Simultaneous establishment of pancreatic cancer organoid and cancer-associated fibroblast using a single-pass endoscopic ultrasound-guided fine-needle biopsy specimen.

Considering the critical roles of cancer-associated fibroblasts (CAFs) in pancreatic cancer, recent studies have attempted to incorporate stromal elements into organoid models to recapitulate the tumor microenvironment. This study aimed to evaluate the feasibility of patient-derived organoid (PDO) and CAF cultures by using single-pass endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) samples from prospectively enrolled pancreatic cancer patients. The obtained samples were split into two portions for PDO and CAF cultures. PDOs and CAFs were cultured successfully in 54.4% (31/57) and 47.4% (27/57) of the cases, respectively. Both components were established in 21 cases (36.8%). Various clinicopathologic factors, including the tumor size, tumor location, clinical stage, histologic subtype, and tumor differentiation, did not influence the PDO establishment. Instead, the presence of necrosis in tumor samples was associated with initial PDO generation but no further propagation beyond passage 5 (P = 0.024). The "poorly cohesive cell carcinoma pattern" also negatively influenced the PDO establishment (P = 0.018). Higher stromal proportion in tumor samples was a decisive factor for successful CAF culture (P = 0.005). Our study demonstrated that the coestablishment of PDOs and CAFs is feasible even with a single-pass EUS-FNB sample, implying an expanding role of endoscopists in future precision medicine.

WT1 Pulsed Human CD141+ Dendritic Cell Vaccine Has High Potential in Solid Tumor-Targeted Immunotherapy.

Dendritic cells (DC) are powerful cells that play critical roles in anti-tumor immunity, and their use in cancer immunotherapy unlocks hidden capabilities as an effective therapeutic. In order to maximize the full potential of DC, we developed a DC vaccine named CellgramDC-WT1 (CDW). CDW was pulsed with WT1, an antigen commonly expressed in solid tumors, and induced with zoledronate to aid DC maturation. Although our previous study focused on using Rg3 as an inducer of DC maturation, problems with quality control and access led us to choose zoledronate as a better alternative. Furthermore, CDW secreted IL-12 and IFN-γ, which induced the differentiation of naïve T cells to active CD8+ T cells and elicited cytotoxic T lymphocyte (CTL) response against cancer cells with WT1 antigens. By confirming the identity and function of CDW, we believe CDW is an improved DC vaccine and holds promising potential in the field of cancer immunotherapy.

Mechanistic loop resolution strategy for short-type single-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography in patients with Roux-en-Y reconstruction after gastrectomy (with video).

BACKGROUND: Endoscopic access to the targeted site is a major challenge for the endoscopic retrograde cholangiopancreatography (ERCP) in patients undergoing Roux-en-Y (R-Y) reconstruction after total or subtotal gastrectomy. We aimed to evaluate the feasibility, reproducibility, and safety of mechanistic loop resolution strategies using a short-type single-balloon enteroscopy (short SBE) system. METHODS: Between February 2020 and March 2022, consecutive patients with a previous R-Y gastrectomy requiring ERCP were prospectively enrolled. Different mechanistic loop resolution strategies for two-dimensional loops, three-dimensionally rotated loops, and loops making a cane or S-shape were applied during the SBE approach. RESULTS: Forty-three short SBE-ERCP procedures were performed on 37 patients, with an approach success rate of 100.0% (43/43). The mean time to reach the jejunojejunal anastomosis and target site were 8.0 (6.0-11.0) minutes and 26.0 (16.0-36.0) minutes, respectively. The major challenges for the approach were the cane or S-shaped loop in the jejunojejunal anastomosis or Treitz ligament. The retroflex positioning of a SBE in front of the papilla was achieved in 86.0% (37/43), and the cannulation success rate in patients with an intact papilla was 90.9% (30/33). The initial, overall therapeutic successes, median total procedure time, and adverse event rate were 87.8%, 92.7%, 77.0 (IQR 56-100.5) minutes, and 11.6%, respectively. CONCLUSIONS: Short SBE-ERCP using standardized mechanistic loop resolution strategies is effective and reproducible in patients with R-Y reconstruction after gastrectomy. TRIAL REGISTRATION: ClinicalTrial.gov (NCT04847167).

Factors affecting the diagnostic yield of endoscopic transpapillary forceps biopsy in patients with malignant biliary strictures.

BACKGROUND AND AIM: Transpapillary biliary forceps biopsy (TBFB) is a common method to obtain histological evidence for the differential diagnosis of biliary stricture. This study aimed to evaluate the factors associated with a positive cancer diagnosis from TBFB and the number of tissue samples required to increase the diagnostic yield in patients with malignant biliary strictures. METHODS: A total of 376 patients who underwent TBFB for investigation of biliary stricture were included. Factors affecting the diagnostic yield of TBFB were determined using univariate analysis and multivariate logistic regression analyses. RESULTS: Bile duct cancer (odds ratio [OR] = 3.50, P = 0.002), intraductal growing type (OR = 9.01, P = 0.001), and number of tissue samples (n < 5 vs 5 ≤ n < 10, OR = 4.13, P = 0.01; n < 5 vs n ≥ 10, OR = 12.25, P < 0.001; 5 ≤ n < 10 vs n ≥ 10, OR = 2.97, P = 0.046) were significant factors associated with positive results for malignancy. In patients with periductal infiltrating-type bile duct cancer, the number of tissue samples was a significant factor for diagnostic sensitivity (54.3% in the n < 5 group, 83.3% in the 5 ≤ n < 10 group and 98.2% in the n ≥ 10 group) (P < 0.001). CONCLUSIONS: Bile duct cancer, intraductal growing type, and five or more tissue samples were significant predictors of positive TBFB results in patients with malignant biliary stricture. Increasing the number of tissue samples by five or more led to higher sensitivity in bile duct cancer patients with the periductal infiltrating type.

Tips for Dealing with Common Beginner's Mistakes Made during Endoscopic Ultrasound-Guided Gallbladder Drainage.

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has been performed as an alternative to percutaneous drainage in surgically high-risk patients. Technical failures of EUS-GBD made by beginners are often attributed to failure of over-the-wire insertion of a fistula-dilating device or stent delivery system into the gallbladder, or stent misplacement in the final technical step. We herein report technical tips to prevent the failure of fistula dilation and provide tricks to avoid inward or outward stent misplacement.

Balloons larger than 15 mm can increase the risk of adverse events following endoscopic papillary large balloon dilation.

BACKGROUND AND AIM: Although endoscopic papillary large balloon dilation (EPLBD) has been widely used to facilitate the removal of difficult common bile duct stones, however, the outcomes have not yet been investigated in terms of the diameter of the balloon used. We aimed to compare the clinical outcomes between EPLBD using smaller (12-15 mm, S-EPLBD) and larger balloons (> 15 mm, L-EPLBD). METHODS: Six hundred seventy-two patients who underwent EPLBD with or without endoscopic sphincterotomy for common bile duct stone removal were enrolled from May 2004 to August 2014 at four tertiary referral centers in Korea. The outcomes, including the initial success rate, the success rate without endoscopic mechanical lithotripsy, the overall success rate, and adverse events between S-EPLBD and L-EPLBD groups, were retrospectively compared. RESULTS: The initial success rate, the success rate without mechanical lithotripsy, the overall success rate, and the overall adverse events were not significantly different between the two groups. The rate of severe-to-fatal adverse events was higher in the L-EPBLD group than in the S-EPLBD group (1.6% vs 0.0%, 0.020). One case of severe bleeding and two cases of fatal perforation occurred only in the L-EPLBD group. In the multivariate analysis, the use of a > 15-mm balloon was the only significant risk factor for severe-to-fatal adverse events (>0.005, 23.8 [adjusted odds ratio], 2.6-214.4 [95% confidence interval]). CONCLUSIONS: L-EPLBD is significantly related to severe-to-fatal adverse events compared with S-EPLBD for common bile duct stone removal.

Comparisons of the Mucosal Healing Process between Flat and Protruded Type after Endoscopic Submucosal Dissection for Gastric Neoplasms.

BACKGROUND/AIMS: The mucosal healing process after endoscopic submucosal dissection (ESD) is mostly scarring change (flat type), but a protruded lesion is occasionally found. We investigated the factors influencing the mucosal healing process, such as the flat and protruded types. METHODS: A total of 2,096 ESD cases were performed from February 2005 to December 2013, and 1,757 underwent follow-up endoscopy after 3 months to check the healing type of the ulceration. We retrospectively reviewed the medical charts to analyze demographic, endoscopic, and pathological findings between the 2 groups. RESULTS: Forty-eight cases were of the protruded type and 1,709 were of the flat type. In univariate analysis, the protruded type was found more in the antrum, anterior wall, and greater curvature (p < 0.001). In protruded types, the Helicobacter pylori (H. pylori) infection rate was lower (p < 0.017), the mean length of ESD specimen was shorter (p < 0.012), the fibrosis rate was lower (p < 0.033), and the mean number of hot biopsy and clips during ESD were less (p < 0.008 and p < 0.001 respectively). CONCLUSIONS: The healing type of mucosal ulceration after ESD seemed to be influenced by location, specimen size, and the presence of an H. pylori infection.

Evaluation of risk factors for recurrent primary common bile duct stone in patients with cholecystectomy.

OBJECTIVES: Recurrence of primary common bile duct (CBD) stone commonly occurs after complete removal of CBD stones in patients with cholecystectomy. This study aimed to investigate potential risk factors for the recurrence of primary CBD stones after endoscopic treatment. MATERIALS AND METHODS: Between January 2005 and December 2015, the endoscopic retrograde cholangiopancreatography (ERCP) database of our medical center was retrospectively reviewed; information regarding eligible patients who had recurrent CBD stones with a history of previous cholecystectomy was collected. The characteristics of the patients, CBD stone, CBD and ERCP-related factors were analyzed. RESULTS: The recurrence rate of CBD stone was 18.5% (115/622) after endoscopic treatment in patients with cholecystectomy. In univariate analysis, the number of CBD stones (≥2), CBD stone diameter (≥10 mm), stone composition, stone consistency, CBD diameter (≥15 mm), bile duct dilatation pattern, sharp bile duct angulation (<145°), balloon dilatation, large balloon (>12 mm) dilatation, endoscopic mechanical lithotripsy, endoscopic sphincterotomy, and endoscopic papillary balloon dilatation alone method were significant between the non-recurrence and recurrence groups. However, in multivariate analysis (based on the binary logistic regression method), the number of CBD stones (≥2) (adjusted odds ratio [AOR] 3.232; 95% confidence interval [CI] 1.344-7.773; p = .009), cholesterol stone (AOR 2.824; 95% CI 1.175-6.786; p =.02) and sharp bile duct angulation (<145°) (AOR 2.462; 95% CI 1.062-5.711; p = .036) were independent risk factors of CBD stone recurrence after cholecystectomy. CONCLUSIONS: CBD stone number (≥2), cholesterol stone and sharp bile duct angulation (<145°) are associated with recurrent common bile duct stones after cholecystectomy.

A prospective randomized trial of EUS-guided tissue acquisition using a 25-gauge core biopsy needle with and without a stylet.

BACKGROUND: Endoscopic ultrasound (EUS)-guided tissue acquisition has become the most effective method of obtaining specimens from a solid lesion adjacent to the gastrointestinal tract. No data exist regarding the use of a stylet in the core biopsy needle during EUS-guided tissue acquisition. The aims of this study were to evaluate the feasibility, safety, and diagnostic yield of a 25-gauge core biopsy needle without (S-) a stylet and to compare its performance with that of a 25-gauge core biopsy needle with (S+) a stylet in patients with solid lesions adjacent to the gastrointestinal tract. METHODS: From November 2013 to January 2016, we performed 114 EUS-guided tissue acquisitions for the diagnosis of solid lesions adjacent to the gastrointestinal tract in a randomized controlled trial. Patients were randomly assigned to the S+ group (n = 57) or the S- group (n = 57). EUS-guided tissue acquisition was performed using a 25-gauge core biopsy needle without an on-site cytopathologist. RESULTS: There were no significant differences in technical success (100 vs. 100%, p = 1.000), the mean number of needle passes (7.0 ± 1.6 vs. 6.8 ± 1.5, p = 0.556), needle malfunction (0 vs. 1.8%, p = 1.000), or complications (1.8 vs. 0%, p = 1.000) between the S+ and S- groups. Both groups exhibited comparable outcomes with respect to cytological diagnostic accuracy (93.0 vs. 91.2%, p = 1.000) and histological diagnostic accuracy (86.0 vs. 87.7%, p = 1.000) for malignancy. The procedure time was significantly shorter in the S- group than in the S+ group (32.4 ± 11.7 vs. 39.7 ± 8.6 min, p < 0.001). CONCLUSIONS: EUS-guided tissue acquisition using a 25-gauge core biopsy needle without a stylet did not decrease the diagnostic yield for malignancy and was associated with a shorter procedure time than that associated with a stylet.

A prospective randomized study of loop-tip versus straight-tip guidewire in wire-guided biliary cannulation.

BACKGROUND: Wire-guided cannulation has been widely accepted as a useful technique for achieving selective biliary access because it has significantly increased the success rate of biliary cannulation compared with conventional contrast-assisted cannulation. Unlike conventional guidewires with a straight tip, a loop-tip guidewire (LGW) has a closed distal loop that may facilitate less traumatic access through the epithelial folds of the intra-duodenal biliary segments. The aim of this study was to compare the performance of a LGW with a straight-tip guidewire (SGW) in achieving successful selective biliary cannulation. METHODS: From December 2014 to December 2015, we performed 192 wire-guided biliary cannulations for a naïve papilla in a randomized controlled trial. Patients were randomly assigned to the LGW group (n = 96) or the SGW group (n = 96). Our study protocol did not include crossover to the other guidewire arm if randomized wire-guided cannulation proved unsuccessful within the first 10 min. RESULTS: There was no significant difference in primary successful biliary cannulation between the two groups (LGW group: 86.5%; SGW group: 77.1%; p = 0.134). The rate and the mean number of unintentional pancreatic duct cannulations during wire-guided biliary cannulation were significantly lower in the LGW group than in the SGW group (LGW group: 14.6%; SGW group: 28.1%; p = 0.034; LGW group: 0.2 ± 0.5; SGW group: 0.6 ± 1.3; p = 0.007). Post-ERCP pancreatitis developed in 5.2% of patients in the LGW group and 8.3% of patients in the SGW group (p = 0.567). CONCLUSIONS: The biliary cannulation rate of the LGW was not significantly different from those of conventional guidewires. Use of the LGW was associated with a lower rate of unintentional pancreatic duct cannulation during wire-guided biliary cannulation than use of the SGW.

Cyclic Change of Sphincter of Oddi Motility and Its Relationship with Small Bowel Migrating Motor Complex in Humans.

BACKGROUND: Several animal and human studies have reported that sphincter of Oddi (SO) motility shows cyclical changes during the fasting state. However, to date, the relationship between the SO motility and the migrating motor complex (MMC) of the small bowel (SB) remains unclear in humans. AIMS: We observed SO motility over a long study period and evaluated its relationship with the MMC of the SB in humans using percutaneous long-term manometry. METHODS: Our study included patients with hepatolithiasis who required percutaneous transhepatic catheter placement and subsequently underwent choledochoscopy and stone removal. Long-term percutaneous transhepatic SO manometry was performed after complete stone removal. SO and SB motility were simultaneously recorded. RESULTS: SO motility showed cyclical phasic changes with periodic high-frequency contractions similar to the MMC contractions of the SB. All high-frequency contractions of the SO coincided with phase III contractions of the MMC of the SB. The proportions of phase III contractions of SO and SB were similar, but the proportions of phase I (P = 0.001) and phase II (P = 0.002) contractions were significantly different. The mean basal SO pressure was observed to significantly increase in phase III compared to phase I (P = 0.001) and phase II (P = 0.001) contractions. CONCLUSIONS: SO motility in humans showed cyclical phasic changes closely coordinated with the MMC of the SB in a fasting state; however, the proportion of phases differed between the SO and the SB. The basal pressure significantly increased during physiological high-frequency phase III contractions of the SO.

Development of Risk Prediction Model for Hepatocellular Carcinoma Progression of Indeterminate Nodules in Hepatitis B Virus-Related Cirrhotic Liver.

OBJECTIVES: This study was performed to evaluate long-term outcome of indeterminate nodules detected on cirrhotic liver and to develop risk prediction model for hepatocellular carcinoma (HCC) progression of indeterminate nodules on hepatitis B virus (HBV)-related cirrhotic liver. METHODS: Indeterminate nodules up to 2 cm with uncertain malignant potential detected on computed tomography of cirrhotic liver during HCC surveillance were analyzed retrospectively. HCC risk prediction model of indeterminate nodules in HBV-related cirrhotic liver was deduced based on result of Cox regression analysis. RESULTS: A total of 494 indeterminate nodules were included. Independent risk factors of HCC progression were old age, arterial enhancement, large nodule size, low serum albumin level, high serum α-fetoprotein (AFP) level, and prior HCC history in all included subjects. In subjects with chronic hepatitis B, old age (year; hazard ratio (HR)=1.06; P<0.001), arterial enhancement (HR=2.62; P=0.005), large nodule size (>1 cm; HR=7.34; P<0.001), low serum albumin level (≤3.5 g/dl; HR=3.57; P=0.001), high serum AFP level (≥100 ng/ml; HR=6.04; P=0.006), prior HCC history (HR=4.24; P=0.001), and baseline hepatitis B e antigen positivity (HR=2.31; P=0.007) were associated with HCC progression. We developed a simple risk prediction model using these risk factors and identified patients at low, intermediate, and high risk for HCC; 5-year cumulative incidences were 1%, 14.5%, and 63.1%, respectively. The developed risk score model showed good performance with area under the curve at 0.886 at 3 years, and 0.920 at 5 years in leave-one-out cross-validation. CONCLUSIONS: We developed a useful and accurate risk score model for predicting HCC progression of indeterminate nodules detected on HBV-related cirrhotic liver.

Higher serum interleukin-17A levels as a potential biomarker for predicting early disease progression in patients with hepatitis B virus-associated advanced hepatocellular carcinoma treated with sorafenib.

BACKGROUND: Although sorafenib is the only available drug with proven efficacy for patients with advanced hepatocellular carcinoma (HCC), the clinical efficacy of sorafenib is variable and unpredictable. The aim of the current study was to identify potential serum biomarkers predicting cancer progression and overall survival (OS) in patients with hepatitis B virus (HBV)-related advanced HCC treated with sorafenib. METHODS: Thirty-four patients with HBV-related advanced HCC (modified Union for International Cancer Control [UICC] stage IVa or IVb) treated with sorafenib for more than 4weeks were retrospectively enrolled. Using a Luminex 200 system, 11 cytokines including interleukin-17A (IL-17A) were measured in baseline serum samples prior to sorafenib administration. Several clinical factors and the serum concentrations of the 11 cytokines were analyzed using Cox regression analysis. RESULTS: In the analysis of progression-free survival (PFS), older age (year; hazard ratio [HR]=1.07; 95% confidence interval [CI]=1.00-1.15; P=0.046) and higher baseline serum IL-17A level (>1.94pg/mL; HR=19.96; 95% CI=3.32-119.86; P=0.001) were identified as significant risk factors for early progression with good predictive power (Harrell's C=0.817, standard error estimates (se)=0.085). In the analysis of OS, higher Child-Pugh score (>5; HR=2.35, 95% CI=1.09-5.10, P=0.030) and lower serum baseline fibroblast growth factor-2 level (≤20.57pg/mL; HR=3.24, 95% CI=1.22-8.60, P=0.018) were identified as negative predictive factors for OS, even though the model did not have significant predictive power (Harrell's C=0.634, se=0.062). CONCLUSION: A higher serum IL-17A level is a potential biomarker for predicting poor PFS in patients with HBV-related advanced HCC treated with sorafenib.

Prediction of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis Using 4-Hour Post-Endoscopic Retrograde Cholangiopancreatography Serum Amylase and Lipase Levels.

Early post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) prediction may allow safe same-day outpatients discharge after ERCP and earlier proper management. This study aimed to assess the usefulness of the 4-hour post-ERCP serum amylase and lipase levels for PEP early prediction and to investigate predictive cut-off values for 4-hour post-ERCP serum amylase and lipase levels for safe discharge and urgent initiation of resuscitation. The data of 516 consecutive patients with native papilla who underwent ERCP between January 2013 and August 2014 were retrospectively reviewed. Serum amylase and lipase levels were measured before, and 4 and 24 hours after ERCP. PEP occurred in 16 (3.1%) patients. The receiver-operator characteristic curve for 4-hour post-ERCP serum amylase and lipase levels showed that the areas under the curve were 0.919 and 0.933, respectively, demonstrating good test performances as predictors for PEP (both P values < 0.001). The amylase level > 1.5 × the upper limit of reference (ULR) was found useful for PEP exclusion with a sensitivity of 93.8%, while 4 × ULR was found useful to guide preventive therapy with the best specificity of 93.2%. Similarly, the lipase level 2 × ULR showed best sensitivity, while 8 × ULR had the best specificity. Logistic regression analysis showed that 4-hour post-ERCP amylase level > 4 × ULR, lipase level > 8 × ULR, precut sphincterotomy, and pancreatic sphincterotomy were significant predictors for PEP. In conclusion, 4-hour post-ERCP amylase and lipase levels are useful early predictors of PEP that can ensure safe discharge or prompt resuscitation after ERCP.

Endoscopic naso-gallbladder drainage versus gallbladder stenting before cholecystectomy in patients with acute cholecystitis and a high suspicion of choledocholithiasis: a prospective randomised preliminary study.

OBJECTIVE: Endoscopic transpapillary gallbladder drainage using a nasocystic tube or plastic stent has been attempted as an alternative to percutaneous drainage for patients with acute cholecystitis who are not candidates for urgent cholecystectomy. We aimed to assess the efficacy of single-step endoscopic drainage of the common bile duct and gallbladder, and to evaluate which endoscopic transpapillary gallbladder drainage method is ideal as a bridge before elective cholecystectomy. MATERIALS AND METHODS: From July 2011 to December 2014, 35 patients with acute moderate-to-severe cholecystitis and a suspicion of choledocholithiasis were randomly assigned to the endoscopic naso-gallbladder drainage (ENGBD) (n = 17) or endoscopic gallbladder stenting (EGBS) (n = 18) group. RESULTS: Bile duct clearance was performed successfully in all cases. No significant differences were found between the ENGBD and EGBS groups in the technical success rates [82.4% (14/17) vs. 88.9% (16/18), p = 0.658] and clinical success rates [by intention-to-treat analysis: 70.6% (12/17) vs. 83.3% (15/18), p = 0.443; by per protocol analysis of technically feasible cases: 85.7% (12/14) vs. 93.8% (15/16), p = 0.586]. Three ENGBD patients and two EGBS patients experienced adverse events (p = 0.658). No significant differences were found in operation time or rate of conversion to open cholecystectomy. CONCLUSIONS: Single-step endoscopic transpapillary drainage of the common bile duct and gallbladder seems to be an acceptable therapeutic modality in patients with acute cholecystitis and a suspicion of choledocholithiasis. There were no significant differences in the technical and clinical outcomes between ENGBD and EGBS as a bridge before cholecystectomy.

Tenofovir-based rescue therapy in chronic hepatitis B patients with suboptimal responses to adefovir with prior lamivudine resistance.

We evaluated the efficacy of tenofovir (TDF)-based rescue therapy and compared the outcomes of TDF monotherapy and TDF-based nucleoside analog (NA) combination therapy in patients with suboptimal response (SOR) to adefovir (ADV) with or without NAs in lamivudine (LAM)-resistant chronic hepatitis B. All study subjects received ADV with or without NAs due to prior LAM resistance, and were then switched to TDF-based rescue therapy due to SOR (hepatitis B virus DNA >20 IU/ml after at least 6 months of therapy). A total of 125 patients were eligible. The overall cumulative proportion of complete virologic response (CVR) was 64 of 74 patients (86.5%) at 48 weeks of treatment. During the follow-up period of 48 weeks, there was no significant difference in CVR rate (P = 0.750) between the TDF monotherapy (n = 18) and the TDF with NA groups (n = 107). Patients with ADV genotypic mutations showed inferior antiviral responses to TDF compared with the patients without ADV genotypic mutations, but this was not statistically significant (P = 0.069). Partial virological response to prior ADV therapy showed higher CVR rates compared to patients with non-response at 12 weeks (P = 0.013), but there was no significant difference after 24 (P = 0.076) and 48 weeks (P = 0.198) of treatment. TDF monotherapy is as effective as TDF plus NA combination therapy in patients with SOR to ADV-based rescue therapy and LAM resistance. TDF, with or without NAs, was effective even in cases of ADV resistance.

Interleukin-8 level as a prognostic marker in patients with hepatitis B virus-associated hepatocellular carcinoma treated with transarterial chemoembolization.

We investigated the association between serum interleukin (IL)-8 levels and post-transarterial chemoembolization (TACE) outcomes in patients with hepatitis B virus (HBV)-associated HCC. We enrolled 119 TACE-treated patients with HBV-associated HCC; TACE refractoriness and liver transplantation (LT)-free survival were evaluated during follow-up. Pre-TACE serum levels of various cytokines (epidermal growth factor [EGF], fibroblast growth factor 2, granulocyte-colony stimulating factor [G-CSF], interferon-γ, IL-8, IL-12, IL-17A, interferon-γ-inducible protein-10, monocyte chemotactic protein-1, tumor necrosis factor-α and vascular endothelial growth factor) were analyzed. During a mean follow-up of 24.3 (1-79) months, 91 patients (76.5%) exhibited TACE refractoriness. In multivariate analyses, multiple tumors (hazard ratio [HR], 2.37; 95% confidence interval [CI], 1.28-4.39; P=0.006), large tumor size (HR, 2.36; 95% CI, 1.38-4.03; P=0.002), and combination of alpha-fetoprotein and IL-8 levels (AFP>400 ng/mL or IL-8>32 pg/mL; HR, 1.72; 95% CI, 1.03-2.85; P=0.037) independently predicted overall TACE refractoriness. Higher EGF (>35 pg/mL) and lower G-CSF levels (⩽ 12.5 pg/mL) were associated with early TACE refractoriness (<1 year; HR, 3.47; 95% CI, 1.01-11.96; P=0.049 and HR, 6.25; 95% CI, 1.62-23.81; P=0.008, respectively). Furthermore, high IL-8 level (>32 pg/mL; HR, 1.68; 95% CI, 1.09-2.59; P=0.020) was associated with poor LT-free survival. In conclusion, pretreatment serum IL-8 is a useful prognostic marker for TACE refractoriness and LT-free survival in TACE-treated patients with HBV-associated HCC.

Non-neoplastic pathology results after endoscopic submucosal dissection for gastric epithelial dysplasia or early gastric cancer.

BACKGROUND AND STUDY AIMS: Endoscopists sometimes face paradoxical cases in which the endoscopic submucosal dissection (ESD) specimen reveals a non-neoplastic pathology result. The aims of the study were to determine the reasons for such results, and to compare the endoscopic characteristics of non-neoplastic and conventional neoplastic pathology groups after ESD. PATIENTS AND METHODS: A total of 1186 gastric ESDs performed between February 2005 and December 2011 were retrospectively reviewed. The ESD specimens included 52 (4.4 %) that were confirmed as negative or indefinite for neoplasia. Patient characteristics and endoscopic and pathological data were reviewed and compared. RESULTS: Non-neoplastic pathology after ESD was due to complete removal of the lesion at biopsy in 45 cases (86.5 %), pathology overestimation in 5 (9.6 %), and incorrect localization of the original tumor with subsequent ESD performed at the wrong site in 2 (3.8 %). The mean length and surface area of the non-neoplastic lesions were 9.2 ±â€Š2.6 mm and 49.6 ±â€Š23.6 mm (2), respectively. Mean sampling ratios were 3.0 ±â€Š1.5 mm/fragment and 16.3 ±â€Š10.0 mm(2)/fragment. Compared with 1134 cases confirmed as neoplastic on the final ESD specimen, non-neoplastic cases showed a significantly smaller tumor size and surface area, and lower sampling ratios in a logistic regression analysis adjusted for potential confounders (P < 0.001 for all). CONCLUSIONS: Complete lesion removal by biopsy, pathology overestimation, and incorrect localization of the original tumor with subsequent ESD at the wrong site were the main reasons for non-neoplastic results after ESD. Small tumor size and surface area, and low sampling ratios were associated with non-neoplastic pathology results after ESD.