Phase 1b/2a randomized study of heterologous ChAdOx1-HBV/MVA-HBV therapeutic vaccination (VTP-300) as monotherapy and combined with low-dose nivolumab in virally-suppressed patients with chronic hepatitis B.

BACKGROUND AND AIM: The induction of effective CD8+ T cells is thought to play a critical role in the functional cure of chronic hepatitis B (CHB). Additionally, the use of checkpoint inhibitors is being evaluated to overcome T cell dysfunction during CHB. APPROACH AND RESULTS: A chimpanzee adenoviral vector (ChAdOx1-HBV) and a Modified vaccinia Ankara boost (MVA-HBV) encoding the inactivated polymerase, core, and S region from a consensus genotype C HBV were studied. The trial enrolled 55 patients with virally-suppressed CHB virus infection and HBsAg <4,000 IU/mL Group 1 received MVA-HBV intramuscularly (IM) on Day 0 and 28, Group 2 received ChAdOx1-HBV on Day 0/MVA-HBV on Day 28 (VTP-300), Group 3 received VTP-300 + low-dose nivolumab (LDN) on Day 28, and Group 4 received VTP-300 plus LDN with both injections. VTP-300 alone and in combination with LDN was well tolerated with no treatment-related serious adverse events. Reductions of HBsAg were demonstrated in the VTP-300 group 2: 3 of 18 patients with starting HBsAg < 50 IU/ml had durable log10 declines > 0.7 log10 2 months post last-dose. Group 3 (N=18) had reductions in HBsAg of 0.76 log10 and 0.80 log10 3 (p<0.001) at 2 and 7 months post last dose. Two developed persistent non-detectable HBsAg levels. CD4+ and CD8+ antigen-specific T cell responses were generated and there was a correlation between IFN-y ELISpot response and HBsAg decline in Group 2. CONCLUSIONS: VTP-300 induced CD4+ and CD8+ T cells and lowered HBsAg in a subset of patients with baseline values below 100 IU/ml. The addition of LDN resulted in significant reduction in surface antigen. VTP-300 is a promising immunotherapeutic to move forward alone or in combination therapies. IMPACT AND IMPLICATIONS: The induction of potent, durable CD8+ T cells may be critical to achieving a functional cure in chronic hepatitis B virus infection. A prime-boost immunotherapeutic consisting of an adenoviral-vector encoding hepatitis B antigens followed by a pox virus boost was shown to induce CD8+ T cells and to lower HBsAg in CHB patients, either alone or more impactfully when administered in conjunction with a checkpoint inhibitor. The use of immunotherapeutics CLINTRIALS: NCT047789.

The relationship between meniscal pathology and osteoarthritis depends on the type of meniscal damage visible on magnetic resonance images: data from the Osteoarthritis Initiative.

OBJECTIVE: To determine the association of different types of meniscal pathology with knee pain, bone marrow lesion (BML) volume, and end-stage knee osteoarthritis (esKOA). DESIGN: Participants were selected from an ancillary project to the Osteoarthritis Initiative (OAI) who had at least one knee with symptomatic osteoarthritis. Baseline magnetic resonance images (MRI) were evaluated for meniscal pathology using a modified International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine (ISAKOS) classification system. We collapsed 10 types of meniscal pathology into five categories: normal, intrameniscal signal, morphological deformity/extrusion (altered meniscal shape and/or extrusion but no apparent substance loss), tear, and maceration. Outcomes included Western Ontario and McMaster Universities osteoarthritis index (WOMAC) knee pain and BML volume at baseline and after 2 years. We defined the prevalence of esKOA based on a validated algorithm. We performed logistic regression and adjusted for age, sex, and body mass index (BMI). RESULTS: The 463 participants (53% male) included in the analysis had mean age 63 (9.2) years, BMI 29.6 (4.6) kg/m2, and 71% had Kellgren-Lawrence grade ≥2. Morphological deformity/extrusion and maceration, but no other types of meniscal pathology, were associated with BML volume (morphological deformity/extrusion odds ratio [OR] = 2.47, 95% CI: 1.49, 4.09, maceration OR = 5.85, 95% CI: 3.40, 10.06) and change in BML volume (morphological deformity/extrusion OR = 2.17, 95% CI: 1.37, 3.45, maceration OR = 3.12, 95% CI: 1.87, 5.19). Only maceration was associated with baseline WOMAC knee pain (OR = 2.82, 95% CI: 1.79, 4.43) and prevalence of esKOA (OR = 7.53, 95% CI: 4.25, 13.31). CONCLUSIONS: Based on MRI, morphologic deformity/extrusion and maceration rather than intrameniscal signal or tear were associated with osteoarthritis severity and progression, which highlights the importance of differentiating distinct types of meniscal pathology.

Osteoarthritis year 2011 in review: clinical.

The purpose of this narrative year in review of clinical studies was to highlight a few publications related to obesity and weight loss, physical activity, and synovitis as well as disease modifying interventions that were published between September 2010 and September 2011. This year clinical research highlighted the extent to which obesity and osteoarthritis (OA) are impacting quality of life among adults in the United States and that reducing excessive body weight or becoming more physically active may be beneficial. In addition to weight loss and physical activity and synovitis, research over the past year has highlighted the diverse methods being pursued for structural modification interventions. In addition to chondroitin sulfate there were interesting preliminary findings that meniscal implants and joint distractions may modify OA progression.

Cross-sectional DXA and MR measures of tibial periarticular bone associate with radiographic knee osteoarthritis severity.

OBJECTIVE: We evaluated the relationship of medial proximal tibial periarticular areal bone mineral density (paBMD) and trabecular morphometry and determined whether these bone measures differed across radiographic medial joint space narrowing (JSN) scores. METHODS: 482 participants of the Osteoarthritis Initiative (OAI) Bone Ancillary Study had knee dual X-ray absorptiometry (DXA) and trabecular bone 3T magnetic resonance imaging (MRI) exams assessed at the same visit. Medial proximal tibial paBMD was measured on DXA and apparent trabecular bone volume fraction (aBV/TV), thickness (aTb.Th), number (aTb.N), and spacing (aTb.Sp) were determined from MR images. Radiographs were assessed for medial JSN scores (0-3). We evaluated associations between medial paBMD and trabecular morphometry. Whisker plots with notches of these measures versus medial JSN scores were generated and presented. RESULTS: Mean age was 63.9 (9.2) years, BMI 29.6 (4.8) kg/m(2), and 53% were male. The Spearman correlation coefficients between DXA-measured medial paBMD and aBV/TV was 0.61 [95% confidence interval (CI) 0.55-0.66]; between paBMD and aTb.Th was 0.38 (95%CI 0.30-0.46); paBMD and aTb.N was 0.65 (95%CI 0.60-0.70); paBMD and aTb.Sp was -0.65 (95%CI -0.70 to -0.59). paBMD and the trabecular metrics were associated with medial JSN scores. CONCLUSION: The moderate associations between periarticular trabecular bone density and morphometry and their relationship with greater severity of knee OA support hypotheses of remodeling and/or microscopic compression fractures in the natural history of OA. Longitudinal studies are needed to assess whether knee DXA will be a predictor of OA progression. Further characterization of the periarticular bone in OA utilizing complementary imaging modalities will help clarify OA pathophysiology.

Bone marrow lesions are associated with altered trabecular morphometry.

OBJECTIVE: Bone marrow lesions (BMLs) are a common magnetic resonance (MR) feature in patients with osteoarthritis, however their pathological basis remains poorly understood and has not been evaluated in vivo. Our aim was to evaluate the trabecular structure associated with the presence and size of BMLs present in the same regions of interest (ROI) using quantitative MR-based trabecular morphometry. DESIGN: 158 participants in the Osteoarthritis Initiative (OAI) were imaged with a coronal 3D fast imaging with steady state precession (FISP) sequence for trabecular morphometry in the same session as the OAI 3 T MR knee evaluation. The proximal medial tibial subchondral bone in the central weight-bearing ROI on these knee 3D FISP images were quantitatively evaluated for apparent bone volume fraction, trabecular number, spacing, and thickness. BMLs were also evaluated in the subchondral bone immediately adjacent to the articular cartilage. BML volume was also evaluated within the same trabecular morphometry ROI and semi-quantitatively classified as none, small, or large. Kruskal-Wallis test was used to determine if mean apparent bone volume fraction, trabecular number, spacing, or thickness differed by BML score. RESULTS: Compared to knees with ROIs containing no BMLs, knees with small or large BMLs had statistically higher apparent bone volume fraction (P < 0.01), trabecular number (P < 0.01), and thickness (P = 0.02), and lower trabecular spacing (P < 0.01). CONCLUSIONS: Compared to knees with ROIs containing no BMLs, knees with ROIs containing small or large BMLs had higher apparent bone volume fraction, trabecular number and thickness, but lower trabecular spacing. These findings may represent areas of locally increased bone remodeling or compression.

Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score).

OBJECTIVE: In an effort to evolve semi-quantitative scoring methods based upon limitations identified in existing tools, integrating expert readers' experience with all available scoring tools and the published data comparing the different scoring systems, we iteratively developed the magnetic resonance imaging (MRI) Osteoarthritis Knee Score (MOAKS). The purpose of this report is to describe the instrument and its reliability. METHODS: The MOAKS instrument refines the scoring of bone marrow lesions (BMLs) (providing regional delineation and scoring across regions), cartilage (sub-regional assessment), and refines the elements of meniscal morphology (adding meniscal hypertrophy, partial maceration and progressive partial maceration) scoring. After a training and calibration session two expert readers read MRIs of 20 knees separately. In addition, one reader re-read the same 20 MRIs 4 weeks later presented in random order to assess intra-rater reliability. The analyses presented here are for both intra- and inter-rater reliability (calculated using the linear weighted kappa and overall percent agreement). RESULTS: With the exception of inter-rater reliability for tibial cartilage area (kappa=0.36) and tibial osteophytes (kappa=0.49); and intra-rater reliability for tibial BML number of lesions (kappa=0.54), Hoffa-synovitis (kappa=0.42) all measures of reliability using kappa statistics were very good (0.61-0.8) or reached near-perfect agreement (0.81-1.0). Only intra-rater reliability for Hoffa-synovitis, and inter-rater reliability for tibial and patellar osteophytes showed overall percent agreement <75%. CONCLUSION: MOAKS scoring shows very good to excellent reliability for the large majority of features assessed. Further iterative development and research will include assessment of its validation and responsiveness.

Low-dose terlipressin plus banding ligation versus low-dose terlipressin alone in the prevention of very early rebleeding of oesophageal varices.

BACKGROUND: Very early rebleeding is frequently encountered in patients with acute oesophageal variceal bleeding. A trial was designed to assess the efficacy and safety in patients with no active bleeding at endoscopy, receiving banding ligation association with terlipressin to prevent very early rebleeding. METHODS: Patients with no active variceal bleeding at endoscopy were evaluated. Eligible patients were randomised to receive terlipressin infusion alone for 5 days (Terlipressin group) or banding ligation plus terlipressin infusion for 2 days (Combined group). Primary endpoints were treatment failure and very early rebleeding. RESULTS: The terlipressin group was composed of 46 patients and the Combined group was composed of 47 patients. Both groups were comparable in terms of baseline data. Forty-eight-hour haemostasis was achieved in 91% in the Terlipressin group and 98% in the Combined group (p = 0.20). Very early rebleeding within 48-120 h occurred in 7 patients (15%) in the Terlipressin group but not in any patients (0%) in the Combined group (p = 0.006). Treatment failure was 24% in the Terlipressin group and 2% in the Combined group (p = 0.002). Multivariate analysis revealed that treatment (OR 0.081; 95% CI 0.010 to 0.627) was the only predictive factor of very early rebleeding. Blood requirement was significantly lower in the Combined group than in the Terlipressin group. Complications and 6-week survival were similar in both groups. CONCLUSIONS: Combination of banding ligation and terlipressin infusion for 2 days was superior to only infusion of terlipressin for 5 days in the reduction of very early rebleeding and treatment failure in patients with inactive variceal bleeding at endoscopy. TRIAL REGISTRATION NUMBER: ISRCTN28353453.

Strong association of MRI meniscal derangement and bone marrow lesions in knee osteoarthritis: data from the osteoarthritis initiative.

INTRODUCTION: Meniscal damage is common in knee Osteoarthritis (OA) and predictive of structural progression, suggesting that their disruption plays a role in the development of OA. The bone marrow lesion (BML) is associated with pain and is a strong risk factor for structural progression. These lesions are associated with abnormal loading in a knee joint. Therefore, our hypothesis was that in those with symptomatic knee OA, large BMLs would be associated with ipsi-compartmental meniscal derangement. METHODS: This was a cross-sectional study of a subsample of the Osteoarthritis Initiative where one set of magnetic resonance (MR) images from each participant was scored for tibiofemoral BMLs and meniscal derangement. We performed chi-squared tests comparing the prevalence of large BMLs in those with ipsi-compartmental meniscal derangement and those without. RESULTS: 160 Participants had a mean age of 61 (+/-9.9), mean BMI of 30.3 (+/-4.7) and 50% were female. 79% of medial and 39% of lateral menisci showed MRI (Magnetic Resonance Imaging) derangement. In those with medial meniscal MRI derangement, 44% had large medial BMLs while in those without medial meniscal derangement, 0% had large BMLs. Similar results were seen in the lateral compartment. CONCLUSION: Medial and lateral MRI meniscal derangement are highly prevalent in symptomatic knee OA and BMLs are highly associated with ipsi-compartmental MRI meniscal derangement.

Bone marrow lesions and joint effusion are strongly and independently associated with weight-bearing pain in knee osteoarthritis: data from the osteoarthritis initiative.

OBJECTIVE: It is widely believed that there are multiple sources of pain at a tissue level in osteoarthritis (OA). Magnetic Resonance Images (MRIs) provide a wealth of anatomic information and may allow identification of specific features associated with pain. We hypothesized that in knees with OA, bone marrow lesions (BMLs), synovitis, and effusion would be associated with weight-bearing and (less so with) non-weight-bearing pain independently. METHODS: In a cross-sectional study of persons with symptomatic knee OA using univariate and multivariate logistic regressions with maximal BML, effusion, and synovitis defined by Boston Leeds Osteoarthritis Knee Score as predictors, and knee pain using weight-bearing and non-weight-bearing Western Ontario and McMaster University OA Index pain questions as the outcome, we tested the association between MRI findings and knee symptoms. RESULTS: 160 participants, mean age 61 (+/-9.9), mean body mass index (BMI) 30.3 (+/-4.7) and 50% female, stronger associations were seen with weight-bearing compared with non-weight-bearing knee pain with adjusted risk ratios (RRs) of weight-bearing knee pain, for increasing maximal BML scores of 1.0 (referent) (maximal BML=0), 1.2, 1.9, and 2.0 (P for trend=0.006). For effusion scores, adjusted RRs of knee pain were 1.0, 1.7, 2.0, and 2.6 (P for trend=0.0004); and for synovitis scores, adjusted ORs were 1.0, 1.4, 1.5, and 1.9 (P for trend=0.22). CONCLUSION: Cross-sectionally, maximal BML and effusion scores are independently associated with weight-bearing and less so with non-weight-bearing knee pain, supporting the idea that pain in OA is multifactorial. These MRI features should be considered as possible new treatment targets in knee OA.

The reliability of a new scoring system for knee osteoarthritis MRI and the validity of bone marrow lesion assessment: BLOKS (Boston Leeds Osteoarthritis Knee Score).

AIM: MRI provides unparalleled visualisation of all the anatomical structures involved in the osteoarthritis (OA) process. There is a need for reliable methods of quantifying abnormalities of these structures. The aim of this work was to assess the reliability of a novel MRI scoring system for evaluating OA of the knee and explore the validity of the bone marrow lesion (BML) scoring component of this new tool. METHODS: After review of the relevant literature, a collaborative group of rheumatologists and radiologists from centres in the UK and USA established preliminary anatomical divisions, items (necessarily broadly inclusive) and scaling for a novel semi-quantitative knee score. A series of iterative reliability exercises were performed to reduce the initial items, and the reliability of the resultant Boston-Leeds Osteoarthritis Knee Score (BLOKS) was examined. A further sample had both the BLOKS and WORMS (Whole Organ MRI Score) bone marrow lesion (BML) score performed to assess the construct validity (relation to knee pain) and longitudinal validity (prediction of cartilage loss) of each scoring method. RESULTS: The BLOKS scoring method assesses nine intra-articular regions and contains eight items, including features of bone marrow lesions, cartilage, osteophytes, synovitis, effusions and ligaments. The scaling for each feature ranges from 0-3. The inter-reader reliability for the final BLOKS items ranged from 0.51 for meniscal extrusion up to 0.79 for meniscal tear. The reliability for other key features was 0.72 for BML grade, 0.72 for cartilage morphology, and 0.62 for synovitis. Maximal BML size on the BLOKS scale had a positive linear relation with visual analogue scale (VAS) pain, however the WORMS scale did not. Baseline BML was associated with cartilage loss on both BLOKS and WORMS scale. This association was stronger for BLOKS than WORMS. CONCLUSION: We have designed a novel scoring system for MRI OA knee, BLOKS, that demonstrates good reliability. Preliminary inspection of the validity of one of the components of this new tool supports the validity of the BLOKS BML scoring method over an existing instrument. Further iterative development will include validation for use in both clinical trials and epidemiological studies.

Clinical trial: percutaneous acetic acid injection vs. percutaneous ethanol injection for small hepatocellular carcinoma--a long-term follow-up study.

BACKGROUND: The long-term outcome of percutaneous acetic acid injection (PAI) and percutaneous ethanol injection (PEI) for treating small hepatocellular carcinoma (HCC) remains unclear. AIM: To compare the long-term outcome of PAI vs. PEI for treating small HCC. METHODS: From July 1998 to July 2004, 125 patients with small HCC were enrolled. Seventy patients receiving PAI and 55 patients receiving PEI were enrolled. There were no significant differences in the clinical characteristics between the two groups. Tumour recurrence and survival rates were assessed. RESULTS: Mean follow-up time was 43 months. The local recurrence rate and new tumour recurrence rate were similar between the PAI and PEI groups. The PAI group had significantly better survival than the PEI group (P = 0.027). Multivariate analysis revealed that PAI was the significant factor associated with overall survival [PAI vs. PEI, RR: 0.639, 95% CI: (0.419-1.975), P = 0.038]. The treatment sessions required to achieve complete tumour necrosis were significantly fewer in the PAI group than in the PEI group (2.4 +/- 1.0 vs. 2.9 +/- 1.3, P = 0.018). CONCLUSION: Percutaneous acetic acid injection required fewer treatment sessions than PEI and provided better survival after long-term follow-up.

Quadruple rescue therapy for Helicobacter pylori infection after two treatment failures.

BACKGROUND: A standard third-line therapy for Helicobacter pylori infection is lacking, and antimicrobial sensitivity data for patients who failed eradication therapy are often unavailable in clinical practice. We therefore designed the prospective study to assess the efficacy of levofloxacin, amoxicillin, bismuth and rabeprazole quadruple therapy as a third-line treatment for H. pylori infection. PATIENTS AND METHODS: From September 2005 to August 2007, 37 consecutive H. pylori-infected patients who had failed standard first-line and second-line treatments underwent a 10-day quadruple therapy comprising rabeprazole (20 mg b.i.d.), bismuth subcitrate (300 mg q.d.s.), amoxicillin (500 mg q.d.s.) and levofloxacin (500 mg o.d.). Follow-up endoscopy with rapid urease test, histological examination and culture was performed at 6 weeks after the end of treatment to evaluate the response to therapy. RESULTS: Helicobacter pylori was successfully eradicated in 31 out of 37 patients (84% by both intention-to-treat analysis and per-protocol analysis). All patients complied with the eradication therapies, and only seven patients (19%) complained of mild-to-moderate adverse events. Amoxicillin- and levofloxacin-resistant strains were observed in 17% and 22% of the patients, respectively. There were no significant differences between H. pylori eradication rates and antibiotic resistances. CONCLUSIONS: The 10-day levofloxacin- and amoxicillin-based quadruple therapy is well tolerated and achieves a high eradication rate as a third-line empirical treatment for H. pylori infection.

A prospective, randomized controlled trial of transjugular intrahepatic portosystemic shunt versus cyanoacrylate injection in the prevention of gastric variceal rebleeding.

BACKGROUND AND STUDY AIMS: Both endoscopic obturation and transjugular intrahepatic portosystemic shunts (TIPSs) have proven to be effective in preventing rebleeding from gastric varices. This study compared the efficacy and complications of these modalities. PATIENTS AND METHODS: Cirrhotic patients with acute bleeding from gastric varices were considered for inclusion. After initial control, eligible patients were randomly allocated to two groups: TIPS (n = 35) and obturation using cyanoacrylate (n = 37). In the cyanoacrylate group, treatment was repeated regularly until gastric varices were obliterated. Patients of both groups received regular follow-up. The end points were gastric variceal rebleeding or death. RESULTS: Stent shunt insertion was successful in all TIPS patients, and mean portal pressure gradient decreased from 21.4 +/- 7.5 mm Hg to 7.5 +/- 3.5 mm Hg ( P < 0.001). Variceal obliteration was achieved in 19 patients in the cyanoacrylate group (51 %) compared with seven TIPS patients (20 %) ( P < 0.02). After a median follow up of 33 months, upper gastrointestinal bleeding occurred in 15 TIPS patients (43 %) and 22 cyanoacrylate patients (59 %) ( P = 0.12). Rebleeding from gastric varices was encountered in four TIPS patients (11 %) and 14 cyanoacrylate patients (38 %) ( P = 0.014; odds ratio 3.6, 95 %CI 1.2 - 11.1). Blood transfusion requirements were lower in the TIPS group than in the cyanoacrylate group ( P < 0.01). Survival and frequency of complications were similar in both groups. CONCLUSIONS: TIPS proved more effective than glue injection in preventing rebleeding from gastric varices, with similar survival and frequency of complications.

Risks of interleukin-1 genetic polymorphisms and Helicobacter pylori infection in the development of gastric cancer.

BACKGROUND: The host genetic factors that determine the clinical outcomes of Helicobacter pylori-infected individuals remain unclear. AIM: To elucidate the risks of host interleukin-1 (IL-1) genetic polymorphisms and H. pylori infection in the development of gastric cancer. METHODS: In a case-control study of 164 controls and 142 patients with gastric cancer, the IL-1B-511 biallelic polymorphisms and the IL-1RN penta-allelic variable number of tandem repeats were genotyped. RESULTS: The carriage of IL-1RN*2, male gender, old age and H. pylori infection independently increased the risk of gastric cancer, with odds ratios of 3.3 [95% confidence interval (CI), 1.4-7.7], 2.1 (95% CI, 1.2-3.8), 5.3 (95% CI, 3.1-9.0) and 2.2 (95% CI, 1.3-3.8), respectively. H. pylori-infected individuals who were carriers of IL-1RN*2 showed increased risks of both intestinal and diffuse types of gastric cancer, with odds ratios of 11.0 and 8.7, respectively. In addition, these individuals also had a higher score of intestinal metaplasia in the corpus than did uninfected non-carriers. CONCLUSIONS: This study is the first to verify IL-1RN*2 as an independent factor governing the development of gastric cancer in Asian individuals. A combination of H. pylori testing and host genotyping may target the eradication of H. pylori to high-risk individuals.

Eradication of Helicobacter pylori prevents ulcer development in patients with ulcer-like functional dyspepsia.

BACKGROUND: Although the eradication of Helicobacter pylori infection benefits patients with gastric or duodenal ulcers, the value of eradicating the infection in the patients with functional dyspepsia (FD) remains controversial. AIMS: To determine whether eradicating H. pylori can prevent the subsequent development of ulcers or relieve the symptoms of functional dyspepsia patients. METHODS: In a double-blind, placebo-controlled trial, 161 patients infected with H. pylori who had functional dyspepsia were randomly assigned to 7 days of treatment with a lansoprazole-based triple therapy or placebo and then followed for 1 year. The main outcome measures were the development of peptic ulcers and the resolution of symptoms. RESULTS: H. pylori was eradicated in 63 out of 81 patients (78%) in the treatment group and none of the 80 patients (0%) in the placebo group. During the follow-up period, two patients in the treatment group and six patients in the placebo group developed peptic ulcers at repeat endoscopy (2.5% vs. 7.5%; 95% CI: -12 to 2). The reduction in ulcer rates was statistically significant in the 'ulcer-like' sub-group (0% vs. 16.7%; 95% CI: -32 to -2), but not in the 'dysmotility-like' and 'unclassifiable' sub-groups. Regarding symptom response, the resolution rates of symptoms were similar between the treatment and placebo groups (58.0% vs. 55.0%, 95% CI: -12 to 18). Additionally, no significant differences existed in the symptom responses between the treatment and control arms in each of the dyspepsia sub-groups. CONCLUSIONS: Eradicating H. pylori can prevent the subsequent development of peptic ulcers in the patients with 'ulcer-like' functional dyspepsia. However, this approach does not significantly reduce the symptoms of functional dyspepsia patients.

Phase II study of mitoxantrone in unresectable primary hepatocellular carcinoma following hepatitis B infection.

A total of 20 patients with histologically proven primary hepatocellular carcinoma (PHC) received mitoxantrone IV at a dose of 10-16 mg/m2 every 3 weeks. All patients had previous hepatitis B infection. None underwent remission after treatment; 2 had stable disease and 18 progressive disease. The median overall survival was 13 weeks (range, 1-59 weeks). There was no evidence of significant antitumor activity for mitoxantrone in our patients with PHC. Hematotoxicity occurred in 100% of the patients with grades 2-4 leukopenia, 89% of those with grades 1-4 anemia, and 26% of those with grades 2-3 thrombocytopenia. Cardiotoxicity occurred in 20% of the patients after 14-30 mg/m2 mitoxantrone; these included complete heart block with fatal outcome in one case, decreased ventricular ejection fraction in one, and sinus tachycardia in two. Nausea, vomiting, fever, diarrhea, and alopecia were mild and occurred in 15%-45% of the patients Therefore, patients with PHC following hepatitis B infection may be less tolerant to mitoxantrone, resulting in the apparent increase in toxicities.

Impact of bacterial eradication on the cell proliferation and p53 protein accumulation in Helicobacter pylori-associated gastritis.

BACKGROUND: This study investigates the cell proliferation and the expression of p53 protein in Helicobacter pylori (H. pylori)-associated gastritis and assesses the effect of bacterial eradication on these epithelial factors. MATERIAL AND METHODS: Seventy-nine patients with H. pylori-associated gastritis were randomized into the control group (n = 38) and anti-H. pylori group (n = 41). Each patient received endoscopic examinations with gastric biopsy before and 8 weeks after the treatment. The specimens from gastric antrum were immunostained for monoclonal antibodies against the proliferating cell nuclear antigen (PCNA) and p53 protein. RESULTS: In the control group, the total labeling index (L.I.) of PCNA and the positive index (P.I.) of p53 in the whole foveolar epithelium were unchanged after treatment. In the anti-H. pylori group, 35 of 41 cases (85.3%) achieved eradication of H. pylori. Amongst the H. pylori-eradicated cases, the total L.I. of PCNA in the whole foveolar epithelium did not meaningfully alter after H. pylori elimination (p > 0.05). However, a significant reduction of L.I. was observed in the middle compartments of the gastric pits (before vs. after treatment: 14.0 vs. 7.3, p < 0.05). With regard to the p53 expression, the P.I.s were significantly decreased in the whole foveolar epithelium (before vs. after treatment: 0.57 vs. 0.17, p < 0.05) and in each compartment of the gastric pits (before vs. after treatment: [upper compartment]: 0.34 vs. 0.15, p < 0.05; [middle compartment]: 0.67 vs. 0.23, p < 0.05; [lower compartment]: 0.71 vs. 0.20, p < 0.05) after eradication of H. pylori. CONCLUSIONS: Bacterial eradication reverses the hyperproliferating status of the foveolar epithelium in patients with H. pylori gastritis and leads to a decrease in p53 accumulation in the epithelial cells.

Endoscopic balloon dilatation is a safe method in the management of common bile duct stones.

BACKGROUNDS AND AIMS: Endoscopic sphincterotomy is a widely accepted treatment for patients with common bile duct stones. Despite improvement in this technique, endoscopic sphincterotomy is still associated with some biliary complications. Endoscopic balloon dilatation is a less traumatic and sphincter preserving method for removal of common bile duct stones. However, the results of controlled studies in comparison with these two methods are contradictory. The aim of this study is to compare the safety and efficacy of endoscopic balloon dilatation and endoscopic sphincterotomy in Chinese patients. PATIENTS AND METHODS: A total of 104 patients with common bile duct stones on endoscopic retrograde cholangiopancreatography were enrolled. They were randomly assigned to endoscopic balloon dilatation or endoscopic sphincterotomy. Endoscopic balloon dilatation was performed by using a balloon dilator to dilate the sphincter for 5 min. The common bile duct stones were then removed by a Dormia basket after endoscopic balloon dilatation or endoscopic sphincterotomy. Mechanical lithotripsy was performed if the stones were difficult to remove by Dormia basket. After discharge, patients were regularly followed up for biliary complications. RESULTS: The successful bile duct stone clearance rate was 94.1% in endoscopic balloon dilatation group and 100% in endoscopic sphincterotomy group. Post-procedural significant haemorrhage was higher in endoscopic sphincterotomy group than in endoscopic balloon dilatation group (14/53 versus 1/48, P < 0.001). The bleeding patient from endoscopic balloon dilatation group was a case of uremia and bleeding occurred 48 h after endoscopic balloon dilatation. All the patients with post-procedural haemorrhage were controlled endoscopically. The post-procedural serum amylase level showed no significant difference in both groups and none of them developed clinical pancreatitis. After a mean 16 months follow-up, three patients (6.3%) in endoscopic balloon dilatation group and four patients (7.5%) in endoscopic sphincterotomy group developed recurrent common bile duct stones. The recurrent common bile duct stones were multiple and muddy in consistency. They were successfully removed endoscopically. CONCLUSION: Both endoscopic balloon dilatation and endoscopic sphincterotomy are safe and effective techniques for the treatment of common bile duct stones. Endoscopic balloon dilatation can be safely applied in patients with coagulopathy and does not increase the incidence of pancreatitis or bleeding.

Endoscopic 13C-urea breath test for the diagnosis of Helicobacter pylori infection.

BACKGROUND: Endoscopic 13C-urea breath test may avoid contamination of oral urease and rapidly discriminate Helicobacter pylori-positive and Helicobacter pylori-negative patients. AIMS: To compare the accuracy of endoscopic 13C-urea breath test with conventional invasive methods in diagnosis of Helicobacter pylori infection. PATIENTS: One hundred patients who attended for routine upper gastrointestinal endoscopy were included. METHODS: 13C-urea was applied to the stomach through the working channel of endoscope at the end of endoscopic examination. Breath samples were collected before endoscopy and 2, 4, 6, 8, 10 min after consumption of 100 or 50 mg 13C-urea. Helicobacter pylori infection was defined as those with positive culture or positive results of both histology and CLO test. RESULTS: The accuracy of 100 mg endoscopic 13C-urea breath test was significantly higher than that of culture and CLO test (100% vs. 88% and 92%, p = 0.02 and 0.03, respectively). The accuracy of 50 mg endoscopic 13C-urea breath test was higher than that of histology and CLO test (98% vs. 90% and 96%, respectively), although the differences were not statistically significant. CONCLUSIONS: Endoscopic 13C-urea breath test has a higher accuracy compared with biopsy-based modalities. It may be a good choice to diagnose Helicobacter pylori infection if endoscopy is indicated for a dyspeptic patient.