Effects of Nigella sativa on outcome of hepatitis C in Egypt

AIM: To evaluate the safety, efficacy and tolerability of Nigella sativa (N. sativa ) in patients with hepatitis C not eligible for interferon (IFN)-α. METHODS: Thirty patients with hepatitis C virus (HCV) infection, who were not eligible for IFN/ribavirin therapy, were included in the present study. Inclusion criteria included: patients with HCV with or without cirrhosis, who had a contraindication to IFN-α therapy, or had refused or had a financial constraint to IFN-α therapy. Exclusion criteria included: patients on IFN-α therapy, infection with hepatitis B or hepatitis Ⅰ virus, hepatocellular carcinoma, other malignancies, major severe illness, or treatment non-compliance. Various parameters, including clinical parameters, complete blood count, liver function, renal function, plasma glucose, total antioxidant capacity (TAC), and polymerase chain reaction, were all assessed at baseline and at the end of the study. Clinical assessment included: hepato and/ or splenomegaly, jaundice, palmar erythema, flapping tremors, spider naevi, lower-limb edema, and ascites. N. sativa was administered for three successive months at a dose of (450 mg three times daily). Clinical response and incidence of adverse drug reactions were assessed initially, periodically, and at the end of the study. RESULTS: N. sativa administration significantly improved HCV viral load (380808.7 ± 610937 vs 147028.2 ± 475225.6, P = 0.001) and TAC (1.35 ± 0.5 vs 1.612 ± 0.56, P = 0.001). After N. sativa administration, the following laboratory parameters improved: total protein (7.1 ± 0.7 vs 7.5 ± 0.8, P = 0.001), albumin (3.5 ± 0.87 vs 3.69 ± 0.91, P = 0.008), red blood cell count (4.13 ± 0.9 vs 4.3 ± 0.9, P = 0.001), and platelet count (167.7 ± 91.2 vs 198.5 ± 103, P = 0.004). Fasting blood glucose (104.03 ± 43.42 vs 92.1 ± 31.34, P = 0.001) and postprandial blood glucose (143.67 ± 72.56 vs 112.1 ± 42.9, P = 0.001) were significantly decreased in both diabetic and non-diabetic HCV patients. Patients with lower-limb edema de     

Increased international normalized ratio level in hepatocellular carcinoma patients with diabetes mellitus

AIM: To determine the association of diabetes mellitus (DM) and international normalized ratio (INR) level in hepatocellular carcinoma (HCC) patients. METHODS: Our present study included 375 HCC patients who were treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period from January 2003 to April 2012, and with a hospital discharge diagnosis of HCC. The demographic, clinical, laboratory, metabolic and instrumental features were analyzed. χ2 test, Student’s t test and Mann-Whitney U test were used to compare the differences between HCC patients with and without DM. Unconditional multivariable logistic regression analysis was used to determine the association of DM and INR level in HCC patients. A sub-group analysis was performed to assess the effect of liver cirrhosis or hepatitis B virus (HBV) infection on the results. The Pearson correlation test was used to determine the relationship between INR level and fasting glucose. In addition, association between diabetes duration, and diabetes treatment and INR level was determined considering the potentially different effects. RESULTS: Of the total, 63 (16.8%) patients were diabetic (diabetic group) and 312 (83.2%) patients were diagnosed without diabetes (non-diabetic group). Their mean age was 56.4 ± 11.0 years and 312 (83.2%) patients were male. Compared with patients without DM, the HCC patients with diabetes were older (59.5 ± 10.3 vs 55.8 ± 11.1, P=0.015), had a lower incidence of HBV infection (79.4% vs 89.1%, P=0.033), had increased levels of systolic blood pressure (SBP) (133 ± 17 vs 129 ± 16 mmHg, P=0.048) and INR (1.31 ± 0.44 vs 1.18 ± 0.21, P=0.001), had lower values of hemoglobin (124.4 ± 23.9 vs 134.2 ± 23.4, P=0.003) and had a platelet count (median/interquartile-range: 113/64-157 vs 139/89-192, P=0.020). There was no statistically significant difference in the percentages of males, overweight or obesity, drinking, smoking, cirrhosis and Child classification. After controlling for the confounding eff     

Long-term outcomes and prognostic factors of patients with obstructive colorectal cancer: A multicenter retrospective cohort study

AIM: To investigate the long-term oncologic outcomes and prognostic factors in patients with obstructive colorectal cancer(CRC) at multiple Japanese institutions.METHODS: We identified 362 patients diagnosed with obstructive colorectal cancer from January 1, 2002 to December 31, 2012 in Yokohama Clinical Oncology Group's department of gastroenterological surgery. Among them, 234 patients with stage Ⅱ/Ⅲ disease who had undergone surgical resection of their primary lesions were analyzed, retrospectively. We report the long-term outcomes, the risk factors for recurrence, and the prognostic factors.RESULTS: The five-year disease free survival and cancer-specific survival were 50.6% and 80.3%, respectively. A multivariate analysis showed the ASAPS(HR = 2.23, P = 0.026), serum Albumin ≤ 4.0 g/d L(HR = 2.96, P = 0.007), T4 tumor(HR = 2.73, P = 0.002) and R1 resection(HR = 6.56, P = 0.02) to be independent risk factors for recurrence. Furthermore, poorly differentiated cancers(HR = 6.28, P = 0.009), a T4 tumor(HR = 3.46, P = 0.011) and R1 resection(HR = 6.16, P = 0.006) were independent prognostic factors in patients with obstructive CRC.CONCLUSION: The outcomes of patients with obstructive CRC was poor. T4 tumor and R1 resection were found to be independent prognostic factors for both recurrence and survival in patients with obstructive CRC.     

Centrilobular necrosis in acute presentation of Japanese patients with type 1 autoimmune hepatitis

AIM:To compare clinicopathological features of acute presentation of type 1 autoimmune hepatitis(AIH) with or without centrilobular necrosis(CN).METHODS:Our study comprised 41 patients with biopsy-proven acute presentation(acute exacerbation phase 36,acute hepatitis phase 5) of type 1 AIH at our hospital from 1975 to 2009.Elevated serum alanine aminotransferase(ALT)(> 5x upper limit of normal) identified acute presentation of the disease.We compared clinicopathological features of these AIH patients with or without CN.The data used for analysis included patient background(age,sex,type of disease,presence of complications with other autoimmune diseases,human leukocyte antigen,and International Autoimmune Hepatitis Group score),clinical parameters at presentation(ALT,alkaline phosphatase,IgG,anti-nuclear antibodies,and anti-smooth muscle antibodies),histology and therapy.RESULTS:CN was found in 13(31.7%) patients with acute presentation(acute exacerbation phase 10,acute hepatitis phase 3) of AIH.Serum IgG levels of patients with CN were significantly lower than those of patients without CN(mean:2307 mg/dL vs 3126 mg/dL,P < 0.05),while antinuclear antibody-negative rates were significantly higher(30.7%vs 3.5%,P < 0.05).However,other clinical features were similar between the two groups.The frequency of advanced fibrosis in patients with CN was significantly lower than in patients without CN(F0-2:84.6% vs 35.7%,F3-4:15.4% vs 64.3%,P < 0.05).Other histological features were similar between the two groups.Although there was no significant difference between groups when evaluated using the revised original score(12 vs 14),the simplified AIH score of patients with CN was significantly lower(6 vs 7,P < 0.05).Frequency of DR4 was similar between patients with and without CN.CONCLUSION:CN is observed in both Japanese patients with acute hepatitis phase and acute exacerbation phase of type 1 AIH,although AIH with CN often shows clinical features of the genuine acute form.     

Lymph node dissection in esophageal carcinoma: Minimally invasive esophagectomy vs open surgery

AIM: To compare lymph node dissection results of minimally invasive esophagectomy(MIE) and open surgery for esophageal squamous cell carcinoma.METHODS: We retrospectively reviewed data from patients who underwent MIE or open surgery for esophageal squamous cell carcinoma from January 2011 to September 2014. Number of lymph nodes resected, positive lymph node(p N+) rate, lymph node sampling(LNS) rate and lymph node metastatic(LNM) rate were evaluated. R E S U LT S : A m o n g 4 4 7 p a t i e n t s i n c l u d e d, 1 2 3 underwent MIE and 324 underwent open surgery. The number of lymph nodes resected did not significantly differ between the MIE and open surgery groups(21.1 ± 4.3 vs 20.4 ± 3.8, respectively, P = 0.0944). The p N+ rate of stage T3 esophageal squamous cell carcinoma in the open surgery group was higher than that in the MIE group(16.3% vs 11.4%, P = 0.031), but no differences was observed for stages T1 and T2 esophageal squamous cell carcinoma. The LNS rate at left para-recurrent laryngeal nerve(RLN) site was significantly higher for open surgery than for MIE(80.2% vs 43.9%, P 0.001), but no differences were noted at other sites. The LNM rate at left para-RLN site in the open surgery group was significantly higher than that in the MIE group, regardless of pathologic T stage. CONCLUSION: For stages T1 and T2 esophageal squamous cell carcinoma, the lymph node dissection result after MIE was comparable to that achieved by open surgery. However, the efficacy of MIE in lymphadenectomy for stage T3 esophageal squamous cell carcinoma, particularly at left para-RLN site, remains to be improved.     

Vascular resection in pancreatic adenocarcinoma with portal or superior mesenteric vein invasion

AIM:To evaluate long-term survival after the Whipple operation with superior mesenteric vein/portal vein resection(SMV/PVR)in relation to resection length.METHODS:We evaluated 118 patients who underwent the Whipple operation for pancreatic adenocarcinoma at our Department of Hepatobiliary Pancreatic Surgery between 2005 and 2010.Fifty-eight of these patients were diagnosed with microscopic PV/SMV invasion by frozen-section examination and underwent SMV/PVR.In 28 patients,the length of SMV/PVR was≤3 cm.In the other 30 patients,the length of SMV/PVR was>3cm.Clinical and survival data were analyzed.RESULTS:SMV/PVR was performed successfully in 58patients.There was a significant difference between the two groups(SMV/PVR≤3 cm and SMV/PVR>3 cm)in terms of the mean survival time(18 mo vs 11 mo)and the overall 1-and 3-year survival rates(67.9%and14.3%vs 41.3%and 5.7%,P<0.02).However,there was no significant difference in age(64 years vs 58years,P=0.06),operative time(435 min vs 477 min,P=0.063),blood loss(300 mL vs 383 mL,P=0.071)and transfusion volume(85.7 mL vs 166.7 mL,P=0.084)between the two groups.CONCLUSION:Patients who underwent the Whipple operation with SMV/PVR≤3 cm had better long-term survival than those with>3 cm resection.     

Substance P,vasoactive intestinal peptide,and leu-enkephalin in plasma and gastric juice of patients with precancerous lesions and gastric cancer

AIM: To investigate the changes of the brain-gut-peptide concentrations in the plasma and gastric juice and their relations to gastric diseases. METHODS: A total of 83 subjects were part of the study. Of those, 28 had chronic atrophic gastritis with precancerous lesions, 22 had gastric cancer in an advanced stage, and 33 were healthy subjects for a control group. Samples of fasting blood and gastric juice were collected. Levels of substance P (SP), vasoactive intestinal peptide (VIP) and leu-enkephalin (LEK) in plasma and gastric juice were measured with radioimmunoassay kits expressed as ng/L. RESULTS: In patients with gastric cancer, the SP levels (83.7 ± 11.0 vs 39.6 ± 4.5, P < 0.01; 24.0 ± 1.6 vs 17.8 ± 1.5, P < 0.05) and LEK in plasma and gastric juice (226.2 ± 15.4 vs 180.3 ± 13.1, P < 0.01; 55.0 ± 3.4 vs 30.7 ± 2.4, P < 0.05), and VIP of gastric juice (80.5 ± 2.9 vs 64.3 ± 4.1, P < 0.05) were higher than those in the controls. The SP and LEK levels of plasma correlated with those of gastric juice (r = 0.432 and 0.516, P < 0.05). In the post-surgical gastric cancer, plasma levels of SP and gastric juice LEK were lower than the pre-surgical levels (P < 0.05). In the precancerous lesions, plasma and gastric juice LEK levels and gastric juice VIP levels were increased (P < 0.05), and the plasma LEK level correlated with the gastric juice LEK level (r = 0.398, P < 0.05). CONCLUSION: Measurement of concentrations of SP, VIP, and LEK in plasma and gastric juice is of clinical significance in detecting certain stomach diseases.     

Low-dose amitriptyline combined with proton pump inhibitor for functional chest pain

AIM:To investigate the efficacy of amitriptyline with proton pump inhibitor(PPI)for the treatment of functional chest pain(FCP).METHODS:This was a randomized,open-label trial investigating the addition of low dose amitriptyline(10 mg at bedtime)to a conventional dose of rabeprazole(20 mg/d)(group A,n = 20)vs a double-dose of rabeprazole(20 mg twice daily)(group B,n = 20)for patients with FCP whose symptoms were refractory to PPI.The primary efficacy endpoints were assessed by global symptom score assessment and the total number of individuals with > 50% improvement in their symptom score.RESULTS:The between-group difference in global symptom scores was statistically significant during the last week of treatment(overall mean difference;3.75 ± 0.31 vs 4.35 ± 0.29,the between-group difference;P < 0.001).Furthermore,70.6% of patients in group A had their symptoms improve by > 50%,whereas only 26.3% of patients in group B had a similar treatment response(70.6% vs 26.3%,P = 0.008).Specifically,patients in group A had a significantly greater improvement in the domains of body pain and general health perception than did patients in group B(52.37 ± 17.00 vs 41.32 ± 12.34,P = 0.031 and 47.95 ± 18.58 vs 31.84 ± 16.84,P = 0.01,respectively).CONCLUSION:Adding amitriptyline to a PPI was more effective than a double-dose of PPI in patients with FCP refractory to a conventional dose of PPI.     

Survival outcome of patients with spontaneously ruptured hepatocellular carcinoma treated surgically or by transarterial embolization

AIM: To evaluate clinical outcomes of patients that underwent surgery, transarterial embolization (TAE), or supportive care for spontaneously ruptured hepatocellular carcinoma (HCC). METHODS: A consecutive 54 patients who diagnosed as spontaneously ruptured HCC at our institution between 2003 and 2012 were retrospectively enrolled. HCC was diagnosed based on the diagnostic guidelines issued by the 2005 American Association for the Study of Liver Diseases. HCC rupture was defined as disruption of the peritumoral liver capsule with enhanced fluid collection in the perihepatic area adjacent to the HCC by dynamic liver computed tomography, and when abdominal paracentesis showed an ascitic red blood cell count of > 50000 mm 3 /mL in bloody fluid. RESULTS: Of the 54 patients, 6 (11.1%) underwent surgery, 25 (46.3%) TAE, and 23 (42.6%) supportive care. The 2-, 4and 6-mo cumulative survival rates at 2, 4 and 6 mo were significantly higher in the surgery (60%, 60% and 60%) or TAE (36%, 20% and 20%) groups than in the supportive care group (8.7%, 0% and 0%), respectively (each, P < 0.01), and tended to be higher in the surgical group than in the TAE group. Multivariate analysis showed that serum bilirubin (HR = 1.09, P < 0.01), creatinine (HR = 1.46, P = 0.04), and vasopressor requirement (HR = 2.37, P = 0.02) were significantly associated with post-treatment mortality, whereas surgery (HR = 0.41, P < 0.01), and TAE (HR = 0.13, P = 0.01) were inversely associated with posttreatment mortality. CONCLUSION: Post-treatment survival after surgery or TAE was found to be better than after supportive care, and surgery tended to provide better survival benefit than TAE.     

Comparative analysis of endoscopic precut conventional and needle knife sphincterotomy

AIM:To compare the efficacy,complications and postprocedural hyperamylasemia in endoscopic pre-cut conventional and needle knife sphincterotomie.METHODS:We performed a retrospective analysis of two pre-cut sphincterotomy(PS) techniques,pre-cut conventional sphincterotomy(PCS),and pre-cut needle knife(PNK).The study included 143 patients;the classic technique was used in 59 patients(41.3%),and the needle knife technique was used in 84 patients(58.7%).We analyzed the efficacy of bile duct access,the need for a two-step procedure,the rates of complications and hyperamylasemia 4 h after the procedure,"endoscopic bleeding" and the need for bleeding control.Furthermore,to assess whether the anatomy of the Vater’s papilla,indications for the procedure or the need for additional procedures could inform the choice of the PS method,we evaluated the additive hyperamylasemia risk 4 h after the procedure with respect to the above mentioned variables.RESULTS:The bile duct access efficacy with PNK and PCS was 100% and 96.6%,respectively,and the difference between the two groups was not significant(P = 0.06).However,the needle knife technique required two-step access significantly more often,in 48.8% vs8.5% of cases(P < 0.0001).The only complication noted was post-ercp pancreatitis(PEP),which was observed in 4/84(4.8%) and 2/59(3.4%) patients submitted to PNK and PSC,respectively;the difference between the two procedures was not significant(P = 0.98).An analysis of other consequences of the techniques yielded the following results in the PNK and PCS groups:hyperamylasemia 4 h after the procedure > 80 U/L,41/84 vs 23/59(P = 0.32);hyperamylasemia 4 h after the procedure > 240 U/L,19/84 vs 11/59(P = 0.71);pancreatic pain,13/84 vs 7/59(P = 0.71);endoscopic bleeding,10/84 vs 8/59(P = 0.97);and the need for bleeding control,10/84 vs 7/59(P = 0.79).In the next part of the study,we analyzed the influence of the method chosen on the risk of hyperamylasemia with respect to an indication for endoscopic retrograde cholangiopancr     

应用米兰标准微波消融治疗肝细胞癌患者预后及其影响因素分析*

目的 探讨应用米兰标准施行微波消融术(MWA)治疗肝细胞癌(HCC)患者影响生存的因素。方法 2013年1月～2016年12月我院消化内科住院的94例直径≤5 cm的HCC患者接受超声引导下MWA治疗,随访5年。分析不同HCC结节个数和不同肿瘤直径对总生存率(OS)和无进展生存率(PFS)的影响。结果 随访5年,本组HCC患者OS为64.9%,1 a和2 a 肿瘤复发率分别为12.8%和53.2%;HCC直径> 3 cm患者的PFS显著短于直径≤3 cm的患者(P=0.005),PFS≤2年的HCC患者OS显著低于PFS> 2年的患者(48.0%对 84.1%,P<0.001);多因素回归分析显示HCC直径> 3 cm (HR=0.42,95%CI:0.21～0.83,P=0.01)是MWA术后肿瘤复发的独立危险因素,而白细胞计数< 4.0×10⁹ /L (HR=0.38, 95%CI:0.18～0.84,P=0.017)和PFS≤2 年(HR=0.24, 95%CI:0.10～0.56,P=0.001)是影响HCC患者OS的独立危险因素。结论 直径> 3 cm的HCC患者PFS较短,但似乎不影响OS,因为大多数肝内复发的HCC患者仍然可进行重复MWA治疗。     

Habitual rapid food intake and ineffective esophageal motility

AIM:To study non-cardiac chest pain(NCCP) in relation to ineffective esophageal motility(IEM) and rapid food intake.METHODS:NCCP patients with a self-reported habit of fast eating underwent esophageal manometry for the diagnosis of IEM.Telephone interviews identified eating habits of additional IEM patients.Comparison of manometric features was done among IEM patients with and without the habit of rapid food intake and healthy controls.A case study investigated the effect of 6-mo gum chewing on restoration of esophageal motility in an IEM patient.The Valsalva maneuver was performed in IEM patients and healthy controls to assess the compliance of the esophagus in response to abdominal pressureincrease.RESULTS:Although most patients diagnosed with NCCP do not exhibit IEM,remarkably,all 12 NCCP patients who were self-reporting fast eaters with a main complaint of chest pain(75.0%) had contraction amplitudes in the mid and distal esophagus that were significantly lower compared with healthy controls [(23.45 mmHg(95%CI:14.06-32.85)vs 58.80 mmHg(95%CI:42.56-75.04),P < 0.01 and 28.29 mmHg(95%CI:21.77-34.81) vs 50.75 mmHg(95%CI:38.44-63.05),P < 0.01,respectively)].In 7 normal-eating IEM patients with a main complaint of sensation of obstruction(42.9%),the mid amplitude was smaller than in the controls [30.09 mmHg(95%CI:19.48-40.70) vs 58.80 mmHg(95%CI:42.56-75.04),P < 0.05].There was no statistically significant difference in manometric features between the fast-eating and normal-eating groups.One NCCP patient who self-reported fast eating and was subsequently diagnosed with IEM did not improve with proton-pump inhibition but restored swallow-induced contractions upon 6-mo gum-chewing.The Valsalva maneuver caused a markedly reduced pressure rise in the mid and proximal esophagus in the IEM patients.CONCLUSION:Habitual rapid food intake may lead to IEM.A prospective study is needed to validate this hypothesis.Gum-chewing might strengthen weakened esophageal muscles.     

Silencing SMYD3 in hepatoma demethylates RIZI promoter induces apoptosis and inhibits cell proliferation and migration

AIM: To investigate the role of SMYD3 in hepatocellular carcinoma (HCC) development and progression and to verify whether its regulation activity was through RIZ1 inactivation. METHODS: Expression of SMYD3 in HCC cell lines and tissues were measured; silencing of SMYD3 by RNA interference (RNAi) was effectuated, hepatoma cell proliferation, migration and apoptosis were tested, with RIZ1 CpG promoter methylation, and corresponding mRNA expression were investigated. RESULTS: SMYD3 over-expression in HCC was associated with RIZ1 hypermethylation and mRNA down-expression. Suppression of SMYD3 expression de-methylated RIZ1 CpG promoter (P < 0.01) and increased RIZ1 mRNA expression (P < 0.01). Consequently, SMYD3 down-expression with RIZ1 de-methylation strongly inhibited hepatoma cell growth (MTT inhibitory rates: Pgenesil-1-s1 60.95% ± 7.97%, Pgenesil-1-s2 72.14% ± 9.68% vs Pgenesil-1-hk 6.89% ± 4.12%, P < 0.01) and migration (Pgenesil-1-s1 4.24% ± 1.58%, Pgenesil-1-s1 4.87% ± 0.73% vs Pgenesil-1 19.03% ± 4.63%, Pgenesil-1-hk 19.95% ± 5.21%, P < 0.01) and induced apoptosis (FCM subG1 phase Pgenesil-1-s1 19.07% ± 1.78%, Pgenesil-1-s2 17.68% ± 2.36% vs Pgenesil-1 0.47% ± 0.12%, Pgenesil-1-hk 1.46% ± 0.28%, P < 0.01. TUNEL-positive cells: Pgenesil-1-s1 40.24% ± 5.18%, Pgenesil-1-s2 38.48% ± 4.65% vs Pgenesil-1 2.18% ± 1.34%, Pgenesil-1-hk 2.84% ± 1.22%, P < 0.01) in HepG2 cells. CONCLUSION: These results demonstrate that SMYD3 plays a critical role in the carcinogenesis and progression of HCC. The proliferation, migration induction and apoptosis inhibition activities of SMYD3 may be mediated through RIZ1 CpG promoter hypermethylation.     

个性化疼痛护理在缓解妇科腹腔镜术后非切口性疼痛中的疗效观察

[目的]探讨个性化疼痛护理对妇科腹腔镜术(LS)后非切口性疼痛中的缓解作用。[方法]选择我院接受妇科LS术的病人96例,随机分成观察组和对照组各48例,观察组病人在手术期间给予个性化的疼痛护理,对照组仅给予常规护理。护理前后利用数字评分法(VAS)疼痛评分对两组病人的疼痛情况进行评价,并进行护理满意度调查。[结果]观察组病人非切口性疼痛发生率、重度疼痛率和疼痛持续时间分别为41.7%、4.2%和4.4h±3.9h,对照组分别为72.9%、25.0%和16.2h±5.8h,两组比较差异有统计学意义(P<0.05);两组病人术前VAS评分相比,差异无统计学意义(P>0.05),观察组术后12h和术后24hVAS评分明显低于对照组,差异有统计学意义(P<0.05);观察组护理满意度为91.7%,对照组护理满意度为68.8%,两组差异均有统计学意义(P<0.05)。[结论]个性化疼痛护理对妇科LS术后非切口性疼痛具有显著的缓解作用,可提高病人对护理服务的满意度。     

Twist2 is a valuable prognostic biomarker for colorectal cancer

AIM: To investigate the significance of Twist2 for colorectal cancer (CRC). METHODS: In this study, 93 CRC patients were included who received curative surgery in Eastern Hepatobiliary Surgery Hospital from January 1999 to December 2010. Records of patients’ clinicopathological characteristics and follow up data were reviewed. Formalin-fixed, paraffin-embedded tissue blocks were used to observe the protein expression of Twist2 and E-cadherin by immunohistochemistry. Two independent pathologists who were blinded to the clinical information performed semiquantitative scoring of immunostaining. A total score of 3-6 (sum of extent + intensity) was considered as Twist2-positive expression. The expression of E-cadherin was divided into two levels (preserved and reduced). An exploratory statistical analysis was conducted to determine the association between Twist2 expression and clinicopathological parameters, as well as E-cadherin expression. Furthermore, the variables associated with prognosis were analyzed by Cox’s proportional hazards model. Kaplan-Meier analysis was used to plot survival curves according to different expression levels of Twist2. RESULTS: Twist2-positive expression was observed in 66 (71.0%) samples and mainly located in the cytoplasm. Forty-three (46.2%) samples showed reduced expression of E-cadherin. There were no significant correlations between Twist2 expression and any of the clinicopathological parameters. However, Twist2-positive expression was significantly associated with reduced expression of E-cadherin (P=0.040). Multivariate analysis revealed that bad M-stage [hazard ratio (HR)=7.694, 95%CI: 2.927-20.224,P < 0.001] and Twist2-positive (HR=5.744, 95%CI: 1.347-24.298,P=0.018) were the independent risk factors for poor overall survival (OS), while Twist2-positive (HR=3.264, 95%CI: 1.455-7.375, P=0.004), bad N-stage (HR=2.149, 95%CI: 1.226-3.767, P=0.008) and bad M-stage (HR=10.907, 95%CI: 4.937-24.096, P < 0.001) were independently associated with poor disease-free survival (DFS     

Prognostic role of neutrophil-lymphocyte ratio in operable esophageal squamous cell carcinoma

AIM: To determine the prognostic significance of preoperative serum neutrophil-lymphocyte ratio(NLR) in esophageal squamous cell carcinoma(ESCC).METHODS: Data from 371 eligible patients with ESCC who had undergone surgery with curative intent at our institution between October 2000 and May 2007 were retrospectively recruited for analysis. The cutoff value of NLR was 3.0 as determined by the receiver operating characteristic curve, which discriminated between survival and death; the area under the curve was 0.709, and the sensitivity and specificity were 66.1% and 69.1%, respectively, at the cutoff point. The correlation between the NLR and clinicopathological characteristics was analyzed using a χ2 test. The prognostic influence of the NLR and other clinicopathological factors on cancer-specific survival(CSS) and recurrence-free survival(RFS) was studied using the Kaplan-Meier method. To evaluate the independent prognostic value of NLR, multivariate Cox regression models were applied.RESULTS:The median age of the patients was 57.0years,and 276/371(74.4%)patients were male.The NLR was≤3.0 in 80.1%(297/371)of the patients,and the remaining 19.9%(74/371)had an NLR3.0.Median postoperative follow-up was 66.0 mo[interquartile range(IQR):49.0-76.0 mo],with a follow-up rate of 94%.Follow-up was not significantly different between patients with an NLR≤and3.0(63.13±1.64 vs 61.52±3.66,P=0.711).However,higher preoperative serum NLR was associated with significantly increased risks of higher pathological tumor status(P=0.007).A significant,independent association between high preoperative serum NLR and poor clinical outcome was identified in a multivariate analysis for CSS(HR=1.591;P=0.007)and RFS(HR=1.525;P=0.013).Moreover,when patients were stratified by pathological tumor-node-metastasis(TNM)staging,the adverse effects of preoperative serum NLR on CSS(HR=2.294;P=0.008)and RFS(HR=2.273;P=0.008)were greatest in those patients with stageⅢA disease.CONCLUSION:Preoperative serum NLR is a useful prognostic marker to complement TNM staging for operable ESCC patients,particularly in patients with stageⅢA disease.     

Growth hormone abolishes the negative effects of everolimus on intestinal wound healing

AIM: To investigate whether the simultaneous treatment with human growth hormone(h GH) abolishes the negative effects of everolimus on anastomotic healing.METHODS: Forty-eight male Sprague-Dawley-rats were randomized to three groups of 16 animals each(Ⅰ: vehicle; Ⅱ: everolimus 3 mg/kg po; Ⅲ: everolimus 3 mg/kg po + h GH 2.5 mg/kg sc). Animals were pretreated with h GH and/or everolimus daily for seven days. Then a standard anastomosis was created in the descending colon and treatment was continued for another seven days. The anastomosis was resected in toto and the bursting pressure was assessed as a mechanical parameter of intestinal healing. Moreover, biochemical(Hydroxyproline, PCNA, MPO, MMP-2 and MMP-9) and histological(cell density, angiogenesis, amount of granulation tissue) parameters of intestinal healing were assessed.RESULTS: Anastomotic bursting pressure was significantly reduced by everolimus and a simultaneous treatment with h GH resulted in considerably higher values(Ⅰ: 134 ± 19 mm Hg, Ⅱ: 85 ± 25 mm Hg, Ⅲ: 114 ± 25 mm Hg; P 0.05,Ⅰvs Ⅱ; P = 0.09,Ⅰvs Ⅲ and Ⅱ vs Ⅲ) Hydroxyproline concentration was significantly increased by h GH compared to everolimus alone(Ⅰ: 14.9 ± 2.5 μg/mg, Ⅱ: 8.9 ± 3.6 μg/mg, Ⅲ: 11.9 ± 2.8 μg/mg; P 0.05,?Ⅰvs Ⅱ/Ⅲ and Ⅱ vs Ⅲ). The number of MPO-positive cells was reduced significantly by h GHcompared to everolimus alone(Ⅰ: 10 ± 1 n/mm~2, Ⅱ: 15 ± 3 n/mm~2, Ⅲ: 9 ± 2 n/mm~2; P 0.05,Ⅰvs Ⅱ and Ⅱ vs Ⅲ), while the number of PCNA-positive cells were increased by h GH(Ⅰ: 28 ± 3 /mm~2, Ⅱ: 12 ± 3 /mm~2, Ⅲ: 26 ± 12 /mm~2; P 0.05,?Ⅰ?vs Ⅱ and Ⅱ vs Ⅲ). Corresponding to these biochemical findings, HEhistology revealed significantly increased amount of granulation tissue in h GH-treated animals.CONCLUSION: Inhibition of intestinal wound healing by everolimus is partially neutralized by simultaeous treatment with h GH. Both inflammation as well as collagen deposition is influenced by h GH.     

Disease progression in chronic hepatitis C patients with normal alanine aminotransferase levels

AIM:To investigate whether the disease progression of chronic hepatitis C patients with normal alanine aminotransferase(ALT) levels differs by ALT levels.METHODS:A total of 232 chronic hepatitis C patients with normal ALT(< 40 IU/L) were analyzed.The patients were divided into "high-normal" and "low-normal" ALT groups after determining the best predictive cutoff level associated with disease progression for each gender.The incidence of disease progression,as defined by the occurrence of an increase of ≥ 2 points in the Child-Pugh score,spontaneous bacterial peritonitis,bleeding gastric or esophageal varices,hepatic encephalopathy,the development of hepatocellular carcinoma,or death related to liver disease,were compared between the two groups.RESULTS:Baseline serum ALT levels were associatedwith disease progression for both genders.The best predictive cutoff baseline serum ALT level for disease progression was 26 IU/L in males and 23 IU/L in females.The mean annual disease progression rate was 1.2% and 3.9% for male patients with baseline ALT levels ≤ 25 IU/L(low-normal) and > 26 IU/L(highnormal),respectively(P = 0.043),and it was 1.4% and 4.8% for female patients with baseline ALT levels ≤ 22 IU/L(low-normal) and > 23 IU/L(high-normal),respectively(P = 0.023).ALT levels fluctuated during the follow-up period.During the follow-up,more patients with "high-normal" ALT levels at baseline experienced ALT elevation(> 41 IU/L) than did patients with "lownormal" ALT levels at baseline(47.7% vs 27.9%,P = 0.002).The 5 year cumulative incidence of disease progression was significantly lower in patients with persistently "low-normal" ALT levels than "high-normal" ALT levels or those who exhibited an ALT elevation > 41 U/L during the follow-up period(0%,8.3% and 34.3%,P < 0.001).CONCLUSION:A "high normal" ALT level in chronic hepatitis C patients was associated with disease progression,suggesting that the currently accepted normal threshold of serum ALT should be lowered.     

Changes in patients&rsquo; symptoms and gastric emptying after Helicobacter pylori treatment

AIM: To investigate the changes in clinical symptoms and gastric emptying and their association in functional dyspepsia (FD) patients. METHODS: Seventy FD patients were enrolled and divided into 2 groups Helicobacter pylori (H. pylori)-negative group (28 patients), and H. pylori-positive group (42 patients). Patients in the H. pylori-positive group were further randomly divided into groups: H. pylori-treatment group (21 patients) and conventional treatment group (21 patients). Seventy two healthy subjects were selected as the control group. The proximal and distal stomach area was measured by ultrasound immediately after patients took the test meal, and at 20, 40, 60 and 90 min; then, gastric half-emptying time was calculated. The incidence of symptoms and gastric half-emptying time between the FD and control groups were compared. The H. pylori-negative and conventional treatment groups were given conventional treatment: domperidone 0.6 mg/(kg/d) for 1 mo. The H. pylori-treatment group was given H. pylori eradication treatment + conventional treatment: lansoprazole 30 mg once daily, clarithromycin 0.5 g twice daily and amoxicillin 1.0 g twice daily for 1 wk, then domperidone 0.6 mg/(kg/d) for 1 mo. The incidence of symptoms and gastric emptying were compared between the FD and control groups. The relationship between dyspeptic symptoms and gastric half-emptying time in the FD and control groups were analyzed. Then total symptom scores before and after treatment and gastric half-emptying time were compared among the 3 groups. RESULTS: The incidence of abdominal pain, epigastric burning sensation, abdominal distension, nausea, belching, and early satiety symptoms in the FD group were significantly higher than in the control group (50.0% vs 20.8%; 37.1% vs 12.5%; 78.6% vs 44.4%; 45.7% vs 22.2%; 52.9% vs 15.3%; 57.1% vs 19.4%; all P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the FD group were slower than in the control group (93.7 ± 26.2 vs 72.0 ± 14.3; 102.2 ± 26.4 vs 87.5 ± 18.2; 102.1 ± 28.6 vs 78.3 ± 14.1; all P < 0.05). Abdominal distension, belching and early satiety had an effect on distal gastric half-emptying time (P < 0.05). Abdominal distension and abdominal pain had an effect on the gastric half-emptying time of the whole stomach (P < 0.05). All were risk factors (odds ratio > 1). The total symptom score of the 3 groups after treatment was lower than before treatment (P < 0.05). Total symptom scores after treatment in the H. pylori-treatment group and H. pylori-negative group were lower than in the conventional treatment group (5.15 ± 2.27 vs 7.02 ± 3.04, 4.93 ± 3.22 vs 7.02 ± 3.04, All P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the H. pylori-negative and H. pylori-treatment groups were shorter than in the conventional treatment group (P < 0.05). CONCLUSION: FD patients have delayed gastric emptying. H. pylori infection treatment helps to improve symptoms of dyspepsia and is a reasonable choice for treatment in clinical practice.     

Association of arterial stiffness with coronary flow reserve in revascularized coronary artery disease patients

AIM: To investigate the association of arterial wave reflection with coronary flow reserve(CFR) in coronary artery disease(CAD) patients after successful revascularization.METHODS: We assessed 70 patients with angiographically documented CAD who had undergone recent successful revascularization. We measured(1) reactive hyperemia index(RHI) using fingertip peripheral arterial tonometry(RH-PAT Endo-PAT);(2) carotid to femoral pulse wave velocity(PWVc-Complior);(3) augmentation index(AIx), the diastolic area(DAI%) and diastolic reflection area(DRA) of the central aortic pulse wave(Arteriograph);(4) CFR using Doppler echocardiography; and(5) blood levels of lipoprotein-phospholipase A2(LpPLA2).RESULTS: After adjustment for age, sex, blood pressure parameter, lipidemic, diabetic and smoking status, we found that coronary flow reserve was independently related to AIx(b =-0.38, r = 0.009), DAI(b = 0.36, P = 0.014), DRA(b = 0.39, P = 0.005) and RT(b =-0.29,P = 0.026). Additionally, patients with CFR 2.5 had higher PWVc(11.6 ± 2.3 vs 10.2 ± 1.4 m/s, P = 0.019), SBPc(139.1 ± 17.8 vs 125.2 ± 19.1 mm Hg, P = 0.026), AIx(38.2% ± 14.8% vs 29.4% ± 15.1%, P = 0.011) and lower RHI(1.26 ± 0.28 vs 1.50 ± 0.46, P = 0.012), DAI(44.3% ± 7.9% vs 53.9% ± 6.7%, P = 0.008), DRA(42.2 ± 9.6 vs 51.6 ± 11.4, P = 0.012) and Lp PLA2(268.1 ± 91.9 vs 199.5 ± 78.4 ng/m L, P = 0.002) compared with those with CFR ≥ 2.5. Elevated Lp PLA2 was related with reduced CFR(r =-0.33, P = 0.001), RHI(r =-0.37, P 0.001) and DRA(r =-0.35, P = 0.001) as well as increased PWVc(r = 0.34, P = 0.012) and AIx(r = 0.34, P = 0.001). CONCLUSION: Abnormal arterial wave reflections are related with impaired coronary flow reserve despite successful revascularization in CAD patients. There is a common inflammatory link between impaired aortic wall properties, endothelial dysfunction and coronary flow impairment in CAD.