Prediction of response to entecavir therapy in patients with HBeAg-positive chronic hepatitis B based on on-treatment HBsAg, HBeAg and HBV DNA levels

Summary. Quantitative hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) assays are emerging as effective tools of on‐treatment predictors of response to antiviral agents, in addition to monitoring serum HBV DNA levels. However, the dynamic relationship between quantitative HBsAg, as well as HBeAg and HBV DNA, and the predictability of subsequent clinical outcomes during entecavir (ETV) therapy remain unclear. Eighty‐two patients with HBeAg‐positive chronic hepatitis B (CHB) received ETV therapy for ≥3 years. Virologic response (VR) after 3 years of ETV therapy was achieved in 73 (89.0%) patients. Among baseline and on‐treatment factors, on‐treatment HBV DNA levels performed better with respect to the prediction of response than HBsAg and HBeAg levels. Especially, the performance of absolute values of HBV DNA with respect to response was superior to HBV DNA decline from the baseline. The best predictive value was an absolute HBV DNA level of 2.3 log₁₀ IU/mL at month 6 (areas under the curve [AUROC], 0.977; 95% CI, 0.940–1.000; P < 0.001). HBeAg seroconversion after 3 years of therapy was achieved in 26 (31.7%) patients. On‐treatment HBeAg levels performed better with respect to the prediction of seroconversion than HBsAg and HBV DNA levels. The best cut‐off value for the HBeAg level at month 12 for the prediction of seroconversion was 0.62 log₁₀ PEIU/mL. Although the HBsAg level at baseline is often used to predict the antiviral potency of entecavir, on‐treatment HBV DNA and HBeAg levels are more helpful for prediction of subsequent clinical outcomes in HBeAg‐positive CHB patients with entecavir treatment.     

Respiratory involvement in IgG4-related Mikulicz’s disease

'Immunoglobulin G4 (IgG4)-related disease' is a new clinical concept of multi-organ diseases, with Mikulicz's disease (MD) being a clinical phenotype of IgG4-related disease. To clarify the clinical characteristics of respiratory involvement associated with IgG4-related MD, we retrospectively assessed 25 patients with MD, 11 (44%) of whom had allergic symptoms, and 7 (28%) of whom complained of respiratory problems. Thirteen patients (52%) presented with pulmonary and/or mediastinal lesions (P-MD) on chest computed tomography (CT), and 11 (44%) had lesions limited to the lacrimal and/or salivary glands (L-MD). Mean serum total protein, IgG, and IgG4 concentrations were significantly higher and CH50 was significantly lower in the P-MD than in the L-MD group. Immune complex was present only in the P-MD group. Chest CT images showed bronchial wall thickening, consolidation, nodule(s), interlobular thickening, ground glass opacity, pleural thickening/effusion, and mediastinal lymphadenopathy. Five of seven patients who underwent histological examination of the lungs had abundant IgG4-positive plasma cell infiltrates (IgG4/IgG-positive plasma cells >40%), but the other two did not. These findings suggest that respiratory lesions are not rare in patients with IgG4-related MD, and that they present with various manifestations. IgG4-related MD should be differentiated from similar diseases, such as sarcoidosis, bronchial asthma, Sj?gren's syndrome, and malignant lymphoma.     

ACC/AHA classification of coronary lesions reflects medical resource use in current percutaneous coronary interventions

Objectives : The purpose of this study was to investigate the association between ACC/AHA type classification of coronary lesions and medical resource utilization. Background : It is not known whether the classification of coronary lesions by the ACC/AHA system reflects the consumption of medical resources in current percutaneous coronary interventions (PCI). Methods : We identified coronary artery lesions treated with PCI from our PCI database between January 1, 2009 and December 31, 2009. Lesions were classified into type A, type B1, type B2, and type C according to the ACC/AHA definition. Total PCI cost, total contrast volume, and total fluoroscopy time were compared among the groups. Results : A total of 447 lesions were analyzed. The number of type A, type B1, type B2, and type C lesion were 75 (16.8%), 98 (21.9%), 145 (32.4%), and 129 (28.9%), respectively. Total PCI cost for type A, type B1, type B2, and type C lesions were $7,262 ± 1,397, $8,126 ± 1,891, $9,126 ± 3,128, and $13,243 ± 4,678, respectively (P < 0.0001). Total contrast volume and fluoroscopy time were also stratified according to the order of type A, type B1, type B2, and type C lesions (P < 0.0001 for total contrast volume; P < 0.0001 for total fluoroscopy time). Conclusions : Total PCI cost, total contrast volume, and total fluoroscopy time were clearly stratified according to the order of type A, type B1, type B2, and type C lesions. Lesion classification by the ACC/AHA system reflects medical resource use in current PCI. © 2011 Wiley Periodicals, Inc.     

Repeat percutaneous coronary revascularization: Indications and outcomes in a “Real World” cohort

Objectives : To investigate rates of and reasons for second and subsequent stent procedures in an unselected, “real‐world” population. Background : Repeat stenting is the primary difference reported in clinical trials of alternative revascularization strategies. The incidence, indication, and outcome for repeat stenting in contemporary practice outside the more selective populations of trials and registries has not been described. Method : All patients undergoing a first percutaneous coronary intervention (PCI) procedure with stenting from January 2001 to August 2009 (10,509) from a large UK tertiary referral and district general hospital were identified. Mortality and the incidence, timing, and indication for repeat revascularization in this population were investigated from patient records. Results : Of 10,509 patients undergoing a first PCI and stent implant 23.5% underwent repeat angiography of which 11.2% required repeat PCI and 2% coronary artery bypass grafting (median follow‐up of 3.8 years). A total of 1.3% went on to a third PCI. The commonest indication for repeat stenting was disease progression remote from the original stent (46%) and planned staged PCI (23%); 21% had a stent‐related indication. Functional assessment before repeat stenting was used in one‐third of stable patients. Mortality was 2.5% per annum. Conclusions : In contemporary practice, patients undergoing a first stenting procedure have a low subsequent mortality, and the substantial majority (86.4%) requires no further revascularization over a median 3.8 year follow‐up. For those who do require repeat stenting, this is most commonly at a site remote from the first stent. © 2012 Wiley Periodicals, Inc.     

Korean guidelines for colorectal cancer screening and polyp detection

Colorectal cancer is the second most common cancer in males and the fourth most common in females in Korea. Since the most of colorectal cancer occur through the prolonged transformation of adenomas into carcinomas, early detection and removal of colorectal adenomas are one of the most effective methods to prevent colorectal cancer. Considering the increasing incidence of colorectal cancer and polyps in Korea, it is very important to establish Korean guideline for colorectal cancer screening and polyp detection. Korean Multi-Society Take Force developed the guidelines with evidence-based methods. Parts of the statements drawn by systematic reviews and meta-analyses. Herein we discussed the epidemiology of colorectal cancers and adenomas in Korea, optimal screening methods for colorectal cancer, and detection for adenomas including fecal occult blood tests, radiologic tests, and endoscopic examinations.     

A case of nonpolypoid cancer arising from colonic muco-submucosal elongated polyp

A colonic muco-submucosal elongated polyp (CMSEP) was identified at colonoscopy in a 53-year-old male patient with lower gastrointestinal bleeding. Non-polypoid depressed type of early cancer was noted at the tip of the colonic polyp. The CMSEP is very rare and incidentally found in most cases. Moreover, its association with colonic neoplasia is extremely rare. To our knowledge, this is the second case report of CMSEP associated with a cancerous transformation.     

Elimination of esophageal multiple precancerous lesions by chemotherapy: potential chemoprevention of metachronous multiple cancer development after curative treatment

Background

Dysplastic squamous epithelium is a precancerous lesion for squamous cell carcinoma. It is often present in the esophagus and head and neck region, and can be visualized as a Lugol-voiding lesion (LVL) by iodine chromoendoscopy. However, effective treatment for such dysplastic epithelia has not yet been developed.

Methods

Between March 2008 and July 2011, 40 consecutive patients with advanced esophageal squamous cell carcinoma were treated by two cycles of neoadjuvant chemotherapy (NAC) (5-fluorouracil, 800?mg/m², d 1?C5; cisplatin, 80?mg/m², d 1: q 21?days) at Kyoto University Hospital, and received iodine chromoendoscopy both before and after NAC. Iodine chromoendoscopy findings were divided into 4 groups: group?A, absence of LVLs; group?B, several (??10/one endoscopic view) small (??5?mm) LVLs; group?C, many (??10/one endoscopic view) small (??5?mm) LVLs; group?D, numerous irregular-shaped multiform LVLs. Group?C and D are defined as multiple LVLs. Endoscopic changes of LVLs before and after NAC were investigated retrospectively.

Results

Before NAC, 6, 12, 9, and 13 cases were classified in group?A, B, C, and D, respectively. All cases in group?A before NAC remained in group?A after NAC. Multiple LVLs (group?C and D) were significantly improved in 17 of 22 patients (77.3?%), while several small LVLs (group?B) were improved in only 4 of 12 cases (33.3?%) (p?=?0.025 by Fisher??s exact test).

Conclusions

Multiple dysplastic lesions tended to improve by chemotherapy. In contrast, there was little change in the mucosa with fewer dysplastic lesions after chemotherapy. These data show that chemotherapy has the potential to eliminate precancerous lesions.     

Replication of Caucasian loci associated with bone mineral density in Koreans

Summary

Most bone mineral density (BMD) loci were reported in Caucasian genome-wide association studies (GWAS). This study investigated the association between 59 known BMD loci (+200 suggestive SNPs) and DXA-derived BMD in East Asian population with respect to sex and site specificity. We also identified four novel BMD candidate loci from the suggestive SNPs.

Introduction

Most GWAS have reported BMD-related variations in Caucasian populations. This study investigates whether the BMD loci discovered in Caucasian GWAS are also associated with BMD in East Asian ethnic samples.

Methods

A total of 2,729 unrelated Korean individuals from a population-based cohort were analyzed. We selected 747 single-nucleotide polymorphisms (SNPs). These markers included 547 SNPs from 59 loci with genome-wide significance (GWS, p value less than 5?×?10^?8) levels and 200 suggestive SNPs that showed weaker BMD association with p value less than 5?×?10^?5. After quality control, 535 GWS SNPs and 182 suggestive SNPs were included in the replication analysis.

Results

Of the 535 GWS SNPs, 276 from 25 loci were replicated (p?<?0.05) in the Korean population with 51.6 % replication rate. Of the 182 suggestive variants, 16 were replicated (p?<?0.05, 8.8 % of replication rate), and five reached a significant combined p value (less than 7.0?×?10^?5, 0.05/717 SNPs, corrected for multiple testing). Two markers (rs11711157, rs3732477) are for the same signal near the gene CPN2 (carboxypeptidase N, polypeptide 2). The other variants, rs6436440 and rs2291296, were located in the genes AP1S3 (adaptor-related protein complex 1, sigma 3 subunit) and RARB (retinoic acid receptor, beta).

Conclusion

Our results illustrate ethnic differences in BMD susceptibility genes and underscore the need for further genetic studies in each ethnic group. We were also able to replicate some SNPs with suggestive associations. These SNPs may be BMD-related genetic markers and should be further investigated.