Helicobacter pylori in Thai patients with cholangiocarcinoma and its association with biliary inflammation and proliferation

Objectives

To investigate whether Helicobacter spp. infection and the cagA of H. pylori are associated with hepatobiliary pathology, specifically biliary inflammation, cell proliferation and cholangiocarcinoma (CCA).

Methods

Helicobacter species including H. pylori, H. bilis and H. hepaticus were detected in the specimens using the polymerase chain reaction (PCR). Biliary inflammation of the liver and gallbladders was semi-quantitatively graded on hematoxylin and eosin (H&E)-stained slides. Biliary proliferation was evaluated by immunohistochemistry using the Ki-67-labelling index.

Results

Helicobacter pylori was found in 66.7%, 41.5% and 25.0% of the patients in the CCA, cholelithiasis and control groups (P < 0.05), respectively. By comparison, H. bilis was found in 14.9% and 9.4% of the patients with CCA and cholelithiasis, respectively (P > 0.05), and was absent in the control group. The cagA gene of H. pylori was detected in 36.2% and 9.1% of the patients with CCA and cholelithiasis, respectively (P < 0.05). Among patients with CCA, cell inflammation and proliferation in the liver and gallbladder were significantly higher among those DNA H. pylori positive than negative.

Conclusions

The present findings suggest that H. pylori, especially the cagA-positive strains, may be involved in the pathogenesis of hepatobiliary diseases, especially CCA through enhanced biliary cell inflammation and proliferation.     

In vitro fracture strength of teeth restored with different all-ceramic crown systems

STATEMENT OF PROBLEM: There is insufficient knowledge of the strength of all-ceramic crowns bonded to natural teeth to warrant the use of all-ceramic crowns in place of metal-ceramic crowns. PURPOSE: The purpose of this study was to evaluate and compare fracture resistance of crowns made of 3 different types of 2 all-ceramic crown systems-0.4-mm and 0.6-mm aluminum oxide coping crowns and zirconia ceramic coping crowns-and metal-ceramic crowns. MATERIAL AND METHODS: Forty intact, noncarious human maxillary central incisors were divided into 4 groups (n=10): Group MCC (control), metal-ceramic crown (JRVT High Noble Alloy); Group AC4, crown with 0.4-mm aluminum oxide coping (Procera AllCeram); Group AC6, crown with 0.6-mm aluminum oxide coping (Procera AllCeram); and Group ZC6, crown with 0.6-mm zirconia ceramic coping (Procera AllZirkon). Teeth were prepared for complete-coverage all-ceramic crowns so that a final dimension of 5.5 +/- 0.5 mm was achieved incisocervically, mesiodistally, and faciolingually. A 1.0-mm deep shoulder finish line was used with a rounded internal line angle. All restorations were treated with bonding agent (Clearfil SE Bond) and luted with phosphate-monomer-modified adhesive cement (Panavia 21). Fracture strength was tested with a universal testing machine at a crosshead speed of 2 mm per minute with an angle of 30 degrees to the long axis of the tooth after restorations were stored in 100% relative humidity of a normal saline solution for 7 days. The mode of fracture was examined visually. Means were calculated and analyzed with 1-way ANOVA and Tukey's HSD (alpha=.05). RESULTS: The means of fracture strength were: Group MCC, 405 +/- 130 N; Group AC4, 447 +/- 123 N; Group AC6, 476 +/- 174 N; and Group ZC6, 381 +/- 166 N. There was no significant difference between groups ( P =.501). The mode of failure for all specimens was fracture of the natural tooth. CONCLUSIONS: There was no significant difference in the fracture strength of the teeth restored with all-ceramic crowns with 0.4- and 0.6-mm aluminum oxide copings, 0.6-mm zirconia ceramic copings, and metal ceramic crowns.     

Significance of S100P as a biomarker in diagnosis,prognosis and therapy of opisthorchiasis‐associated cholangiocarcinoma

Cholangiocarcinoma (CCA) is a malignancy of bile duct with the difficulty in early diagnosis, poor prognosis and less alternation in therapy. S100P is a member of S100 family proteins and plays important roles in cancers. We investigated the S100P expression and its correlation with clinicopathology in 78 cases of opisthorchiasis‐associated CCA, and the effects of S100P knockdown with shRNA interference on the proliferation, cell cycle, migration, apoptosis and sensitivity to anti‐cancer drug. Extremely high expression of S100P mRNA was detected in the CCA tumor tissues. The increased S100P protein expression was immunohistochemically confirmed and localized in the CCA cytoplasm and/or nuclei as well as in the hyperneoplasia and dysplasia bile ducts, but not in normal bile ducts. The intensity of immunostaining was correlated with survival, tumor stage and metastasis, and the high expression could be an independent prognostic factor. High levels of S100P were detected in the serum and bile fluid of CCA patients. The shRNA‐mediated knockdown of S100P expression inhibited the proliferation in vitro and in vivo, and migration of CCA cells, arrested cell cycle with the up‐regulated expression of cell cycle arrest related factors, p21, p27, GADD45A, and 14‐3‐3 zeta. S100P knockdown also promoted CCA cell apoptosis by up‐regulating expression of apoptosis related factors, DR5, TRADD, caspase 3 and BAX, and increased the sensitivity of CCA cells to the chemotherapeutic agents sunitinib and apigenin. Taken together, this study indicates that S100P might be a promising biomarker for the diagnosis, prognosis and therapy of CCA.     

A Prospective Study of 7-Year Experience Using Percutaneous 14-French Pigtail Catheters for Traumatic Hemothorax/Hemopneumothorax at a Level-1 Trauma Center: Size Still Does Not Matter

Background

The effectiveness of 14-French (14F) pigtail catheters (PCs) compared to 32-40F chest tubes (CTs) in patients with traumatic hemothorax (HTX) and hemopneumothorax (HPTX) is becoming more well known but still lacking. The aim of our study was to analyze our cumulative experience and outcomes with PCs in patients with traumatic HTX/HPTX. We hypothesized that PCs would be as effective as CTs.

Methods

Using our PC database, we analyzed all trauma patients who required chest drainage for HTX/HPTX from 2008 to 2014. Primary outcomes of interest, comparing PCs to CTs, included initial drainage output in milliliters (mL), tube insertion-related complications, and failure rate. For our statistical analysis, we used the unpaired Student’s t test, Chi-square test, and Wilcoxon rank-sum test. We defined statistical significance as P < 0.05.

Results

During the 7-year period, 496 trauma patients required chest drainage for traumatic HTX/HPTX: 307 by CTs and 189 by PCs. PC patients were older (52 ± 21 vs. 42 ± 19, P < 0.001), demonstrated a significantly higher occurrence of blunt trauma (86 vs. 55%, P ≤ 0.001), and had tubes placed in a non-emergent fashion (Day 1 [interquartile range (IQR) 1–3 days] for PC placement vs. Day 0 [IQR 0–1 days] for CT placement, P < 0.001). All primary outcomes of interest were similar, except that the initial drainage output for PCs was higher (425 mL [IQR 200–800 mL] vs. 300 mL [IQR 150–500], P < 0.001). Findings for subgroup analysis among emergent and non-emergent PC placement were also similar to CT placement.

Conclusion

PCs had similar outcomes to CTs in terms of failure rate and tube insertion-related complications, and the initial drainage output from PCs was not inferior to that of CTs. The usage of PCs was, however, selective. A future multi-center study is needed to provide additional support and information for PC usage in traumatic HTX/HPTX.

     

Strong expression of CD133 is associated with increased cholangiocarcinoma progression

AIM:To determine the role of CD133 in cholangiocarcinoma progression. METHODS:CD133 protein expression was evaluated by immunohistochemistry in 34 cholangiocarcinoma specimens.In addition,proliferation,chemoresistance and invasive properties of CD133-enriched(CD133 + ) and CD133-depleted(CD133 )RMCCA1 cholangiocarcinoma cells were studied and compared. RESULTS:Strong CD133 expression was observed in 67.6%(23/34)of the cholangiocarcinoma specimens. Strong expression of CD133 was significantly associated with...     

Defining incidence and outcome of contrast-induced nephropathy among trauma: is it overhyped?

Contrast-induced nephropathy (CIN) in trauma patients is uncommon and the incidence is unknown. We studied the incidence of CIN and its outcome. A retrospective chart review of trauma patients 16 years of age and older who were admitted to our Level I trauma center during 2005 was performed. Patients who received the intravenous contrast CT scan and had their serum creatinine (Cr) monitored at admission and at 48 to 72 hours were identified. CIN was defined as a 0.5-mg/dL rise of serum Cr or a 25 per cent increase from the baseline if the baseline Cr was abnormal. We excluded patients transferred from an outside facility, patients without repeated serum Cr measurements, patients who had cardiac arrest or persistent hypotension, and patients who had received N-acetylcysteine (Mucomyst) before their CT scan. We compared CIN and non-CIN groups. During 2005, 543 fit our study criteria, of whom 19 (3.5%) had CIN. CIN (vs non-CIN) had a higher baseline serum Cr (1.48 + 0.23 vs 1.06 + 0.02, P < 0.001), a longer intensive care unit stay (17 vs 5 days, P < 0.001), and a longer hospital stay (19 vs 8 days, P < 0.001); the mortality rate was not different (10 vs 4%, P = 0.2). We found elevated baseline serum Cr (OR, 1.92; 95% CI, 1.13 to 3.27; P = 0.016) to be associated with increased risk for CIN. All but two serum Cr levels peaked within 48 hours; all returned to baseline. One patient with an underlying congenital kidney disease required temporary dialysis. CIN incidence in trauma is low and the clinical course is benign.     

Seatbelt triad: severe abdominal wall disruption, hollow viscus injury, and major vascular injury

The triad of seatbelt-related severe abdominal wall disruption, hollow viscus injury, and distal abdominal aortic injury after a motor vehicle collision is uncommon. We present a small case series involving those three clinical features with the goal of preventing a future missed diagnosis of the distal abdominal aortic injury in particular.     

Increased EphB2 expression predicts cholangiocarcinoma metastasis

The activation of Ephrin (Eph) receptors, the largest tyrosine kinase families of cell surface receptor, has recently been addressed in human cholangiocarcinoma (CCA). Therefore, the present study aimed to investigate the role of Eph receptors and its ligands in CCA. Of all 50 cases of human CCA tested, immunohistochemical staining demonstrated that EphB2, EphB4, ephrinB1, and ephrinB2 were 100 % positive in CCA tissues with overexpressions of the above proteins as 56, 56, 70, and 48 % of cases, respectively. High expression of EphB2 was significantly correlated with the metastatic status of patients (P?=?0.027). We also found that the high co-expression level of EphB2/ephrinB1 or EphB2/ephrinB2 were significantly correlated with the metastatic status of the patients (P?=?0.034 and P?=?0.024). Furthermore, we showed that the high co-expression level of EphB4/MVD and ephrinB1/MVD were significantly correlated with the metastasis status of CCA patients (P?=?0.012 and P?=?0.029). We further demonstrated that the EphB2 suppression using siRNA significantly reduced CCA cell migration by decreasing the phosphorylation of focal adhesion kinase (FAK) and paxillin. In conclusion, the upregulation of EphB2 receptors and its specific ligands (ephrinB1 and ephrinB2) leads to CCA metastasis. Suppression of EphB2 expression as well as inhibition of its downstream signaling proteins might serve as possible therapeutic strategies in human CCA.     

Survey of activated kinase proteins reveals potential targets for cholangiocarcinoma treatment

Improving therapy for patients with cholangiocarcinoma (CCA) presents a significant challenge. This is made more difficult by a lack of a clear understanding of potential molecular targets, such as deregulated kinases. In this work, we profiled the activated kinases in CCA in order to apply them as the targets for CCA therapy. Human phospho-receptor tyrosine kinases (RTKs) and phospho-kinase array analyses revealed that multiple kinases are activated in both CCA cell lines and human CCA tissues that included cell growth, apoptosis, cell to cell interaction, movement, and angiogenesis RTKs. Predominately, the kinases activated downstream were those in the PI3K/Akt, Ras/MAPK, JAK/STAT, and Wnt/β-catenin signaling pathways. Western blot analysis confirms that Erk1/2 and Akt activation were increased in CCA tissues when compared with their normal adjacent tissue. The inhibition of kinase activation using multi-targeted kinase inhibitors, sorafenib and sunitinib led to significant cell growth inhibition and apoptosis induction via suppression of Erk1/2 and Akt activation, whereas drugs with specificity to a single kinase showed less potency. In conclusion, our study reveals the involvement of multiple kinase proteins in CCA growth that might serve as therapeutic targets for combined kinase inhibition.