Intravenous iron supplementation may be superior to observation in acute isovolemic anemia after gastrectomy for cancer

AIM:To determine whether the application of postoperative intravenous(IV)-iron for acute isovolemic anemia after gastrectomy for cancer may be effective.METHODS:Among 2078 gastric cancer patients who underwent surgery between February 2007 and August2009 at the National Cancer Center Korea,368 patients developed post-operative anemia[hemoglobin-(Hb)-level<9 g/dL]within the first postoperative week.Patients requiring transfusions were excluded.IV-iron was administered to 63 patients(iron group).Sixty patients were observed without treatment(observation group).The clinical outcomes of the groups were compared concerning clinicopathologic data,morbidity,and changes in Hb levels using Fisher’s exact test,Student’s t-test and the Z-test.RESULTS:The initial Hb level was higher in the iron group than in the observation group(7.3±1.0 g/dL vs8.4±0.5 g/dL,P<0.001).The slope of the changes in the Hb level was significantly higher in the iron group than in the observation group(0.648±0.054 vs 0.349±0.038,P<0.001).The Hb level 1 and 3 mo postoperatively increased from 10.7±1.3 to 11.9±1.3g/dL in the iron group(P=0.033)and from 10.1±1.0to 10.8±1.4 g/dL in the observation group(P<0.001).The postoperative hospital stay was significantly longer in the iron group than in the observation group(10.5±6.8 d vs 7.6±5.5 d,P=0.011).There were no significant differences in the major and surgical complications between the groups(6.3%vs 13.3%,P=0.192;9.5%vs 3.3%,P=0.164).CONCLUSION:IV-iron supplementation may be an effective treatment for post-operative isovolemic postgastrectomy anemia and may be a better alternative than observation.     

Effectiveness and safety of continuous wound infiltration for postoperative pain management after open gastrectomy

AIM: To prospectively evaluate the effectiveness and safety of continuous wound infiltration(CWI) for pain management after open gastrectomy. METHODS: Seventy-five adult patients with American Society of Anesthesiologists(ASA) Physical Status Classification System(ASA) grade 1-3 undergoing open gastrectomy were randomized to three groups. Group 1 patients received CWI with 0.3% ropivacaine(group CWI). Group 2 patients received 0.5 mg/m L morphine intravenously by a patient-controlled analgesia pump(PCIA)(group PCIA). Group 3 patients received epidural analgesia(EA) with 0.12% ropivacaine and 20 μg/m L morphine with an infusion at 6-8 m L/h for 48 h(group EA). A standard general anesthetic technique was used for all three groups. Rescue analgesia(2 mg bolus of morphine, intravenous) was given when the visual analogue scale(VAS) score was ≥ 4. The outcomes measured over 48 h after the operation were VAS scores both at rest and during mobilization, total morphine consumption, relative side effects, and basic vital signs. Further results including time to extubation, recovery of bowel function, surgical wound healing,mean length of hospitalization after surgery, and the patient's satisfaction were also recorded.RESULTS: All three groups had similar VAS scores during the first 48 h after surgery. Group CWI and group EA, compared with group PCIA, had lower morphine consumption(P 0.001), less postoperative nausea and vomiting(1.20 ± 0.41 vs 1.96 ± 0.67, 1.32 ± 0.56 vs 1.96 ± 0.67, respectively, P 0.001), earlier extubation(16.56 ± 5.24 min vs 19.76 ± 5.75 min, P 0.05, 15.48 ± 4.59 min vs 19.76 ± 5.75 min, P 0.01), and earlier recovery of bowel function(2.96 ± 1.17 d vs 3.60 ± 1.04 d, 2.80 ± 1.38 d vs 3.60 ± 1.04 d, respectively, P 0.05). The mean length of hospitalization after surgery was reduced in groups CWI(8.20 ± 2.58 d vs 10.08 ± 3.15 d, P 0.05) and EA(7.96 ± 2.30 d vs 10.08 ± 3.15 d, P 0.01) compared with group PCIA. All three groups had similar patient satisfaction and wound healing, but group PCIA was prone to higher sedation scores when compared with groups CWI and EA, especially during the first 12 h after surgery. Group EA had a lower mean arterial pressure within the first postoperative 12 h compared with the other two groups.CONCLUSION : CWI with ropivacaine yields a satisfactory analgesic effect within the first 48 h after open gastrectomy, with lower morphine consumption and accelerated recovery.     

Eradication rate and histological changes after Helicobacter pylori eradication treatment in gastric cancer patients following subtotal gastrectomy

AIM: To investigate the eradication rate and histological changes after Helicobacter pylori(H. pylori) eradication treatment following subtotal gastrectomy for gastric cancer.METHODS: A total of 610 patients with H. pylori infection who had undergone surgery for either early or advanced gastric adenocarcinoma between May 2004 and December 2010 were retrospectively studied. A total of 584 patients with proven H. pylori infection after surgery for gastric cancer were enrolled in this study. Patients received a seven day standard triple regimen as first-line therapy and a 10 d bismuthcontaining quadruple regimen as second-line therapy in cases of eradication failure. The patients underwent an esophagogastroduodenoscopy(EGD) between six and 12 mo after surgery, followed by annual EGDs. A further EGD was conducted 12 mo after confirming the result of the eradication and the histological changes. A gastric biopsy specimen for histological examination and Campylobacter-like organism testing was obtained from the lesser and greater curvature of the corpus of the remnant stomach. Histological changes in the gastric mucosa were assessed using the updated Sydney system before eradication therapy and at follow-up after 12 mo.RESULTS: Eradication rates with the first-line and second-line therapies were 78.4%(458/584) and 90%(36/40), respectively, by intention-to-treat analysis and 85.3%(458/530) and 92.3%(36/39), respectively, by per-protocol analysis. The univariate and multivariate analyses revealed that Billroth Ⅱ surgery was an independent factor predictive of eradication success in the eradication success group(OR = 1.53, 95%CI: 1.41-1.65, P = 0.021). The atrophy and intestinal metaplasia(IM) scores 12 mo after eradication were significantly lower in the eradication success group than in the eradication failure group(0.25 ± 0.04 vs 0.47 ± 0.12, P = 0.023; 0.27 ± 0.04 vs 0.51 ± 0.12, P = 0.015, respectively). The atrophy and IM scores 12 mo after successful eradication were significantly lower in the Billroth Ⅱ group than in the Billroth I group(0.13 ± 0.09 vs 0.31 ± 0.12, P = 0.029; 0.32 ± 0.24 vs 0.37 ± 0.13, P = 0.034, respectively).CONCLUSION: Patients with H. pylori following subtotal gastrectomy had a similar eradication rate to patients with an intact stomach. H. pylori eradication is recommended after subtotal gastrectomy.     

KRAS and BRAF gene mutations and DNA mismatch repair status in Chinese colorectal carcinoma patients

AIM:To investigate gene mutations and DNA mismatch repair(MMR) protein abnormality in Chinese colorectalcarcinoma(CRC) patients and their correlations with clinicopathologic features.METHODS:Clinical and pathological information for 535 patients including 538 tumors was reviewed and recorded.Mutation analyses for exon 2 of KRAS gene and exon 15 of BRAF gene were performed by Sanger sequencing except that in 9 tumors amplification refractory mutation system PCR was used.Expression of MMR proteins including MHL1,MSH2,MSH6 and PMS2 was evaluated by immunohistochemistry.Correlations of KRAS and BRAF mutation status and the expression status of MMR proteins with age,gender,cancer stage,location,and histology were analyzed.Correlations between KRAS or BRAF mutations and MMR protein expression were also explored.RESULTS:The overall frequencies of KRAS and BRAF mutations were 37.9% and 4.4%,respectively.KRAS mutations were more common in patients ≥ 50 years old(39.8% vs 22% in patients 50 years old,P 0.05).The frequencies of BRAF mutants were higher in tumors from females(6.6% vs males 2.8%,P 0.05),located in the right colon(9.6% vs 2.1% in the left colon,1.8% in the rectum,P 0.01),with mucinous differentiation(9.8% vs 2.8% without mucinous differentiation,P 0.01),or being poorly differentiated(9.5% vs 3.4% well/moderately differentiated,P 0.05).MMR deficiency was strongly associated with proximal location(20.5% in the right colon vs 9.2% in the left colon and 5.1% in the rectum,P 0.001),early cancer stage(15.0% in stages Ⅰ-Ⅱ vs 7.7% in stages Ⅲ-Ⅳ,P 0.05),and mucinous differentiation(20.2% vs 9.2% without mucin,P 0.01).A higher frequency of MLH1/PMS2 loss was found in females(9.2% vs 4.4% in males,P 0.05),and MSH2/MSH6 loss tended to be seen in younger(50 years old) patients(12.0% vs 4.0% ≥ 50 years old,P 0.05).MMR deficient tumors were less likely to have KRAS mutations(18.8% vs 41.7% in MMR proficient tumors,P 0.05) and tumorswith abnormal MLH1/PMS2 tended to harbor BRAF mutations(15.4% vs 4.2% in MMR proficient tumors,P 0.05).CONCLUSION:The frequency of sporadic CRCs having BRAF mutation,MLH1 deficiency and MSI in Chinese population may be lower than that in the Western population.     

A short review of malabsorption and anemia

Anemia is a frequent finding in most diseases which cause malabsorption. The most frequent etiology is the combination of iron and vitamin B12 deficiency. Celiac disease is frequently diagnosed in patients referred for evaluation of iron deficiency anemia （IDA）, being reported in 1.8%-14.6% of patients. Therefore, duodenal biopsies should be taken during endoscopy if no obvious cause of iron deficiency （ID） can be found. Cobalamin deficiency occurs frequently among elderly patients, but it is often unrecognized because the clinical manifestations are subtle; it is caused primarily by food-cobalamin malabsorption and pernicious anemia. The classic treatment of cobalamin deficiency has been parenteral administration of the vitamin. Recent data suggest that alternative routes of cobalamin administration （oral and nasal） may be useful in some cases. Anemia is a frequent complica- tion of gastrectomy, and has been often described after bariatric surgery. It has been shown that banding procedures which maintain digestive continuity with the antrum and duodenum are associated with low rates of ID. Helicobacter pylori （H pylori） infection may be considered as a risk factor for IDA, mainly in groups with high demands for iron, such as some children and adolescents. Further controlled trials are needed before making solid recommendations about H pylori eradication in these cases.     

Minimizing tacrolimus decreases the risk of new-onset diabetes mellitus after liver transplantation

AIM: To investigate the impact of minimum tacrolimus(TAC) on new-onset diabetes mellitus(NODM) after liver transplantation(LT).METHODS: We retrospectively analyzed the data of 973 liver transplant recipients between March 1999 and September 2014 in West China Hospital Liver Transplantation Center. Following the exclusion of ineligible recipients, 528 recipients with a TAC-dominant regimen were included in our study. We calculated and determined the mean trough concentration of TAC(c TAC) in the year of diabetes diagnosis in NODM recipients or in the last year of the follow-up in nonNODM recipients. A cutoff of mean c TAC value for predicting NODM 6 mo after LT was identified using a receptor operating characteristic curve. TAC-related complications after LT was evaluated by χ~2 test, and the overall and allograft survival was evaluated using the Kaplan-Meier method. Risk factors for NODM after LT were examined by univariate and multivariate Cox regression.RESULTS: Of the 528 transplant recipients, 131(24.8%) developed NODM after 6 mo after LT, and the cumulative incidence of NODM progressively increased. The mean c TAC of NODM group recipients was significantly higher than that of recipients in the non-NODM group(7.66 ± 3.41 ng/m L vs 4.47 ± 2.22 ng/m L, P 0.05). Furthermore, NODM group recipients had lower 1-, 5-, 10-year overall survival rates(86.7%, 71.3%, and 61.1% vs 94.7%, 86.1%, and 83.7%, P 0.05) and allograft survival rates(92.8%, 84.6%, and 75.7% vs 96.1%, 91%, and 86.1%, P 0.05) than the others. The best cutoff of mean c TAC for predicting NODM was 5.89 ng/m L after 6 mo after LT. Multivariate analysis showed that old age at the time of LT( 50 years), hypertension pre-LT, and high mean c TAC(≥ 5.89 ng/m L) after 6 mo after LT were independent risk factors for developing NODM. Concurrently, recipients with a low c TAC( 5.89 ng/m L) were less likely to become obese(21.3% vs 30.2%, P 0.05) or to develop dyslipidemia(27.5% vs 44.8%, P 0.05), chronic kidney dysfunction(14.6% vs 22.7%, P 0.05), and moderate to severe infection(24.7% vs 33.1%, P 0.05) after LT than recipients in the high mean c TAC group. However, the two groups showed no significant difference in the incidence of acute and chronic rejection, hypertension, cardiovascular events and newonset malignancy. CONCLUSION: A minimal TAC regimen can decrease the risk of long-term NODM after LT. Maintaining a c TAC value below 5.89 ng/m L after LT is safe and beneficial.     

Outcome after gastrectomy in gastric cancer patients with type 2 diabetes

AIM: To evaluate the prognosis of type II diabetes mellitus (T2DM) after gastrectomy and related factors in gastric cancer patients.METHODS: 403 gastric cancer patients with T2DM were studied, who underwent gastrectomy between May 2003 and September 2009. A review of medical records and telephone interviews was performed in this cross-sectional study. The factors included in the statistical analysis were as follows: gender, age, type of surgery, preoperative body mass index (BMI), current BMI, BMI reduction ratio, preoperative insulin or oral diabetic medicine requirement, follow-up duration, and current state of diabetes. Assessment of diabetes status after surgery was classified into four categories according to the change in hypoglycemic agents after surgery and present status of T2DM: resolution, improvement, same, and worse.RESULTS: The mean follow-up duration was 33.7 mo (± 20.6 mo), preoperative BMI was 24.7 kg/m² (± 3.0 kg/m²), and BMI reduction ratio was 9.8% (± 8.6%). After surgery, T2DM was cured in 58 patients (15.1%) and was improved in 117 patients (30.4%). According to the type of surgery, the BMI reduction ratio was significantly higher in the total gastrectomy and Roux-en-Y reconstruction group [14.2% ± 9.2% vs 9.2% ± 7.7% (Billroth II group), P < 0.001] and significantly lower in the subtotal gastrectomy and Billroth I reconstruction group [7.6% ± 8.0%, 9.2% ± 7.7% (Billroth II group), P < 0.001]. The BMI reduction ratio, follow-up duration after surgery, type of surgery, extent of gastrectomy, and performance of duodenal bypass were significantly correlated to the course of T2DM (P < 0.05). The BMI reduction ratio was the most influential factor on T2DM status. In a subgroup analysis of patients with a BMI reduction ratio of 10% or less (n = 206), T2DM was cured in 15 (7.6%) patients and was improved in 57 (28.8%) patients after surgery, and only the duration of surgery was significantly correlated to T2DM status (P = 0.022).CONCLUSION: The course of T2DM was significantly correlated to the BMI reduction ratio but not to the type of surgery without a significant change in BMI.     

Study of celiac artery variations and related surgical techniques in gastric cancer

AIM: To investigate celiac artery variations in gastric cancer patients and the impact on gastric cancer surgery,and also to discuss the value of the ultrasonic knife in reducing the risk caused by celiac artery variations.METHODS: A retrospective analysis was conducted to investigate the difference in average operation time,intraoperative blood loss, number of harvested lymph nodes, average postoperative drainage within 3 d,and postoperative hospital stay between the group with vascular variations and no vascular variations,and between the ultrasonic harmonic scalpel and conventional electric scalpel surgery group.RESULTS: One hundred and fifty-eight cases presented with normal celiac artery, and 80 presented with celiac artery variation(33.61%). The average operation time,blood loss, average drainage within 3 d after surgery in the celiac artery variation group were significantly more than in the no celiac artery variation group(215.7 ± 32.7 min vs 204.2 ± 31.3 min, 220.0 ± 56.7mL vs 163.1 ± 52.3 mL, 193.6 ± 41.4 mL vs 175.3± 34.1 mL, respectively, P 0.05). In celiac artery variation patients, the average operation time, blood loss, average drainage within 3 d after surgery in the ultrasonic harmonic scalpel group were significantly lower than in the conventional electric scalpel surgery group(209.5 ± 34.9 min vs 226.9 ± 29.4 min, 207.5 ±57.1 mL vs 235.6 ± 52.9 mL, 184.4 ± 38.2 mL vs 205.0± 42.9 mL, respectively, P 0.05), and the number of lymph node dissections was significantly higher than in the conventional surgery group(25.5 ± 9.2 vs 19.9 ±7.8, P 0.05).CONCLUSION: Celiac artery variation increases thedifficulty and risk of radical gastrectomy. Preoperative imaging evaluation and the application of ultrasonic harmonic scalpel are conducive to radical gastrectomy.     

Indomethacin but not a selective cyclooxygenase-2 inhibitor inhibits esophageal adenocarcinogenesis in rats

AIM:To evaluate the effects of indomethacin [dual cyclooxygenase(COX)-1/COX-2 inhibitor] and 3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl) phenyl)2-(5H)-furanone(MF-tricyclic)(COX-2 selective inhibitor) in a rat experimental model of Barrett's esophagus and esophageal adenocarcinoma.METHODS:A total of 112 surviving post-surgery rats were randomly divided into three groups:the control group(n = 48),which did not receive any treatment;the indomethacin group(n = 32),which were given 2 mg/kg per day of the COX-1/COX-2 inhibitor;and the MF-tricyclic group(n = 32),which received 10 mg/kg per day of the selective COX-2 inhibitor.Randomly selected rats were killed either 8 wk or 16 wk after surgery.The timing of the deaths was in accordance with a previous study performed in our group.Only rats that were killed at the times designated by the protocol were included in the study.We then assessed the histology and prostaglandin E2(PGE2) expression levels in the rat esophagi.An additional group of eight animals that did not undergo esophagojejunostomy were included in order to obtain normal esophageal tissue as a control.RESULTS:Compared to a control group with no treatment(vehicle-treated rats),indomethacin treatment was associated with decreases in ulcerated esophageal mucosa(16% vs 35% and 14% vs 17%,2 mo and 4 mo after surgery,respectively;P = 0.021),length of intestinal metaplasia in continuity with anastomosis(2 ± 1.17 mm vs 2.29 ± 0.75 mm and 1.25 ± 0.42 mm vs 3.5 ± 1.54 mm,2 mo and 4 mo after surgery,respectively;P = 0.007),presence of intestinal metaplasia beyond anastomosis(20% vs 71.4% and 0% vs 60%,2 mo and 4 mo after surgery,respectively;P = 0.009),severity of dysplasia(0% vs 71.4% and 20% vs 85.7% high-grade dysplasia,2 mo and 4 mo after surgery,respectively;P = 0.002),and adenocarcinoma incidence(0% vs 57.1% and 0% vs 60%,2 mo and 4 mo after surgery,respectively;P 0.0001).Treatment with the selective COX-2 inhibitor,MF-tricyclic,did not prevent development of intestinal metaplasia or adenocarcinoma.In parallel,we observed a significant decrease in PGE2 levels in indomethacin-treated rats,but not in those treated with MF-tricyclic,at both 2 mo and 4 mo.Compared to control rats that did not undergo surgery(68 ± 8 ng/g,P = 0.0022 Kruskal-Wallis test) there was a significant increase in PGE2 levels in the esophageal tissue of the rats that underwent surgery either 2 mo(1332 ± 656 ng/g) or 4 mo(1121 ± 1015 ng/g) after esophagojejunostomy.However,no differences were found when esophageal PGE2 levels were compared 2 mo vs 4 mo post-esophagojejunostomy.At both the 2-and 4-mo timepoints,we observed a significant decrease in PGE2 levels in indomethacin-treated rat esophagi compared to those in either the control or MF-tricyclic groups(P = 0.049 and P = 0.017,respectively).No differences in PGE2 levels were found when we compared levels in rats treated with MF-tricyclic to not-treated rats.CONCLUSION:In this rat model of gastrointestinal reflux,indomethacin was associated with a decrease in the severity of esophagitis and reduced development of esophageal intestinal metaplasia and adenocarcinoma.     

Helicobacter pylori infection in patients with selective immunoglobulin E deficiency

AIM: To investigate the prevalence and clinical characteristics of Helicobacter pylori(H.pylori)-infected dyspeptic patients with selective immunoglobulin E deficiency(IgE d).METHODS: All individuals who underwent serum totalimmunoglobulin E(Ig E) measurement at the Leumit Healthcare Services(Israel) in 2012 were identified in an electronic database search(n = 18487).From these,selected case group subjects were ≥ 12 years of age and had serum total Ig E 2 k IU/L(n = 158).The control group was selected from a random sampling of the remaining subjects ≥ 12 years of age to obtain a case-control ratio of 1:20(n = 3160).Dyspeptic diseases,diagnosed no more than 5 years before serum total Ig E testing,were identified and retrieved from the electronic database using specific International Classification of Diseases diagnostic codes.Results of C13-urea breath tests were used to identify subjects infected with H.pylori.Categorical variables between case and control subjects were analyzed using Fisher's exact tests,whereas continuous variables were analyzed using χ2 tests.RESULTS: Dyspepsia was present in 27.2%(43/158) of case subjects and 22.7%(718/3160) of controls.Of these,significantly more case subjects(32/43,74.4%) than controls(223/718,31.1%) were positive for H.pylori(P 0.01).Esophagogastroduodenoscopy was performed in 19 case and 94 control subjects,revealing that gastritis was more prevalent in IgE d case subjects than in controls(57.9% vs 29.8%,P 0.05).Furthermore,a significantly greater proportion of case subjects presented with peptic duodenal ulcers(63.2% vs 15.9%,P 0.01).Histopathologic examination showed marked chronic inflammation,lymphoid follicle formation and prominent germinal centers,with polymorphonuclear cell infiltration of gastric glands,that was similar in case and control biopsy tissues.Finally,Ig Ed case subjects that underwent esophagogastroduodenoscopy were more likely to exhibit treatment-refractory H.pylori infections that require second-line triple antibiotic therapy(47.4% vs 11.7%,P 0.01).CONCLUSION: IgE d is associated with higher rates ofH.pylori-associated gastritis and peptic duodenal ulcers.     

Preoperative predictors of short-term survival after hepatectomy for multinodular hepatocellular carcinoma

AIM: To investigate preoperative factors associated with poor short-term outcome after resection for multinodular hepatocellular carcinoma (HCC) and to assess the contraindication of patients for surgery.METHODS: We retrospectively analyzed 162 multinodular HCC patients with Child-Pugh A liver function who underwent surgical resection. The prognostic significance of preoperative factors was investigated by univariate analysis using the log-rank test and by multivariate analysis using the Cox proportional hazards model. Each independent risk factor was then assigned points to construct a scoring model to evaluate the indication for surgical intervention. A receiver operating characteristics (ROC) curve was constructed to assess the predictive ability of this system.RESULTS: The median overall survival was 38.3 mo (range: 3-80 mo), while the median disease-free survival was 18.6 mo (range: 1-79 mo). The 1-year mortality was 14%. Independent prognostic risk factors of 1-year death included prealbumin < 170 mg/L [hazard ratio (HR): 5.531, P < 0.001], alkaline phosphatase > 129 U/L (HR: 3.252, P = 0.005), α fetoprotein > 20 μg/L (HR: 7.477, P = 0.011), total tumor size > 8 cm (HR: 10.543; P < 0.001), platelet count < 100 × 10⁹/L (HR: 9.937, P < 0.001), and γ-glutamyl transpeptidase > 64 U/L (HR: 3.791, P < 0.001). The scoring model had a strong ability to predict 1-year survival (area under ROC: 0.925, P < 0.001). Patients with a score ≥ 5 had significantly poorer short-term outcome than those with a score < 5 (1-year mortality: 62% vs 5%, P < 0.001; 1-year recurrence rate: 86% vs 33%, P < 0.001). Patients with score ≥ 5 had greater possibility of microvascular invasion (P < 0.001), poor tumor differentiation (P = 0.003), liver cirrhosis with small nodules (P < 0.001), and intraoperative blood transfusion (P = 0.010).CONCLUSION: A composite preoperative scoring model can be used as an indication of prognosis of HCC patients after surgical resection. Resection should be considered with caution in patients with a score ≥ 5, which indicates a contraindication for surgery.     

Mechanism of QHF-cisplatin against hepatocellular carcinoma in a mouse model

AIM: To study the effects of QHF-cisplatin on H22 hepatocellular carcinoma(HCC) and their mechanisms of action.METHODS: Sixty BALB/c mice were randomly divided into a model group(n = 48) and a normal control group(n = 12). An HCC xenograft tumor was created by injecting H22 cells directly into the liver parenchyma of the mice. The 48 BALB/c mice in the model group were randomly divided into four groups: QHF, DDP(cisplatin), QHF plus DDP, and model control. The inhibitory effects of these drugs on tumor growth were evaluated by calculating the rate of tumor growth inhibition. The mice were examined by observing their general condition, body weight and survival time. Changes in tumor tissue were observed under anoptical microscope. Aspartate aminotransferase(AST), alanine aminotransferase(ALT) and α-fetoprotein(AFP) levels in serum were measured. Hepatocyte growth factor(HGF), c-mesenchymal-epithelial transition(c-Met) factor, phosphorylated(p)-c-Met, p38, p-p38, extracellular signal-regulated kinase(ERK), p-ERK and vascular endothelial growth factor(VEGF) levels were evaluated in tumor and liver tissues using western blotting. RESULTS: Compared with the DDP group, a lower incidence of toxic reactions and a higher survival time were observed in the QHF plus DDP group. Tumor weight was significantly lower in the QHF, DDP and QHF plus DDP groups than in the model control group(0.24 ± 0.07, 0.18 ± 0.03 and 0.14 ± 0.01 g vs 0.38 ± 0.05 g, respectively), and the differences were statistically significant(P 0.01). The rate of tumor growth inhibition in the QHF, DDP and QHF plus DDP groups was 38.7%, 52.6% and 63.5%, respectively. AST, ALT and AFP levels in serum were significantly lower in the QHF, DDP and QHF plus DDP groups compared to the model control group(P 0.05). Similarly, HGF, p-c-Met, p-p38, p-ERK and VEGF levels in tumor tissue were significantly lower in the QHF, DDP and QHF plus DDP groups(P 0.05).CONCLUSION: QHF and DDP have an antiangiogenic effect on H22 HCC in mice. QHF inhibits tumor growth via blocking the HGF/c-Met signaling pathway, inhibiting p38, ERK and VEGF signaling.     

Case-matched comparison of laparoscopy-assisted and open distal gastrectomy for gastric cancer

AIM: To compare shortand long-term outcomes of laparoscopy-assisted and open distal gastrectomy for gastric cancer. METHODS: A retrospective study was performed by comparing the outcomes of 54 patients who underwent laparoscopy-assisted distal gastrectomy (LADG) with those of 54 patients who underwent open distal gastrectomy (ODG) between October 2004 and October 2007. The patients’ demographic data (age and gender), date of surgery, extent of lymphadenectomy, and differentiation and tumor-node-metastasis stage of the tumor were examined. The operative time, intraoperative blood loss, postoperative recovery, complications, pathological findings, and follow-up data were compared between the two groups.RESULTS: The mean operative time was significantly longer in the LADG group than in the ODG group (259.3 ± 46.2 min vs 199.8 ± 40.85 min; P < 0.05), whereas intraoperative blood loss and postoperative complications were significantly lower (160.2 ± 85.9 mL vs 257.8 ± 151.0 mL; 13.0% vs 24.1%, respectively, P < 0.05). In addition, the time to first flatus, time to initiate oral intake, and postoperative hospital stay were significantly shorter in the LADG group than in the ODG group (3.9 ± 1.4 d vs 4.4 ± 1.5 d; 4.6 ± 1.2 d vs 5.6 ± 2.1 d; and 9.5 ± 2.7 d vs 11.1 ± 4.1 d, respectively; P < 0.05). There was no significant difference between the LADG group and ODG group with regard to the number of harvested lymph nodes. The median followup was 60 mo (range, 5-97 mo). The 1-, 3-, and 5-year disease-free survival rates were 94.3%, 90.2%, and 76.7%, respectively, in the LADG group and 89.5%, 84.7%, and 82.3%, respectively, in the ODG group. The 1-, 3-, and 5-year overall survival rates were 98.0%, 91.9%, and 81.1%, respectively, in the LADG group and 91.5%, 86.9%, and 82.1%, respectively, in the ODG group. There was no significant difference between the two groups with regard to the survival rate. CONCLUSION: LADG is suitable and minimally invasive for treating distal gastric cancer and can achieve si     

Clinicopathologic features of remnant gastric cancer over time following distal gastrectomy

AIM: To investigate remnant gastric cancer(RGC) at various times after gastrectomy, and lay a foundation for the management of RGC.METHODS: Sixty-five patients with RGC 2 years and 10 years after gastrectomy(RGC Ⅰ) and forty-nine with RGC 10 years after gastrectomy(RGC Ⅱ) who underwent curative surgery were enrolled in the study.The clinicopathologic factors, surgical outcomes, and prognosis were compared between RGC Ⅰ and RGC Ⅱ.RESULTS: There was no significant difference in surgical outcomes between RGC Ⅰ and RGC Ⅱ. For patients reconstructed with Billroth Ⅱ, significantly more patients were RGC Ⅱ compared with RGC(71.9%vs 21.2%, P 0.001), and more RGC Ⅱ patients had anastomotic site locations compared to RGC Ⅰ(31.0%vs 56.3%, P = 0.038). The five-year survival rates for the patients with RGC Ⅰ and RGC Ⅱ were 37.6%and 47.9%, respectively, but no significant difference was observed. Borrmann type and tumor stage were confirmed to be independent prognostic factors in both groups.CONCLUSION: RGC Ⅱ is located on the anastomotic site in higher frequency and more cases develop after Billroth Ⅱ reconstruction than RGC Ⅰ.     

Routine diagnosis of intestinal tuberculosis and Crohn’s disease in Southern India

AIM:To investigate whether routinely measured clinical variables could aid in differentiating intestinal tuberculosis(ITB)from Crohn’s disease(CD).METHODS:ITB and CD patients were prospectively included at four South Indian medical centres from October 2009 to July 2012.Routine investigations included case history,physical examination,blood biochemistry,ileocolonoscopy and histopathological examination of biopsies.Patients were followed-up after 2 and 6 mo of treatment.The diagnosis of ITB or CD was re-evaluated after 2 mo of antituberculous chemotherapy or immune suppressive therapy respectively,based on improvement in signs,symptoms and laboratory variables.This study was considered to be an exploratory analysis.Clinical,endoscopic and histopathological features recorded at the time of inclusion were subject to univariate analyses.Disease variables with sufficient number of recordings and P<0.05 were entered into logistic regression models,adjusted for known confounders.Finally,we calculated the odds ratios with respective confidence intervals for variables associated with either ITB or CD.RESULTS:This study included 38 ITB and 37 CD patients.Overall,ITB patients had the lowest body mass index(19.6 vs 22.7,P=0.01)and more commonly reported weight loss(73%vs 38%,P<0.01),watery diarrhoea(64%vs 33%,P=0.01)and rural domicile(58%vs 35%,P<0.05).Endoscopy typically showed mucosal nodularity(17/31 vs 2/37,P<0.01)and histopathology more frequently showed granulomas(10/30vs 2/35,P<0.01).The CD patients more frequently reported malaise(87%vs 64%,P=0.03),nausea(84%vs 56%,P=0.01),pain in the right lower abdominal quadrant on examination(90%vs 54%,P<0.01)and urban domicile(65%vs 42%,P<0.05).In CD,endoscopy typically showed involvement of multiple intestinal segments(27/37 vs 9/31,P<0.01).Using logistic regression analysis we found weight loss and nodularity of the mucosa were independently associated with ITB,with adjusted odds ratios of 8.6(95%CI:2.1-35.6)and 18.9(95%CI:3.5-102.8)respectively.Right lower abdominal quadrant pain on examination and involvement of≥3 intestinal segments were independently associated with CD with adjusted odds ratios of 10.1(95%CI:2.0-51.3)and 5.9(95%CI:1.7-20.6),respectively.CONCLUSION:Weight loss and mucosal nodularity were associated with ITB.Abdominal pain and excessive intestinal involvement were associated with CD.ITB and CD were equally common.     

Factors associated with early virological response to peginterferon-α-2a/ribavirin in chronic hepatitis C

AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to pegin-terferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400 000 vs ≥ 400 000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d).RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventyeight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41%) and 1200 mg/d (41%). The planned treatm