Preloaded 22-gauge fine-needle system facilitates placement of a higher number of fiducials for image-guided radiation therapy compared with traditional backloaded 19-gauge approach.

BACKGROUND AND AIMS: Image-guided radiation therapy (IGRT) often relies on EUS-guided fiducial markers. Previously used manually backloaded fiducial needles have multiple potential limitations including safety and efficiency concerns. Our aim was to evaluate the efficacy, feasibility, and safety of EUS-guided placement of gold fiducials using a novel preloaded 22-gauge needle compared with a traditional, backloaded 19-gauge needle. METHODS: This was a single-center comparative cohort study. Patients with pancreatic and hepatobiliary malignancy who underwent EUS-guided fiducial placement (EUS-FP) between October 2014 and February 2018 were included. The main outcome was the technical success of fiducial placement. Secondary outcomes were mean procedure time, fiducial visibility during IGRT, technical success of IGRT delivery, and adverse events. RESULTS: One hundred fourteen patients underwent EUS-FP during the study period. Of these, 111 patients had successful placement of a minimum of 2 fiducials. Fifty-six patients underwent placement using a backloaded 19-gauge needle and 58 patients underwent placement using a 22-gauge preloaded needle. The mean number of fiducials placed successfully at the target site was significantly higher in the 22-gauge group compared with the 19-gauge group (3.53 ± .96 vs 3.11 ± .61, respectively; P = .006). In the 22-gauge group, the clinical goal of placing 4 fiducials was achieved in 78%, compared with 23% in the 19-gauge group (P < .001). In univariate analyses, gender, age, procedure time, tumor size, and location did not influence the number of successfully placed fiducials. Technical success of IGRT with fiducial tracking was high in both the 19-gauge (51/56, 91%) and the 22-gauge group (47/58, 81%; P = .12). CONCLUSIONS: EUS-FP using a preloaded 22-gauge needle is feasible, effective, and safe and allows for a higher number of fiducials placed when compared with the traditional backloaded 19-gauge needle.

Endoscopic ultrasound-guided parenchymal liver biopsy: a systematic review and meta-analysis.

BACKGROUND: Endoscopic ultrasonography (EUS)-guided liver biopsy is a novel technique to obtain adequate liver samples for diagnosis of liver parenchymal diseases. There are studies that have evaluated the feasibility and safety of EUS-guided parenchymal liver biopsy (EUS-LB), however, factors that can influence specimen quality are yet to be determined. Our aim was to determine the diagnostic accuracy of EUS-LB and evaluate factors associated with specimen quality. METHODS: We performed a detailed search of PubMed/MEDLINE and Web of Science™ databases to identify studies in which results of EUS-guided liver parenchymal biopsies were reported published up to July 2020. A random effects model was used to estimate pooled values (mean ± SE) for total specimen length (TSL) and complete portal tracts (CPT). Subgroup analyses were applied to find out the procedural factors associated with better specimen quality using Cochran's Q test. A total of 10 meta-analyses were done focusing on international studies. Total of 1326 patients who underwent EUS-LB. EUS-LBs performed for suspicion of parenchymal liver disease. Pooled mean values for TSL and CPT with subgroup analyses. RESULTS: Twenty-three studies with a total of 1326 patients were included in our meta-analysis. Overall pooled mean TSL and CPT were 45.3 ± 4.6 mm and 15.8 ± 1.5, respectively. In subgroup analysis, core biopsy needles proved to better in terms of CPT than fine-needle aspiration needles (18.4 vs 10.99, p = 0.003). FNB with slow-pull or suction technique provided a similar TSL (44.3 vs 53.9 mm, p = 0.40), however, slow-pull technique was better in terms of CPT (30 vs 14.6, p < 0.001). Heterogeneity was present among the studies. Another limitation is the low number randomized control trials. CONCLUSION: EUS-guided parenchymal liver biopsy is a good alternative to other methods of liver sampling. Using FNB needles with a slow-pull technique can provide better results.

Effectiveness of a Deep-learning Polyp Detection System in Prospectively Collected Colonoscopy Videos With Variable Bowel Preparation Quality.

BACKGROUND: Colonoscopy is the gold standard for polyp detection, but polyps may be missed. Artificial intelligence (AI) technologies may assist in polyp detection. To date, most studies for polyp detection have validated algorithms in ideal endoscopic conditions. AIM: To evaluate the performance of a deep-learning algorithm for polyp detection in a real-world setting of routine colonoscopy with variable bowel preparation quality. METHODS: We performed a prospective, single-center study of 50 consecutive patients referred for colonoscopy. Procedural videos were analyzed by a validated deep-learning AI polyp detection software that labeled suspected polyps. Videos were then re-read by 5 experienced endoscopists to categorize all possible polyps identified by the endoscopist and/or AI, and to measure Boston Bowel Preparation Scale. RESULTS: In total, 55 polyps were detected and removed by the endoscopist. The AI system identified 401 possible polyps. A total of 100 (24.9%) were categorized as "definite polyps;" 53/100 were identified and removed by the endoscopist. A total of 63 (15.6%) were categorized as "possible polyps" and were not removed by the endoscopist. In total, 238/401 were categorized as false positives. Two polyps identified by the endoscopist were missed by AI (false negatives). The sensitivity of AI for polyp detection was 98.8%, the positive predictive value was 40.6%. The polyp detection rate for the endoscopist was 62% versus 82% for the AI system. Mean segmental Boston Bowel Preparation Scale were similar (2.64, 2.59, P=0.47) for true and false positives, respectively. CONCLUSIONS: A deep-learning algorithm can function effectively to detect polyps in a prospectively collected series of colonoscopies, even in the setting of variable preparation quality.

Cryptogenic liver cirrhosis and hepatitis E virus (HEV): Are they related?

INTRODUCTION AND OBJECTIVES: Hepatitis E virus (HEV) is one of the most common causes of acute hepatitis. In recent years, its role in the development of chronic hepatitis and cirrhosis especially in immunosuppressed patients and its wide range of extrahepatic involvement have increased the amount of research on HEV. In this study we aimed to investigate the presence of HEV infection in individuals with cryptogenic cirrhosis. MATERIALS AND METHODS: HEV antibodies were analysed using the Anti HEV enzyme-linked immunosorbent assay (ELISA) kit (anti-HEV ELISA; Diapro Prodiagnostic Bioprobes, Milan, Italy). HEV RNA was isolated with using QIAMP Viral RNA mini kit (QIAGEN, Hilden, Germany). The HEV RNA titre was detected with the Rotor Gene 3000 real time polymerase chain reaction (PCR) system using GenoSen's HEV (Rotor Gene) Quantitative Real Time PCR Kit (Genome Diagnostics Private Limited, the Netherlands). RESULTS: Our study included 21 healthy volunteers (12 males) and 35 cryptogenic cirrhosis patients (19 males). The ages of the patients and the controls were similar (46±12.1 vs. 37.5±9.7years). The mean Child-Pugh score was 8±2.5. The anti HEV immunoglobulin G(IgG) positivity rate was 9.5% and 25.7% in the control and patient groups respectively (p>0.05). HEV RNA positivity was not detected in the control group, but 3 cases (8.6%) in the patient group were positive (p>0.05). The HEV RNA, aspartate aminotransferase (AST) and alanine aminotransferase(ALT) levels for these 3 cases were 326.461copies/mL, 91IU/L and 67IU/L; 480copies/mL, 68IU/L and 36IU/L and 72copies/mL, 42IU/L and 24IU/L respectively. There were positive correlations between HEV RNA levels and AST and ALT levels (p<0.05). CONCLUSIONS: Anti HEVIgG and HEV RNA positivity rates are high in cryptogenic cirrhosis although it is not statistically significant and there is a positive correlation between HEV RNA and aminotransferases.

Tenofovir disoproxil fumarate has a substantial efficacy against multidrug-resistant strains of hepatitis B virus.

BACKGROUND & AIMS: To evaluate the efficacy of tenofovir in chronic hepatitis B (CHB) patients with adefovir resistance (ADF-R) and suboptimal response to adefovir (ADF-S). METHODS: Nucleos(t)ide analogue (NA)-naïve patients and patients with previous adefovir failure receiving tenofovir therapy for at least 6 months were included in the study. Biochemical and virological tests were obtained at baseline and 3-month intervals in the first year and every 6 months thereafter. The primary outcome measure was complete virological response (CVR) (HBVDNA < 20 IU/ml). CVR rates were calculated by Kaplan-Meier analysis, and a multivariate Cox proportional hazard model was generated to find out factors independently associated with CVR. RESULTS: A total of 165 patients (118 men, mean age 42 ± 12, 64 HBeAg(+) ) were included in the study. There were 105 patients in NA-naïve, 32 patients in ADF-S and 28 patients in ADF-R groups. All patients in the ADF-R group had multidrug resistance patterns. Mean duration of tenofovir treatment was 29 ± 14 months. CVR rates in NA-naïve, ADF-S and ADF-R groups were 65% vs. 75% vs. 58% at 12th month, 77% vs. 87% vs. 79% at 24th month and 83% vs. 94% vs. 79% at 36th month respectively. According to multivariate Cox regression model, HBeAg positivity (HR = 0.56, 95%CI 0.36-0.86, P = 0.008), high baseline HBVDNA level (HR = 0.64, 95%CI 0.55-0.74, P < 0.001) and ADF-R (HR = 0.47, 95%CI 0.28-0.81, P = 0.006) were independent predictors for CVR. Seven patients encountered mild renal dysfunction and were managed by dose adjustments. CONCLUSION: CVR rates during the follow-up show that tenofovir has a decreased, yet still potent in vivo efficacy against multidrug-resistant strains of HBV.

Effects of polymorphisms in interferon λ 3 (interleukin 28B) on sustained virologic response to therapy in patients with chronic hepatitis D virus infection.

BACKGROUND & AIMS: We investigated the association between interferon λ 3 (IFNL3) genotype (also known as interleukin 28B) and response to IFNα therapy in patients with chronic hepatitis D virus (HDV) infection. METHODS: We studied IFNL3 genotypes of 32 patients (19 men; median age, 42.5 y) with chronic HDV infection. Nineteen patients (59%) were treated with pegylated IFNα and 13 patients (41%) were treated with standard IFNα, for at least 12 months. Levels of HDV RNA were measured before the initiation of treatment and every 6 months thereafter; patients were followed up for a median time of 16 months (range, 6-164 mo) after treatment ended. We used real-time polymerase chain reaction to classify the IFNL3 polymorphism rs12979860 as CC, CT, or TT, and rs8099917 as TT, GT, or GG. A virologic response was defined as undetectable HDV RNA in serum, and a sustained virologic response (SVR) was defined as undetectable HDV RNA after cessation of treatment until the end of the follow-up period. We evaluated the association between IFNL3 polymorphism and treatment response using univariate and multivariate analyses. RESULTS: After treatment, a response was achieved in 16 patients (50%) and an SVR was achieved in 9 (28%). The percentages of patients with CC, CT, and TT at rs12979860 were 47%, 47%, and 6%, respectively; the percentages of patients with TT, GT, and GG at rs8099917 were 69%, 28%, and 3%, respectively. Rates of SVR were 27%, 27%, and 50% in patients with CC, CT, TT at rs12979860 (P = .78 for CC vs CT vs TT) and 36%, 11%, and 0% in patients with TT, GT, and GG at rs8099917 (P = .30 for TT vs GT vs GG). CONCLUSIONS: The IFNL3 polymorphisms rs12979860 and rs8099917 do not significantly affect responses of patients with chronic HDV infection to treatment with IFNα.

Efficacy of tenofovir in patients with Lamivudine failure is not different from that in nucleoside/nucleotide analogue-naive patients with chronic hepatitis B.

We evaluated the efficacy of tenofovir disoproxil fumarate (TDF) in patients with lamivudine failure (LAM-F) in comparison with that in nucleoside/nucleotide analogue (NA)-naïve patients with chronic hepatitis B (CHB). The criteria for inclusion were being NA naïve or having previous LAM-F and receiving TDF therapy for at least 6 months. Biochemical and virological tests were performed at the baseline, at 3-month intervals in the first year, and every 6 months thereafter. The primary outcome measure for efficacy was a complete virological response (CVR), defined as an HBV DNA level of <20 IU/ml. CVR rates were calculated by Kaplan-Meier analysis, and a multivariate Cox proportional-hazard model was generated in order to find predictive factors independently associated with the time to a CVR. We included 197 patients in the study (136 males; mean age, 43 ± 12 years; 105 patients were NA naïve). Sixty-five patients had hepatitis B e antigen (HBeAg)-positive CHB. The median duration of TDF treatment was 29 (range, 6 to 52) months. Seventy-one patients (77%) in the LAM-F group were treated with TDF add-on therapy. The CVR rates of the NA-naïve and LAM-F groups were comparable in HBeAg-negative (94% versus 96% at month 36, P = 0.10) and HBeAg-positive patients (67% versus 83% at month 36, P = 0.48). According to the multivariate Cox regression model, only HBeAg positivity (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.26 to 0.59; P < 0.001) and a high baseline HBV DNA level (HR, 0.44; 95% CI, 0.29 to 0.67; P < 0.001) had a significant influence on the time to a CVR. The similar cumulative CVR rates during the follow-up show that TDF has comparable efficacy in lamivudine-experienced and NA-naïve patients, and the presence of resistance mutations did not alter the response rates.

Is the Y90-radioembolization treatment effective on the intermediate-advanced stage of hepatocellular carcinoma and what is the albumin-bilirubin score's prediction factor for survival?

Background and Aim: Radioembolization (RE) is a one of the palliative treatments that have been used to down stage and/or increase the survival time in intermediate-advanced stages of HCC. We aimed to evaluate the clinical impact of RE and the clinical use of the albumin-bilirubin (ALBI) score as a predictor for survival in HCC patients. Materials and Methods: Fifty-nine unresectable hepatocellular carcinoma (HCC) patients were enrolled. RE was performed in 28 of them (group 1) and 31 patients were followed up in the natural course (NC) (group 2). Patients were classified according to the Child-Pugh score (only cirrhotic patients), Barcelona clinic liver cancer (BCLC) staging, and ALBI scores were also calculated. Results: All patients in Group 1 were cirrhotic and their BCLC stages were as follows: 60.7% stage B and 39.3% stage C. In Group 2, 83.9% of patients were cirrhotic and their BCLC stages were as follows: 9.7% stage B, 51.6% stage C, and 38.7% stage D. Mortality rates were 82% and 100% in Groups 1 and 2, respectively. The median overall survival (OS) was 13.5 months (95% CI: 10.4-16.6 months) and 4.5 months (95% CI: 3.5-5.5 months) in Groups 1 and 2, respectively (p=0.000). When RE was applied to patients with ALBI Grade 1 and 2, the median OS was statistically higher than in the NC group, respectively (p<0.001, p<0.001). Conclusion: RE is an effective treatment method at the advanced stages of HCC. The ALBI score is a more useful and practical than the other prognostic tools.

Cyclosporine Therapy as a Rescue Treatment in Steroid Refractory Acute Severe Ulcerative Colitis: A Real Life Data From a Tertiary Center.

BACKGROUND: Cyclosporine is a rescue treatment alternative to avoid colectomy in corticosteroid refractory acute severe ulcerative colitis. In this study, we aimed to evaluate the long-term efficacy and safety of cyclosporine therapy in acute severe ulcerative colitis patients. METHODS: Acute severe ulcerative colitis (basal Lichtiger score > 10) patients who did not respond to 40 mg intravenous methylpredniso- lone therapy after 3-5 days were included in the study. The presence of clinical response and remission was assessed at 1st week, 1st, 6th, and 12th month according to the Lichtiger index. RESULTS: In this study, 40 patients, whose steroid refractory acute severe ulcerative colitis and basal Lichtiger score > 10 points were enrolled. The median disease duration was 49.3 months (2-204). All patients received cyclosporine for 132 ± 78 days (7-270). Clinical response was obtained on seventh day in 82.5%. The clinical response rates of the first and sixth months were 72.5% and 62.5%, respectively. A total of 17/40 (42.5%) patients underwent colectomy within 1 year. In the patients who underwent colectomy, the basal LS (14.2 ± 1.9 vs 12.3 ± 1.7) (P = .002) was higher and the basal hemoglobin value (11.8 ± 2.3 vs 10.1 ± 1.5) (P = .037) was lower than those who did not undergo colectomy. CONCLUSION: Our findings suggest that cyclosporine treatment may be successfully and safely used in steroid refractory acute severe ulcerative colitis patients. Cyclosporine is a drug that has recently started to come up again with the introduction of new maintenance treatments. Especially in patients who develop a loss of response to infliximab therapy, or where infliximab therapy is contraindicated, or who have azathioprine intolerance, or are unresponsive.