Endoscopic therapy of upper gastrointestinal bleeding remains challenging with conventional endoscopic devices. Use of Hemospray, where a nanopowder with clotting abilities is sprayed onto the ...bleeding site, had been highly effective for management of arterial bleeding in a heparizined animal model. The safety and effectiveness of Hemospray for hemostasis of active peptic ulcer bleeding in humans was evaluated.
In a prospective, single-arm, pilot clinical study, consecutive adults with confirmed peptic ulcer bleeding (Forrest score Ia or Ib), who had all given informed consent to participation, underwent upper gastrointestinal endoscopy and application of Hemospray within 24 hours of hospital admission once hemodynamically stable. Up to two applications of Hemospray, not exceeding a total of 150 g were allowed. Bleeding recurrence was monitored post procedurally, by second-look endoscopy (72 hours post treatment), and by phone at 30 days. Rate of hemostasis, recurrent bleeding, mortality, need for surgical intervention, and treatment-related complications were assessed.
20 patients were recruited (18 men, 2 women; mean age 60.2 years). Acute hemostasis was achieved in 95 % (19 / 20) of patients; 1 patient had a pseudoaneurysm requiring arterial embolization. Bleeding recurred in 2 patients within 72 hours (shown by hemoglobin drop); neither had active bleeding identified at the 72-hour endoscopy. No mortality, major adverse events, or treatment- or procedure-related serious adverse events were reported during 30-day follow-up.
These pilot results indicate that Hemospray is safe in humans. Hemospray was effective in achieving acute hemostasis in active peptic ulcer bleeding.
Upper gastrointestinal bleeding (UGIB), especially peptic ulcer bleeding, remains one of the most important cause of hospitalisation and mortality world wide. In Asia, with a high prevalence of ...Helicobacter pylori infection, a potential difference in drug metabolism, and a difference in clinical management of UGIB due to variable socioeconomic environments, it is considered necessary to re-examine the International Consensus of Non-variceal Upper Gastrointestinal Bleeding with emphasis on data generated from the region. The working group, which comprised experts from 12 countries from Asia, recommended the use of the Blatchford score for selection of patients who require endoscopic intervention and which would allow early discharge of patients at low risk. Patients' comorbid conditions should be included in risk assessment. A pre-endoscopy proton pump inhibitor (PPI) is recommended as a stop-gap treatment when endoscopy within 24 h is not available. An adherent clot on a peptic ulcer should be treated with endoscopy combined with a PPI if the clot cannot be removed. Routine repeated endoscopy is not recommended. High-dose intravenous and oral PPIs are recommended but low-dose intravenous PPIs should be avoided. COX-2 selective non-steroidal anti-inflammatory drugs combined with a PPI are recommended for patients with very high risk of UGIB. Aspirin should be resumed soon after stabilisation and clopidogrel alone is no safer than aspirin plus a PPI. When dual antiplatelet agents are used, prophylactic use of a PPI reduces the risk of adverse gastrointestinal events.
Gastric carcinogenesis is a multistep process involving genetic and epigenetic alteration of protein-coding proto-oncogenes and tumor-suppressor genes. Recent discoveries have shed new light on the ...involvement of a class of noncoding RNA known as microRNA (miRNA) in gastric cancer. A substantial number of miRNAs show differential expression in gastric cancer tissues. Genes coding for these miRNAs have been characterized as novel proto-oncogenes and tumor-suppressor genes based on findings that these miRNAs control malignant phenotypes of gastric cancer cells. In this connection, miRNA dysregulation promotes cell-cycle progression, confers resistance to apoptosis, and enhances invasiveness and metastasis. Moreover, certain polymorphisms in miRNA genes are associated with increased risks for atrophic gastritis and gastric cancer, whereas circulating levels of miRNAs may serve as biomarkers for early diagnosis. Several miRNAs have also been shown to correlate with gastric cancer progression, and thus may be used as prognostic markers. Elucidating the biological aspects of miRNA dysregulation may help us better understand the pathogenesis of gastric cancer and promote the development of miRNA-directed therapeutics against this deadly disease.
Summary
Background
The performance of faecal occult blood tests (FOBTs) to screen proximally located colorectal cancer (CRC) has produced inconsistent results.
Aim
To assess in a meta‐analysis, the ...diagnostic accuracy of FOBTs for relative detection of CRC according to anatomical location of CRC.
Methods
Diagnostic studies including both symptomatic and asymptomatic cohorts assessing performance of FOBTs for CRC were searched from MEDINE and EMBASE. Primary outcome was accuracy of FOBTs according to the anatomical location of CRC. Bivariate random‐effects model was used. Subgroup analyses were performed to evaluate test performance of guaiac‐based FOBT (gFOBT) and immunochemical‐based FOBT (iFOBT).
Results
Thirteen studies, with 17 cohorts, reporting performance of FOBT were included; a total of 26 342 patients (mean age 58.9 years; 58.1% male) underwent both colonoscopy and FOBT. Pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of FOBTs for CRC detection in the proximal colon were 71.2% (95% CI 61.3–79.4%), 93.6% (95% CI 90.7–95.7%), 11.1 (95% CI 7.8–15.8) and 0.3 (95% CI 0.2–0.4) respectively. Corresponding findings for CRC detection in distal colon were 80.1% (95% CI 70.9–87.0%), 93.6% (95% CI 90.7–95.7%), 12.6 (95% CI 8.8–18.1) and 0.2 (95% CI 0.1–0.3). The area‐under‐curve for FOBT detection for proximal and distal CRC were 90% vs. 94% (P = 0.0143). Both gFOBT and iFOBT showed significantly lower sensitivity but comparable specificity for the detection of proximally located CRC compared with distal CRC.
Conclusion
Faecal occult blood tests, both guaiac‐ and immunochemical‐based, show better diagnostic performance for the relative detection of colorectal cancer in the distal colon than in the proximal bowel.
Summary
Background
Complementary and alternative medicine (CAM), particularly herbal therapy, is widely used by patients with inflammatory bowel disease (IBD) but controlled data are limited.
Aim
To ...systematically review the literature on the efficacy of herbal therapy in the treatment of ulcerative colitis (UC) and Crohn's disease (CD).
Methods
Publications in English and non‐English literatures (MEDLINE, EMBASE, EBM Reviews, AMED, Global Health) were searched from 1947 to 2013 for controlled clinical studies of herbal therapy in IBD. Outcome measures included response and remission rates.
Results
Twenty‐one randomised controlled trials (14 UC; 7 CD) including a total of 1484 subjects (mean age 41, 50% female) were analysed. In UC, aloe vera gel, Triticum aestivum (wheat grass juice), Andrographis paniculata extract (HMPL‐004) and topical Xilei‐san were superior to placebo in inducing remission or response, and curcumin was superior to placebo in maintaining remission; Boswellia serrata gum resin and Plantago ovata seeds were as effective as mesalazine, whereas Oenothera biennis (evening primrose oil) had similar relapse rates as omega‐3 fatty acids in the treatment of UC. In CD, Artemisia absinthium (wormwood) and Tripterygium wilfordii were superior to placebo in inducing remission, and preventing clinical recurrence of post‐operative CD respectively.
Conclusions
Randomised controlled trials of herbal therapy for the treatment of IBD show encouraging results but studies remain limited and heterogenous. Larger controlled studies with stricter endpoints and better‐defined patient groups are required to obtain more conclusive results on the use of CAM therapies in IBD.
The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine ...aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty‐one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1–4), bridging fibrosis (F0–2 vs F3–4) and liver cirrhosis (F0–3 vs F4) was 0.80 (95% CI: 0.68–0.92), 0.87 (95% CI: 0.82–0.93) and 0.93 (95% CI: 0.89–0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.
Using microRNA (miRNA) expression array, we identified that miR-7 was deregulated in colorectal cancer (CRC). We studied the biological role and molecular target of miR-7 in CRC. miR-7 was ...downregulated in six out of seven colon cancer cell lines. Ectopic expression of miR-7 suppressed colon cancer cell proliferation (P<0.05), induced apoptosis (P<0.05) and caused cell-cycle arrest in G1 phase (P<0.05). The tumor suppressive function of miR-7 was further confirmed in nude mice (P<0.05). The 3'-untranslated region (3'UTR) of Yin Yang 1 (YY1) mRNA contains an evolutionarily conserved miR-7 binding site using in silico searches, luciferase reporter assay and western blot analysis confirmed that miR-7 directly bound to YY1 3'UTR to negatively regulate the protein expression of YY1 in colon cancer cell lines HCT116 and LOVO. Intriguingly, knock-down of YY1 in three colon cancer cell lines (HCT116, LOVO and DLD1) consistently suppressed cell proliferation (P<0.01) and induced apoptosis (P<0.01), indicating the opposite functions of miR-7 and YY1 in CRC. Consistent with these data, ectopic expression of YY1 promoted cell growth by increasing proliferation (P<0.01) and suppressing apoptosis (P<0.001). The tumorigenic ability of YY1 was further confirmed in vivo in xenograft-nude mouse model (P<0.01). In addition, pathway analyses revealed that the oncogenic effect by YY1 was associated with inhibiting p53 and modulating its downstream effectors p15, caspase cascades and C-Jun, and activating Wnt signaling pathway through activating β-catenin, anti-apoptotic survivin and fibroblast growth factor 4. Furthermore, multivariate analysis revealed that patients with YY1 protein high expression had a significant decrease in overall survival, and Kaplan-Meier survival curves showed that these patients had significantly shorter survival than others (P<0.0001). In conclusion, MiR-7 is a novel miRNA with tumor suppressive function in colon cancer by targeting oncogenic YY1. YY1 promotes colon cancer growth through inhibiting p53 and promoting Wnt signaling pathways and serves as an independent prognostic biomarker for CRC patients.
Aliment Pharmacol Ther 2010; 32: 1323–1331
Summary
Background On‐treatment predictors of response to peginterferon can guide individualization of therapy in chronic hepatitis B virus infection.
Aim ...To investigate the use of serum hepatitis B surface antigen quantification to predict sustained response.
Methods Hepatitis B e antigen‐positive chronic hepatitis B patients who received peginterferon for 32–48 weeks with or without lamivudine combination were studied. Sustained response was defined as hepatitis B e antigen seroconversion and chronic hepatitis B virus DNA <10 000 copies/mL until 12 months post‐treatment.
Results Twenty‐one of 92 (23%) patients achieved sustained response. At month 6, the area under receiver operating characteristics curve for hepatitis B surface antigen to predict sustained response was 0.77 (95% confidence interval 0.65–0.89, P < 0.001). An hepatitis B surface antigen cutoff at 300 IU/mL at month 6 could give the maximum combination of sensitivity (62%) and specificity (89%) to predict sustained response. Nine of 21 (43%) sustained responders vs. 9 of 71 (13%) nonsustained responders had >1 log hepatitis B surface antigen reduction at month 6 (P < 0.001). Combined hepatitis B surface antigen ≤300 IU/mL and >1 log reduction at month 6 had sensitivity, specificity, positive and negative predictive values of 43%, 96%, 75% and 85% to predict sustained response, respectively.
Conclusion On‐treatment serum hepatitis B surface antigen can predict response to peginterferon therapy in chronic hepatitis B.
Endocrine treatment is recommended by clinical guidelines as the preferred treatment option for premenopausal as well as postmenopausal women with hormone receptor-positive, HER2-negative metastatic ...breast cancer. In real-world clinical practice, however, a substantial number of patients are treated with chemotherapy. We aimed to compare the clinical antitumour activity and safety of palbociclib plus endocrine therapy with that of capecitabine chemotherapy in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer.
This multicentre, open-label, randomised, phase 2 study was done in 14 academic institutions in South Korea. Premenopausal women aged 19 years or older with hormone receptor-positive, HER2-negative breast cancer that had relapsed or progressed during previous tamoxifen therapy and with an Eastern Cooperative Oncology Group performance status of 0–2 were included. One line of previous chemotherapy for metastatic breast cancer was allowed. Patients were randomly assigned, using a random permuted block design (with a block size of two), to receive palbociclib plus combination endocrine therapy (oral exemestane 25 mg per day for 28 days and oral palbociclib 125 mg per day for 21 days every 4 weeks plus leuprolide 3·75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1250 mg/m2 twice daily for 2 weeks every 3 weeks). Randomisation was stratified by previous chemotherapy for metastatic breast cancer and visceral metastasis. The primary endpoint was progression-free survival. All analyses were done in a modified intention-to-treat population that excluded patients who did not receive study medication. This study is registered with ClinicalTrials.gov, NCT02592746, and is ongoing for follow-up of overall survival.
Between June 15, 2016, and Dec 10, 2018, 189 patients were enrolled, of whom 184 were randomly assigned to the palbociclib plus endocrine therapy group (n=92) or the capecitabine group (n=92). Six patients in the capecitabine group withdrew from the study before drug administration; therefore, 92 patients in the palbociclib plus endocrine therapy group and 86 patients in the capecitabine group were included in the modified intention-to-treat analyses. 46 (50%) of 92 patients in the palbociclib plus endocrine therapy group and 45 (51%) of 92 in the capecitabine group were treatment naive for metastatic breast cancer. During a median follow-up of 17 months (IQR 9–22), median progression-free survival was 20·1 months (95% CI 14·2–21·8) in the palbociclib plus endocrine therapy group versus 14·4 months (12·1–17·0) in the capecitabine group (hazard ratio 0·659 95% CI 0·437–0·994, one-sided log-rank p=0·0235). Treatment-related grade 3 or worse neutropenia was more common in the palbociclib plus endocrine therapy group than in the capecitabine group (69 75% of 92 vs 14 16% of 86 patients). 2 (2%) patients in the palbociclib plus endocrine therapy group and 15 (17%) patients in the capecitabine group had treatment-related serious adverse events. No treatment-related deaths occurred.
Exemestane plus palbociclib with ovarian function suppression showed clinical benefit compared with capecitabine in terms of improved progression-free survival in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Palbociclib plus exemestane with ovarian suppression is an active treatment option in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer who have been pretreated with tamoxifen.
Pfizer, Shinpoong, and Daewoong Korea and Takeda.
Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia ...Pacific Working Group aimed to provide an updated set of consensus recommendations.
Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements.
Age range for CRC screening is defined as 50-75 years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening.
Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region.
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