Systemic immune-inflammation index predicts prognosis of sequential therapy with sorafenib and regorafenib in hepatocellular carcinoma.

BACKGROUND: Regorafenib has shown promising results as a second-line therapy for patients with hepatocellular carcinoma (HCC) who progressed on sorafenib. Although there have been several data regarding the efficacy of sequential therapy with sorafenib and that of regorafenib in real-life, specific inflammation markers for predicting the prognosis have not been studied. This study aimed to investigate prognostic value of systemic inflammatory markers in patients with HCC who received sorafenib-regorafenib sequential therapy. METHODS: We retrospectively analyzed medical data of patients who received regorafenib for the treatment of HCC after sorafenib failure. Progression free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier survival curves. Univariate and multivariate analyses were performed to analyze the factors associated with survival. RESULTS: A total of 58 patients who received at least one dose of regroafenib and fulfilled the eligibility criteria, good performance status (Eastern Cooperative Oncology Group [ECOG] 0-1) and preserved liver function (Child-Pugh-A), were included in the analysis. The median PFS was 3 months (95% confidence interval [CI] = 0.981-5.019) and the median OS was 8 months (95% CI = 5.761-10.239). Elevated systemic immune-inflammation index (SII ≥340) was independently associated with poor OS. In multivariate analysis, the SII (hazard ratio [HR] = 2.211, 95% CI = 1.089-4.489, P = 0.028) and alpha-fetoprotein (AFP) (HR = 2.750, 95% CI = 1.259-6.010, P = 0.011) were independent predictors of OS. CONCLUSION: Elevated SII is associated with poor OS in patients with HCC who received sequential therapy with sorafenib and regorafenib. In addition, when selecting a treatment strategy, the SII can be used in combination with the AFP level as a promising prognostic tool for HCC.

Direct-Acting Antivirals Improve Treatment Outcomes in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma Treated with Transarterial Chemoembolization: A Nationwide, Multi-center, Retrospective Cohort Study.

BACKGROUND AND AIMS: The influence of direct-acting antivirals (DAAs) on chronic hepatitis C (CHC)-related hepatocellular carcinoma (HCC) remains controversial. We investigated the effect of eradicating CHC using DAAs on treatment outcomes in patients with CHC-related HCC treated with transarterial chemoembolization (TACE). METHODS: This nationwide, multi-center, retrospective study recruited patients with CHC-related HCC treated with TACE as the first-line anti-cancer treatment, and who achieved a sustained virological response (SVR) using DAAs (DAA group) between 2006 and 2017. Patients achieving an SVR following interferon-based treatment (IFN group) and those without treatment (control group) were also recruited for comparison. RESULTS: A total of 425 patients were eligible for the study. Of these, 356 (83.8%), 26 (6.1%), and 43 (10.1%) were allocated to the control, IFN, and DAA groups, respectively. A multivariate analysis showed that liver cirrhosis, segmental portal vein thrombosis, and larger maximal tumor size independently predicted an increased risk of progression (all p < 0.05), whereas, the DAA group (vs. IFN and control groups) independently predicted a reduced risk of progression (hazard ratio (HR) = 0.630, 95% confidence interval 0.411-0.966, p = 0.034). The cumulative incidence rate of HCC progression in the DAA group was significantly lower than that in the IFN and control groups (p = 0.033, log-rank test). In addition, the DAA group (vs. IFN and control groups) was independently associated with a reduced risk of mortality (p = 0.042). CONCLUSIONS: DAA treatment provided significantly prolonged progression-free survival in patients with CHC-related HCC treated with TACE compared to that in patients administered IFN or no treatment.

Pretreatment peripheral neutrophils, lymphocytes and monocytes predict long-term survival in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is an inflammation-related cancer, where nonresolving inflammation contributes to its development and progression. Peripheral inflammatory cells have been shown to be associated with the prognosis of various types of cancer. The present study investigated the utility of pretreatment peripheral inflammatory cells in the prognosis of patients with HCC. METHODS: We retrospectively analyzed data regarding peripheral inflammatory cell, and patient and tumor characteristics from patients with HCC who were diagnosed between November 2008 and March 2018. Baseline data, including peripheral inflammatory cell counts, were recorded before treatment. The relationships between overall survival (OS) and study variables were assessed. RESULTS: A total of 1681 patients who were diagnosed with HCC were included. In univariate and multivariate analyses, individual neutrophil, lymphocyte and monocyte cell counts were found as independent indicators of poor OS. High neutrophil (≥3100 × 106/L) and, monocyte (≥470 × 106/L) counts and low lymphocyte counts (< 1640 × 106/L) significantly associated with reduced OS (p < 0.05). Neutrophil and, monocyte cell counts rose and lymphocyte counts decreased in association with advancing the Barcelona Clinic Liver Cancer stage (P < 0.001). CONCLUSIONS: Pretreatment peripheral neutrophils, lymphocytes, and monocytes are independently associated with outcomes of patients with HCC. These cells provides a noninvasive, low-cost, easy, and reproducible biomarker that can be used in routine clinical practice to predict the prognosis of patients with HCC.

Risk factors of early recurrence after curative hepatectomy in hepatocellular carcinoma.

Early recurrence is common after curative hepatectomy for hepatocellular carcinoma and is associated with poor prognosis. This study aimed to identify risk factors of early recurrence after curative hepatectomy in hepatocellular carcinoma. Overall, 63 patients who underwent curative hepatectomy for hepatocellular carcinoma were enrolled. Patients were divided into the early recurrence group, who developed recurrence within 12 months after hepatectomy (n = 10), and the non-early recurrence group (n = 53). Clinicopathological factors of early recurrence were retrospectively analyzed. Among the 63 patients, 10 (15.9%) patients experienced early recurrence. Univariate analysis showed tumor necrosis (p = 0.012), level of PIVKA-II (prothrombin induced by vitamin K absence or antagonist-II; p = 0.002), and microvascular invasion (p = 0.029) to be associated with early recurrence. By multivariate analysis, there were significant differences in high PIVKA-II (p < 0.001) and tumor necrosis (p = 0.012) in patients with early recurrence. The optimal cutoff values of PIVKA-II and tumor necrosis were 46 mAU/mL and 3% of total tumor volume, respectively. Patients with a high preoperative PIVKA-II level and extent of tumor necrosis, which are independent risk factors for early recurrence, should be actively treated and monitored closely after hepatectomy.

Effect of yttrium-90 radioembolization on outcomes in Asian patients with early to advanced stage hepatocellular carcinoma.

AIM: The aim of this study was to investigate the effect of yttrium-90 radioembolization on the outcome of Asian patients with early to advanced stage hepatocellular carcinoma (HCC). METHODS: Sixty-two patients were screened and 50 patients (80.6%) were eligible. Response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST), and overall survival was estimated using the Kaplan-Meier method. RESULTS: The Barcelona Clinic Liver Cancer (BCLC) stage was A in 40% of patients, B in 24%, and C in 36%; 66% of patients had hepatitis B virus infections. According to RECIST criteria, partial responses occurred in 40% of patients, and stable disease was achieved in 46%. Tumor response was significantly associated with BCLC stage (P = 0.003). The median overall time to progression was 5.8 months (range, 0.9-46.1 months). Follow-up treatments after radioembolization were carried out in 31 patients due to remnant HCC (n = 18) or HCC progression (n = 13). The median overall survival was 40.9 months (95% confidence interval, 10.2-71.6 months). Treatment was tolerable except for one lung toxicity and two hepatic toxicities. CONCLUSION: Yttrium-90 radioembolization appears to be well tolerated and effective in Asian patients with BCLC stage A-C HCC. Follow-up treatments after radioembolization can be safely provided.

Urgency to treat patients with chronic hepatitis C in Asia.

Chronic hepatitis C (CHC) infection poses a global healthcare burden, being associated with serious complications if untreated. The prevalence of hepatitis C virus (HCV) infection is highest in areas of Central, South, and East Asia; over 50% of HCV patients worldwide live in the region, where HCV genotypes 1b, 2, 3, and 6 are the most prevalent. Treatment outcomes for chronic hepatitis C vary by ethnicity, and Asian patients achieve higher sustained virologic response rates following interferon (IFN)-based therapy than non-Asians. However, low efficacy, poor safety profile, and subcutaneous administration limit the use of IFN-based therapies. Superior virologic outcomes have been observed with different classes of direct-acting antivirals (DAAs) alone or in combination, and several all-oral DAA regimens are available in Asia. These regimens have shown excellent efficacy and favorable tolerability in clinical trials, yet there is a need for further studies of DAAs in a real world context, particularly in Asia. Furthermore, IFN-free treatment may not be accessible for many patients in the region, and IFN-based regimens remain an option in some countries. There is a need to improve current clinical practices for HCV management in Asia, including effective screening, disease awareness, and prevention programs, and to further understand the cost-effectiveness of IFN-free regimens. The evolution of potent treatments makes HCV eradication a possibility that should be available to all patients. However, access to these therapies in Asian countries has been slow, primarily because of economic barriers that continue to present a hurdle to optimal treatment.

Factors associated with clinical failure of self-expandable metal stent for malignant gastroduodenal obstruction.

OBJECTIVE: Endoscopic self-expandable metal stent (SEMS) placement has emerged as an effective palliative treatment for inoperable malignant gastric outlet obstruction (GOO). In spite of successful stent placement, some patients complain of ongoing dysphagia and vomiting. Most reported data on SEMS to date are about technical success of different types of stents and low complication rates. The aim of this study was to evaluate the associated factors of clinical failure after endoscopic SEMS placement for inoperable malignant GOO. METHODS: A total 122 patients who underwent successful endoscopic SEMS placement for malignant GOO in an academic referral center were included in the analyses. We retrospectively evaluated variables associated with clinical outcomes after successful SEMS placement. RESULTS: The clinical success rate was 81.1%. The common causes of GOO were pancreatic (39%) and gastric cancers (32%). The mean length of the stents (± standard deviation) was 10.06 ± 2.42 cm. Multivariate analysis revealed that gallbladder cancer (p = 0.016, OR 6.486, 95% CI, 1.509-59.655), poor performance status (ECOG ≥ 3) (p = 0.001, OR 10.200, 95% CI, 2.435-42.721), the presence of carcinomatosis peritonei (p < 0.001, OR 35.714, 95% CI, 5.556-250.000) and the failure of endoscope passage (p = 0.039, OR 6.945, 95% CI, 1.101-43.818). CONCLUSION: Our results suggest that gallbladder cancer, poor performance status (ECOG ≥ 3) and the presence of carcinomatosis peritonei related with clinical failure of palliative SEMS placement.

A 96-week randomized trial of switching to entecavir in patients who achieved virological suppression on lamivudine therapy.

BACKGROUND AND AIM: There are limited data assessing whether patients who achieved virological suppression on lamivudine but remain hepatitis B "e" antigen-positive should be switched to a more potent antiviral with a high genetic barrier to resistance or continue with lamivudine. We compared the safety and efficacy of switching with entecavir versus continuing lamivudine. METHODS: This was a Phase IV, randomized, open-label, prospective study in a tertiary care setting. Seventy-three chronic hepatitis B patients who achieved virological suppression on lamivudine (serum hepatitis B virus DNA < 60 International Unit (IU)/mL) were enrolled. Entecavir or lamivudine were administered orally for up to 96 weeks. Virologic and serologic responses were measured throughout the study. RESULTS: A significantly higher proportion of patients in the entecavir group achieved hepatitis B virus DNA < 60 IU/mL at Weeks 48 (100% [38/38] vs 62.8% [22/35]; P < 0.001) and 96 (97.4% [37/38] vs 57.1% [20/35]; P<0.001). A greater number of patients had virologic breakthrough (Week 96 cumulative incidence 42.9% vs 2.6%; P<0.001) and genotypic lamivudine resistance (28.6% [10/35] vs 0% [0/38]; P<0.001) in the lamivudine group. No serious adverse events or laboratory abnormalities were reported. CONCLUSIONS: Even after achieving virological suppression on lamivudine therapy, the risk of emergent lamivudine resistance increases over time. Switching to entecavir resulted in a maintained virologic response and superior serologic responses versus continued lamivudine therapy. This study supports a rationale for switching to entecavir in chronic hepatitis B patients with virological suppression on lamivudine.

Trends and Patterns of Hepatocellular Carcinoma Treatment in Korea.

Multiple therapeutic modalities are available for hepatocellular carcinoma (HCC) treatment. We aimed to evaluate the trends for HCC treatment in Korea. Recent trends and patterns in treatment modalities were assessed in HCC patients who first registered for the Health Insurance Review Assessment Service between 2008 and 2012. From 2009 to 2012, 57,690 patients were diagnosed with HCC. Transcatheter arterial chemoembolization (TACE) was the most common treatment modality for initial treatment. Curative treatment modalities like hepatic resection, liver transplantation, and local ablation therapy increased gradually. The 3 most common treatment modalities (hepatic resection, local ablation therapy, TACE) used after initial treatment in 2009 were studied. Following initial hepatic resection, 44.5% of patients required re-treatment. TACE was the most common modality (in 48.3% of cases), while 15.0% of patients received local ablation therapy. After local ablation therapy, 55.4% of patients were re-treated, wherein 45.0% of patients received TACE and 31.5% received local ablation therapy. Following initial TACE, 73.9% patients were re-treated, most commonly with TACE (57.7%) followed by local ablation therapy (12.8%). While there were no significant differences between the initial and re-treatment modalities, various multiple treatments followed the initial treatment. The treatment modalities were interchangeable.

The Prescription Pattern of Acetaminophen and Non-Steroidal Anti-Inflammatory Drugs in Patients with Liver Cirrhosis.

Analgesics, known to be hepatotoxic drugs, are frequently prescribed to patients with liver cirrhosis who are prone to drug-induced liver injury. No guidelines are available regarding the prescription of analgesics in these patients. Therefore, we aimed to evaluate the prescription pattern of most frequently used analgesics in patients with cirrhosis. We assessed the prescription pattern of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) in patients with liver cirrhosis registered in Health Insurance Review Assessment Service database between January 1, 2012 and December 31, 2012. A total of 125,505 patients with liver cirrhosis were registered from January 1, 2012 to December 31, 2012. Of that group, 50,798 (40.5%) patients claimed reimbursement for at least one prescription for acetaminophen or NSAIDs during the one year follow-up period. Overall, NSAIDs (82.7%) were more prescribed than acetaminophen (64.5%). NSAIDs were more prescribed than acetaminophen even in decompensated cirrhosis compared with compensated cirrhosis (71.5% vs. 68.8%, P value < 0.001). There was a marked difference in prescription preference between acetaminophen and NSAIDs among physicians. Internists more frequently prescribed acetaminophen than NSAIDs compared to other physicians (50.9% vs. 76.2%, P < 0.001). Gastroenterologists more frequently prescribed acetaminophen over NSAIDs compared to other internists (80.9% vs. 51.2%, P < 0.001). Analgesics were prescribed in 40.5% of patients with cirrhosis. NSAIDs were more frequently prescribed although they should be avoided. The prescription pattern of analgesics were different significantly among physicians in patients with liver cirrhosis. The harmful effects of NSAIDs in patients with cirrhosis should be reminded to all physicians prescribing analgesics.

Two-year treatment outcome of chronic hepatitis B infection treated with besifovir vs. entecavir: results from a multicentre study.

BACKGROUND & AIMS: We aimed to compare the viral suppression, safety and rate of drug resistance between besifovir (a new acyclic nucleotide analogue) and entecavir. METHODS: Treatment-naïve chronic hepatitis B patients receiving besifovir 90 mg (n=31), 150 mg (n=28) and entecavir 0.5 mg (n=30) were monitored for liver biochemistry, viral serology, HBV DNA levels, development of drug resistance mutations, and adverse events throughout 96 weeks of treatment. RESULTS: The mean decline of HBV DNA levels from baseline to week 96 were 5.29, 5.15, and 5.67 logs IU/ml for patients receiving besifovir 90 mg, 150 mg and entecavir 0.5 mg, respectively (p>0.05). Undetectable HBV DNA (<20 IU/ml) were achieved in 80.7%, 78.6%, and 80%; ALT normalization in 90.3%, 78.6%, and 93.3%; and loss of HBeAg in 20%, 21.4%, and 22.2% of patients respectively (all p>0.05). One patient receiving besifovir 90 mg had a virological breakthrough due to drug non-compliance. No patient developed drug resistance mutations. Ten patients had serious adverse events, which were not related to the study medications. The most common side effect related to besifovir was carnitine depletion. Carnitine supplements were prescribed to 83.9% and 100% of patients, who had low carnitine level for any one time during follow-up, receiving besifovir 90 mg and 150 mg respectively. No patient had increased creatinine>0.5 mg/dl from baseline. CONCLUSIONS: Besifovir had the same antiviral property as compared to entecavir over 96 weeks of treatment for chronic hepatitis B patients. Besifovir was well tolerated and also had a good clinical safety profile.

Lack of difference among terlipressin, somatostatin, and octreotide in the control of acute gastroesophageal variceal hemorrhage.

UNLABELLED: Vasoactive drugs are recommended to be started as soon as possible in suspected variceal bleeding, even before diagnostic endoscopy. However, it is still unclear whether the therapeutic efficacies of the various vasoactive drugs used are comparable. The aim of this prospective, multicenter, randomized, noninferiority trial was to characterize the effects of terlipressin, somatostatin, and octreotide when they are initiated before endoscopic treatment in patients with acute variceal bleeding. Patients with liver cirrhosis and significant upper gastrointestinal bleeding were randomly assigned to receive early administration of terlipressin, somatostatin, or octreotide, followed by endoscopic treatment. Patients with nonvariceal bleeding were excluded after endoscopy. The primary endpoint was 5-day treatment success, defined as control of bleeding without rescue treatment, rebleeding, or mortality, with a noninferiority margin of 0.1. In total, 780 patients with variceal bleeding were enrolled: 261 in the terlipressin group; 259 in the somatostatin group; and 260 in the octreotide group. At the time of initial endoscopy, active bleeding was noted in 43.7%, 44.4%, and 43.5% of these patients, respectively (P=0.748), and treatment success was achieved by day 5 in 86.2%, 83.4%, and 83.8% (P=0.636), with similar rates of control of bleeding without rescue treatment (89.7%, 87.6%, and 88.1%; P=0.752), rebleeding (3.4%, 4.8%, and 4.4%; P=0.739), or mortality (8.0%, 8.9%, and 8.8%; P=0.929). The absolute values of the lower bound of confidence intervals for terlipressin versus somatostatin, terlilpressin versus octreotide, and octreotide versus somatostatin were 0.095, 0.090, and 0.065, respectively. CONCLUSION: Hemostatic effects and safety did not differ significantly between terlipressin, somatostatin, and octreotide as adjuvants to endoscopic treatment in patients with acute gastroesophageal variceal bleeding.

Risk factors associated with diagnostic discrepancy of gastric indefinite neoplasia: Who need en bloc resection?

BACKGROUND: Endoscopic forceps biopsy is insufficient for a definitive diagnosis of dysplastic lesions. It is difficult to decide clinical management of gastric indefinite neoplasia diagnosed by endoscopic forceps biopsy when early gastric cancer (EGC) is macroscopically suspected. The aim of this study was to discuss the final results of gastric indefinite neoplasia and associated clinical factors predictive of early gastric cancer. METHODS: The medical records of 119 patients who were diagnosed with gastric indefinite neoplasia by index forceps biopsy were retrospectively reviewed. The initial endoscopic findings were analyzed, and predictive factors of EGC were evaluated. RESULTS: The final pathologic diagnoses of 119 patients included early gastric cancer (n = 26, 21.8%), adenoma (n = 6, 5.0%) and non-neoplasm (n = 87, 73.1%). Univariate analysis showed that lesion size greater than 10 mm, surface nodularity and surface redness were associated risk factors. In the multivariate analysis, lesions diameter (p = 0.021, OR 11.401, 95% CI 1.432-90.759) and surface redness (p = 0.014, OR 3.777, 95% CI 1.306-10.923) were significant risk factors. CONCLUSIONS: Patients with gastric indefinite neoplasia with larger size (≥10 mm) and surface redness might need further diagnostic investigation rather than simple follow-up endoscopy.

High Dose Proton Pump Inhibitor Infusion Versus Bolus Injection for the Prevention of Bleeding After Endoscopic Submucosal Dissection: Prospective Randomized Controlled Study.

BACKGROUND: A high dose of continuous intravenous infusion of proton pump inhibitor (PPI) is the standard treatment for peptic ulcer bleeding. The optimal dose for the prevention of bleeding after endoscopic submucosal dissection (ESD) is unclear. AIM: The purpose of this study was to determine whether stronger acid suppression more effectively prevents bleeding and high risk ulcer stigma (HRS) after gastric ESD. METHODS: A total of 273 patients who underwent ESD were randomly assigned to one of two treatment groups: the continuous infusion group and the bolus injection group. Second-look endoscopy was performed on the following day after ESD. The incidences and risk factors of HRS identified by second-look endoscopy and delayed bleeding were analyzed. RESULTS: There were no differences in the incidences of HRS and delayed bleeding between two treatment groups. The incidence of HRS was 15.8 % (43/273) and the gross morphology (flat or depressed) was identified as a significant factor associated with HRS. The incidence of delayed bleeding was 8.4 % (23/273) and the gross morphology (flat) and the presence of submucosal invasive cancer were identified as the associated risk factors for delayed bleeding. CONCLUSION: The incidences of delayed bleeding and HRS identified by second-look endoscopy were not affected by PPI infusion methods. Flat or depressed morphologic lesions and submucosal invasive cancer should be closely monitored.

Phase IIb multicentred randomised trial of besifovir (LB80380) versus entecavir in Asian patients with chronic hepatitis B.

BACKGROUND: Besifovir (LB80380) is an acyclic nucleotide phosphonate effective in hepatitis B virus (HBV) DNA suppression for both treatment-naive and lamivudine-resistant chronic hepatitis B (CHB) patients in preliminary studies. DESIGN: We aimed to compare the safety and antiviral activity of two doses of besifovir (90 mg and 150 mg daily) with entecavir 0.5 mg daily in CHB patients. 114 patients were randomised to receive besifovir 90 mg daily (n=36), besifovir 150 mg daily (n=39) or entecavir 0.5 mg daily (n=39). HBV DNA and liver biochemistry, including serum L-carnitine levels, were monitored. RESULTS: At week 48, in the intention-to-treat population, the proportion of patients achieving undetectable HBV DNA (<20 IU/mL) were 63.6%, 62.9% and 58.3%, respectively (p>0.05). The serum mean log10 HBV DNA changes from baseline for the HBeAg-positive patients were -5.84, -5.91 and -6.18, respectively; and for the HBeAg-negative patients were -4.65, -4.55 and -4.67, respectively (p>0.05). There were no differences in the proportions of patients achieving normalisation of alanine aminotransferase (91.7%, 76.9%, 89.7%, respectively) and HBeAg seroconversion (11.11%, 15%, 9.52%, respectively) among all three groups. None of the patients had resistant mutations or increase in serum creatinine of >0.5 mg/dL from baseline. 64 (94.1%) patients on besifovir had lowering of serum L-carnitine (not tested in entecavir patients). L-carnitine levels returned to normal with carnitine supplement. CONCLUSIONS: At 48 weeks, 90 mg and 150 mg daily of besifovir were non-inferior to entecavir 0.5 mg daily in treatment-naive CHB patients. The only significant side effect of besifovir was L-carnitine depletion, requiring carnitine supplementation.

Clinical outcomes of second-look endoscopy after gastric endoscopic submucosal dissection: predictive factors with high risks of bleeding.

BACKGROUND: A second-look endoscopy is routinely performed after endoscopic submucosal dissection (ESD) in many institutions, although the need is questionable. Additional hemostatic procedures might be necessary for the post-ESD ulcer with a high risk of bleeding. We investigated the predictive factors for post-ESD ulcers with a high risk of bleeding. METHODS: Second-look endoscopy was performed on the day following ESD. The post-ESD ulcers were categorized into two risk groups according to the Forrest classification: high-risk ulcer stigma (type I and IIa) and low-risk ulcer stigma. We analyzed the risk factors associated with high-risk ulcer stigma and late delayed bleeding. RESULTS: During the study period, 616 ESD procedures were performed. Second-look endoscopy revealed that the incidence of high-risk ulcer stigma post-ESD was 15.1%. Early and late delayed bleeding rates were 3.7 and 1.9%, respectively. Multivariate analysis revealed that submucosal fibrosis and nausea were significantly related to high-risk ulcer stigma after ESD. Multivariate analysis revealed that surface erosion, location of the lesion, and high-risk ulcer stigma identified by second-look endoscopy were significantly associated with late delayed bleeding. CONCLUSIONS: The effective use of selective second-look endoscopy will help limit unnecessary procedures. Submucosal fibrosis and nausea were risk factors associated with high-risk ulcer stigma after ESD.

The risk factors for discrepancy after endoscopic submucosal dissection of gastric category 3 lesion (low grade dysplasia).

BACKGROUND: Treatment with endoscopic submucosal dissection (ESD) for gastric category 3 lesion (low grade dysplasia, LGD) diagnosed by endoscopic forceps biopsy (EFB) is controversial. AIMS: The purpose of the present study was to validate the use of ESD for gastric LGD diagnosed by EFB and to evaluate predictable factors for pathologic upgrade diagnosis to category 4 (high grade dysplasia, HGD) or 5 (early gastric cancer, EGC) lesions. METHODS: Between November 2008 and October 2011, a retrospective analysis of a prospective database was conducted at a single tertiary referral center. A total of 218 ESD procedures were carried out for gastric LGD lesions identified by EFB. The under-diagnosis rate by EFB and the predictable factors for upgrade diagnosis to category 4 or 5 lesions were analyzed. RESULTS: Pathologic discrepancy between EFB and surgical resection was 20.1 % (44/218). Thirty eight lesions (17.4 %) were diagnosed HGD or EGC by ESD. Gastric HGD lesions were 14 cases (6.4 %) and EGC lesions were 24 cases (23 mucosal and 1 submucosal cancer) (11.0 %). Multivariate analysis revealed that lesion diameter more than 1 cm (OR 3.496 [95 % CI 1.375-8.849]), surface redness (OR 6.493 [95 % CI 2.557-16.666]) and nodular surface (OR 2.762 [95 % CI 1.237-6.172]) were significant risk factors. CONCLUSIONS: Endoscopic resection can be recommended if a LGD lesion has risk factors such as a size of 1 cm or greater, surface redness or surface nodulariy. For lesions without the risk factors, follow-up endoscopy may be recommended.

Development of chimeric antigen receptor (CAR)-T cells targeting A56 viral protein implanted by oncolytic virus.

To address the challenge of solid tumor targeting in CAR-T therapy, we utilized the A56 antigen, which is uniquely expressed on a diverse range of cancer cells following the systemic administration of an oncolytic vaccinia virus (OVV). Immunohistochemical assays precisely confirmed exclusive localization of A56 to tumor tissues. In vitro studies demonstrated a distinct superiority of A56-dependent CAR-T cytotoxicity across multiple cancer cell lines. Building on these in vitro observations, we strategically administered A56 CAR-T cells, OVV, and hydroxyurea (HU) combination in HCT-116 tumor-bearing non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, leading to a significant reduction in tumor size and an extended time to progression. Consequently, A56-targeting combinatorial immunotherapy provides the benefit of reducing inadvertent CAR-T effects on normal cells while preserving its effectiveness against cancer cells. Furthermore, our approach of implanting A56 via OVV on tumors facilitates a wide therapeutic application of CAR-T cells across various solid tumors.

Comparison of endoscopic resection therapies for rectal carcinoid tumor: endoscopic submucosal dissection versus endoscopic mucosal resection using band ligation.

BACKGROUND: Endoscopic mucosal resection (EMR) has been the endoscopic treatment of choice for rectal carcinoid tumors <10 mm in size. Endoscopic submucosal dissection (ESD) may cause more severe complications, longer operation time, and higher cost than EMR. AIM: : To compare EMR using band ligation (EMR-B) method with ESD for the endoscopic treatment of rectal carcinoid tumors. METHODS: From November 2008 to September 2011, we enrolled consecutive patients with rectal carcinoid tumors <10 mm in diameter and without lymph node enlargement. Rate of complete resection rate, incidence of complications, and length of procedures were evaluated. RESULTS: Sixty patients were enrolled (31 ESD cases and 29 EMR-B cases). The mean age was 48.03±13.09 years. Both groups had similar mean tumor diameter (EMR-B 4.34±1.75 vs. ESD 5.22±2.09 mm; P=0.084). Resection time was longer in the ESD group than in the EMR-B group (15.09±5.73 vs. 6.37±5.52 min; P<0.001). The complete resection rate was 80.6% (25 of 31) in the ESD group and 82.8% (24 of 29) in the EMR-B group (P=0.833). In incomplete resection cases, neither local recurrence nor distant metastasis was detected during the follow-up period. CONCLUSIONS: Compared with ESD, EMR-B resulted in a comparable histologically complete resection rate and took less time to perform. Given the advantages of easier and shorter procedure time, EMR-B may be considered the treatment of choice for small rectal carcinoid tumors.

Long-term outcomes of endoscopic submucosal dissection for early gastric cancer: a single-center experience.

BACKGROUND: In Korea, endoscopic submucosal dissection (ESD) has been widely accepted for the treatment of early gastric cancers (EGCs). However, the understanding of the long-term clinical outcome of ESD for EGC remains insufficient. Therefore, the aim of the present study was to assess the long-term clinical outcome and efficacy of ESD for the treatment of EGCs, including the clinical application of the expanded criteria for ESD. METHODS: From January 2006 to December 2010, a total of 515 patients with 522 EGCs were treated by ESD in our hospital; study enrollment was based on the expanded criteria. Comparisons of resectability (en bloc or piecemeal resection), curability (curative or non-curative), and complications (bleeding and perforation) between the standard and expanded groups were assessed. Thereafter, 336 patients with 342 EGCs were finally included in a long-term analysis of local tumor recurrence, development of synchronous and metachronous cancers, and overall and disease-specific survival rates. RESULTS: En bloc and curative resection rates of 96.7 % and 88.3 %, respectively, were achieved. The curative resection rate was significantly lower in the expanded group than in the standard group (82.1 % vs. 91.5 %, p = 0.001). During a median follow-up of 24 months, the local tumor recurrence rate was also higher in the expanded group than in the standard group (7.0 % vs. 1.8 %, p = 0.025). Local recurrence was more frequent in lesions with non-curative resection than in those with curative resection (20.0 % vs. 1.3 %, p < 0.001). The 5-year overall and disease-specific survival rates were 88 % and 100 %, respectively; the difference between the standard and expanded groups was not significant (p = 0.834). CONCLUSIONS: ESD appears to be a feasible and effective method for treating EGCs, based on the standard and expanded criteria. Close follow-up surveillance, after ESD, should be standard for all patients.