The importance of evaluating specific myeloid malignancies in epidemiological studies of environmental carcinogens.

INTRODUCTION: Although myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) - including chronic myeloid leukemia (CML) - and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are largely clinically distinct myeloid malignancies, epidemiological studies rarely examine them separately and often combine them with lymphoid malignancies, limiting possible etiological interpretations for specific myeloid malignancies. METHODS: We systematically evaluated the epidemiological literature on the four chemical agents (1,3-butadiene, formaldehyde, benzene, and tobacco smoking, excluding pharmaceutical, microbial and radioactive agents, and pesticides) classified by the International Agency for Research on Cancer as having sufficient epidemiological evidence to conclude that each causes "myeloid malignancies." Literature searches of IARC Monographs and PubMed identified 85 studies that we critically assessed, and for appropriate subsets, summarized results using meta-analysis. RESULTS: Only two epidemiological studies on 1,3-butadiene were identified, but reported findings were inadequate to evaluate specific myeloid malignancies. Studies on formaldehyde reported results for AML and CML - and not for MDS or MPN - but reported no increased risks. For benzene, several specific myeloid malignancies were evaluated, with consistent associations reported with AML and MDS and mixed results for CML. Studies of tobacco smoking examined all major myeloid malignancies, demonstrating consistent relationships with AML, MDS and MPN, but not with CML. CONCLUSIONS: Surprisingly few epidemiological studies present results for specific myeloid malignancies, and those identified were inconsistent across studies of the same exposure, as well as across chemical agents. This exercise illustrates that even for agents classified as having sufficient evidence of causing "myeloid malignancies," the epidemiological evidence for specific myeloid malignancies is generally limited and inconsistent. Future epidemiological studies should report findings for the specific myeloid malignancies, as combining them post hoc - where appropriate - always remains possible, whereas disaggregation may not. Furthermore, combining results across possibly discrete diseases reduces the chances of identifying important malignancy-specific causal associations.

Transplantation After Successful Downstaging by Multimodal Treatments of American Joint Committee on Cancer Stage IIIB Hepatocellular Carcinoma With Portal Vein Thrombi: A Case Report.

The effective treatment for hepatocellular carcinoma (HCC) with American Joint Committee on Cancer stage IIIB remains controversial and challenging because of the high recurrence rate after resection and low survival rate. The median survival of those with macroscopic portal vein tumor thrombus (PVTT) is short. We reported such a case which received liver transplantation (LT) after successful consecutive downstaging therapies. A 40-year-old man with alcohol related liver cirrhosis and repeated esophageal varices bleeding had HCC with tumor thrombi in right main portal vein and the second portal branch of segment VI (stage IIIB). The received percutaneous alcohol injection, radiofrequency ablation, 8 sessions of transcatheter hepatic arterial chemoembolization, radiotherapy, and target therapy with sorafenib. Computed tomography (CT) scan and magnetic resonance imaging after treatments showed no viable fragments in the tumor and revealed both the right main portal vein and V1 branch were patent. One month later, the patient received a deceased LT. The perioperative course was rather smooth. After discharge, the interval follow-up CT studies of the chest and liver and whole body bone scan showed no tumor recurrence or metastasis up to 20 months postoperation.

Expression pattern of heat shock protein 90 in patients with oral squamous cell carcinoma in northern Taiwan.

Heat shock protein 90 (HSP90), which is expressed in cancer cells, profoundly affects progression, invasion, and metastasis. However, to our knowledge, in East Asia, the correlation between the expression of HSP90 and clinicopathological variables has seldom been discussed. We therefore investigated this and its prognostic value in 36 patients newly diagnosed with oral squamous cell carcinoma (SCC) in northern Taiwan. Samples of tumour and normal samples from the patients were compared immunohistochemically. HSP90 was expressed mainly in the samples of tumour, and was significantly higher in these than in the normal epithelium (p<0.001). Metastases to the lymph nodes in the 36 patients also correlated with expression of HSP90. Correlation between expression of HSP90 and the size of the tumour or pathological staging was not significant, but strong expression correlated with poor survival. In general, expression was low among our samples (30/36). It was significantly higher in the tumour samples than in normal samples, and correlated with metastases to lymph nodes in the neck.

Early Detection of a Hepatic Artery Pseudoaneurysm After Liver Transplantation Is the Determinant of Survival.

BACKGROUND: Hepatic artery pseudoaneurysm (PA) after liver transplantation (LT) is a rare but potentially fatal complication. Among a series of 50 patients of LT, we experienced 3 such cases. Some authors also have reported cases of PA, either intrahepatic or extrahepatic. The aim of this study was to investigate the important factors that affect the treatment outcome. METHODS: Three patients were presented. To analyze the factors, not only our patients but also the patients with PA reported in the literature (including 10 case series and 23 case reports) were enrolled for analysis. The possible factors probably affecting the survival were compared statistically, including age, sex, clinical manifestation as bleeding (including gastrointestinal bleeding, hemobilia, or intra-abdominal bleeding), treatment (with embolization or surgical exploration or stent), diagnosis establishment before or after bleeding, and so forth. RESULTS: From univariate analysis, the significant factors that affect survival are sex (female) (P = .036), stent treatment (P = .006), and early detection (P = .036), whereas age (P = .493) and presentation with hemorrhage (P = .877) are not significant factors. However, according to multivariate analysis, stent treatment has a borderline significance (P = .056). CONCLUSIONS: Early detection of such a life-threatening complication is a key determinant of survival. "Early" does not refer to early postoperative days but means the detection prior to the rupture of the pseudoaneurysm. Postoperative imaging studies such as computed tomographic scan or magnetic resonance cholangiopancreatography early and periodically to follow up the graft status is recommended, especially for those who had received other interventions before or after the liver transplantation.

Factors associated with subsequent nontuberculous mycobacterial lung disease in patients with a single sputum isolate on initial examination.

Very few studies have focused on the outcome and management of patients with a single sputum isolate of nontuberculous mycobacterium (NTM) on initial examination. Patients with a single isolate of Mycobacterium avium complex (MAC), M. chelonae-abscessus, M. kansasii, or M. fortuitum from at least three sputum samples collected within 1 month were retrospectively identified. Those with follow-up sputum samples within 1 year were included in the analysis. Among the 202 patients included, M. fortuitum (n = 71, 35.1%) and MAC (n = 70, 34.7%) were the most common NTM species isolated, followed by M. chelonae-abscessus (n = 40, 19.8%) and M. kansasii (n = 21, 10.4%). The mean clinical follow-up period was 26.2 months. Forty-four patients (21.8%) had subsequent positive cultures of the same NTM species, while eight (4.0%) had bronchiectasis and developed NTM lung disease (NTM-LD). Neither patients without bronchiectasis nor those with M. fortuitum subsequently developed NTM lung disease. Among bronchiectatic patients with NTM other than M. fortuitum, age ≤65 years (p 0.006, OR 32.13), malignancy (p 0.048, OR 14.35), and initial radiographic score >2 (p 0.027, OR 20.06) were associated with subsequent NTM-LD. In all of the NTM patients, bronchiectasis (p <0.001, OR 5.46) and age ≤65 years (p 0.002, OR 3.29) were significantly associated with subsequent positive NTM culture. In patients with a single isolation of NTM from respiratory specimens, the presence of bronchiectasis and younger age indicates higher risk of subsequent culture-positivity and NTM-LD. Single isolation of M. fortuitum is of little clinical significance. Other patients with NTM, younger age, and more severe radiographic pulmonary lesion also warrant further attention.

Intentional examination of esophagus by narrow-band imaging endoscopy increases detection rate of cervical inlet patch.

Foci of heterotopic gastric mucosa have been identified at different sites in the human body and the most common location is the proximal esophagus which is referred to as cervical inlet patch (CIP). The true prevalence of CIP varies and it is usually incidental findings during endoscopy. Because CIP is always asymptomatic, it was believed to be of little clinical relevance. However, emerging studies have described the acid-secreting characteristics of heterotopic gastric mucosa and associations of CIP with gastroesophageal reflux disease (GERD). In addition, complications such as stricture, fistula, infection, mucosal hyperplasia, and malignant transformation have been reported. In this study, we investigated the prevalence of CIP, its associations with clinical manifestations, and the effect of intentional screening upper esophagus by magnifying endoscopy-narrow-band imaging (ME-NBI) system. Consecutive healthy adults who underwent panendoscopy were separated into two groups. Patients in group I (n = 471) were examined by an endoscopist who intended to find CIPs by ME-NBI. Patients in group II (n = 428) were examined by two endoscopists who were unaware of the study and performed white-light imaging endoscopy. Participants provided questionnaires on GERD-related symptoms. Higher CIP prevalence (11.7% vs. 1.9%, P < 0.0001) and longer duration of esophageal examination (mean ± standard deviation, 17.50 ± 12.40 vs. 15.24 ± 10.78 seconds, P = 0.004) were noted in group I than in group II. Analyzing group I patients revealed the higher prevalences of reflux symptoms (32.7% vs. 18.3%, P = 0.013) and erosive esophagitis (43.6% vs. 25.5%, P = 0.005) in patients with CIP than in those without. CIP was not associated with globus or dysphagia symptoms. More small CIPs (< 5 mm) were detected by ME-NBI than by white-light imaging (85.3% vs. 41.4%, P = 0.001). In conclusion, CIP prevalence was not low under intentional ME-NBI examination of the upper esophagus. The clinical relevance of CIP and its association with GERD require further investigation.

Intrahepatic segmental portal vein thrombosis after living-related donor liver transplantation.

BACKGROUND: Intrahepatic segmental portal vein thrombosis after living-related liver transplantation (LRLT) is uncommon. The cause remains unclear. METHODS: After providing written informed consent, 25 recipients receiving LRLT at our institution from January 2011 to September 2013 were enrolled in this study. We performed triphase computerized tomographic (CT) study of the liver graft of each recipient 1 month after LRLT. The patencies of hepatic artery, portal vein, and hepatic vein were evaluated in detail. The triphase CT scans of the liver of each donor before transplantation also were reviewed. Thrombosis of the intrahepatic segmental portal vein was defined as the occlusion site of the portal vein being intrahepatic. Extrahepatic portal vein thrombosis was excluded in this study. RESULTS: Among the 25 patients, 2 (8%) developed thrombosis of intrahepatic segmental portal vein. One 47-year-old man received LRLT for hepatitis B viral infection-related liver cirrhosis (Child-Pugh class C) with 3 hepatocellular carcinomas (total tumor volume <8 cm). Another 53-year-old man received LRLT for alcoholic liver cirrhosis (Child-Pugh class C). Both had developed progressive jaundice and cholangitis 1 month after surgery. Intrahepatic biliary stricture was found on the follow-up magnetic resonance images. However, liver triphase CT study demonstrated occlusion of intrahepatic portal vein of segment 8 in each patient. Radiologic interventions and balloon dilatation therapy via percutaneous transhepatic biliary drainage route improved the symptoms and signs of cholangitis and obstructive jaundice for both. CONCLUSIONS: Thrombosis of intrahepatic segmental portal vein is not common but is usually associated with complications of intrahepatic bile duct. Early detection is important, and follow-up CT study of liver is suggested.

Case report: maximum-intensity projection and minimum-intensity projection of computed tomography are helpful in the diagnosis of Budd-Chiari syndrome in complicated liver cirrhosis.

BACKGROUND: Early detection of Budd-Chiari syndrome (BCS) to give the appropriate therapy in time is crucial. Angiography remains the golden standard to diagnose BCS. However, to establish the diagnosis of BCS in complicated cirrhotic patients remains a challenge. We used maximum intensity projection (Max IP) and minimum intensity projection (Min IP) from computed tomographic (CT) images to detect this syndrome in such a patient. CASE REPORT: A 55-year-old man with a history of chronic hepatitis B infection and alcoholism had undergone previously a left lateral segmentectomy for hepatic epitheloid angiomyolipoma (4.6 × 3.5 × 3.3 cm) with a concomitant splenectomy. Liver decompensation with intractable ascites and jaundice occurred 4 months later. The reformed images of the venous phase of enhanced CT images with Max IP and Min IP showed middle hepatic vein thrombosis. He then underwent a living-related donor liver transplantation with a right liver graft from his daughter. Intraoperatively, we noted thrombosis of his middle hepatic vein protruding into inferior vena cava. The postoperative course was unevenful. Microscopic findings revealed micronodular cirrhosis with mixed inflammation in the portal areas. Some liver lobules exhibited congestion and sinusoidal dilation compatible with venous occlusion clinically. CONCLUSIONS: We recommend Max IP and Min IP of CT images as simple and effective techniques to establish the diagnosis of BCS, especially in complicated cirrhotic patients, thereby avoiding invasive interventional procedures.

Reduction in vasovagal reaction rate in young first-time blood donors by collecting 350 mL rather than 450 mL.

BACKGROUND: There is a paucity of studies on the magnitude of reduction of vasovagal reaction by reduced collection volume. This study was thus conducted to determine the difference in reaction rates between two collection volumes among the young first-time donors who are at particular risk of reaction. STUDY DESIGN AND METHODS: This retrospective study analyzed 38,436 whole blood donations made by young (aged 16 to 18 years) first-time donors. The effect of collection volume on vasovagal reaction was compared among different weight subgroups for both sexes by chi-square test. RESULTS: For females in all weight subgroups and two of the male lower-weight subgroups, the reduction percentages ranged from 35% to 58% (p < 0.05). It was also noted that, among the females, a higher weight was associated with a higher percent reduction in the reaction rate. CONCLUSION: With reduced collection volume, this study detected large and significant reduction in reaction rates among all females, as well as lower-weight males.

Long-term clinical outcomes after Streptococcus bovis isolation in asymptomatic blood donors in Hong Kong.

BACKGROUND: Risk of transfusion-transmitted bacterial sepsis has been substantially reduced by a bacterial surveillance program (BST). However, new problems emerge as asymptomatic bacteremia is detected in blood donors. Streptococcus bovis bacteremia, which is known to associate with infective endocarditis and colonic carcinoma, is an example. STUDY DESIGN AND METHODS: A retrospective study was conducted to examine the demographic and clinical outcome of this group of donors. All confirmed culture-positive cases under the BST were retrieved and those donors with S. bovis bacteremia were contacted for follow-up. Viable culture samples were sent for detailed microbiologic analysis. RESULTS: From 1998 to 2012, a total of 16 donors were found to have S. bovis bacteremia, giving an estimated prevalence of 1 in 110,800 donations. They consisted of nine men and seven women with median age of 43.5 years. Eight donors had undergone colonoscopy with colonic carcinoma detected in two and benign adenoma in four. Five of the 16 isolates could be retrieved for 16S DNA sequencing. Four were identified as S. gallolyticus ssp. pasteurianus and one as S. gallolyticus ssp. gallolyticus. The two patients with colonic carcinoma had one each of subspecies pasteurianus and gallolyticus. CONCLUSION: The findings highlight a close association of S. bovis and colonic carcinoma. We recommend prompt donor follow-up if S. bovis bacteremia is detected. Besides, all confirmed S. bovis should be fully characterized by molecular technique.

A study of the predonation hemoglobin and iron status among Hong Kong Chinese blood donors.

BACKGROUND: Predonation hemoglobin (PDH) is used to safeguard donors' welfare, and low hemoglobin (Hb) is known to be the most frequent reason for donor deferral. A study was initiated to assess the PDH and iron status of blood donors in Hong Kong. STUDY DESIGN AND METHODS: This observational study was designed with four groups of whole blood donors invited (group 1-eligible first time donors, group 2-eligible repeat donors with zero or one donation in preceding 12 months, group 3-eligible repeat donors with at least two donations in preceding 12 months, group 4-repeat donors being deferred for low PDH). Predonation blood samples were obtained for blood counts and iron status. Mann-Whitney test, Kruskal-Wallis test, and chi-square test for trend were applied for statistical analysis. RESULTS: A total of 836 donors were recruited, of which 35 were excluded because of hemoglobinopathy. An inverse relationship between serum ferritin level and number of donations in the preceding 12 months was observed in both sexes. Iron deficiency was significantly seen in 35.1% of male and 65.3% of female deferred donors. More importantly, up to 7.2, 5.8, and 29.5% of the female donors in groups 1, 2, and 3 were found to be iron deficient despite having a high enough PDH. CONCLUSION: This is the first study to assess PDH and iron status in Chinese blood donors. Iron depletion is noted with increasing number of blood donations in the preceding 12 months. Advice on iron repletion is a necessary step for donor welfare and strategies should be developed to ensure that donors have adequate PDH.

Anti-hepatitis C virus activity of 3-hydroxy caruilignan C from Swietenia macrophylla stems.

Chronic hepatitis C virus (HCV) infection ultimately leads to chronic hepatitis, hepatic cirrhosis and hepatocellular carcinoma (HCC). As the standard treatment is not completely efficacious, a safer and more effective agent against HCV infection needs to be developed. In this report, we demonstrated that 3-hydroxy caruilignan C (3-HCL-C) isolated from Swietenia macrophylla stems exhibited high anti-HCV activity at both protein and RNA levels at nontoxic concentrations, with an EC(50) value of 10.5 ± 1.2 µm. Combinations of 3-HCL-C and interferon-α (IFN-α), an HCV NS5B polymerase inhibitor (2'-C-methylcytidine; NM-107) or an HCV NS3/4A protease inhibitor (Telaprevir; VX-950) increased the suppression of HCV RNA replication. The results suggested that 3-HCL-C may be a potential anti-viral agent. We then demonstrated that 3-HCL-C interfered with HCV replication by inducing IFN-stimulated response element transcription and IFN-dependent anti-viral gene expression.

A method of utrophin up-regulation through RNAi-mediated knockdown of the transcription factor EN1.

The aim of this study was to induce up-regulation of the dystrophin-related gene UTRN that encodes the protein utrophin, to determine whether this could compensate for the lack of dystrophin function in Duchenne muscular dystrophy. The human UTRN promoter, which contains two putative binding sites for homeobox protein engrailed-1 (EN1), was analysed. It was found that EN1 binding site 2 in the UTRN gene promoter directly interacted with transcription factor EN1 in vitro. Chromatin immunoprecipitation assays of the EN1-UTRN promoter complex from rhabdomyosarcoma and HeLa cell lines confirmed that endogenous EN1 interacted with this region in vivo. The findings suggest that EN1 directly interacts with the UTRN promoter. Small interfering RNA was used to inhibit EN1 gene expression. Higher utrophin mRNA levels were observed in EN1-inhibited cells compared with controls. The increase in utrophin mRNA in rhabdomyosarcoma cells and HeLa cells may have resulted from inhibition of EN1 expression.

Bacteremia caused by Brevundimonas species at a tertiary care hospital in Taiwan, 2000-2010.

We investigated clinical and microbiological characteristics of 30 patients with Brevundimonas bacteremia treated at a tertiary care hospital in Taiwan during 2000-2010. All the 30 bacteria isolates were confirmed to the species level by 16S rRNA sequencing analysis. Minimum inhibitory concentrations (MICs) of 11 antimicrobial agents against these isolates were determined by the agar dilution method. Seventeen (57%) patients had underlying malignancy, 12 (40%) had undergone central catheter placement, and 13 (43%) had received chemotherapy within the previous three months. Eight (27%) patients had community-acquired bacteremia and the remaining 22 patients (73%) had healthcare-associated bacteremia. The overall 14-day and 30-day mortality rates were 13% and 17%, respectively. Among the 30 isolates, B. vesicularis constituted most commonly (n = 22, 63%), followed by B. nasdae (n = 5) and B. diminuta (n = 3). All isolates were susceptible to piperacillin-tazobactam and amikacin, while all were resistant to ciprofloxacin and colistin. Tigecycline (MICs at which 90% of isolates are inhibited [MIC(90)] was 0.12 mg/L) and doripenem (MIC(90) of 1 mg/L) both possessed good in vitro activities. In conclusions, Brevundimonas should be considered a pathogen that can cause bacteremia in immunocompromised hosts. Piperacillin-tazobactam, amikacin, doripenem, and tigecycline exhibit good in vitro activities against these ciprofloxacin- and colistin-resistant Brevundimonas species.

Halogenated POPs and PAHs in blood plasma of Hong Kong residents.

The objective of this study was to quantify organic chlorinated pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and polycyclic aromatic hydrocarbons (PAHs) in blood plasma collected from 111 healthy residents in Hong Kong to assess the levels of these pollutants in the general population during the period of March to April, 2008. Concentrations of these residues in blood plasma obtained from the Hong Kong Red Cross Blood Transfusion Service were determined by gas chromatography-mass spectrometry. Naphthalene, phenanthrene, p,p'-DDE, PCB-180, and PBDE-47 were detected in 100% of the participants. Females had significantly greater concentrations of acenaphthylene (female: 93.3 ng/g lipid; male: 39.8, p < 0.05), anthracene (22.3; 15.3, p < 0.05), fluoranthene (138; 125, p < 0.05), p,p'-DDE, p,p'-DDT, PCB-183, BDE-99 than males. Blood of smokers contained significantly greater (p < 0.05) concentrations of acenaphthene, benzo(a)pyrene, p,p'-DDE, p,p'-DDT, PCB-138, BDE-47, and BDE-99 than did blood of nonsmokers. Positive correlations were found between concentrations of each class of pollutant, with respect to seafood diet habit, Body Mass Index (BMI), and age. Concentrations of HCHs and DDTs in blood plasma of healthy Hong Kong residents were greater than those of other countries, and it was found that smoking, consumption of a seafood diet, BMI, and age could influence concentrations in human blood.