vascularity observed using contrast-enhanced 3D ultrasonography and pathological changes in human hepatocellular carcinoma (HCC) and surrounding non-tumorous areas after sorafenib treatment. Materials and methods: Twelve patients with HCC were enrolled in this clinical study. The maximum tumor diameter as measured using sonography ranged from 15 to 33 mm (mean, 24.0 mm; SD, 5.7 mm). Assessments using contrast-enhanced (0.2 mL of Sonazoid suspension; Daiichi Sankyo, Tokyo, Japan) 3D ultrasonography (LOGIQ 7; GE Healthcare, Milwaukee) were performed in all the patients before and 1 week after sorafenib treatment. The microvessel density (MVD) of the HCC and surrounding non-tumorous area was evaluated based on the immunohistochemical staining of microvessels using an antigen for CD34. Results: Blood flow in the tumor was decreased in all 12 cases after sorafenib treatment. The MVD of the tumorous area at 1 week after sorafenib administration (38.8 ± 5.2) was significantly lower than that observed before sorafenib administration (72.4 ± 13.0) (P < 0.01). Blood flow in the non-tumorous area had decreased in 6 cases at 1 week after sorafenib treatment and had not changed in the 6 other cases. In the reduced blood flow group, the MVD of the non-tumorous area at 1 week after sorafenib administration had decreased significantly, compared with the MVD of the non-tumorous area before sorafenib administration. However, in the group with no change in blood flow, the MVD of the non-tumorous area at 1 week after sorafenib treatment had not changed, compared with the MVD of the non-tumorous area before sorafenib treatment. Conclusion: Contrast-enhanced 3D ultrasonography studies showed a correlation between vascularity and pathological changes in human HCC and the surrounding non-tumorous area after sorafenib treatment.

Activation of Signal Transduction and Activator of Transcription 3 Signaling Contributes to Helicobacter-Associated Gastric Epithelial Proliferation and Inflammation.

BACKGROUND/AIM: Although IL-6-mediated activation of the signal transduction and activator of transcription 3 (STAT3) axis is involved in inflammation and cancer, the role of STAT3 in Helicobacter-associated gastric inflammation and carcinogenesis is unclear. This study investigated the role of STAT3 in gastric inflammation and carcinogenesis and examined the molecular mechanism of Helicobacter-induced gastric phenotypes. METHODS: To evaluate the contribution of STAT3 to gastric inflammation and carcinogenesis, we used wild-type (WT) and gastric epithelial conditional Stat3-knockout (Stat3Δgec ) mice. Mice were infected with Helicobacter felis and euthanized at 18 months postinfection. Mouse gastric organoids were treated with recombinant IL-6 (rIL-6) or rIL-11 and a JAK inhibitor (JAKi) to assess the role of IL-6/STAT3 signaling in vitro. RESULTS: Inflammation and mucous metaplasia were more severe in WT mice than in Stat3Δgec mice. The epithelial cell proliferation rate and STAT3 activation were increased in WT mice. Application of rIL-6 and rIL-11 induced expression of intestinal metaplasia-associated genes, such as Tff2; this induction was suppressed by JAKi administration. CONCLUSIONS: Loss of STAT3 signaling in the gastric mucosa leads to decreased epithelial cell proliferation, atrophy, and metaplasia in the setting of Helicobacter infection. Therefore, activation of STAT3 signaling may play a key role in Helicobacter-associated gastric carcinogenesis.

Effects of Vonoprazan Compared with Esomeprazole on the Healing of Artificial Postendoscopic Submucosal Dissection Ulcers: A Prospective, Multicenter, Two-Arm, Randomized Controlled Trial.

BACKGROUND: Vonoprazan affords more clinical benefits than proton pump inhibitors (PPIs) during the healing of gastroduodenal ulcers. However, it remains controversial whether vonoprazan is more effective than PPIs when used to heal artificial ulcers arising after endoscopic submucosal dissection (ESD). AIM: This study investigated the effects of vonoprazan compared with esomeprazole on the healing of post-ESD artificial ulcers. METHODS: Sixty patients who underwent gastric ESD between May 2015 and May 2017 were randomized to treatment with vonoprazan (V group) or esomeprazole (E group) for 8 weeks. Upper endoscopy was performed at 4 and 8 weeks after ESD, and drug effects were estimated based on the ulcer healing rates and shrinkage rates. RESULTS: Fifty-three patients were analyzed. The respective 4- and 8-week ulcer healing rates did not differ significantly between V and E groups (8.0 versus 11.5%, P = 0.669; 88.9 versus 84.6%, P = 0.420). Similarly, the respective 4- and 8-week ulcer shrinkage rates did not differ significantly between V and E groups (96.8 versus 97.5%, P = 0.656; 100 versus 100%, P = 0.257). CONCLUSION: The healing of artificial ulcers after ESD did not differ using vonoprazan or esomeprazole. Both vonoprazan and esomeprazole were effective when used to promote artificial ulcer healing after ESD.

Correction to: Helicobacter-induced gastric inflammation alters the properties of gastric tissue stem/progenitor cells.

CORRECTION: Unfortunately, the original article [1] contained an error incorporated during production. A duplicated version of Table 1 was published in place of Table 2. Table 2 has been corrected in the original article and is also included correctly below.

A new device for fiducial registration of image-guided navigation system for liver RFA.

PURPOSE: Radiofrequency ablation for liver tumors (liver RFA) is widely performed under ultrasound guidance. However, discriminating between the tumor and the needle is often difficult because of cavitation caused by RFA-induced coagulation. An unclear ultrasound image can lead to complications and tumor residue. Therefore, image-guided navigation systems based on fiducial registration have been developed. Fiducial points are usually set on a patient's skin. But the use of internal fiducial points can improve the accuracy of navigation. In this study, a new device is introduced to use internal fiducial points using 2D US. METHODS: 3D Slicer as the navigation software, Polaris Vicra as the position sensor, and two target tumors in a 3D abdominal phantom as puncture targets were used. Also, a new device that makes it possible to obtain tracking coordinates in the body was invented. First, two-dimensional reslice images from the CT images using 3D Slicer were built. A virtual needle was displayed on the two-dimensional reslice image, reflecting the movement of the actual needle after fiducial registration. A phantom experiment using three sets of fiducial point configurations: one conventional case using only surface points, and two cases in which the center of the target tumor was selected as a fiducial point was performed. For each configuration, one surgeon punctured each target tumor ten times under guidance from the 3D Slicer display. Finally, a statistical analysis examining the puncture error was performed. RESULTS: The puncture error for each target tumor decreased significantly when the center of the target tumor was included as one of the fiducial points, compared with when only surface points were used. CONCLUSION: This study introduces a new device to use internal fiducial points and suggests that the accuracy of image-guided navigation systems for liver RFA can be improved by using the new device.

Vonoprazan- vs proton-pump inhibitor-based first-line 7-day triple therapy for clarithromycin-susceptible Helicobacter pylori: A multicenter, prospective, randomized trial.

BACKGROUND: The eradication rate of vonoprazan-based first-line triple therapy (combined with clarithromycin and amoxicillin) (V-AC) was reported to be 97.6% in patients with clarithromycin (CAM)-susceptible Helicobacter pylori in a phase III study, whereas our real-world, prospective, multicenter cohort study yielded an eradication rate <90%. OBJECTIVE: To validate the eradication rate of V-AC using CAM-susceptible testing in a multicenter, prospective, randomized trial. METHODS: We included 147 treatment-naïve H. pylori-positive patients [41 with CAM-resistant infections and 106 with CAM-susceptible infections]. The CAM-susceptible group patients were randomized to either the V-AC group (vonoprazan 20 mg bid, amoxicillin 750 mg bid, and clarithromycin 200 or 400 mg bid) or PPI-AC group (lansoprazole 30 mg, rabeprazole 10 mg, or esomeprazole 20 mg bid; amoxicillin 750 mg bid; and clarithromycin 200 or 400 mg bid). All CAM-resistant H. pylori were eradicated by V-AC, as measured by the urea breath test around 8 weeks after eradication. Safety was evaluated by patient questionnaires. RESULTS: The intention-to-treat and per-protocol eradication rates of V-AC in the CAM-susceptible H. pylori-infected patients were 87.3% (95% confidence interval 75.5%-94.7%) and 88.9% (77.4%-95.8%). The respective eradication rates of PPI-AC were 76.5% (62.5%-87.2%) and 86.7% (73.2%-94.9%). No significant difference was observed between the V-AC and PPI-AC regimes in terms of the intention-to-treat (P = .21) or per-protocol (P = .77) analyses. The questionnaire scores did not differ significantly between the groups. Both the intention-to-treat and per-protocol eradication rates of V-AC in the CAM-resistant patients were 82.9% (67.9%-92.8%). CONCLUSION: The eradication rate of V-AC treatment in the CAM-susceptible H. pylori-infected patients was <90%, as was that by PPI-AC, thus V-AC is not ideal regimen in CAM-susceptible H. pylori. However, the 82.9% eradication rate of V-AC in the CAM-resistant infections may indicate the potential of V-AC with modified dose, dosing interval, and treatment duration. (UMIN000016337).