Overproduction of nitric oxide inhibits vascular reactivity in portal hypertensive rats

ＯｖｅｒｐｒｏｄｕｃｔｉｏｎｏｆｎｉｔｒｉｃｏｘｉｄｅｉｎｈｉｂｉｔｓｖａｓｃｕｌａｒｒｅａｃｔｉｖｉｔｙｉｎｐｏｒｔａｌｈｙｐｅｒｔｅｎｓｉｖｅｒａｔｓＬＩＸｉＲｕ,ＷＵＪｉｎＳｈｅｎｇ,ＨＥＺｅＳｈｅｎｇ,ＭＡＱｉｎｇＪｉｕａｎｄＧＡＯ...     

Effects of tetrandrine on gastric mucosa and liver in portal hypertensive rats

ＥｆｅｃｔｓｏｆｔｅｔｒａｎｄｒｉｎｅｏｎｇａｓｔｒｉｃｍｕｃｏｓａａｎｄｌｉｖｅｒｉｎｐｏｒｔａｌｈｙｐｅｒｔｅｎｓｉｖｅｒａｔｓＭＵＹｉ，ＳＨＥＮＹａｏＺｏｎｇａｎｄＣＨＵＹｉＦａｎｇＳｕｂｊｅｃｔｈｅａｄｉｎｇｓｌｉｖｅｒｇａｓｔｒｉｃｍ...     

Osteopontin: A non-invasive parameter of portal hypertension and prognostic marker of cirrhosis

AIM: To investigate the relationship between osteopontin plasma concentrations and the severity of portal hypertension and to assess osteopontin prognostic value.METHODS: A cohort of 154 patients with confirmed liver cirrhosis(112 ethylic, 108 men, age 34-72 years)were enrolled in the study. Hepatic venous pressure gradient(HVPG) measurement and laboratory and ultrasound examinations were carried out for all patients. HVPG was measured using a standard catheterization method with the balloon wedge technique. Osteopontin was measured using the enzyme-linked immunosorbent assay(ELISA) method in plasma. Patients were followed up with a specific focus on mortality. The control group consisted of 137 healthy age- and sex- matched individuals.RESULTS: The mean value of HVPG was 16.18 ± 5.6 mm Hg. Compared to controls, the plasma levels of osteopontin in cirrhotic patients were significantly higher(P 0.001). The plasma levels of osteopontin were positively related to HVPG(P = 0.0022, r = 0.25) and differed among the individual Child-Pugh groups of patients. The cut-off value of 80 ng/m L osteopontin distinguished patients with significant portal hypertension(HVPG above 10 mm Hg) at 75% sensitivity and 63% specificity. The mean follow-up of patients was 3.7 ± 2.6 years. The probability of cumulative survival was 39% for patients with HVPG 10 mm Hg and 65% for those with HVPG ≤ 10 mm Hg(P = 0.0086, odds ratio(OR), 2.92, 95% confidence interval(CI): 1.09-7.76). Osteopontin showed a similar prognostic value to HVPG. Patients with osteopontin values above 80 ng/m L had significantly lower cumulative survival compared to those with osteopontin ≤ 80 ng/m L(37% vs 56%, P = 0.00035; OR = 2.23, 95%CI: 1.06-4.68).CONCLUSION: Osteopontin is a non-invasive parameter of portal hypertension that distinguishes patients with clinically significant portal hypertension. It is a strong prognostic factor for survival.     

Should temporary extracorporeal continuous portal diversion replace meso/porta-caval shunts in “small-for-size” syndrome in porcine hepatectomy?

AIM:To investigate the feasibility of temporary extracorporeal continuous porta-caval diversion(ECPD) to relieve portal hyperperfusion in "small-for-size" syndrome following massive hepatectomy in pigs.METHODS:Fourteen pigs underwent 85%-90% liver resection and were then randomly divided into thecontrol group(n = 7) and diversion group(n = 7).In the diversion group,portal venous blood was aspirated through the portal catheter and into a tube connected to a centrifugal pump.After filtration,the blood was returned to the pig through a double-lumen catheter inserted into the internal jugular or subclavian vein.With the conversion pump,portal venous inflow was partially diverted to the inferior vena cava through a catheter inserted via the gastroduodenal vein at 100-130 m L/min.Portal hemodynamics,injury,and regeneration in the liver remnant were compared between the two groups.RESULTS:Compared to the control group,porta-caval diversion via ECPD significantly mitigated excessive portal venous flow and portal vein pressure(PVP); the portal vein flow(PVF),hepatic artery flow(HAF),and PVP in the two groups were not significantly different at baseline; however,the PVF(431.8 ± 36.6 vs 238.8 ± 29.3,P 0.01; 210.3 ± 23.4 vs 122.3 ± 20.6,P 0.01) and PVP(13.8 ± 2.6 vs 8.7 ± 1.4,P 0.01; 15.6 ± 2.1 vs 10.1 ± 1.3,P 0.05) in the control group were significantly higher than those in the diversion group,respectively.The HAF in the control group was significantly lower than that in the diversion group at 2 h and 48 h post hepatectomy,and ECPD significantly attenuated injury to the sinusoidal lining and hepatocytes,increased the regeneration index of the liver remnant,and relieved damage that the liver remnant suffered due to endotoxin and bacterial translocation.CONCLUSION:ECPD,which can dynamically modulate portal inflow,can reduce injury to the liver remnant and facilitate liver regeneration,and therefore should replace permanent meso/porta-caval shunts in "smallfor-size" syndrome.     

Excisional hemorrhoidal surgery and its effect on anal continence

AIM: To investigate the role of anal cushions in hemorrhoidectomy and its effect on anal continence of the patients.METHODS: Seventy-six consecutive patients (33 men and 43 women) with a mean age of 44 years were included. They underwent Milligan-Morgan hemorrhoidectomy because of symptomatic third- and fourth-degree hemorrhoids and failure in conservative treatment for years. Wexner score was recorded and liquid continence test was performed for each patient before and two months after operation using the techniques described in our previous work. The speed-constant rectal lavage apparatus was prepared in our laboratory. The device could output a pulsed and speed-constant saline stream with a high pressure, which is capable of overcoming any rectal resistance change. The patients were divided into three groups, group A (< 900 mL), group B (900-1200 mL) and group C (> 1200 mL) according to the results of the preoperative liquid continence test.RESULTS: All the patients completed the study. The average number of hemorrhoidal masses excised was 2.4. Most patients presented with hemorrhoidal symptoms for more than one year, including a mean duration of incontinence of 5.2 years. The most common symptoms before surgery were anal bleeding (n = 55), prolapsed lesion (n = 34), anal pain (n = 12) and constipation (n = 17). There were grade III hemorrhoids in 39 (51.3%) patients, and grade IV in 37 (48.7%) patients according to Goligher classification. Five patients had experienced hemorrhoid surgery at least once. Compared with postoperative results, the retained volume in the preoperative liquid continence test was higher in 40 patients, lower in 27 patients, and similar in the other 9 patients. The overall preoperative retained volume in the liquid continence test was 1130.61 ± 78.35 mL, and postoperative volume was slightly decreased (991.27 ± 42.77 mL), but there was no significant difference (P = 0.057). Difference was significant in the test value before and after hemorrhoidectomy in group A (858.24 ± 32.01 mL vs 574.18 ± 60.28 mL, P = 0.011), but no obvious difference was noted in group B or group C. There was no significant difference in Wexner score before and after operation (1.68 ± 0.13 vs 2.10 ± 0.17, P = 0.064). By further stratified analysis, there was significant difference before and 2 months after operation in group A (2.71 ± 0.30 vs 3.58 ± 0.40, P = 0.003). In contrast, there were no significant differences in group B or group C (1.89 ± 0.15 vs 2.11 ± 0.19, P = 0.179; 0.98 ± 0.11 vs 1.34 ± 0.19, P = 0.123).CONCLUSION: There is no difference in the continence status of patients before and after Milligan-Morgan hemorrhoidectomy. However, patients with preoperative compromised continence may have further deterioration of their continence, hence Milligan-Morgan hemorrhoidectomy should be avoided in such patients.     

Appropriate treatment strategies improve survival of hepatocellular carcinoma patients with portal vein tumor thrombus

AIM:To evaluate the survival benefits of different treatment strategies for hepatocellular carcinoma(HCC)patients with portal vein tumor thrombus(PVTT)and to determine the prognosis factors.METHODS:Between 2007 and 2009,338 HCC patients treated for PVTT were retrospectively studied.The patients were divided into 4 groups that underwent different treatments:the conservative treatment group(n=75),the transarterial chemoembolization(TACE)group(n=86),the hepatic resection group(n=90),and the hepatic resection associated with postoperative TACE group(n=87).Survival rates were determined using the Kaplan-Meier method and differences between the groups were identified through log-rankanalysis.Cox’s proportional hazard model was used to identify the risk factors for survival.RESULTS:The mean survival periods for patients in the conservative treatment,TACE,hepatic resection and hepatic resection associated with postoperative TACE groups were 3.8,7,8.2 and 15.1 mo,respectively.Significant differences were observed in the survival rates.For the surgical resection associated with postoperative TACE group,the survival rates after 1,2 and3 years were 49%,37%and 19%,respectively.These results were significantly higher than those of the other groups(P<0.05).Meanwhile,the 1,2 and 3 year survival rates for the surgical resection group were 28%,20%and 15%,whereas those for the TACE group were17.5%,0%and 0%,respectively.These values significantly increased after hepatic resection compared with those after TACE(P<0.05).CONCLUSION:Surgical resection is the most effective therapeutic strategy for HCC patients with PVTT and results in high hepatic functional reserve.For patients who can tolerate the procedure,postoperative TACE is necessary to prevent recurrence and prolong the survival period.     

Clinical observations on the treatment of prolapsing hemorrhoids with tissue selecting therapy

AIM:To compare the effects and postoperative complications between tissue selecting therapy stapler(TST)and Milligan-Morgan hemorrhoidectomy(M-M).METHODS:Four hundred and eighty patients with severe prolapsing hemorrhoids,who were admitted to the Shenyang Coloproctology Hospital between 2009and 2012,were randomly divided into observation(n=240)and control(n=240)groups.Hemorrhoidectomies were performed with TST in the observation group and with the M-M technique in the control group.The therapeutic effects,operation security,and postoperative complications in the two groups were compared.The immediate and long-term complications were assessed according to corresponding criteria.Pain was assessed on a visual analogue scale.The efficacy was assessed by specialized criteria.The follow-up was conducted one year after the operation.RESULTS:The total effective rates of the observation and control groups were 99.5%(217/218)and 98.6%(218/221)respectively;the difference was not statistically significant(P=0.322).Their were significant differences between observation and control groups in intraoperative blood loss(5.07±1.14 vs 2.45±0.57,P=0.000),pain(12 h after the surgery:5.08±1.62 vs 7.19±2.01,P=0.000;at first dressing change:2.64±0.87 vs 4.34±1.15,P=0.000;first defecation:3.91±1.47 vs 5.63±1.98,P=0.001),urine retention(n=22 vs n=47,P=0.001),anal pendant expansion after the surgery(2.35±0.56 vs 5.16±1.42,P=0.000),operation time(18.3±5.6 min vs 29.5±8.2 min,P=0.000),and the length of hospital stay(5.3±0.6 d vs 11.4±1.8 d,P=0.000).Moreover TST showed significant reductions compared to M-M in the rates of long-term complications such as fecal incontinence(n=3 vs n=16,P=0.003),difficult bowel movement(n=1 vs n=9,P=0.011),intractable pain(n=2 vs n=12,P=0.007),and anal discharge(n=3 vs n=23,P=0.000).CONCLUSION:TST for severe prolapsing hemorrhoids is a satisfactory technique for more rapid recovery,lower complication rates,and higher operation security.     

Effect of interferon-γ and tumor necrosis factor-α on hepatitis B virus following lamivudine treatment

AIM: To evaluate anti-hepatitis B virus (HBV) activity and cytotoxicity of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) following lamivudine treatment of HepG2.2.15 cells.METHODS: HepG2.2.15 cells were treated with 2 μmol/L lamivudine for 16 d (lamivudine group), cultured for 10 d, followed by 5 ng/mL TNF-α and 1000 U/mL IFN-γ for 6 d (cytokine group), or treated with 2 μmol/L lamivudine for 10 d followed by 5 ng/mL TNF-α and 1000 U/mL IFN-γ for 6 d (sequential group), or cultured without additions for 16 d (control group). Intracellular DNA was extracted from 3 × 10⁵ HepG2.2.15 cells from each group. The extracted DNA was further purified with mung bean nuclease to remove HBV relaxed circular DNA that may have remained. Both HBV covalently closed circular DNA (cccDNA) and HBV DNA were examined with real-time polymerase chain reaction. The titers of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were quantified with enzyme-linked immunosorbent assay. Cell viability was measured with the cell counting kit-8 assay.RESULTS: Compared to lamivudine alone (22.63% ± 0.12%), both sequential (51.50% ± 0.17%, P = 0.034) and cytokine treatment (49.66% ± 0.06%, P = 0.041) showed a stronger inhibition of HBV cccDNA; the difference between the sequential and cytokine groups was not statistically significant (51.50% ± 0.17% vs 49.66% ± 0.06%, P = 0.88). The sequential group showed less inhibition of HBV DNA replication than the lamivudine group (67.47% ± 0.02% vs 82.48% ± 0.05%, P = 0.014); the difference between the sequential and cytokine groups was not statistically significant (67.47% ± 0.02% vs 57.45% ± 0.07%, P = 0.071). The levels of HBsAg and HBeAg were significantly decreased in the sequential treatment group compared to the other groups [HBsAg: 3.48 ± 0.04 (control), 3.09 ± 0.08 (lamivudine), 2.55 ± 0.13 (cytokine), 2.32 ± 0.08 (sequential), P = 0.042 for each between-group comparison; HBeAg: 3.48 ± 0.01 (control), 3.08 ± 0.08 (lamivudine), 2.57 ± 0.15 (cytokine), 2.34 ± 0.12 (sequential), P = 0.048 for each between-group comparison]. Cell viability in the cytokine group was reduced to 58.03% ± 8.03% compared with control cells (58.03% ± 8.03% vs 100%, P = 0.000). Lamivudine pretreatment significantly reduced IFN-γ + TNF-α-mediated toxicity of HepG2.2.15 cells [85.82% ± 5.43% (sequential) vs 58.03% ± 8.03% (cytokine), P = 0.002].CONCLUSION: Sequential treatment overcame the lower ability of lamivudine alone to inhibit cccDNA and precluded the aggressive cytotoxicity involving IFN-γ and TNF-α by decreasing the viral load.     

Post-hepatectomy survival in advanced hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To analyze hepatocellular carcinoma(HCC) patients with portal vein tumor thrombosis(PVTT) using the tumor-node-metastasis(TNM) staging system.METHODS: We retrospectively analyzed 372 patients with HCC who underwent hepatectomy between 1980 and 2009.We studied the outcomes of HCC patients with PVTT to evaluate the American Joint Committee on Cancer TNM staging system(7th edition) for stratifying and predicting the prognosis of a large cohort of HCC patients after hepatectomy in a single-center.Portal vein invasion(vp) 1 was defined as an invasion or tumor thrombus distal to the second branch of the portal vein,vp2 as an invasion or tumor thrombus in the second branch of the portal vein,vp3 as an invasion or tumor thrombus in the first branch of the portal vein,and vp4 as an invasion or tumor thrombus in the portal trunk or extending to a branch on the contralateral side.RESULTS: The cumulative 5-year overall survival(5yr OS) and 5-year disease-free survival(5yr DFS) rates of the 372 patients were 58.3% and 31.3%,respectively.The 5yr DFS and 5yr OS of vp3-4 patients(n = 10) were 20.0%,and 30.0%,respectively,which was comparable with the corresponding survival rates of vp1-2 patients(P = 0.466 and 0.586,respectively).In the subgroup analysis of patients with macroscopic PVTT(vp2-4),the OS of the patients who underwent preoperative transarterial chemoembolization was comparable to that of patients who did not(P = 0.747).There was a significant difference in the DFS between patients with stage Ⅰ HCC and those with stage Ⅱ HCC(5yr DFS 39.2% vs 23.1%,P 0.001); however,theDFS for stage Ⅱ was similar to that for stage Ⅲ(5yrD FS 23.1% vs 13.8%,P = 0.330).In the subgroup analysis of stage Ⅱ-Ⅲ HCC(n = 148),only alpha-fetoprotein(AFP) 100 mg/dL was independently associated with DFS.CONCLUSION: Hepatectomy for vp3-4 HCC results in a survival rate similar to hepatectomy for vp1-2.AFP stratified the stage Ⅱ-Ⅲ HCC patients according to prognosis.     

Laparoscopic vs open extended right hemicolectomy for colon cancer

AIM:To evaluate the feasibility,safety,and oncologic outcomes of laparoscopic extended right hemicolectomy(LERH)for colon cancer.METHODS:Since its establishment in 2009,the Southern Chinese Laparoscopic Colorectal Surgical Study(SCLCSS)group has been dedicated to promoting patients’quality of life through minimally invasive surgery.The multicenter database was launched by combining existing datasets from members of the SCLCSS group.The study enrolled 220 consecutive patients who were recorded in the multicenter retrospective database and underwent either LERH(n=119)or open extended right hemicolectomy(OERH)(n=101)for colon cancer.Clinical characteristics,surgical outcomes,and oncologic outcomes were compared between the two groups.RESULTS:There were no significant differences in terms of age,gender,body mass index(BMI),history of previous abdominal surgery,tumor location,and tumor stage between the two groups.The blood loss was lower in the LERH group than in the OERH group[100(100-200)mL vs 150(100-200)mL,P<0.0001].The LERH group was associated with earlier first flatus(2.7±1.0 d vs 3.2±0.9 d,P<0.0001)and resumption of liquid diet(3.6±1.0 d vs 4.2±1.0 d,P<0.0001)compared to the OERH group.The postoperative hospital stay was significantly shorter in the LERH group(11.4±4.7 d vs 12.8±5.6 d,P=0.009)than in the OERH group.The complication rate was 11.8%and17.6%in the LERH and OERH groups,respectively(P=0.215).Both 3-year overall survival[LERH(92.0%)vs OERH(84.4%),P=0.209]and 3-year disease-free survival[LERH(84.6%)vs OERH(76.6%),P=0.191]were comparable between the two groups.CONCLUSION:LERH with D3 lymphadenectomy for colon cancer is a technically feasible and safe procedure,yielding comparable short-term oncologic outcomes to those of open surgery.     

Curcumin prevents indomethacin-induced gastropathy in rats

AIM: To investigate the effects of curcumin on gastric microcirculation and inflammation in rats with indomethacin-induced gastric damage.METHODS: Male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control group, n = 5) was fed with olive oil and 5% NaHCO₃^- (vehicle). Group 2 [indomethacin (IMN) group, n = 5] was fed with olive oil 30 min prior to indomethacin 150 mg/kg body weight (BW) dissolved in 5% NaHCO₃^- at time 0th and 4th h. Group 3 (IMN + Cur group, n = 4) was fed with curcumin 200 mg/kg BW dissolved in olive oil 0.5 mL, 30 min prior to indomethacin at 0th and 4th h. Leukocyte-endothelium interactions at postcapillary venules were recorded after acridine orange injection. Blood samples were determined for intercellular adhesion molecule (ICAM)-1 and tumor necrosis factor (TNF)-α levels using enzyme linked immunosorbent assay method. Finally, the stomach was removed for histopathological examination for gastric lesions and grading for neutrophil infiltration.RESULTS: In group 2, the leukocyte adherence in postcapillary venules was significantly increased compared to the control group (6.40 ± 2.30 cells/frame vs 1.20 ± 0.83 cells/frame, P = 0.001). Pretreatment with curcumin caused leukocyte adherence to postcapillary venule to decline (3.00 ± 0.81 cells/frame vs 6.40 ± 2.30 cells/frame, P = 0.027). The levels of ICAM-1 and TNF-α increased significantly in the indomethacin-treated group compared with the control group (1106.50 ± 504.22 pg/mL vs 336.93 ± 224.82 pg/mL, P = 0.011 and 230.92 ± 114.47 pg/mL vs 47.13 ± 65.59 pg/mL, P = 0.009 respectively). Pretreatment with curcumin significantly decreased the elevation of ICAM-1 and TNF-α levels compared to treatment with indomethacin alone (413.66 ± 147.74 pg/mL vs 1106.50 ± 504.22 pg/mL, P = 0.019 and 58.27 ± 67.74 pg/mL vs 230.92 ± 114.47 pg/mL, P = 0.013 respectively). The histological appearance of the stomach in the control group was normal. In the indomethacin-treated group, the stomachs showed a mild to moderate neutrophil infiltration score. Gastric lesions were erosive and ulcerative. In rats treated with indomethacin and curcumin, stomach histopathology improved and showed only a mild neutrophil infiltration score and fewer erosive lesions in the gastric mucosa.CONCLUSION: The results indicate that curcumin prevents indomethacin-induced gastropathy through the improvement of gastric microcirculation by attenuating the level of ICAM-1 and TNF-α.     

Influence of histological inflammatory activity on regenerative capacity of liver after percutaneous transhepatic portal vein embolization

Percutaneous transhepatic portal vein embolization (PTPE) produces regenerative hypertrophy in the nonembolized part of the liver, but the regenerative capacity after PTPE in patients with chronic hepatitis is unknown. We studied 34 patients with hepatocellular carcinoma and chronic hepatitis who underwent PTPE at the right portal vein. Hepatic lobular volumes were calculated by computed tomography before and 2 weeks after PTPE. The increase in left lobular volume was analyzed using a stepwise multiple regression method incorporating 11 factors: age; portal venous pressure; proportional volume of the right lobe; indocyanine green retention test; platelet count; serum levels of aspartate transaminase, alanine transaminase, total bilirubin, and albumin; and histological inflammatory grade and stage of fibrosis, according to the criteria of the International Association for the Study of the Liver recommended at their 1994 meeting. The median volume of the left lobe had increased from 405 to 554 cm³ (P < 0.0001) by 2 weeks after PTPE. Inflammatory grade was the only independent factor predicting regenerative hypertrophy (regeneration ratio (%) = 80.3 − 20.1 × grade; standard correlation coefficient = −0.566; P = 0.0014). Histological inflammatory activity was the essential factor regulating liver regeneration after PTPE in patients with chronic hepatitis. (Received May 14, 1998; accepted Aug. 28, 1998)     

肝硬化脾切除术后门静脉系统血栓形成的危险因素分析*

目的 分析影响肝硬化患者脾切除术后门静脉系统血栓形成（PVT）的危险因素。方法 2015年1月~2018年6月我院收治的肝硬化患者94例,接受脾切除联合食管下段周围曲张血管离断术,使用彩色多普勒超声检查门静脉系统。采用多因素Logistic回归分析影响术后PVT形成的危险因素。结果 术后1个月随访,经彩色多普勒超声检查,发现PVT形成30例,未发生PVT患者64例;PVT组有腹水者为56.7%,显著高于无PVT组的32.8%（P<0.05）,脾脏厚度为（75.8±9.4） mm,显著大于无PVT组【（69.1±8.8） mm,P<0.05】,脾脏体积为（141.7±18.1） mm2,显著大于无PVT组【（126.8±17.2） mm2,P<0.05】,门静脉内径为（16.2±2.1） mm,显著大于无PVT组【（14.1±1.9） mm,P<0.05】,门静脉血流流速为（12.2±1.5） cm/s,显著慢于无PVT组【（14.6±1.6） cm/s,P<0.05】;应用低分子右旋糖苷或低分子肝素抗凝干预患者所占比例显著低于无PVT组（P<0.05）;Logistic回归分析显示,未应用抗凝治疗（OR=0.503,P=0.023）、门静脉流速减慢（OR=0.491,P=0.014）、脾脏体积增加（OR=1.872,P=0.044）和门静脉内径增宽（OR=1.982,P=0.021）是肝硬化脾切除术患者术后PVT形成的独立危险因素。结论 肝硬化脾切除术患者术后可能存在PVT形成,了解一些危险因素并给予积极的干预可能减少PVT形成的发生,使患者获益。     

Prognostic factors in non-malignant and non-cirrhotic patients with portal cavernoma: An 8-year retrospective single-center study

AIM:To evaluate the outcome of non-malignant and non-cirrhotic patients with portal cavernoma and to determine the predictors for survival.METHODS:Between July 2002 and June 2010,we retrospectively enrolled all consecutive patients admitted to our department with a diagnosis of portal cavernoma without abdominal malignancy or liver cirrhosis.The primary endpoint of this observational study was death and cause of death.Independent predictors of survival were identified using the Cox regression model.RESULTS:A total of 64 patients were enrolled in the study.During a mean follow-up period of 18±2.41mo,7 patients died.Causes of death were pulmonary embolism(n=1),acute leukemia(n=1),massive esophageal variceal hemorrhage(n=1),progressive liver failure(n=2),severe systemic infection secondary to multiple liver abscesses(n=1)and accident(n=1).The cumulative 6-,12-and 36-mo survival rates were 94.9%,86%and 86%,respectively.Multivariate Cox regression analysis demonstrated that the presence of ascites(HR=10.729,95%CI:1.209-95.183,P=0.033)and elevated white blood cell count(HR=1.072,95%CI:1.014-1.133,P=0.015)were independent prognostic factors of non-malignant and non-cirrhotic patients with portal cavernoma.The cumulative 6-,12-and 36-mo survival rates were significantly different between patients with and without ascites(90%,61.5%and 61.5%vs 97.3%,97.3%and 97.3%,respectively,P=0.0008).CONCLUSION:The presence of ascites and elevated white blood cell count were significantly associated with poor prognosis in non-malignant and non-cirrhotic patients with portal cavernoma.     

Murine study of portal hypertension associated endothelin-1 hypo-response

AIM:To investigate endothelin-1 hypo-responsive associated with portal hypertension in order to improve patient treatment outcomes.METHODS:Wild type,e NOS-/-and i NOS-/-mice receivedpartial portal vein ligation surgery to induce portal hypertension or sham surgery.Development of portal hypertension was determined by measuring the splenic pulp pressure,abdominal aortic flow and portal systemic shunting.To measure splenic pulp pressure,a microtip pressure transducer was inserted into the spleen pulp.Abdominal aortic flow was measured by placing an ultrasonic Doppler flow probe around the abdominal aorta between the diaphragm and celiac artery.Portal systemic shunting was calculated by injection of fluorescent microspheres in to the splenic vein and determining the percentage accumulation of spheres in liver and pulmonary beds.Endothelin-1 hypo-response was evaluated by measuring the change in abdominal aortic flow in response to endothelin-1 intravenous administration.In addition,thoracic aorta endothelin-1contraction was measured in 5 mm isolated thoracic aorta rings ex-vivo using an ADI small vessel myograph.RESULTS:In wild type and i NOS-/-mice splenic pulp pressure increased from 7.5±1.1 mm Hg and 7.2±1 mm Hg to 25.4±3.1 mm Hg and 22±4 mm Hg respectively.In e NOS-/-mice splenic pulp pressure was increased after 1 d(P=NS),after which it decreased and by 7 d was not significantly elevated when compared to 7 d sham operated controls(6.9±0.6 mm Hg and 7.3±0.8 mm Hg respectively,P=0.3).Abdominal aortic flow was increased by 80%and 73%in 7 d portal vein ligated wild type and i NOS when compared to shams,whereas there was no significant difference in 7 d portal vein ligated e NOS-/-mice when compared to shams.Endothelin-1 induced a rapid reduction in abdominal aortic blood flow in wild type,e NOS-/-and i NOS-/-sham mice(50%±8%,73%±9%and 47%±9%respectively).Following portal vein ligation endothelin-1 reduction in blood flow was significantly diminished in each mouse group.Abdominal aortic flow was reduced by 19%±9%,32%±10%and 9%±9%in wild type,e NOS-/-and i NOS-/-mice respectively.CONCLUSION:Aberrant endothelin-1 response in murine portal hypertension is NOS isoform independent.Moreover,portal hypertension in the portal vein ligation model is independent of ET-1 function.     

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To evaluate the prognostic factors and efficacy of hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis. METHODS: Fifty hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) were treated using hepatic arterial infusion chemotherapy (HAIC) via a subcutaneously implanted port. The epirubicin-cisplatin-5-fluorouracil (ECF) chemotherapeutic regimen consisted of 35 mg/m 2 epirubicin on day 1, 60 mg/m 2 cisplatin for 2 h on day 2, and 500 mg/m 2 5-fluorouracil for 5 h on days 1-3. The treatments were repeated every 3 or 4 wk. RESULTS: Three (6%) of the 50 patients achieved a complete response (CR), 13 (26%) showed partial responses (PR), and 22 (44%) had stable disease (SD).The median survival and time to progression were 7 and 2 mo, respectively. After 2 cycles of HAIC, CR was achieved in 1 patient (2%), PR in 10 patients (20%) and SD in 26 patients (52%). Significant pre-treatment prognostic factors were a tumor volume of < 400 cm 3 (P = 0.01) and normal levels of protein induced by vitamin K absence or antagonist (PIVKA)-Ⅱ (P = 0.022). After 2 cycles of treatment, disease control (CR + PR + SD) (P = 0.001), PVTT response (P = 0.003) and α-fetoprotein reduction of over 50% (P = 0.02) were independent factors for survival. Objective response (CR + PR), disease control, PVTT response, and combination therapy during the HAIC were also significant prognostic factors. Adverse events were tolerable and successfully managed. CONCLUSION: HAIC may be an effective treatment modality for advanced HCC with PVTT in patients with tumors < 400 cm 3 and good prognostic factors.     

Chronic bile duct hyperplasia is a chronic graft dysfunction following liver transplantation

AIM: To investigate pathological types and influential factors of chronic graft dysfunction (CGD) following liver transplantation (LT) in rats.METHODS: The whole experiment was divided into three groups: (1) normal group (n = 12): normal BN rats without any drug or operation; (2) syngeneic transplant group (SGT of BN-BN, n = 12): both donors and recipients were BN rats; and (3) allogeneic transplant group (AGT of LEW-BN, n = 12): Donors were Lewis and recipients were BN rats. In the AGT group, all recipients were subcutaneously injected by Cyclosporin A after LT. Survival time was observed for 1 year. All the dying rats were sampled, biliary tract tissues were performed bacterial culture and liver tissues for histological study. Twenty-one day after LT, 8 rats were selected randomly in each group for sampling. Blood samples from caudal veins were collected for measurements of plasma endotoxin, cytokines and metabonomic analysis, and faeces were analyzed for intestinal microflora.RESULTS: During the surgery of LT, no complications of blood vessels or bile duct happened, and all rats in each group were still alive in the next 2 wk. The long term observation revealed that a total of 8 rats in the SGT and AGT groups died of hepatic graft diseases, 5 rats in which died of chronic bile duct hyperplasia. Compared to the SGT and normal groups, survival ratio of rats significantly decreased in the AGT group (P < 0.01). Moreover, liver necrosis, liver infection, and severe chronic bile duct hyperplasia were observed in the AGT group by H and E stain. On 21 d after LT, compared with the normal group (25.38 ± 7.09 ng/L) and SGT group (33.12 ± 10.26 ng/L), plasma endotoxin in the AGT group was remarkably increased (142.86 ± 30.85 ng/L) (both P < 0.01). Plasma tumor necrosis factor-α and interleukin-6 were also significantly elevated in the AGT group (593.6 ± 171.67 pg/mL, 323.8 ± 68.30 pg/mL) vs the normal (225.5 ± 72.07 pg/mL, 114.6 ± 36.67 pg/mL) and SGT groups (321.3 ± 88.47 pg/mL, 205.2 ± 53.06 pg/mL) (P < 0.01). Furthermore, Bacterial cultures of bile duct tissues revealed that the rats close to death from the SGT and AGT groups were strongly positive, while those from the normal group were negative. The analysis of intestinal microflora was performed. Compared to the normal group (7.98 ± 0.92, 8.90 ± 1.44) and SGT group (8.51 ± 0.46, 9.43 ± 0.69), the numbers of Enterococcus and Enterobacteria in the AGT group (8.76 ± 1.93, 10.18 ± 1.64) were significantly increased (both P < 0.01). Meanwhile, compared to the normal group (9.62 ± 1.60, 9.93 ± 1.10) and SGT group (8.95 ± 0.04, 9.02 ± 1.14), the numbers of Bifidobacterium and Lactobacillus in the AGT group (7.83 ± 0.72, 8.87 ± 0.13) were remarkably reduced (both P < 0.01). In addition, metabonomics analysis showed that metabolic profiles of plasma in rats in the AGT group were severe deviated from the normal and SGT groups.CONCLUSION: Chronic bile duct hyperplasia is a pathological type of CGD following LT in rats. The mechanism of this kind of CGD is associated with the alterations of inflammation, intestinal barrier function and microflora as well as plasma metabolic profiles.     

Effectiveness of Saccharomyces boulardii in a rat model of colitis

AIM: To investigate the effects of Saccharomyces boulardii (S. boulardii) in an experimental rat model of trinitrobenzene sulfonic acid (TNBS)-induced colitis.METHODS: Thirty-two Wistar albino female rats were categorized into five groups. On the first day of the study, 50 mg TNBS was administered via a rectal catheter in order to induce colitis in all rats, except those in the control group. For 14 d, the rats were fed a standard diet, without the administration of any additional supplements to either the control or TNBS groups, in addition to 1 mg/kg per day S. boulardii to the S. boulardii group, 1 mg/kg per day methyl prednisolone (MP) to the MP group. The animals in the S. boulardii + MP group were coadministered these doses of S. boulardii and MP. During the study, weight loss, stool consistency, and the presence of obvious blood in the stool were evaluated, and the disease activity index (DAI) for colitis was recorded. The intestines were examined and colitis was macro- and microscopically scored. The serum and tissue levels of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) were determined, and fungemia was evaluated in the blood samples.RESULTS: The mean DAI scores for the MP and S. boulardii + MP groups was significantly lower than the TNBS group (3.69 ± 0.61 vs 4.46 ± 0.34, P = 0.018 and 3.77 ± 0.73 vs 4.46 ± 0.34, P = 0.025, respectively). While no significant differences between the TNBS and the S. boulardii or MP groups could be determined in terms of serum NO levels, the level of serum NO in the S. boulardii + MP group was significantly higher than in the TNBS and S. boulardii groups (8.12 ± 4.25 μmol/L vs 3.18 ± 1.19 μmol/L, P = 0.013; 8.12 ± 4.25 μmol/L vs 3.47 ± 1.66 μmol/L, P = 0.012, respectively). The tissue NO levels in the S. boulardii, MP and S. boulardii + MP groups were significantly lower than the TNBS group (16.62 ± 2.27 μmol/L vs 29.72 ± 6.10 μmol/L, P = 0.002; 14.66 ± 5.18 μmol/L vs 29.72 ± 6.10 μmol/L, P = 0.003; 11.95 ± 2.34 μmol/L vs 29.72 ± 6.10 μmol/L, P = 0.002, respectively). The tissue NO levels in the S. boulardii, MP and S. boulardii + MP groups were similar. The mean serum and tissue TNF-α levels were determined to be 12.97 ± 18.90 pg/mL and 21.75 ± 15.04 pg/mL in the control group, 18.25 ± 15.44 pg/mL and 25.27 ± 11.95 pg/mL in the TNBS group, 20.59 ± 16.15 pg/mL and 24.39 ± 13.06 pg/mL in the S. boulardii group, 9.05 ± 5.13 pg/mL and 24.46 ± 10.85 pg/mL in the MP group, and 13.95 ± 10.17 pg/mL and 24.26 ± 10.37 pg/mL in the S. boulardii + MP group. Significant differences in terms of the levels of serum and tissue TNF-α and the macroscopic and microscopic scores were not found between the groups. S. boulardii fungemia was not observed in any of the rats. However, Candida fungemia was detected in one rat (14%) in the TNBS group, two rats (28%) in the S. boulardii group, three rats (50%) in the MP group, and three rats (42%) in S. boulardii + MP group.CONCLUSION: S. boulardii does not demonstrate considerable effects on the DAI, pathological scores, or cytokine levels but does decrease the tissue NO levels.     

p53 antibodies, metallothioneins, and oxidative stress markers in chronic ulcerative colitis with dysplasia

AIM:To investigate the role of p53 antibodies (p53Abs),metallothioneins (MTs) and oxidative stress markers in the early detection of dysplasia in chronic ulcerative colitis (UC).METHODS:The study included 30 UC patients,15 without dysplasia (group Ⅱ) and 15 with dysplasia (group Ⅲ),in addition to 15 healthy volunteers (group Ⅰ,control subjects).The enzyme-linked immunosorbent assay technique was used to measure serum p53Abs and MTs,while advanced oxidation protein products (AOPPs),and reduced glutathione (G...     

Clinical efficacy of antiviral therapy in patients with hepatitis B-related cirrhosis after transjugular intrahepatic portosystemic shunt

BACKGROUNDAs a country with a high burden of hepatitis B, China has about 86 million cases of hepatitis B virus infection, ranking the first in the world. Currently, there are about 390000 deaths due to hepatitis B-related complications such as liver cirrhosis and liver cancer every year. Consequently, how to control portal hypertension, improve liver functional reserve, and reduce the incidence of hepatic failure and liver cancer in such patients is the focus of current clinical attention. Previous clinical study in our center suggested that at 24 mo after transjugular intrahepatic portosystemic shunt (TIPS), the liver functional reserve of patients with hepatitis B cirrhosis was better than that of patients with alcohol-induced and immune cirrhosis, which may be related to the effective etiological treatment.AIMTo investigate the clinical efficacy of three first-line antiviral drugs recommended by the guidelines of prevention and treatment for chronic hepatitis B in China (2019) in the treatment of patients with hepatitis B-related cirrhosis who had received a TIPS.METHODSThe clinical data of 137 patients with hepatitis B-related cirrhosis with portal hypertension after receiving TIPS at our centre between March 2016 and December 2020 were analysed retrospectively. According to different anti-viral drugs, the patients were divided into entecavir (ETV) (n = 70), tenofovir alafenamide fumarate (TAF) (n = 32), and tenofovir disoproxil fumarate (TDF) (n = 35) groups. The cumulative incidence of hepatic encephalopathy and hepatocellular carcinoma, survival, and changes in hepatic reserve function and glomerular filtration rate in patients treated with different antiviral drugs within 24 mo after surgery were investigated.RESULTSAt 24 mo after surgery, the Child–Pugh score in the TAF group (6.97 ± 0.86) was lower than that in the TDF (7.49 ± 0.82; t = -2.52, P = 0.014) and ETV groups (7.64 ± 1.17; t = -2.92, P = 0.004). The model for end-stage liver disease score in the TAF group at 24 mo after surgery was 9.72 ± 1.5, which was lower than that in the TDF (10.74 ± 2.33; t = -2.09, P = 0.040) and ETV groups (10.97 ± 2.17; t = -2.93, P = 0.004). At 24 mo after surgery, the estimated glomerular filtration rate (eGFR) in the TAF group (104.41 ± 12.54) was higher than that in the TDF (93.54 ± 8.97) and ETV groups (89.96 ± 9.86) (F = 21.57, P < 0.001).CONCLUSIONAt 24 mo after surgery, compared with TDF and ETV, TAF has significant advantages in the improvement of liver functional reserve and eGFR.