Practice guidance for the use of terlipressin for liver cirrhosis-related complications.

Background: Liver cirrhosis is a major global health burden worldwide due to its high risk of morbidity and mortality. Role of terlipressin for the management of liver cirrhosis-related complications has been recognized during recent years. This article aims to develop evidence-based clinical practice guidance on the use of terlipressin for liver cirrhosis-related complications. Methods: Hepatobiliary Study Group of the Chinese Society of Gastroenterology of the Chinese Medical Association and Hepatology Committee of the Chinese Research Hospital Association have invited gastroenterologists, hepatologists, infectious disease specialists, surgeons, and clinical pharmacists to formulate the clinical practice guidance based on comprehensive literature review and experts' clinical experiences. Results: Overall, 10 major guidance statements regarding efficacy and safety of terlipressin in liver cirrhosis were proposed. Terlipressin can be beneficial for the management of cirrhotic patients with acute variceal bleeding and hepatorenal syndrome (HRS). However, the evidence regarding the use of terlipressin in cirrhotic patients with ascites, post-paracentesis circulatory dysfunction, and bacterial infections and in those undergoing hepatic resection and liver transplantation remains insufficient. Terlipressin-related adverse events, mainly including gastrointestinal symptoms, electrolyte disturbance, and cardiovascular and respiratory adverse events, should be closely monitored. Conclusion: The current clinical practice guidance supports the use of terlipressin for gastroesophageal variceal bleeding and HRS in liver cirrhosis. High-quality studies are needed to further clarify its potential effects in other liver cirrhosis-related complications.

Acute kidney injury defined by cystatin C may be superior for predicting the outcomes of liver cirrhosis with acute gastrointestinal bleeding.

BACKGROUND & AIMS: Acute kidney injury (AKI) is conventionally evaluated by a dynamic change of serum creatinine (Scr). Cystatin C (CysC) seems to be a more accurate biomarker for assessing kidney function. This retrospective multicenter study aims to evaluate whether AKI re-defined by CysC can predict the in-hospital outcomes of patients with liver cirrhosis and acute gastrointestinal bleeding. METHODS: Overall, 677 cirrhotic patients with acute gastrointestinal bleeding, in whom both Scr and CysC levels were detected at admissions, were screened. eGFRScr, eGFRCysC, and eGFRScr-CysC were calculated. MELD-Na score and AKI were re-evaluated by CysC instead of Scr. Odds ratios (ORs) were calculated in the logistic regression analyses. The receiver operating characteristic (ROC) curve analyses were performed. RESULTS: Univariate logistic regression analyses demonstrated that baseline Scr and CysC levels, eGFRScr, eGFRCysC, eGFRScr-CysC, original MELD-Na score defined by Scr, MELD-Na score re-defined by CysC, and AKI re-defined by CysC, but not conventional AKI defined by Scr, were significantly associated with in-hospital death. ROC analyses showed that baseline CysC level, eGFRScr, eGFRCysC, eGFRScr-CysC, original MELD-Na score defined by Scr, and MELD-Na score re-defined by CysC, but not baseline Scr level, could significantly predict the risk of in-hospital death. CONCLUSIONS: AKI re-defined by CysC may be superior for predicting the in-hospital mortality of cirrhotic patients with acute gastrointestinal bleeding.

Effect of Body Mass Index on the Prognosis of Liver Cirrhosis.

Objective: At present, the association of body mass index (BMI) with the prognosis of liver cirrhosis is controversial. Our retrospective study aimed to evaluate the impact of BMI on the outcome of liver cirrhosis. Methods: In the first part, long-term death was evaluated in 436 patients with cirrhosis and without malignancy from our prospectively established single-center database. In the second part, in-hospital death was evaluated in 379 patients with cirrhosis and with acute gastrointestinal bleeding (AGIB) from our retrospective multicenter study. BMI was calculated and categorized as underweight (BMI <18.5 kg/m2), normal weight (18.5 ≤ BMI < 23.0 kg/m2), and overweight/obese (BMI ≥ 23.0 kg/m2). Results: In the first part, Kaplan-Meier curve analyses demonstrated a significantly higher cumulative survival rate in the overweight/obese group than the normal weight group (p = 0.047). Cox regression analyses demonstrated that overweight/obesity was significantly associated with decreased long-term mortality compared with the normal weight group [hazard ratio (HR) = 0.635; 95% CI: 0.405-0.998; p = 0.049] but not an independent predictor after adjusting for age, gender, and Child-Pugh score (HR = 0.758; 95%CI: 0.479-1.199; p = 0.236). In the second part, Kaplan-Meier curve analyses demonstrated no significant difference in the cumulative survival rate between the overweight/obese and the normal weight groups (p = 0.094). Cox regression analyses also demonstrated that overweight/obesity was not significantly associated with in-hospital mortality compared with normal weight group (HR = 0.349; 95%CI: 0.096-1.269; p = 0.110). In both of the two parts, the Kaplan-Meier curve analyses demonstrated no significant difference in the cumulative survival rate between underweight and normal weight groups. Conclusion: Overweight/obesity is modestly associated with long-term survival in patients with cirrhosis but not an independent prognostic predictor. There is little effect of overweight/obesity on the short-term survival of patients with cirrhosis and with AGIB.

Terlipressin May Decrease In-Hospital Mortality of Cirrhotic Patients with Acute Gastrointestinal Bleeding and Renal Dysfunction: A Retrospective Multicenter Observational Study.

BACKGROUND: Acute gastrointestinal bleeding (GIB) rapidly reduces effective blood volume, thereby precipitating acute kidney injury (AKI). Terlipressin, which can induce splanchnic vasoconstriction and increase renal perfusion, has been recommended for acute GIB and hepatorenal syndrome in liver cirrhosis. Thus, we hypothesized that terlipressin might be beneficial for cirrhotic patients with acute GIB and renal impairment. METHODS: In this Chinese multi-center study, 1644 cirrhotic patients with acute GIB were retrospectively enrolled. AKI was defined according to the International Club of Ascites (ICA) criteria. Renal dysfunction was defined as serum creatinine (sCr) > 133 µmol/L at admission and/or any time point during hospitalization. Incidence of renal impairment and in-hospital mortality were the primary end-points. RESULTS: The incidence of any stage ICA-AKI, ICA-AKI stages 1B, 2, and 3, and renal dysfunction in cirrhotic patients with acute GIB was 7.1%, 1.8%, and 5.0%, respectively. The in-hospital mortality was significantly increased by renal dysfunction (14.5% vs. 2.2%, P < 0.001) and ICA-AKI stages 1B, 2, and 3 (11.1% vs. 2.8%, P = 0.011), but not any stage ICA-AKI (5.7% vs. 2.7%, P = 0.083). The in-hospital mortality was significantly decreased by terlipressin in patients with renal dysfunction (3.6% vs. 20.0%, P = 0.044), but not in those with any stage ICA-AKI (4.5% vs. 6.0%, P = 0.799) or ICA-AKI stages 1B, 2, and 3 (0.0% vs. 14.3%, P = 0.326). CONCLUSION: Renal dysfunction increased the in-hospital mortality of cirrhotic patients with acute GIB. Terlipressin might decrease the in-hospital mortality of cirrhotic patients with acute GIB and renal dysfunction. TRIAL REGISTRATION: NCT03846180 ( https://clinicaltrials.gov ).

TFAM depletion overcomes hepatocellular carcinoma resistance to doxorubicin and sorafenib through AMPK activation and mitochondrial dysfunction.

Mitochondrial transcription factor A (TFAM), which is required for mitochondrial DNA (mtDNA) transcription, has been linked to metabolic changes that contribute to tumorigenesis and chemoresistance. In this work, we investigated the expression pattern and role of TFAM in hepatocellular carcinoma (HCC). TFAM expression level is similar in 18 out of 20 paired normal liver and HCC tissues with only 2 HCC tissues showing 1.8-fold increase in TFAM. Similar phenomenon was observed in HCC cell lines compared to normal liver lines. Interestingly, TFAM expression is upregulated in resistant HCC cells regardless of the differential TFAM expression level in their parental lines and mechanism of resistance. TFAM depletion led to inhibition of growth and survival but not migration, and sensitization to doxorubicin and sorafenib treatment, through AMPK activation, reduction of nucleoside triphosphates and mitochondrial respiration in HCC cells. In addition, we demonstrated that resistant HCC cell lines were more sensitive to TFAM inhibition than parental lines, and this might be due to the increased mitochondrial biogenesis in resistant HCC cell lines. Our work reveals the preferential role of TFAM in HCC cell response to standard of care drugs, which suggests a potential sensitizing therapeutic target for HCC treatment.

Development of hyponatremia after terlipressin in cirrhotic patients with acute gastrointestinal bleeding: a retrospective multicenter observational study.

Background: Terlipressin can effectively control acute gastrointestinal bleeding (GIB) in cirrhotic patients by acting on the V1 receptors, but may lead to the development of dilutional hyponatremia by acting on the V2 receptors.Research design and methods: This retrospective multicenter study enrolled 674 cirrhotic patients with acute GIB in whom serum sodium concentrations were tested before and during the use of terlipressin. ΔSodium reduction ≥5 mmol/L, hyponatremia (sodium <130 mmol/L), and severe hyponatremia (sodium <125 mmol/L) during the use of terlipressin were evaluated. Logistic regression analyses were employed to identify the risk factors.Results: The incidence of Δsodium reduction ≥5 mmol/L, hyponatremia, and severe hyponatremia was 37.1%, 26.3%, and 13.0%, respectively. All of them were not significantly associated with in-hospital mortality (p = 0.973; p = 0.789; p = 0.887). In multivariate logistic regression analyses, the independent risk factors of Δsodium reduction ≥5 mmol/L were higher baseline sodium concentration, lower serum creatinine and prothrombin time, and larger dosage of terlipressin; those of hyponatremia were lower baseline sodium concentration and longer duration of terlipressin; those of severe hyponatremia were lower baseline sodium concentration and prothrombin time and longer duration of terlipressin.Conclusions: Hyponatremia was common in cirrhotic patients with acute GIB treated with terlipressin, but might not significantly increase the in-hospital mortality.

Surgery versus external beam radiation therapy for AJCC stage I hepatocellular carcinoma.

PURPOSE: To compare the survival of American Joint Committee on Cancer (AJCC) stage I hepatocellular carcinoma (HCC) treated with surgery versus external beam radiation therapy (EBRT). METHODS: Surveillance, Epidemiology, and End Results (SEER) database was used to identify the patients diagnosed with HCC between 2004 and 2013. Overall survival (OS) and liver-specific survival (LSS) were compared between patients treated with surgery and EBRT. A 1:1 propensity score matching (PSM) analysis was employed by matching age, sex, and race. RESULTS: Among the 1553 patients with HCC ≤2cm, there was no significant difference in OS (p=0.605, before PSM; p=0.891, after PSM) and LSS (p=0.281, before PSM; p=0.346, after PSM) between patients treated with surgery and EBRT. Among the 1752 patients with HCC >2cm and ≤3cm, patients treated with surgery had significantly better OS (p=0.001) than those treated with EBRT, but statistically similar LSS (p=0.072) before PSM; however, there was no significant difference in OS (p=0.139) and LSS (p=0.722) between patients treated with surgery and EBRT after PSM. Additionally, 1157, 723, and 1331 patients had HCC >3cm and ≤4cm, HCC >4cm and ≤5cm, and HCC >5cm, respectively; among them, patients treated with surgery had significantly better OS and LSS than those treated with EBRT regardless of PSM. CONCLUSIONS: At the AJCC stage I, the survival after EBRT might be comparable to that after surgery for HCC ≤3cm, but the survival after EBRT was inferior to that after surgery for HCC >3cm.

Development and Validation of CAGIB Score for Evaluating the Prognosis of Cirrhosis with Acute Gastrointestinal Bleeding: A Retrospective Multicenter Study.

INTRODUCTION: Acute gastrointestinal bleeding (GIB) is a major cause of death in liver cirrhosis. This multicenter study aims to develop and validate a novel and easy-to-access model for predicting the prognosis of patients with cirrhosis and acute GIB. METHODS: Patients with cirrhosis and acute GIB were enrolled and randomly divided into the training (n = 865) and validation (n = 817) cohorts. In the training cohort, the independent predictors for in-hospital death were identified by logistic regression analyses, and then a new prognostic model (i.e., CAGIB score) was established. Area under curve (AUC) of CAGIB score was calculated by receiver operating characteristic curve analysis and compared with Child-Pugh, model for end-stage liver disease (MELD), MELD-Na, and neutrophil-lymphocyte ratio (NLR) scores. RESULTS: In the training cohort, hepatocellular carcinoma (HCC), diabetes, total bilirubin (TBIL), albumin (ALB), alanine aminotransferase (ALT), and serum creatinine (Scr) were independent predictors of in-hospital death. CAGIB score = diabetes (yes = 1, no = 0) × 1.040 + HCC (yes = 1, no = 0) × 0.974 + TBIL (µmol/L) × 0.005 - ALB (g/L) × 0.091 + ALT (U/L) × 0.001 + Scr (µmol/L) × 0.012 - 3.964. In the training cohort, the AUC of CAGIB score for predicting in-hospital death was 0.829 (95% CI 0.801-0.854, P < 0.0001), which was higher than that of Child-Pugh (0.762, 95% CI 0.732-0.791), MELD (0.778, 95% CI 0.748-0.806), MELD-Na (0.765, 95% CI 0.735-0.793), and NLR (0.587, 95% CI 0.553-0.620) scores. In the validation cohort, the AUC of CAGIB score (0.714, 95% CI 0.682-0.746, P = 0.0006) remained higher than that of Child-Pugh (0.693, 95% CI 0.659-0.725), MELD (0.662, 95% CI 0.627-0.695), MELD-Na (0.660, 95% CI 0.626-0.694), and NLR (0.538, 95% CI 0.503-0.574) scores. CONCLUSION: CAGIB score has a good predictive performance for prognosis of patients with cirrhosis and acute GIB.

Efficacy and safety of external-beam radiation therapy for hepatocellular carcinoma: An overview of current evidence according to the different target population.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. During the recent years, external-beam radiation therapy (EBRT) has been safely and effectively employed for the management of HCC. We overviewed the current evidence regarding the efficacy and safety of EBRT for HCC according to the different target population. PubMed database was searched for identifying English-language full-text articles regarding EBRT for the treatment of HCC. Search items were "hepatocellular carcinoma AND radiation therapy". Until now, preliminary evidence has suggested the following role of EBRT for HCC. 1) EBRT, especially stereotactic body radiation therapy, is an emerging choice of therapy for small HCC. 2) EBRT combined with non-surgical treatment can achieve an excellent intrahepatic tumor control and a potential survival benefit for huge HCC. 3)Adjunctive EBRT may improve the efficacy of transarterial chemoembolization for HCC with portal vein tumor thrombosis. 4) EBRT can relieve the pain and improve the quality of life for patients with extrahepatic metastases. 5) EBRT may be a bridge to liver transplantation by minimizing the tumor progression. 6) Adjunctive EBRT may reduce the tumor recurrence and improve the survival after resection. In summary, EBRT is a promising choice of treatment of HCC. However, more high-quality evidence is needed to further establish the status of EBRT for the management of HCC.

Terlipressin for the treatment of acute variceal bleeding: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Acute variceal bleeding (AVB) is life-threatening. We aimed to systematically review the current evidence regarding the efficacy and safety of terlipressin for AVB in liver cirrhosis. METHODS: We searched the PubMed, EMBASE, and Cochrane Library databases. The reference list was also hand-searched. Using a random-effect model, we combined the data obtained according to the different time points when the events developed. Odds ratio (OR) and weighted mean difference (WMD) were calculated. Quality of evidence was evaluated by the GRADE methodology. RESULTS: Thirty randomized controlled trials with 3344 patients were included. Compared with no vasoactive drug, terlipressin significantly improved the control of bleeding within 48 hours (OR = 2.94, P = .0008) and decreased the in-hospital mortality (OR = 0.31, P = .008). Compared with somatostatin, terlipressin had a significantly higher risk of complications (OR = 2.44, P = .04). Compared with octreotide, terlipressin had a significantly inferior control of bleeding within 24 hours (OR = 0.37, P = .007). Compared with vasopressin, terlipressin had a significantly lower risk of complications (OR = 0.15, P = .02). Compared with terlipressin combined with endoscopic variceal ligation, terlipressin alone had significantly higher 5-day treatment failure (OR = 14.46, P = .01) and transfusion requirements within 49 to 120 hours (WMD = 1.20, P = .002). No outcome was significantly different between terlipressin and sclerotherapy. Compared with balloon tamponade, terlipressin significantly decreased the 30-day rebleeding (OR = 0.05, P = .001) and transfusion requirements (WMD = -2.70, P = .02). Quality of evidence was very low to moderate. CONCLUSION: Our findings were in accordance with the current recommendations regarding terlipressin for the treatment of AVB in cirrhosis. However, due to low quality of evidence, further studies are recommended.

A systematic review and meta-analysis of treatment for hepatorenal syndrome with traditional Chinese medicine.

BACKGROUND: Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver diseases. It has been reported that traditional Chinese medicine (TCM) may improve liver function, delay disease progression, alleviate symptoms, and improve quality of life in HRS patients. The study aims to systematically review the efficacy of TCM for the treatment of HRS. METHODS: Publications were searched electronically from China National Knowledge Infrastructure (CNKI), Wanfang, VIP, PubMed, and EMBASE databases. Odds ratio (OR) and standardized mean difference (SMD) with 95% confidence interval (CI) were calculated. Heterogeneity was assessed. The Cochrane Collaboration's tool was used to assess the risk of bias. RESULTS: Fourteen randomized controlled trials involving 788 patients with HRS were included. Random generation sequence was reported in only two studies. Blinding was not used in any study. Compared to conventional treatment without TCM, TCM led to a significant survival benefit during hospitalization (OR: 0.18; 95% CI: 0.08-0.39; P<0.0001), a significantly higher complete response (OR: 3.20; 95% CI: 2.06-4.97; P<0.00001), and a significantly lower no response (OR: 0.20; 95% CI: 0.14-0.30; P<0.00001). Partial response was not significantly different between the two groups (OR: 1.39; 95% CI: 0.90-2.15; P=0.14). Regardless of TCM, blood urea nitrogen and abdominal circumference were significantly decreased, and urine volume was significantly increased after treatment. Compared to conventional treatment without TCM, TCM led to a significantly lower serum creatinine, blood urea nitrogen, bilirubin, plasma ammonia, and abdominal circumference and significantly higher urine volume after treatment. There was significant heterogeneity. CONCLUSIONS: TCM might have a better survival and a higher complete response in patients with HRS. However, the quality of published studies was unsatisfactory.

Selection of treatment modalities for hepatocellular carcinoma at stages T1 and T2: A preliminary analysis based on the Surveillance, Epidemiology, and End Results registry database.

PURPOSE: To explore the selection of treatment modalities for hepatocellular carcinoma (HCC) at stages T1 and/or T2 and to compare the survival of patients treated with surgery alone vs radiation therapy (RT) alone. METHODS: Surveillance, Epidemiology, and End Results (SEER) database was used to identify the patients diagnosed with HCC between 2004 and 2013. The tumor-nodemetastasis (TNM) stage was established according to the American Joint Committee on Cancer (AJCC) Staging. After age, sex, TNM stage, and tumor extension were matched, the survival was further compared between patients undergoing surgery alone vs RT alone. RESULTS: Of 11967 patients at stages T1 (n=7829) and T2 (n=4138), 10449 (87.31%) underwent surgery alone, 1241 (10.37%) RT alone, and 277 (2.32%) surgery combined with RT. Compared with those treated with RT alone and in combination with surgery, patients treated with surgery alone were younger, with smaller tumor size, higher proportion of females, single lesion, and AJCC stage I/II, and lower proportion of regional and distant lymph nodes, bone, brain, and lung invasion. Among them, 758 pairs (surgery alone and RT alone) at stage T1 and 430 pairs (surgery alone and RT alone) at stage T2 were matched. Regardless of stage T1 or T2, patients undergoing surgery alone had a significantly better cumulative survival than those undergoing RT alone (p<0.001). CONCLUSION: The treatment selection of HCC was dependent on the age, sex, tumor size, number of lesions, and extrahepatic invasion. Surgery alone should be the preferred treatment modality of HCC at stages T1 and T2.

Albumin-to-bilirubin score for assessing the in-hospital death in cirrhosis.

BACKGROUND: To evaluate the ability of albumin-to-bilirubin (ALBI) score for assessing the in-hospital death in cirrhotic patients. METHODS: Overall, 1,067 cirrhotic patients admitted between January 2009 and December 2014 were retrospectively enrolled. We calculated the Child-Pugh, model for end-stage liver disease (MELD), and ALBI scores. We performed receiver operating characteristic curve (ROC) analyses to assess the in-hospital death. We calculated the area under the ROC curve (AUC). RESULTS: In the overall analysis, all of the three scores can significantly assess the in-hospital death (Child-Pugh score AUC =0.750, 95% CI: 0.713-0.784, P<0.0001; MELD score AUC =0.728, 95% CI: 0.689-0.765, P<0.0001; ALBI score AUC =0.698, 95% CI: 0.667-0.727, P<0.0001). In the subgroup analysis of hepatitis B virus, Child-Pugh and ALBI scores were suitable to assess in-hospital death (Child-Pugh score AUC =0.752, 95% CI: 0.679-0.816, P<0.0001; ALBI score AUC =0.803, 95% CI: 0.751-0.849, P=0.0002) and both were superior to the MELD score (AUC=0.564, 95% CI: 0.483-0.643, P=0.5357). In the subgroup analysis of alcohol abuse, Child-Pugh and MELD scores properly assessed in-hospital death (Child-Pugh score AUC =0.791, 95% CI: 0.727-0.846, P<0.0001; MELD score AUC =0.720, 95% CI: 0.647-0.786, P=0.0023), rather than ALBI score (AUC =0.646, 95% CI: 0.588-0.702, P=0.1360). CONCLUSIONS: ALBI score might be an alternative index for assessing the in-hospital death in patients with liver cirrhosis.

Association of conventional haemostasis and coagulation tests with the risk of acute upper gastrointestinal bleeding in liver cirrhosis: a retrospective study.

OBJECTIVE: A retrospective study was performed to compare the difference in platelet count (PLT), prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT), between cirrhotic patients with and without acute upper gastrointestinal bleeding (AUGIB) or acute oesophageal variceal bleeding (AEVB). METHODS: Between January 2012 and June 2014, a total of 1734 cirrhotic patients were enrolled and were classified into 'AUGIB' (n = 497) and 'no AUGIB' (n = 1237) groups according to their disease history. They were further divided into 'AEVB' (n = 297) and 'no AEVB' (n = 1259) groups according to the endoscopic findings. Additionally, 178 patients with AUGIB were not assigned to either the 'AEVB' or 'no AEVB' groups due to the absence of any endoscopic findings. RESULTS: Compared with the 'no AUGIB' group, the 'AUGIB' group had similar PLT (99.99 ± 89.90 vs.101.47 ± 83.03; P = 0.734) and APTT (42.96 ± 15.20 vs.43.77 ± 11.01; P = 0.219), but significantly higher PT (17.30 ± 5.62 vs.16.03 ± 4.68; P < 0.001) and INR (1.45 ± 0.69 vs.1.31 ± 0.59; P < 0.001). A lower PT was independently associated with the absence of AUGIB (OR = 0.968; 95% CI: 0.942-0.994). Compared with the 'no AEVB' group, the 'AEVB' group had significantly lower PLT (86.87 ± 62.14 vs.101.74 ± 83.62; P = 0.004) and APTT (40.98 ± 7.9 vs.43.72 ± 10.97; P < 0.001), but similar PT (16.53 ± 3.71 vs.16.04 ± 4.68; P = 0.088) and INR (1.35 ± 0.41 vs.1.31 ± 0.59; P = 0.225). A higher PLT was independently associated with the absence of AEVB (OR = 1.004; 95% CI: 1.002-1.006; P = 0.001). CONCLUSIONS: PLT was associated with the occurrence of portal hypertension-related bleeding in liver cirrhosis.

Novel insights into the development of portal vein thrombosis in cirrhosis patients.

The prognostic impact of portal vein thrombosis (PVT) in liver cirrhosis remains controversial among studies, primarily because the risk stratification of PVT is often lacking. A definition of clinically significant PVT should be proposed and actively improved. Moreover, the risk factors for the development of PVT in liver cirrhosis should be fully recognized to screen and identify high-risk patients. Currently, well-recognized risk factors include a reduced portal vein flow velocity, a worse liver function, splenectomy, liver transplantation, and factor V Leiden and prothrombin G20210A mutations. Novel risk factors include an increased flow volume of portosystemic collateral vessel, thrombopoietin receptor agnonists, and non-selective beta-blockers. In contrast to the traditional perspectives, the abnormalities of procoagulant and anticoagulant factors may not contribute to the development of PVT in liver cirrhosis. Further studies should explore the role of other risk factors, such as antiphospholipid antibodies, methylenetetrahydrofolate reductase C677T gene mutation, hyperhomocysteinemia, and myeloproliferative neoplasms.

Sensorized guidewires with MEMS tri-axial force sensor for minimally invasive surgical applications.

This paper describes the design of a tri-axial microelectromechanical force sensor (FS) that can be mounted on the tip of the guidewire. Piezoresistive silicon nanowires (SiNW) are embedded into a cross cantilever design with a manoeuvrable stylus to allow the detection of force in all directions. The electrical resistance changes in the four SiNWs are used to decode an arbitrary force applied onto the FS. The sensitivity of the device can be improved by two orders of magnitude compared to bulk Si thanks to the giant piezoresistive effects offered by the SiNW. Robustness of the FS is improved due to the novel design by incorporating a mechanical stopper at the tip of the stylus. Finite element analysis (FEM) analysis was used in designing the FS.

KAI1 is a potential target for anti-metastasis in pancreatic cancer cells.

AIM: To investigate whether KAI1, as a metastasis suppressor gene, is associated with invasive and metastatic ability of pancreatic cancer cells. METHODS: KAI1 gene was transfected into pancreatic cancer cell line MiaPaCa II by liposomes selected with G418. Expression of transfected cells was measured by Western blotting, immunofluorescence and immunocytochemistry. Tumor cell invasion and metastatic ability were detected through gelatinase activity and reconstituted basement membrane (Matrigel) assay. pCMV-KAI1 was directly injected into the heterotopic human pancreatic adenocarcinoma successfully established in the groin of BALB/C nude mice, by subcutaneous injection of MiaPaCa II pancreatic cancer cells. The statistical analysis between groups was determined by Student's two tailed t test. RESULTS: By Western blotting, MiaPaCa II cells transfected by KAI1 gene indicated KAI1 expression at approximately 29.1 kDa. Cytoplasm staining was positive and uniformly spread in transfected cancer cells, using immunohistochemistry and immunofluorescence. The most obvious difference was present after 30 h (MiaPaca II 43.6 +/- 9.42, pCMV-MiaPaca II 44.8 +/- 8.56, pCMV-KAI1-MiaPaca II 22.0 +/- 4.69, P < 0.05). Gelatinolysis revealed a wider and clearer band of gelatinolytic activity in non-transfected than in transfected cells (MiaPaCa II cells 30.8 +/- 0.57, transfected cells 28.1 +/- 0.65, P < 0.05). In vivo tumor growth rates of KAI1 transfectants with KAI1-Lipofectamine 1.22 +/- 0.31 in A group were lower than control 4.61 +/- 1.98 and pCMV-KAI 11.67 +/- 0.81. Analyses of metastases with and without KAI1 transfection in mice were different in liver and lung between controls 1.62 +/- 0.39, 0.45 +/- 0.09, pCMV-KAI 1.01 +/- 0.27, 0.33 +/- 0.09 and KAI1-Lipofectamine 0.99 +/- 0.21, 0.30 +/- 0.09 respectively (P < 0.05). CONCLUSION: High expression of KAI1 gene was found in transfected MiaPaCa II human pancreatic cancer cells with lower metastatic ability. KAI1 gene plays an important role in inhibiting metastasis of pancreatic cancer after direct injection into pancreatic adenocarcinoma. These results show that the suppressed invasion and motor function of pancreatic cancer cells may be a key reason why the KAI1 gene controls pancreatic cancer cell metastasis.