Impact of Traction Direction in Traction-Assisted Gastric Endoscopic Submucosal Dissection (with Videos).

BACKGROUND: The impact of traction direction in traction-assisted gastric endoscopic submucosal dissection (ESD) has not been adequately investigated. A clip with line (CWL) is a classical single-directional traction device. In contrast, a spring and loop with clip (SLC; S-O clip) is a newly developed multidirectional traction device. AIMS: To investigate the impact of traction direction in gastric ESD by comparing the procedure-related outcomes of CWL-assisted ESD (CWL-ESD) and SLC-assisted ESD (SLC-ESD). METHODS: We retrospectively examined 140 patients with superficial gastric neoplasms who underwent SLC-ESD or CWL-ESD by a single ESD expert during November 2017-September 2020. The traction direction was classified based on the endoscopic finding in the following five categories: proximal, diagonally proximal, vertical, diagonally distal, and distal. In SLC-ESD, we set vertical traction, using the multidirectional traction function. Propensity score matching was conducted to compensate for the differences in lesion size, injection function of electrosurgical knife, ulcerative lesion, lesion location, and lesion position. The primary outcome was gastric ESD procedure time. RESULTS: Propensity score matching created 42 pairs. The median gastric ESD procedure time in the SLC-ESD group was significantly shorter than that in the CWL-ESD group (28.3 min vs. 51.0 min, P = 0.022). All traction direction in the SLC-ESD group was vertical, while only 16.7% in the CWL-ESD group. En bloc resection was attained without perforation in all the patients in both groups. CONCLUSION: Our findings suggest that SLC can provide vertical traction, which reduces the gastric ESD procedure time. Multidirectional traction devices can provide vertical traction in most cases of gastric ESD, unlike single-directional traction devices. Vertical traction may reduce the gastric ESD procedure time.

[Two cases of lesser omentum infarction with suggestive findings in esophagogastroduodenoscopy].

We report two cases of lesser omentum infarction with suggestive findings in esophagogastroduodenoscopy (EGD). Both patients were admitted to our hospital who presented with upper abdominal pain accompanied by signs of peritoneal irritation. EGD was performed to rule out gastroduodenal ulcer. No mucosal erythema and ulceration were observed, but we observed two signs suggesting lesser omentum infarction. First, EGD showed a submucosal tumor-like mass at the angular region of the lesser curvature of the stomach in both patients. Second, one of the patients exhibited great tenderness at the site of the tumor when this was depressed by biopsy forceps. We diagnosed the two patients with lesser omentum infarction from the results of abdominal computed tomography, abdominal ultrasonography, and EGD. Conservative management was applied;the patients received analgesic drugs and gradually became asymptomatic. Lesser omentum infarction presents with abdominal pain and sometimes signs of peritoneal irritation, and almost all cases can be successfully managed with conservative treatment. Diagnosing the disease carefully and precisely is essential. We report suggestive findings in EGD, which can assist in the diagnosis of lesser omentum infarction.

Prospective study for an independent predictor of prognosis in liver cirrhosis based on the new sarcopenia criteria produced by the Japan Society of Hepatology.

AIM: There are limited data from prospective studies showing the clinical usefulness of the new criteria for sarcopenia in liver disease produced by the Japan Society of Hepatology. Therefore, we aimed to evaluate the clinical usefulness of this new criteria for prognosis in cirrhotic patients. METHODS: This prospective study was performed at six centers. The 300 enrolled patients, aged more than 20 years with liver cirrhosis, were evaluated over a 3-year period for skeletal muscle mass index and grip strength. Sarcopenia was defined according to the Japan Society of Hepatology criteria by grip strength and computed tomography-based skeletal muscle mass index values. We investigated the correlation between sarcopenia and the survival rate of cirrhotic patients. RESULTS: Among the 300 assessed patients there were 99 (33%) patients with sarcopenia. The number of deaths in the sarcopenia and non-sarcopenia groups was 34 (34.3%) and 38 (18.9%), respectively (p = 0.002). Multivariate analysis confirmed that sarcopenia, decompensated phase, albumin-bilirubin grade, and hepatocellular carcinoma (HCC) stage 3/4 were independent factors correlated with death in patients with liver cirrhosis during the observation period. The interaction between sarcopenia and the presence of HCC was statistically significant (p < 0.001), and the presence of HCC had the highest hazard ratio of 6.665 for deaths in cirrhotic patients when non-sarcopenia and the absence of HCC were used as references. CONCLUSIONS: The new Japan Society of Hepatology criteria for sarcopenia are accurate predictors of poor prognosis in patients with liver cirrhosis.

Comparing a conventional and a spring-and-loop with clip traction method of endoscopic submucosal dissection for superficial gastric neoplasms: a randomized controlled trial (with videos).

BACKGROUND AND AIMS: Several traction methods have sought to overcome the technical difficulties of endoscopic submucosal dissection (ESD). However, traction direction has remained limited in most of these methods, with lack of clarity about the optimal method and traction direction for gastric ESD. A spring-and-loop with clip (SLC) has been developed as a multidirectional traction device. Here, we investigated whether SLC traction-assisted ESD (SLC-ESD) improved procedure-related outcomes compared with conventional ESD (C-ESD) among patients with superficial gastric neoplasms. METHODS: This single-center randomized controlled trial included patients with superficial gastric neoplasms undergoing SLC-ESD or C-ESD between October 2018 and December 2019. Using the multidirectional traction function, we set traction vertical to the gastric wall for SLC-ESD. The primary outcome was the median procedure time for gastric ESD. RESULTS: The SLC-ESD and C-ESD groups comprised 40 patients each, and all the enrolled patients underwent the assigned treatment. The median ESD procedure time was significantly shorter in the SLC-ESD group (29.1 minutes) than in the C-ESD group (52.6 minutes; P = .005). SLC had a mean attachment time of 1.82 minutes. En bloc resection was achieved without perforation in all the patients in both groups. CONCLUSIONS: Our findings suggest that SLC-ESD reduces gastric ESD procedure time without increasing the risk of perforation and that the vertical direction to the gastric wall is the appropriate traction direction for gastric ESD. (Clinical trial registration number: UMIN 000034533.).

Safety and Efficacy of Lenvatinib Treatment in Child-Pugh A and B Patients with Unresectable Hepatocellular Carcinoma in Clinical Practice: A Multicenter Analysis.

PURPOSE: To assess the safety, efficacy and prognostic impact of clinical factors related to lenvatinib treatment in Child-Pugh class A (CP-A) and class B (CP-B) patients with unresectable hepatocellular carcinoma (u-HCC). METHODS: Patients with u-HCC who were treated with lenvatinib at multiple centers in Japan were retrospectively analyzed for treatment outcomes according to their respective CP status. Radiological objective response (OR) was assessed using modified response evaluation criteria in solid tumors (mRECIST) guidelines. RESULTS: Baseline demographic parameters were comparable between 126 (69.6%) patients with CP-A disease and 55 patients (30.4%) with CP-B disease. Frequency of lenvatinib-related adverse events, including decreased appetite (P=0.034), diarrhea (P=0.040), elevated serum bilirubin (P=0.016) and vomiting (P=0.009), were higher in CP-B than in CP-A patients. Relative dose intensity (RDI) was significantly higher in CP-A (0.69) than CP-B patients (0.50, P <0.001). Furthermore, OR rate (44.0%) was markedly higher in CP-A5 patients as compared to CP-A6 (25.5%), CP-B7 (22.2%), and CP-B8 patients (5.3%), respectively (P=0.002). In multivariable analysis, performance status (0 vs 1, 2, P=0.026), CP class (A vs B, P=0.045) and RDI (≥0.7 vs <0.7, P=0.034) were identified as factors associated with response to lenvatinib treatment. Overall survival (OS) at 12 months was significantly different between CP-A (66.3%) and CP-B patients (30.0%, P=0.002), and between CP 5-7 (59.2%) and CP 8 patients (34.8%, P=0.003). In multivariable analysis, CP class (A vs B, P=0.007) and Barcelona clinic liver cancer (BCLC) stage (B vs C, P=0.002) were associated with OS following lenvatinib treatment. CONCLUSION: Lenvatinib treatment offers significant benefits in patients with good liver function in real-world practice. The various characteristics identified in this study might be helpful as clinical predictors of response to lenvatinib and survival in clinical practice. Further studies are required to address eligibility for lenvatinib treatment in CP 7 patients.

Efficacy and Tolerability of Ombitasvir/Paritaprevir/Ritonavir in HCV Genotype 1-infected Elderly Japanese Patients.

INTRODUCTION AND AIM: We assessed the characteristics of virological response to a combination treatment of ombitasvir, paritaprevir, and ritonavir in hepatitis C virus genotype 1-infected elderly Japanese patients. MATERIAL AND METHODS: This multicenter prospective study was conducted at six locations in Japan. Seventy patients with chronic hepatitis C virus genotype 1b infection were orally administered ombitasvir/paritaprevir/ritonavir once daily for 12 weeks. The primary endpoint was the proportion of elderly patients with sustained virological response (SVR) 12 weeks after the completion of treatment. Adverse events were also recorded to evaluate drug safety and tolerability during the trial period. SVR in elderly patients (age > 65; 94% [47 / 50]) was lower than that in younger patients (100% [20 / 20]). RESULTS: No significant differences in SVR 12 weeks after the completion of treatment were observed between the age groups (P = 0.153). Adverse events were observed in 16 patients (23.3%). Multivariate analysis confirmed that the change or discontinuation of concomitant drugs owing to drug interactions was independent of risk factors for adverse events associated with this drug combination (P = 0.015; odds ratio, 15.9; 95% confidence interval, 1.79 - 148). Ombitasvir/paritaprevir/ritonavir combination treatment was highly effective in elderly patients. CONCLUSION: Tolerability should be monitored in older patients for whom concomitant medications are discontinued or changed because of drug interactions.

Risk factors for loss of skeletal muscle mass in patients with cirrhosis.

AIM: The present study aimed to assess the correlation between loss of skeletal muscle mass (LSMM) and the clinical characteristics of patients with liver cirrhosis. METHODS: This multicenter, prospective study was undertaken at five locations in Japan and involved a 12-month observation period. After baseline assessment, the change in the skeletal muscle index per year (ΔSMI/y) was evaluated in the enrolled patients; LSMM was defined as ΔSMI/y < 0. We evaluated the relationships between LSMM and baseline clinical characteristics in patients with liver cirrhosis. RESULTS: A total of 166 patients with cirrhosis were enrolled and, of these, 123 patients (74.1%) showed LSMM. Multivariate analysis confirmed that hepatic encephalopathy, Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP) (≥1.86), age (≥60 years), and grip strength (<18 kg for women and <26 kg for men) were independent predictors of skeletal muscle decline (P = 0.042, odds ratio [OR] 8.997, 95% confidence interval [CI] 1.083-74.71; P = 0.023, OR 3.970, 95% CI 1.468-6.177; P = 0.037, OR 2.526, 95% CI 1.056-6.045; and P = 0.002, OR 3.970, 95% CI 1.691-9.322, respectively). CONCLUSIONS: Advanced age, low grip strength, hepatic encephalopathy, and high WFA+ -M2BP might be risk factors for LSMM in liver cirrhosis patients.

Wisteria floribunda agglutinin-positive human Mac-2 binding protein in decompensated cirrhosis.

BACKGROUND AND AIM: An assay for Wisteria floribunda agglutinin-positive human Mac-2 binding protein (WFA+ -M2BP) has been reported as a useful non-invasive marker for the evaluation of the staging of fibrosis in several chronic liver diseases. However, available data on the effect of WFA+ -M2BP level in decompensated cirrhosis patients were limited. It is important that these investigations can validate the diagnostic utility of WFA+ -M2BP in the full range of patients with liver cirrhosis. METHODS: A multicenter study was conducted at five locations in Japan. A total of 207 patients with liver cirrhosis were enrolled in the present study. To determine whether or not the WFA+ -M2BP value was associated with a progression of fibrosis among cirrhosis, this study examined WFA+ -M2BP levels between patients with cirrhosis in the decompensated and compensated groups. RESULTS: The numbers and proportions of compensated and decompensated patients were 113 (54.6%) and 94 (45.4%), respectively. The average WFA+ -M2BP levels were 2.22 ± 1.61 in the compensated group and 6.91 ± 5.04 in the decompensated group. Significantly higher WFA+ -M2BP levels were observed in the decompensated group than those in the compensated group (P < 0.0001). The respective cut-off index values for decompensated cirrhosis were estimated using receiver-operating characteristic curves for WFA+ -M2BP levels. Using a cut-off index value of 3.37 for WFA+ -M2BP, predicting decompensated cirrhosis had a sensitivity of 77.8% and a specificity of 86.7%. CONCLUSIONS: WFA+ -M2BP values were higher in patients with decompensated liver cirrhosis.

Relationship of hepatitis B virus infection to the recurrence of hepatocellular carcinoma after direct acting antivirals.

Recently, two conflicting articles about recurrence of hepatocellular carcinoma (HCC) after direct acting antivirals (DAA) against hepatitis C virus (HCV) were published. We investigated the relationship between DAA and HCC recurrence. Eligible patients were (1) history of HCC and treated curatively with interventions, and (2) interferon-free DAA therapy was initiated after eradication of HCC. We analyzed contributing factor for HCC recurrence. Ten out of 23 participants (43%) encountered recurrence of HCC. Age, sex, diabetes mellitus, fibrosis score, chemistry, and alpha-fetoprotein did not differ between patients with recurrence and patients without recurrence. The patients with recurrence had significantly higher values of antibody to hepatitis B core antigen (anti-HBc) than the patients without recurrence, 6.06±3.75 vs. 0.91±2.43 (p=0.0019). The relative risk of HCC recurrence comparing anti-HBc positive to negative was 5.2 (95% confidence interval 1.40 to 19.32). Odds ratio was 22.0 (95% confidence interval 2.5 to 191.1). We conclude that anti-HBc positivity was a strong contributing factor for HCC recurrence after DAA therapy.

Long-term evaluation of partial splenic embolization followed by interferon therapy in patients with hepatitis C virus (HCV) cirrhosis and thrombocytopenia.

OBJECTIVE: Patients with hepatitis C virus (HCV) cirrhosis and thrombocytopenia are often excluded from receiving interferon therapy because the treatment results in severe platelet depletion. Surgical splenectomy or partial splenic embolization (PSE) is a promising procedure for increasing the platelet count before interferon therapy. We performed PSE and evaluated the long-term clinical course in HCV cirrhotic patients. METHODS: Patients with HCV cirrhosis and thrombocytopenia were included (n=108) in this study. The straight-coiled PSE procedure (Takatsuka method) was performed. The platelet count, hemodynamic changes, rate of a sustained virological response (SVR) and prevalence of hepatocellular carcinoma (HCC) were evaluated. RESULTS: PSE resulted in a significant increase in the platelet count (before PSE: 7.9±2.3×10(4)/µL, two weeks after PSE: 16.7±6.6×10(4)/µL (p<0.001). Therefore, all participants were started on regular-dose interferon therapy. The SVR rate was 24% for serotype 1 and 62% for serotype 2. In the biochemical responders (BR) with SVR, the overall survival rate was 94.6% over five years and 89.3% over 10 years. In the non-responders (NR), the overall survival rate was 78.7% over five years and 62.2% over 10 years. The overall survival rate of the patients with SVR+BR was significantly higher than that observed in the patients with NR (p=0.0082). There were no differences in the prevalence of HCC between the patients with SVR+BR and NR. CONCLUSION: PSE enabled the induction of regular-dose interferon therapy in patients with HCV cirrhosis and thrombocytopenia. Although the prevalence of HCC did not differ between the SVR+BR and NR patients, there was a significant survival benefit in the patients with SVR+BR.

Possible role of early transabdominal ultrasound in patients undergoing cytapheresis for active ulcerative colitis.

BACKGROUND: Cytaphresis (CAP) is an effective modality in the treatment of active ulcerative colitis (UC), but the time lag before a notable clinical response on scheduled therapy frequently causes a significant delay in the modification of treatment. We previously reported that the clinical response after CAP was predicted by early application of transabdominal ultrasound (TAUS), but the predictability of long-term outcome after CAP still remains uncertain. METHODS PATIENTS: Twenty-six patients with active UC who received CAP were followed for 1 year. In addition to CAP they received pharmaceutical regimens, such as corticosteroid, 5-aminosalicylic acid, and immunomodulator, as indicated clinically. The mean UC-DAI score was 9.7 before CAP, and 3.2 at 1 year after CAP. Prognostic factor: Total colonic wall thickness was measured by TAUS at 2 to 3 weeks after the initiation of the treatment, and decrement from baseline was calculated. Early ultrasonographic response (EUR) was defined as a decrement statistically. UC-DAI score of 2 or less at 1 year was defined as sustained clinical remission. Score of 6 or more was defined as clinical relapse. RESULTS: EUR was defined as a decrement in wall thickness by at least 2.5 mm from the baseline. EUR was noted in 11 patients, and the remaining 15 did not attain EUR. OUTCOME MEASURES: In the UC-DAI score measured at 1 year after initiation of treatment 90.9% of patients with EUR, whereas 40.0% with non-EUR (p<0.05) showed sustained clinical remission. Regarding relapse, within 1 year 9.1% of patients with EUR relapsed whereas 46.7% with non-EUR (p<0.05) relapsed. CONCLUSION: Early application of TAUS may predict the long-term clinical outcome after CAP in patients with active UC.

Two week induction of interferon-beta followed by pegylated interferon alpha-2b and ribavirin for chronic infection with hepatitis C.

OBJECTIVES: To elucidate the efficacy of interferon (IFN)-beta induction therapy followed by pegylated IFN alpha and ribavirin for chronic infection with hepatitis C virus (HCV). METHODS: Patients chronically infected with HCV genotype 1, high titer were enrolled. Twice daily bolus injections of 3 million units IFN-beta were administered for 14 days. Thereafter, weekly injection of pegylated IFN alpha 2b and daily intake of ribavirin were followed. Therapy duration was adjusted according to the response to the therapy. When time to an undetectable HCV-RNA was 1, 2, 4, 8, and 12 weeks, total duration of therapy was 12, 24, 36, 48 and 60 weeks, respectively. Patients who failed to achieve an undetectable HCV-RNA within 12 weeks discontinued therapy on 12 week. RESULTS: Among the 101 patients treated, 56 (55.4%) achieved sustained virological response (SVR). SVR rate for each treatment duration was 10/10 for 12 weeks, 12/14 for 24 weeks, 18/19 for 36 weeks, 15/26 for 48 weeks, 1/4 for 60 weeks and 0/28 for patients who discontinued therapy at 12 weeks. Mean time to an undetectable HCV-RNA was 35.5 +/- 2.7 days. Mean therapy duration was 27.3 +/- 1.4 weeks. Using a cut off value of 21.5 fmol/L of HCV core-antigen in the first week, SVR could be predicted by sensitivity of 0.91 and specificity of 0.78. CONCLUSION: IFN-beta induction therapy resulted in acceptable SVR rates despite short therapy duration. Steep reduction of HCV by IFN-beta enables us to predict SVR in the first week of therapy.