Endoscopic variceal ligation versus propranolol for the primary prevention of oesophageal variceal bleeding in patients with hepatocellular carcinoma: an open-label, two-centre, randomised controlled trial.

OBJECTIVE: This randomised trial aimed to address whether endoscopic variceal ligation (EVL) or propranolol (PPL) is more effective at preventing initial oesophageal variceal bleeding (EVB) in patients with hepatocellular carcinoma (HCC). DESIGN: Patients with HCC and medium-to-large oesophageal varices (EVs) but without previous EVB were randomised to receive EVL (every 3-4 weeks until variceal eradication) or PPL (up to 320 mg daily) at a 1:1 ratio. Long-term follow-up data on EVB, other upper gastrointestinal bleeding (UGIB), non-bleeding liver decompensation, overall survival (OS) and adverse events (AEs) were analysed using competing risk regression. RESULTS: Between June 2011 and April 2021, 144 patients were randomised to receive EVL (n=72) or PPL (n=72). In the EVL group, 7 patients experienced EVB, and 30 died; in the PPL group, 19 patients had EVB, and 40 died. The EVL group had a lower cumulative incidence of EVB (Gray's test, p=0.009) than its counterpart, with no mortality difference (Gray's test, p=0.085). For patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B, EVL was better than PPL in reducing EVB (p<0.001) and mortality (p=0.003). For patients beyond BCLC stage B, between-group outcomes were similar. Other UGIB, non-bleeding liver decompensation and AEs did not differ between groups. A competing risk regression model confirmed the prognostic value of EVL. CONCLUSION: EVL is superior to PPL in preventing initial EVB in patients with HCC. The benefits of EVL on EVB and OS may be limited to patients with BCLC stage A/B and not to those with BCLC stage C/D. TRIAL REGISTRATION NUMBER: NCT01970748.

A Randomized Controlled Trial of Propranolol Use During Ligation Program for Secondary Prophylaxis of Esophageal Variceal Bleeding.

INTRODUCTION: Endoscopic variceal ligation (EVL) plus nonselective ß-blockers (NSBB) is the standard of care for secondary prophylaxis of esophageal variceal bleeding (EVB). This trial aimed to compare the rebleeding rates between EVL plus NSBB till eradication of esophageal varices (EEV) and EVL plus long-term NSBB. METHODS: After control of acute EVB, patients with cirrhosis were randomized into 2 groups, with group A patients receiving EVL plus propranolol till EEV, while group B patients received standard of care with continuation of propranolol. Recurrent varices were ligated at follow-up endoscopy in both groups. RESULTS: The median follow-up period was 23.0 months in group A (n = 106) and 23.6 months in group B (n = 106). Twelve patients (11.3%) in group A and 11 (10.4%) in group B had recurrent EVB. The difference in rebleeding rates and the 95% confidence interval (CI) was 0.9% (-7.5% to 9.3%). The upper 95% CI bound of the difference was within the margin of 13.2%, and the noninferiority of group A to group B was established. Thirty-eight patients (35.8%) in group A and 40 (37.7%) in group B had further decompensation, with the difference (95% CI) of -1.9% (-14.9% to 11.1%). Twenty-four patients (22.6%) in group A and 26 (24.5%) in group B expired, with the difference (95% CI) in mortality rates of -1.9% (-13.3% to 9.5%). DISCUSSION: EVL plus propranolol till EEV was noninferior to EVL plus continuing propranolol in secondary prophylaxis of EVB, but the impact on further decompensation and transplantation-free survival deserved further investigation.

Intestinal metaplasia in follow-up endoscopies among Asian patients with short-segment Barrett's esophagus: Regression, sampling error, and associated factors.

BACKGROUND: The percentage of and factors associated with the regression of Barrett's esophagus (BE) or its characteristic intestinal metaplasia (IM) remain unclear, and conflicting results have been reported because of diverse regression and sampling error definitions. Thus, we investigated the rates of IM regression, sampling error, and associated factors. METHODS: Forty-two patients with proven short-segment BE with IM who underwent two follow-up endoscopies with biopsies of Barrett's mucosa were retrospectively analyzed. Additional Alcian blue and MUC2 staining were done on the biopsy specimens without IM in hematoxylin-eosin staining. Only patients with negative hematoxylin-eosin, Alcian blue, and MUC2 staining for IM in both follow-up endoscopies were considered to have true regression. When all three stains were negative for IM in the first, but positive in the second follow-up endoscopy, we considered IM persisting and declared sampling error. RESULTS: Among the 18 patients without IM at the first follow-up endoscopy, only five (11.9%) were judged to have true regression. Prolonged proton-pump inhibitor use was significantly associated with regression. Limited experience of the endoscopist, and insufficient biopsy number were significantly related to sampling error. Receiver operating characteristic (ROC) curve analysis showed the best cut-off value of the biopsy number/maximal-length (cm) ratio to predict sampling error was 2.25. CONCLUSION: In our patients with short-segment BE, 11.9% experienced regression of IM. Prolonged proton-pump inhibitors treatment was associated with regression. An insufficient biopsy number was related to a missed IM, which may be eliminated by maintaining biopsy number/maximal-length (cm) ratio ≥2.25.

Evaluation of combination treatment with DS-1205c, an AXL kinase inhibitor, and osimertinib in metastatic or unresectable EGFR-mutant non-small cell lung cancer: results from a multicenter, open-label phase 1 study.

The objective of this study was to evaluate the safety and tolerability of DS-1205c, an oral AXL-receptor inhibitor, in combination with osimertinib in metastatic or unresectable EFGR-mutant non-small cell lung cancer (NSCLC) patients who developed disease progression during EGFR tyrosine kinase inhibitor (TKI) treatment. An open-label, non-randomized phase 1 study was conducted in Taiwan, in which 13 patients received DS-1205c monotherapy at a dosage of 200, 400, 800, or 1200 mg twice daily for 7 days, followed by combination treatment with DS-1205c (same doses) plus osimertinib 80 mg once daily in 21-day cycles. Treatment continued until disease progression or other discontinuation criteria were met. At least one treatment-emergent adverse event (TEAE) was reported in all 13 patients treated with DS-1205c plus osimertinib; with ≥ 1 grade 3 TEAE in 6 patients (one of whom also had a grade 4 increased lipase level), and 6 patients having ≥ 1 serious TEAE. Eight patients experienced ≥ 1 treatment-related AE (TRAE). The most common (2 cases each) were anemia, diarrhea, fatigue, increased AST, increased ALT, increased blood creatinine phosphokinase, and increased lipase. All TRAEs were non-serious, with the exception of an overdose of osimertinib in 1 patient. No deaths were reported. Two-thirds of patients achieved stable disease (one-third for > 100 days), but none achieved a complete or partial response. No association between AXL positivity in tumor tissue and clinical efficacy was observed. DS-1205c was well-tolerated with no new safety signals in patients with advanced EGFR-mutant NSCLC when administered in combination with the EFGR TKI osimertinib. ClinicalTrials.gov ; NCT03255083.

Resistin-like Molecule α and Pulmonary Vascular Remodeling: A Multi-Strain Murine Model of Antigen and Urban Ambient Particulate Matter Co-Exposure.

Pulmonary hypertension (PH) has a high mortality and few treatment options. Adaptive immune mediators of PH in mice challenged with antigen/particulate matter (antigen/PM) has been the focus of our prior work. We identified key roles of type-2- and type-17 responses in C57BL/6 mice. Here, we focused on type-2-response-related cytokines, specifically resistin-like molecule (RELM)α, a critical mediator of hypoxia-induced PH. Because of strain differences in the immune responses to type 2 stimuli, we compared C57BL/6J and BALB/c mice. A model of intraperitoneal antigen sensitization with subsequent, intranasal challenges with antigen/PM (ovalbumin and urban ambient PM2.5) or saline was used in C57BL/6 and BALB/c wild-type or RELMα-/- mice. Vascular remodeling was assessed with histology; right ventricular (RV) pressure, RV weights and cytokines were quantified. Upon challenge with antigen/PM, both C57BL/6 and BALB/c mice developed pulmonary vascular remodeling; these changes were much more prominent in the C57BL/6 strain. Compared to wild-type mice, RELMα-/- had significantly reduced pulmonary vascular remodeling in BALB/c, but not in C57BL/6 mice. RV weights, RV IL-33 and RV IL-33-receptor were significantly increased in BALB/c wild-type mice, but not in BALB/c-RELMα-/- or in C57BL/6-wild-type or C57BL/6-RELMα-/- mice in response to antigen/PM2.5. RV systolic pressures (RVSP) were higher in BALB/c compared to C57BL/6J mice, and RELMα-/- mice were not different from their respective wild-type controls. The RELMα-/- animals demonstrated significantly decreased expression of RELMß and RELMγ, which makes these mice comparable to a situation where human RELMß levels would be significantly modified, as only humans have this single RELM molecule. In BALB/c mice, RELMα was a key contributor to pulmonary vascular remodeling, increase in RV weight and RV cytokine responses induced by exposure to antigen/PM2.5, highlighting the significance of the genetic background for the biological role of RELMα.

The Association of Prostate Cancer and Urinary Tract Infections: A New Perspective of Prostate Cancer Pathogenesis.

Background and objectives: Microbiota of the urinary tract may be associated with urinary tract malignancy, including prostate cancer. Materials and Methods: We retrospectively collected patients with newly diagnosed prostate cancer and subjects without prostate cancer from the National Health Insurance Research Database (NHIRD) in Taiwan between 1 January 2000 and 31 December 2016. A total of 5510 subjects were recruited and followed until the diagnosis of a primary outcome (urinary tract infection, pyelonephritis, cystitis, and prostatitis). Results: We found that the patients with prostate cancer had a significantly higher risk of urinary tract infections than those without prostate cancer. The adjusted hazard ratios for pyelonephritis, prostatitis, and cystitis were 2.30 (95% CI = 1.36-3.88), 2.04 (95% CI = 1.03-4.05), and 4.02 (95 % CI = 2.11-7.66), respectively. We clearly identified the sites of infection and associated comorbidities in the prostate cancer patients with urinary tract infections. In addition, we found that the patients receiving radiotherapy and androgen deprivation therapy had a lower risk of urinary tract infections than the patients in corresponding control groups. Conclusions: Our study suggests that an abnormal urine microbiome could potentially contribute to the development of prostate cancer through inflammation and immune dysregulation. Furthermore, an imbalanced microbiome may facilitate bacterial overgrowth in urine, leading to urinary tract infections. These findings have important implications for the diagnosis and treatment of prostate cancer. Further research is needed to better understand the role of the urine microbiome in prostate cancer pathogenesis and to identify potential microbiome-targeted therapies for the prevention and treatment of prostate cancer.

Chondrosarcoma of Ureter in an Elderly Patient: A Case Report.

Chondrosarcoma is a rare type of cancer that can affect the upper urinary tract. Because of its rarity, the clinical presentation of chondrosarcoma can be similar to other urinary tract conditions, such as renal colic, hematuria, and urothelial carcinoma. The primary treatment for chondrosarcoma is the surgical removal of the tumor, and radiation or chemotherapy may be used for advanced cases. However, because of the limited number of patients with this condition, there are no established guidelines for chemotherapy, and the outcomes are unclear. In this case, we present a 71-year-old female patient who was diagnosed with ureteral chondrosarcoma. She presented with abdominal pain and hydronephrosis, and a tumor was found beneath a small stone. The patient underwent nephroureterectomy and received oral fluorouracil chemotherapy due to the advanced stage of the disease. Fortunately, the patient survived, and at the 7 months post-operative follow-up there was no evidence of recurrence. In conclusion, the chondrosarcoma of the upper urinary tract is a rare condition that can be difficult to diagnose due to its similarity to other urinary tract conditions. Treatment typically involves the surgical removal of the tumor, with radiation or chemotherapy reserved for advanced cases. However, because of the limited number of patients, there are no established guidelines for chemotherapy, and the outcomes of treatment are unclear.

Randomized Controlled Study of Tenofovir versus Lamivudine Followed by Tenofovir in Severe Exacerbation of Hepatitis B.

Spontaneous severe acute exacerbation (SAE) is not uncommon in the natural history of chronic hepatitis B (CHB). Lamivudine (LAM) has the advantages of low price, quick onset, good efficacy, and no drug resistance within 24 weeks. This study aimed to compare the short-term efficacy of tenofovir disoproxil fumarate (TDF) and LAM for 24 weeks followed by TDF in the treatment of CHB with severe acute exacerbation. Consecutive patients of CHB with SAE were randomized to receive either TDF (19 patients) or LAM for 24 weeks, followed by TDF (18 patients). The primary endpoint was overall mortality or receipt of liver transplantation by week 24. This study was approved by the Institutional Review Board (IRB) of the Kaohsiung Veterans General Hospital (VGHKS12-CT5-10). The baseline characteristics were comparable between the two groups. By week 24, seven (37%) and five (28%) patients in the TDF and LAM-TDF groups died or received liver transplantation (P = 0.487). Multivariate analysis showed that albumin level, prothrombin time (PT), and hepatic encephalopathy were independent factors associated with mortality or liver transplantation by week 24. Early reductions in HBV DNA of more than or equal to 2 log at 1 and 2 weeks were similar between the two groups. The biochemical and virological responses at 12, 24, and 48 weeks were also similar between the two groups. TDF and LAM for 24 weeks followed by TDF achieved a similar clinical outcome in CHB patients with SAE. (This study has been registered at ClinicalTrials.gov under identifier NCT01848743).

Diving, lifting, and horizontal dissection followed by loop-clip traction (DLH+T) can facilitate mucosal flap creation during colorectal ESD.

BACKGROUND: Colorectal ESD is difficult because of the poor maneuverability and difficulty of mucosal flap creation. Diving, Lifting and Horizontal (DLH) dissection technique and loop-clip traction are two different methods to facilitate mucosal trimming and adequate mucosal flap creation. We combined the advantages of these two techniques (DLH+T) in our daily practice colorectal ESD since July 2020. OBJECTIVE: The purpose of this study was to examine the outcomes of DLH+T dissection compared with the conventional dissection. METHODS: We retrospectively reviewed the clinical using DLH+T dissection compared with the conventional dissection since January 2018 at a single tertiary care institution. Postoperative short-term outcomes were investigated after the procedure including mucosal flap creation time, dissection time, dissection speed, en bloc resection rate, and perioperative complications. RESULTS: 28 lesions were in DLH+T dissection group and 39 lesions in the conventional dissection group. The outcomes including en bloc resection rate, dissection speed, and complication between the two groups were similar. The mean mucosal flap creation time (p = 0.035) and the mean dissection speed (p = 0.041) of the DLH+T dissection group was significantly shorter and faster. CONCLUSION: DLH dissection followed by loop-clip traction (DLH+T) technique is a useful technique for safe, efficient, and adequate mucosal flap creation, which can increase the dissection speed and may prevent complication, especially in biopsy-related submucosal fibrosis.

A comparative study of transperineal software-assisted magnetic resonance/ultrasound fusion biopsy and transrectal cognitive fusion biopsy of the prostate.

BACKGROUND: The advantages and disadvantages of transperineal and transrectal biopsies remain controversial in the era of prostate targeted biopsy. In this study, we compared the cancer detection and complication rates of transperineal magnetic resonance/ultrasound (MR/US) fusion biopsy and transrectal cognitive fusion biopsy of the prostate. METHODS: This was a comparative study of two prospectively collected cohorts. Men with clinically suspected prostate cancer and prostate imaging reporting and data system (PI-RADS) score ≥ 3 lesions on multi-parametric magnetic resonance imaging (mpMRI) were enrolled. They underwent either transperineal software fusion biopsy or transrectal cognitive fusion biopsy and systematic biopsy. The detection rates of any prostate cancer and clinically significant prostate cancer (csPC, defined as Gleason score ≥ 3 + 4) and the complication rates between both groups were analysed. RESULTS: Ninety-two and 85 patients underwent transperineal software fusion and transrectal cognitive fusion biopsies, respectively. The detection rate for any prostate cancer was similar between both groups (60.8% vs. 56.4%, p = 0.659). In terms of csPC detection, transperineal fusion biopsy outperformed transrectal fusion biopsy (52.2% vs. 36.5%, p = 0.036). In multivariate regression analysis, age, PI-RADS score > 3, and transperineal route were significant predictors of csPC. Meanwhile, transperineal biopsy resulted in a higher rate of urinary retention than transrectal biopsy (18.5% vs. 4.7%, p = 0.009). No serious infectious complications were noted, although a patient developed sepsis after transrectal biopsy. CONCLUSIONS: Transperineal software fusion biopsy provided a higher csPC detection rate than transrectal cognitive fusion biopsy and carried minimal risk for infectious complications in patients with MRI-visible prostate lesions.

Effects of Chinese herbal medicine in patients with benign prostatic hyperplasia: A nationwide cohort study in Taiwan.

OBJECTIVES: Benign prostatic hyperplasia affects elderly males, with progression presenting the risk of urinary complications and eventual surgical intervention. We aimed to evaluate the effects of Chinese herbal medicine in patients with benign prostatic hyperplasia. METHODS: This retrospective cohort study analyzed claims data in Taiwan's National Health Insurance Research Database from 2001 to 2013. A total of 4142 patients newly diagnosed as benign prostatic hyperplasia were enrolled and divided into cohorts of Chinese herbal medicine users and nonusers by performing 1:1 propensity score matching. The risk of benign prostatic hyperplasia-related complications was assessed by the Cox proportional hazard model. The cumulative incidence of benign prostatic hyperplasia-related surgeries was assessed by Kaplan-Meier method. RESULTS: During the study period, the risk of benign prostatic hyperplasia-related complications was lower in the Chinese herbal medicine cohort than non-Chinese herbal medicine cohort with an adjusted hazard ratio of 0.82 (95% confidence interval 0.73-0.92) after controlling for multiple variables. Subgroup analysis revealed that Chinese herbal medicine users had a significantly lower risk of urinary tract infection (adjusted hazard ratio 0.67, 95% confidence interval 0.50-0.89) and urinary retention (adjusted hazard ratio 0.83, 95% confidence interval 0.72-0.97). In addition, Chinese herbal medicine users also had a lower incidence rate of benign prostatic hyperplasia-related surgery (32.14 vs 40.20, adjusted hazard ratio 0.74, 95% confidence interval 0.61-0.89) and a longer surgery-free interval than non-Chinese herbal medicine users (3.98 vs 3.00 mean person-year, P < 0.001). Data revealed Salviae miltiorrhizae and Ji-Sheng-Shen-Qi-Wan as the most commonly prescribed Chinese herbal medicine by traditional Chinese medicine practitioners. CONCLUSIONS: Our study demonstrated that Chinese herbal medicine might have effects in the benign prostatic hyperplasia-related complications and surgeries in patients with benign prostatic hyperplasia.

Percutaneous Nephrolithotomy Combined Antegrade Flexible Ureteroscope for Complete Staghorn Stones: A Case Report of a New Concept of Stone Surgery.

Percutaneous nephrolithotomy (PCNL) is the treatment of choice for staghorn stones. However, residual stones in calyces remain a challenge due to the limited angle which makes the approach difficult. The new operative technique of endoscopic combined intrarenal surgery (ECIRS), which integrates the advantages of PCNL and retrograde intrarenal surgery (RIRS), was developed to overcome this difficulty. However, two experienced urologists are required to perform ECIRS, and the patient has to be placed in the Galdakao-modified supine Valdivia position or modified prone split-leg position which cannot be achieved in the elderly or patients with ankylosing arthritis, as it may cause harm due to abnormal traction of the joints. In addition, it is difficult for surgeons to create an ideal access tract to perform PCNL in this position. We report the case of a 72-year-old female patient with left staghorn stone. We performed RIRS first and then placed the patient in the decubitus position for PCNL with antegrade flexible ureteroscopy. This method allows patients to be placed in an easier position, with the use of flexible ureteroscopy through a nephroscope to find previously unreachable stones. Moreover, in addition to the more comfortable position both for surgeons and patients, this procedure can also deal with large complex renal stones as with ECIRS. We also created a brand-new definition for stone clearance rate, namely, stone reduction efficiency (SRE). There was a high stone reduction efficiency of 12.64 (mm2/min) in our patient, and no complications occurred. We suggest that this procedure is an ideal alternative treatment for a huge staghorn stone instead of PCNL or ECIRS.

Comparative Outcomes of Robotic Radical Prostatectomy in Patients with Locally Advanced Prostate Cancer.

The effectiveness of radical prostatectomy alone for locally advanced prostate cancer is controversial owing to an increased complication rate and treatment-related morbidity. With technical advances and refinements in surgical techniques, robotic-assisted radical prostatectomy (RARP) has improved the outcomes of patients with locally advanced prostate cancer. RARP therefore plays a role in the treatment of locally advanced prostate cancer. In this study, we enrolled a total of 76 patients with pathologic stage pT3a, pT3b, pT4, or pN1. All patients were followed from surgery to June 2022, and their characteristics, perioperative outcomes, complications, adjuvant therapies and outcomes were analyzed. The median age of the patients was 69 years, and the initial PSA level was 20.5 (IQR 10.8-31.6) ng/mL. The median operative time was 205 (IQR 182-241) minutes. Sixty-six patients (86.8%) regained continence within 1 year, and the continence rate within 3 years of follow-up was 90.8% (69 patients). The overall survival rate was 100%. Twenty-two patients had BCR, of whom 13 received salvage androgen deprivation therapy (ADT), 2 received salvage external beam radiation therapy (EBRT) alone, and 7 received combined ADT and EBRT. No patient had disease progression to castration-resistant prostate cancer during a median 36 months of follow-up after salvage therapy. Our results suggest that RARP can also decrease tumor burden and allow for accurate and precise pathological staging with the need for subsequent treatment. Therefore, we recommend that RARP represents a well-standardized, safe, and oncologically effective option for patients with locally advanced prostate cancer.

Severe acute exacerbation of HCV infection in cancer patients who undergo chemotherapy without antiviral prophylaxis.

No guidelines have been developed for the management of HCV-infected cancer patients receiving chemotherapy. The current study aimed to investigate the incidence of severe acute exacerbation of HCV infection in cancer patients receiving chemotherapy and to search for risk factors predicting severe acute exacerbation of HCV infection. This retrospective cohort study reviewed the clinical data of the cancer patients receiving chemotherapy in our institute from August 2012 to December 2017. Incidences of severe acute exacerbation of HCV infection in different kinds of cancers were assessed, and risk factors were analysed. Cancer patients with HCV infection (n = 306) had a higher frequency of severe acute liver injury (2.3% vs 0.7%; P = .003) than those without HCV infection (n = 4419). The incidence of severe acute exacerbation in HCV-infected haematological cancer patients was higher than that in those with HCC and non-HCC solid tumours (9.4% vs 1.9% and 1.1%). Rituximab-containing chemotherapy and haematological malignancy were the risk factors related to the acute exacerbation (P < .001 and P = .004, respectively). None of the patients with severe acute HCV flares developed hepatic decompensation or mortality. However, 57.1% of them discontinued chemotherapy due to liver dysfunction. In conclusion, HCV infection increases the risk of acute severe liver injury in cancer patients undergoing chemotherapy. Rituximab-containing chemotherapy and haematological malignancy are the risk factors related to severe acute exacerbation of HCV infection in cancer patients undergoing chemotherapy. Pre-chemotherapy HCV testing is therefore mandatory before rituximab-containing chemotherapy for the treatment of haematological malignancy.

Combining prostate health index and multiparametric magnetic resonance imaging in the diagnosis of clinically significant prostate cancer in an Asian population.

OBJECTIVE: To evaluate the practicability of combining prostate health index (PHI) and multiparametric magnetic resonance imaging (mpMRI) for the detection of clinically significant prostate cancer (csPC) in an Asian population. PATIENTS AND METHODS: We prospectively enrolled patients who underwent prostate biopsy due to elevated serum prostate-specific antigen (PSA > 4 ng/mL) and/or abnormal digital rectal examination in a tertiary referral center. Before prostate biopsy, the serum samples were tested for PSA, free PSA, and p2PSA to calculate PHI. Besides, mpMRI was performed using a 3-T scanner and reported in the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2). The diagnostic performance of PHI, mpMRI, and combination of both was assessed. RESULT: Among 102 subjects, 39 (38.2%) were diagnosed with PC, including 24 (23.5%) with csPC (Gleason ≥ 7). By the threshold of PI-RADS ≥ 3, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to predict csPC were 100%, 44.9%, 35.8%, and 100%, respectively. By the threshold of PHI ≥ 30, the sensitivity, specificity, PPV, and NPV to predict csPC were 91.7%, 43.6%, 33.3%, and 94.4%, respectively. The area under the receiver operator characteristic curve of combining PHI and mpMRI was greater than that of PHI alone (0.873 vs. 0.735, p = 0.002) and mpMRI alone (0.873 vs. 0.830, p = 0.035). If biopsy was restricted to patients with PI-RADS 5 as well as PI-RADS 3 or 4 and PHI ≥ 30, 50% of biopsy could be avoided with one csPC patient being missed. CONCLUSION: The combination of PHI and mpMRI had higher accuracy for detection of csPC compared with PHI or mpMRI alone in an Asian population.

Addition of Carvedilol to Gastric Variceal Obturation Does Not Decrease Recurrence of Gastric Variceal Bleeding in Patients With Cirrhosis.

BACKGROUND & AIMS: Gastric variceal bleeding (GVB) frequently recurs after hemostasis by gastric variceal obturation (GVO). We performed a multicenter, randomized controlled trial to determine the efficacy of carvedilol plus GVO in secondary prophylaxis of GVB. METHODS: We performed a prospective study of 121 patients with cirrhosis (ages 20-80 years) with GVB proven by endoscopy within 24 hours of bleeding and stable hemodynamics for at least 3 days after initial GVO. Patients were randomly assigned into a group that underwent repeated GVO (n = 61) or a group received repeated GVO plus carvedilol (n = 60). Recurrent GVB, upper gastrointestinal bleeding (UGIB), adverse events, and survival were compared between the groups. RESULTS: GVB recurred in 21 patients (34%) in the group that received repeated GVO and 14 patients (23%) in the group that received repeated GVO plus carvedilol (P = .18). Ascites (relative risk [RR], 2.69; 95% CI, 1.33-5.48; P = .006) and hepatoma (RR, 2.10; 95% CI, 1.03-4.28; P = .04) were associated with recurrent GVB. Twenty-nine patients (48%) in the group that received repeated GVO and 17 patients (28%) in the group that received repeated GVO plus carvedilol had recurrent UGIB (P = .03). Carvedilol (RR, 0.44; 95% CI, 0.24-0.80; P = .007) was associated with reduced risk of UGIB recurrence. Ascites (RR, 3.02; 95% CI, 1.59-5.73; P = .001) and hepatoma (RR, 2.07; 95% CI, 1.10-3.88; P = .02) were associated with recurrent UGIB. A higher proportion of patients in the group that received repeated GVO plus carvedilol (53%) had adverse events than the group that received repeated GVO (15%) (P < .001). Mean survival times were 21 ± 18 months in the group that received repeated GVO vs 25 ± 20 months in the group that received repeated GVO plus carvedilol (P = .30). CONCLUSION: In a randomized controlled trial, we found that addition of carvedilol to GVO did not decrease recurrence of GVB in patients with cirrhosis but was associated with decreased recurrence of UGIB. However, carvedilol plus GVO produced significantly more adverse events. Mean survival times did not differ significantly between groups. ClinicalTrials.gov no: NCT02504723.

Fecal carriage of multidrug-resistant Escherichia coli by community children in southern Taiwan.

BACKGROUND: The emergence of multidrug-resistant (MDR) Escherichia coli (E. coli), particularly E. coli sequence type ST131, is becoming a global concern. Commensal bacteria, an important reservoir of antibiotic resistance genes, facilitate the spread of such genes to pathogenic bacterial strains. The objective of the study is to investigate the fecal carriage of MDR E. coli and ST131 E. coli in community children in Southern Taiwan. METHODS: In this prospective study, stool samples from children aged 0-18 years were obtained within 3 days of hospitalization from October 2013 to September 2014. Children with a history of underlying diseases, antibiotic treatment, or hospitalization in the 3 months before specimen collection were excluded. E. coli colonies were selected and tested for antimicrobial susceptibility, and O25b-ST131, multilocus sequence typing, and blaCTX-M gene groups were detected. RESULTS: Among 157 E. coli isolates, the rates of nonsusceptibility to ampicillin, amoxycillin + clavulanate, trimethoprim-sulfamethoxazole, and cefazolin were 70, 65.6, 47.1, and 32.5%, respectively. Twenty-nine (18.5%) isolates were nonsusceptible to ciprofloxacin. MDR E. coli accounted for 58 (37%) of all isolates. Thirteen (8.3%) isolates produced extended-spectrum ß-lactamase (ESBL). Furthermore, 26 (16.6%) and 13 (8.3%) isolates were O25b and ST131 positive, respectively. Five (38.5%) of the 13 ESBL-producing E. coli belonged to blaCTX-M group 9, among which were CTXM-14 and 4 (80%) were O25b-ST131 positive. Compared with the non-ESBL and ciprofloxacin-susceptible groups, the ESBL and ciprofloxacin-nonsusceptible groups showed significantly higher rates of O25b-ST131 positivity. CONCLUSIONS: The prevalence of the fecal carriage of nonsusceptible E. coli in children was high; among these E. coli, 37% were MDR, 18.5% were nonsusceptible to ciprofloxacin, and 8.3% produced ESBL. O25b-ST131 was the most common ESBL-producing E. coli clonal group present in the feces of children, and the ESBL and ciprofloxacin-nonsusceptible groups showed significantly higher rates of O25b-ST131 positivity.

Gallbladder function predicts subsequent biliary complications in patients with common bile duct stones after endoscopic treatment?

BACKGROUND: In patients with common bile duct stones (CBDS) and intact gallbladder, further management for the gallbladder after the CBDS clearance is still controversial. The relationship between gallbladder motility and the biliary complications were seldom discussed. Our study is to predict the subsequent biliary complications by gallbladder function test using fatty meal sonography (FMS) in patients with CBDS who had been treated by endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Patients with an intact gallbladder and CBDS after endoscopic clearance of bile duct were enrolled. Patients received a fatty meal sonography after liver function returned to normal. The fasting volume, residual volume, and gallbladder ejection fraction (GBEF) in FMS were measured. Relationships of patients' characteristics, gallbladder function and recurrent biliary complication were analyzed. RESULTS: From 2011 to 2014, 118 patients were enrolled; 86 patients had calculus gallbladders, and 32 patients had acalculous gallbladders. After a mean follow- up of 33 months, 23 patients had recurrent biliary complications. Among 86 patients with calculus gallbladder, 15 patients had spontaneous clearance of gallbladder stones; 14 patients received cholecystectomy due to acute cholecystitis or recurrent colic pain with smooth postoperative courses. In the follow up period, six patients died of non-biliary causes. The GBEF is significant reduced in most patients with a calculus gallbladder in spite of stone color. Calculus gallbladder, alcohol drinking and more than one sessions of initial endoscopic treatment were found to be the risk factors of recurrent biliary complication. CONCLUSIONS: Gallbladder motility function was poorer in patients with a calculus gallbladder, but it cannot predict the recurrent biliary complication. Since spontaneous clearance of gallbladder stone may occur, wait and see policy of gallbladder management after endoscopic treatment of CBDS is appropriate, but regular follow- up in those patients with risk factors for recurrence is necessary.

Cyclodextrin-assisted dispersive liquid-liquid microextraction for the preconcentration of carbamazepine and clobazam with subsequent sweeping micellar electrokinetic chromatography.

A new version of dispersive liquid-liquid microextraction, namely, cyclodextrin-assisted dispersive liquid-liquid microextraction, with subsequent sweeping micellar electrokinetic chromatography has been developed for the preconcentration and sensitive detection of carbamazepine and clobazam. α-Cyclodextrin and chloroform were used as the dispersive agent and extraction solvent, respectively. After the extraction, carbamazepine and clobazam were analyzed using micellar electrokinetic chromatography with ultraviolet detection. The detection sensitivity was further enhanced using the sweeping technique. Under optimal extraction and stacking conditions, the calibration curves of carbamazepine and clobazam were linear over a concentration range of 2.0-200.0 ng/mL. The method detection limits at a signal-to-noise ratio of 3 were 0.6 and 0.5 ng/mL with sensitivity enhancement factors of 3575 and 4675 for carbamazepine and clobazam, respectively. This developed method demonstrated high sensitivity enhancement factors and was successfully applied to the determination of carbamazepine and clobazam in human urine samples. The precision and accuracy for urine samples were less than 4.2 and 6.9%, respectively.

A Randomized Controlled Trial Shows that both 14-Day Hybrid and Bismuth Quadruple Therapies Cure Most Patients with Helicobacter pylori Infection in Populations with Moderate Antibiotic Resistance.

Hybrid therapy is a novel two-step treatment achieving a high eradication rate for Helicobacter pylori infection. Currently, whether this new therapy achieves a higher eradication rate than bismuth quadruple therapy remains an unanswered question. The aim of this prospective, randomized comparative study was to investigate the efficacies of 14-day hybrid therapy and bismuth quadruple therapy in the treatment of H. pylori infection. From July 2013 to June 2015, eligible H. pylori-infected subjects were randomly assigned to receive either 14-day bismuth quadruple therapy (pantoprazole, bismuth subcitrate, tetracycline, and metronidazole for 14 days) or 14-day hybrid therapy (a 7-day dual therapy with pantoprazole plus amoxicillin, followed by a 7-day quadruple therapy with pantoprazole plus amoxicillin, clarithromycin, and metronidazole). H. pylori status was examined 6 weeks after the end of treatment. Three hundred thirty H. pylori-infected participants were randomized to receive 14-day bismuth quadruple therapy (n = 164) or 14-day hybrid therapy (n = 166). The eradication rates by intention-to-treat analysis were similar: 93.9% versus 92.8%, respectively (95% confidence interval [CI], -4.3% to 5.4%; P = 0.68). Per-protocol analysis yielded similar results (96.7% versus 94.9%, respectively; P = 0.44). However, bismuth quadruple therapy had a higher frequency of adverse events than hybrid therapy (55.5% versus 15.7%, respectively; 95% CI, 30.4% to 49.2%; P < 0.001). The two treatments exhibited comparable drug adherence (93.9% versus 97%, respectively). The resistance rates of antibiotics were: clarithromycin, 16.7% of patients; amoxicillin, 1.3%; metronidazole, 25%; and tetracycline, 0%. In the bismuth quadruple therapy group, the eradication rate of metronidazole-resistant strains was lower than that of metronidazole-susceptible strains (70.0% versus 96.4%, respectively; P = 0.04). In the hybrid therapy group, no significant impact of clarithromycin or metronidazole resistance on eradication rates was identified. Both 14-day hybrid and bismuth quadruple therapies cure most patients with H. pylori infection in populations with moderate antibiotic resistance. However, the 14-day hybrid therapy has fewer adverse effects than the bismuth quadruple therapy. (This study has been registered at ClinicalTrials.gov under identifier NCT02541864.).