Optimal follow-up time to determine the sustained virological response in patients with chronic hepatitis C receiving pegylated-interferon and ribavirin

Background and Aim: This study evaluated whether the assessment of hepatitis C virus (HCV)‐RNA at 12 weeks (FW+12) post‐treatment follow‐up was as applicable as FW+24 to evaluate sustained virological response (SVR) using the highly sensitive real‐time polymerase chain reaction (PCR) HCV assay. Methods and Results: Two hundred and twenty‐two patients with chronic hepatitis C were included in this study. Pegylated interferon (Peg‐IFN) and ribavirin were administered for 24–72 weeks based on the genotype and viral load. Serum HCV‐RNA was measured using real‐time PCR at pretreatment, the end of treatment, FW+4, FW+8, FW+12, FW+16, FW+20 and FW+24. Two hundred patients had a virological response at the end of treatment. One hundred and forty‐eight of 200 (74.0%) patients with a virological response at the end of treatment had an SVR at the FW+24. The positive predictive value (PPV) to identify patients with SVR at FW+4, FW+8, FW+12 was 87.1, 96.1, 98.0%, respectively. The viral load showed a reversion to the basal level as early as 8 weeks in relapse patients. There were only three patients who relapsed after FW+12 and all three of these patients were females with genotype Ib and a high viral load. Conclusion: The assessment of serum HCV‐RNA FW+12, using the highly sensitive real‐time PCR assay, is almost as effective as FW+24 to predict SVR. However, there are false negatives in female patients with a high viral load of genotype Ib when the SVR is predicted by FW+12. The current standard with FW+24 is reasonable, but the assessment of serum HCV‐RNA FW+12 may be effective in most patients.     

Expression of OCT4 in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis

AIM: To explore the expression pattern of OCT4 in human esophageal squamous cell carcinoma and its significance in diagnosis and prognosis.METHODS: Using real-time polymerase chain reaction (PCR), Western blotting, immunocytochemistry and immunohistochemistry, the expression of OCT4 in three esophageal squamous cancer cell lines, KYSE70, KYSE140 and KYSE450, was characterized. OCT4 expression was investigated in a series of 153 esophageal squamous cell carcinoma samples using immunohistochemistry and explored its association with clinicopathological features.RESULTS: Immunohistochemically, OCT4 positive immunostaining was observed in cancer cell nuclei. OCT4 was variably expressed in three esophageal squamous cancer cell lines. Among 153 specimens, 105 (68.7%) were negative or weakly positive for OCT4 staining; 21 (13.7%) were moderately positive and 27 (17.6%) were strongly positive. Higher expression level of OCT4 was significantly associated with higher histological grade (P < 0.001) and poor clinic outcome (P < 0.001).CONCLUSION: The expression of OCT4 enables the tumor to have a higher degree of stemness, which in turn results in a poorer clinical outcome for patients with esophageal squamous cell carcinoma.     

Motor vehicle accidents: How should cirrhotic patients be managed?

Motor vehicle accidents (MVAs) are serious social issues worldwide and driver illness is an important cause of MVAs. Minimal hepatic encephalopathy (MHE) is a complex cognitive dysfunction with attention deficit, which frequently occurs in cirrhotic patients independent of severity of liver disease. Although MHE is known as a risk factor for MVAs, the impact of diagnosis and treatment of MHE on MVA-related societal costs is largely unknown. Recently, Bajaj et al demonstrated valuable findings that the diagnosis of MHE by rapid screening using the inhibitory control test (ICT), and subsequent treatment with lactulose could substantially reduce the societal costs by preventing MVAs. Besides the ICT and lactulose, there are various diagnostic tools and therapeutic strategies for MHE. In this commentary, we discussed a current issue of diagnostic tools for MHE, including neuropsychological tests. We also discussed the advantages of the other therapeutic strategies for MHE, such as intake of a regular breakfast and coffee, and supplementation with zinc and branched chain amino acids, on the MVA-related societal costs.     

The outcome of endometrial ablation in women with inherited bleeding disorders

There are currently limited data on the use of endometrial ablation in the treatment of heavy menstrual bleeding (HMB) in women with inherited bleeding disorders (IBDs). A retrospective review of prospectively collected data was performed. Twelve women with IBDs who had received endometrial ablation for the treatment of HMB were identified and their records reviewed. Details of their menstrual history; quality of life (QOL) and amount of menstrual blood loss [as assessed by pictorial blood-loss assessment chart (PBAC) and haemoglobin (Hb) concentration] pre and post-ablation were collected. Twelve women were included. The median duration of follow-up post-ablation was 32 months (range, 6-76). The median duration of menstruation decreased from 11 to 0 days after treatment (P = 0.004). Median PBAC scores decreased from 1208 preop to 0 post-ablation (P = 0.002).The median Hb concentrations (10.5-13.1 g dL(-1)) and QOL scores (median, 17-54) improved significantly after endometrial ablation (P < 0.01). Endometrial ablation appears to be a safe and effective long-term treatment for HMB in women with IDBs. It significantly decreases menstrual blood loss and improves QOL.     

A modified I-PCR to detect the factor VIII Inv22 for genetic diagnosis and prenatal diagnosis in haemophilia A

To explore the effectiveness of modified inversion-polymerase chain reaction (I-PCR) to detect the factor VIII (FVIII) intron 22 inversion (Inv22) for genetic diagnosis and prenatal diagnosis in haemophilia A (HA). Both modified I-PCR and LD-PCR were applied to analyse the FVIII Inv22 for 24 patients with HA. Prenatal diagnosis was performed on six foetuses. Foetal blood samplings were carried out by cordocentesis from 22 to 26 weeks of gestation. Ten patients with FVIII Inv22 in 10 HA families were found, and the remaining 14 patients were found without the Inv22 in 19 HA families. Prenatal diagnosis confirmed that four foetuses were normal and all of them born normally. However, two foetuses had been identified as abnormal and undergone abortion. Compared with LD-PCR, modified I-PCR is more rapid and convenient for detecting the FVIII Inv22 in genetic diagnosis. It is recommended that a patient undergoes both modified I-PCR (to detect the FVIII Inv22) and biochemical assay (to measure the FVIII activity of umbilical cord blood) in prenatal diagnosis. When we have more experience, the DNA samples from chorionic villus or amniotic fluid can be analysed for prenatal diagnosis using the modified I-PCR alone.     

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma and future treatments for the poor responders

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The most common problem associated with HCC is a high risk of intrahepatic recurrence despite radical treatment, and in many patients, this recurrence has fatal consequences. For patients with advanced-stage HCC according to the Barcelona Clinic Liver Cancer staging system, the multikinase inhibitor sorafenib is the current standard of care. In contrast, hepatic arterial infusion chemotherapy (HAIC) is the recommended treatment in Japan for patients with intermediate-stage or advanced-stage HCC. In this review, we describe the use of HAIC for advanced HCC. Furthermore, we demonstrate an alternative therapy for HCC, the iron chelator deferoxamine, and discuss future therapeutic possibilities.     

Addressing the MSICS learning curve: identification of instrument-holding techniques used by experienced surgeons

AIM: To detect the quantitative expression levels of the pro-inflammatory interleukin-8 (IL8), antimicrobial peptides Human beta defense-2 (HBD2), and Human beta defense-3 (HBD3) genes in bacterial conjunctivitis. METHODS: The human conjunctival epithelial cells were obtained using the impression cytology technique from healthy controls and patients. The genes expression levels were determined utilizing a quantitative real-time polymerase chain reaction (RT-PCR). The contribution of causative agent type, the number of isolates and severity of clinical features, in the increase of genes expression was also determined. RESULTS: The RT-PCR showed that IL8, HBD2, and HBD3 expression increased in bacterial conjunctivitis as compared to healthy control (P<0.001). In gram-negative bacterial conjunctivitis, HBD2 was highly up-regulated (P<0.001) compared to other types of bacterial conjunctivitis. In mixed bacterial conjunctivitis, a direct correlation between HBD2 up-regulation and HBD3 up-regulation was observed (P<0.05). The severity of clinical features was related to the up-regulation of IL8 and HBD2 (P<0.05). CONCLUSION: IL8, HBD2, and HBD3 are immune-effectors in infectious conjunctivitis. HBD2 is active during different bacterial conjunctivitis but is more released with gram-negative bacteria compared to gram-positive bacteria. HBD3 is an obvious defender in different bacterial conjunctivitis.     

MK2 plays an important role for the increased vascular permeability that follows thermal injury

We previously reported Rho kinase is involved in vessel hyper-permeability caused by burns. Here we further explore the Rho kinase downstream signaling, it is found that its specific inhibitor Y27632 significantly diminishes the activation of JNK and p38 MAPKs but not ERK that induced by serum from burned rats (burn-serum). JNK activation was found involved in the expression of HUVEC adhesion molecules following thermal injury, although not in the process of stress fiber formation. Inhibition of various MAPKs by specific inhibitors showed that SB203580 (inhibitor of p38), but neither SP600125 (inhibitor of JNK) nor PD98059 (inhibitor of ERK), abolish activation of the p38 downstream kinase MK2. Demonstration of stress fibers by fluorescent-labeled phalloidin showed that inhibition of MK2, either by its specific inhibitor or by dominant negative adeno-viral-carried constructs, significantly reduced burn-serum-induced HUVEC stress-fiber formation, while inhibition of another downstream p38 MAPK kinase, PRAK, had no such effects. Transfection of dominant negative adeno-viral MK2 (Ad-MK2(A)) significantly inhibited thermal injury-induced blood vessel hyper-permeability in rats and, moreover, prolonged the survival of burned rats beyond 72 h following thermal injury. One of the mechanisms behind these phenomena is that Ad-MK2(A) causes a significant depression of burn-serum-induced HSP27-phosphorylation, while the adeno-viral transported dominant negative PRAK (Ad-PRAK(A)) does not block. Although the effect of blockade of MK2 through its adeno-viral approach requires further study and investigation of alternatives to know for sure, we may have found a new pathway behind thermal-injury-induced blood vessel hyper-permeability, namely: Rho kinase > p38 > MK2 > HSP27.