Correlation of human epidermal growth factor receptor 2 expression with clinicopathological characteristics and prognosis in gastric cancer

AIM:To investigate human epidermal growth factor receptor 2(HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristics and survival.METHODS:One hundred and ninety-seven gastric cancer patients who underwent curative surgery procedures were enrolled into this study.HER2 gene amplification and protein expression were examined using fluorescence in-situ hybridization(FISH) and immunohistochemistry(IHC) analysis on formalin-fixed paraffinembedded gastric cancer samples from all patients.For scoring,Hofmann’s HER2 gastric cancer scoring system was adopted.All cases showing IHC3+ or FISH positiv-ity were defined as HER2 positive.Patient clinicopathological data and survival information were collected.Finally,χ 2 statistical analysis was performed to analyze the HER2 positivity rate amongst the subgroups with different clinicopathological characteristics including;gender,age,tumor location,Lauren classification,differentiation,TNM staging,depth of invasion,lymph node metastases and distant metastasis.The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using log rank inspection.RESULTS:According to Hofmann’s HER2 gastric cancer scoring criteria,31 cases(15.74%) were identified as HER2 gene amplified and 19 cases(9.64%) were scored as strongly positive for HER2 membrane staining(3+),25 cases(12.69%) were moderately positive(2+) and 153 cases(77.66%) were HER2 negative(0/1+).The concordance rate between IHC and FISH analyses was 88.83%(175/197).Thirty-six cases were defined as positive for HER2 gene amplification and/or protein expression,with 24 of these cases being eligible for Herceptin treatment according to United States recommendations,and 29 of these cases eligible according to EU recommendations.Highly consistent results were detected between IHC3+,IHC0/1 and FISH(73.68% and 95.42%),but l     

Fibroblast growth factor receptor 4 Gly388Arg polymorphism in Chinese gastric cancer patients

AIM: To investigate the contribution of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism as a genetic risk factor for gastric cancer (GC) and to investigate any associations between this polymorphism and clinicopathological parameters and survival. METHODS: Tumors and matched adjacent non-cancer tissues were collected from 304 GC patients, and 5 mL of venous blood was collected from 62 GC patients and 392 ageand sex-matched healthy controls without cancer history from the same ethnic population. DNA was extracted, and direct sequencing analyses were performed to genotype the FGFR4 Gly388Arg polymorphism in all the samples. Differences in the genotype frequencies of the FGFR4 Gly388Arg polymorphism between GC patients and healthy controls were estimated using the χ 2 test. Binary logistic regression was used for all analysis variables to estimate risk as the ORs with 95%CIs. The relationships between the FGFR4 genotype and clinicopathological parameters were tested with the χ 2 test. The Kaplan-Meier product-limit method, the log-rank test, and the Cox regression model were applied to evaluate the effect of the FGFR4 genotype on the overall survival of patients with GC. RESULTS: In the present GC cohort, 118 patients (38.8%) were homozygous for the Gly388 allele, 124 patients (40.8%) were heterozygous, and 62 patients (20.4%) were homozygous for the Arg388 allele. The frequencies of the Gly/Gly, Gly/Arg, and Arg/Arg genotypes in the healthy controls were 33.6%, 48.0%, and 18.4%, respectively. The distributions of genotypes (χ 2 = 3.589, P = 0.166) and alleles (χ 2 = 0.342, P = 0.559) of the FGFR4 Gly388Arg polymorphism were not different between the GC patients and the healthy controls. Although we observed no correlation between the FGFR4 Gly388Arg polymorphism and clinicopathological parameters or survival in the total cohort of GC patients, the presence of the Arg388 allele was associated with shorter survival time in patients with GC if the tumor was small (log rank χ 2 = 5.449, P =     

Increased expression of DLX2 correlates with advanced stage of gastric adenocarcinoma

AIM:To investigate the expression of distal-less homeobox 2 (DLX2) in gastric adenocarcinoma and its clinicopathological significance. METHODS:Gastric adenocarcinoma tissues were obtained from gastrectomy specimens of 129 patients from the Department of Surgery and Pathology, the Second Affiliated Hospital of Kunming Medical University. Sixty cases of normal gastric tissues were collected from gastrectomy specimens of adjacent gastric cancer margins greater than 5 cm. Patient diagnosis was established pathologically, and no patient had received chemotherapy or radiotherapy before surgery. All tissue specimens were formalin-fixed and paraffin-embedded. Immunohistochemistry was carried out to investigate the expression of DLX2 in 129 gastric adenocarcinoma tissues and 60 adjacent normal tissues. The immunos-taining reaction was semiquantitatively evaluated based on the proportion of positive cells and the median staining intensity in normal gastric epithelial cells or tumor cells. All patients had follow-up records for more than 5 years. Correlations of DLX2 expression with clinicopathological features and prognosis of patients with gastric adenocarcinoma were analyzed. All statistical analyses were performed using the SPSS 17.0 software. RESULTS:The positive expression of DLX2 was detected in 68 (52.7%) cases of 129 gastric adenocarcinoma tissues and 14 (23.3%) cases of 60 adjacent normal tissues. The difference in DLX2 expression between gastric adenocarcinoma tissues and adjacent normal tissues was statistically significant (Ⅹ2 = 14.391, P < 0.001). Moreover, high expression of DLX2 was detected in 48 (37.2%) cases of 129 human gastric cancer tissues, but not in adjacent normal tissues. The expression of DLX2 correlated with the size of tumor (P = 0.001), depth of invasion (P = 0.008), lymph node metastasis (P = 0.023) and tumor-node-metastasis stages (P = 0.020), but was not correlated with age, gender, histological differentiation and distant metastasis. The Kaplan-Meier survival analysis revealed that s     

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     

Overexpression of carbonic anhydrase Ⅱ and Ki-67 proteins in prognosis of gastrointestinal stromal tumors

AIM: To investigate the expression and prognostic value of carbonic anhydrase Ⅱ (CA Ⅱ) and Ki-67 in gastrointestinal stromal tumors (GISTs). METHODS: One hundred and thirteen GIST patients admitted to Chinese People’s Liberation Army General Hospital from January 2004 to December 2010 were retrospectively followed up, and immunohistochemistry was used to detect CA Ⅱ, Ki-67 and CD117 expression in tumor samples. The survival rates of the patients were analyzed using the Kaplan-Meier method. Log-rank test, χ 2 test and Cox proportional hazards model were used to determine the relationships between CA Ⅱ, Ki-67 and CD117 expression and prognostic value in GISTs. RESULTS: The survival rates at 1, 3 and 5 years were 90.0%, 82.0% and 72.0% in all patients. However, in patients with positive CA Ⅱ or Ki-67, the survival rates were 92.0%, 83.0% and 77.0% or 83.0%, 66.6% and 53.0%, respectively. Compared with the negative groups, the survival rates in the positive groups were significantly lower (CA Ⅱ log-rankP = 0.000; Ki-67 logrank P = 0.004). Multivariate Cox analysis revealed that CA Ⅱ, CD117 and Ki-67 were considerable immune factors in prognosis of GIST patients (CA Ⅱ P = 0.043; CD117 P = 0.042; Ki-67 P = 0.007). Besides, tumor diameter, mitotic rate, tumor site, depth of invasion, complete resection, intraoperative rupture, and adjuvant therapy were important prognosis predictive factors. Our study indicated that CA Ⅱ had strong expression in GISTs and the prognosis of GISTs with high CA Ⅱ expression was better than that of GISTs with low or no expression, suggesting that CA Ⅱ is both a diagnostic and prognostic biomarker for GIST. CONCLUSION: CA Ⅱ and Ki-67 are significant prognostic factors for GISTs. CA Ⅱ associated with neovascular endothelia could serve as a potential target for cancer therapy.     

Increased expression of tyrosine phosphatase SHP-2 in Helicobacter pylori-infected gastric cancer

AIM:To explore the alteration of tyrosine phosphatase SHP-2 protein expression in gastric cancer and to assess its prognostic values.METHODS:Three hundred and five consecutive cases of gastric cancer were enrolled into this study.SHP-2 expression was carried out in 305 gastric cancer specimens,of which 83 were paired adjacent normal gastric mucus samples,using a tissue microarray immunohistochemical method.Correlations were analyzed between expression levels of SHP-2 protein and tumor parameters or clinical outcomes.Serum anti-Helicobacter pylori(H.pylori) immunoglobulin G was detected with enzyme-linked immunosorbent assay.Cox proportional hazards model was used to evaluate prognostic values by compassion of the expression levels of SHP-2 and disease-specific survivals in patients.RESULTS:SHP-2 staining was found diffuse mainly in the cytoplasm and the weak staining was also observed in the nucleus in gastric mucosa cells.Thirty-two point five percent of normal epithelial specimen and 62.6% of gastric cancer specimen were identified to stain with SHP-2 antibody positively(P < 0.001).Though SHP-2 staining intensities were stronger in the H.pylori(+) group than in the H.pylori(-) group,no statistically significant difference was found in the expression levels of SHP-2 between H.pylori(+) and H.pylori(-) gastric cancer(P = 0.40).The SHP-2 expression in gastric cancer was not significantly associated with cancer stages,lymph node metastases,and distant metastasis of the tumors(P = 0.34,P = 0.17,P = 0.52).Multivariate analysis demonstrated no correlation between SHP-2 expression and disease-free survival(P = 0.86).CONCLUSION:Increased expression of SHP-2 protein in gastric cancer specimen suggesting the aberrant upregulation of SHP-2 protein might play an important role in the gastric carcinogenesis.     

Overexpression of cyclooxygenase-2 and tumor angiogenesis in human gastric cancer

BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2) protein is overexpressed in various cancers, including esophageal, gastric, colon, and pancreatic. To better comprehend the role of COX-2 in gastric cancer, especially with regard to angiogenesis, we investigated COX-2 and vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) in 108 patients with gastric cancer. METHODOLOGY: We used immunohistochemical analysis of formalin-fixed tissues of gastric cancer. RESULTS: Expression of COX-2 showed diffuse staining in the cytoplasm of tumor cells, however, no staining in normal epithelial cells. Of the 108 tumors examined, 71 (65%) were positive for COX-2 expression, the VEGF-positive cases numbered 43 of 108 cases (39.8%). The intensity of COX-2 expression did not correlate with any clinicopathological characteristics. The positive rate of VEGF expression in COX-2-positive cases was significantly higher than in COX-2-negative ones (47.9% vs. 24.3%, P<0.05). MVD in COX-2-positive cases was significantly higher than in COX-2-negative ones (22.0+/-7.8 vs. 18.5+/-7.5/1 mm2; P<0.05). CONCLUSIONS: Our study provides evidence that COX-2 is closely related with angiogenesis.     

Missed diagnosis of early gastric cancer or high-grade intraepithelial neoplasia

AIM: To investigate the causes of missed diagnosis of early gastric cancer (EGC) or high-grade intraepithelial neoplasia (HGIN) in Chongqing, China. METHODS: The present study summarizes 103 cases of EGC/HGIN detected by esophagogastroduodenos-copy (EGD) and pathological analysis from January 2010 to December 2011. Dimethyl silicone oil was administrated orally 15 min before the EGD procedures. The stomach was cleaned by repeated washing with saline when the gastroscope entered the stomach cavity. Suspected EGC lesions were subject to conventional biopsy sampling and pathological examinations. The correlation between lesion locations, endoscopic morphology of cancerous sites, training level of the examiners, pathological biopsies, and missed diagnosis was analyzed. RESULTS: Twenty-three cases were missed among the 103 cases (22.23%) of EGC/HGIN. The rate of missed EGC in the gastroesophageal junction (8/19, 42.1%) was significantly higher than at other sites (15/84, 17.86%) (χ2 = 5.253, P = 0.022). In contrast, the rate of missed EGC in the lower stomach body (2/14, 14.29%) was lower than at other sites (21/89,23.6%), but there were no significant differences (χ2 = 0.289, P = 0.591). The rate of missed EGC in the gastric antrum (5/33, 15.15%) was lower than at other sites (18/70, 25.71%), but there were no significant differences (χ2 = 1.443, P = 0.230). Endoscopists from less prestigious hospitals were more prone to not diagnosing EGC than those from more prestigious hospitals (χ2 = 4.261, P = 0.039). When the number of biopsies was < 4, the rate of missed diagnosis was higher (20/23, 89.96%) than for when there were > 4 biopsies (3/23, 13.04%) (P < 0.001). In addition, there was no significant difference in the rate of missed diagnosis in patients with 1-3 biopsy specimens (χ2 = 0.141, P = 0.932). CONCLUSION: Endoscopists should have a clear understanding of the anatomical characteristics of the esophagus/stomach, and endoscopic identification of early lesions increases with the number of biopsie     

&beta;-elemene enhances the radiosensitivity of gastric cancer cells by inhibiting Pak1 activation

AIM: To explore the potential of β-elemene as a radiosensitizer for gastric cancer cells and the underlying mechanisms. METHODS: SGC7901, MKN45, MKN28, N87, and AGS human gastric cancer cell lines were used to screen for radioresistant gastric cancer cell lines. A 3-(4,5-dimeth-ylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay was used to determine the effects of β-elemene and IPA-3 on cell viability in MKN45 and SGC7901 gastric cancer cell lines. A clonogenic survival assay and annexin V-FITC/PI apoptosis detection assay were used to evaluate cellular radiosensitivity and radiation-induced cell death, respectively. A proteomic method, isobaric tags for relative and absolute quantitation (iTRAQ), was employed to screen the proteins regulated by β-elemene pretreatment prior to ionizing radiation (IR) in SGC7901 gastric cancer cell line. IPA-3 was used as a specific small molecule inhibitor of p21-activated protein kinase 1 (Pak1) to target Pak1 signaling. Protein levels of PAK1IP1 (p21-activated protein kinase-interacting protein 1), total Pak1 (t-Pak1), phospho-Pak1 (T423), phospho-ERK1/2 (Thr202/Tyr204), and cleaved caspase-3 (17 kDa) were assessed by western blotting. RESULTS: MKN45 and SGC7901 gastric cancer cell lines were relatively more resistant to IR. β-elemene pretreatment decreased clonogenic survival following IR in MKN45 and SGC7901 gastric cancer cell lines. Additionally, β-elemene pretreatment prior to IR increased radiation-induced cell death compared with IR alone in MKN45 (10.4% ± 0.9% vs 34.8% ± 2.8%, P < 0.05) and SGC7901 (11.6% ± 0.9% vs 46.7% ± 5.2%, P < 0.05) human gastric cancer cell lines, respectively, consistent with the level of cleaved caspase-3 (17 kDa). Through iTRAQ analysis and western blot validation, we found that β-elemene upregulated PAK1IP1 and downregulated phospho-Pak1 (T423) and phospho-ERK1/2 in SGC7901 gastric cancer cells. IR increased the level of phospho-Pak1 (T423). Pretreatment with β-elemene decreased radiation-induced Pak1 and ERK1/2 phosphorylation. Inhibition of Pak1 using IPA-3 decreased clonogenic survival following IR. In addition, IPA-3 increased radiation-induced cell death in MKN45 (13.4% ± 0.3% vs 26.6% ± 1.0%, P < 0.05) and SGC7901 (16.0% ± 0.6% vs 37.3% ± 1.7%, P < 0.05) gastric cancer cell lines, respectively, consistent with the level of cleaved caspase-3 (17 kDa). Western blotting showed that IPA-3 decreased radiation-induced Pak1 and ERK1/2 phosphorylation. CONCLUSION: This is the first demonstration that β-elemene enhances radiosensitivity of gastric cancer cells, and that the mechanism involves inhibition of Pak1 signaling.     

Studies on surgical operations and prognosis of extrahepatic bile duct cancer

AIM: To perform a clinical evaluation of the surgical procedures of extrahepatic bile duct cancer and their influence on prognosis. METHODS: A total of 55 patients with pathologically and clinically verified extrahepatic bile duct cancer treated in our department between January 1984 and December 1993 were analyzed retrospectively. Clinical courses, with respect to the surgical procedures, investigated by follow-up and the survival period was assessed. RESULTS: Among the 55 patients, 24 received surgery that involved the upper third of extrahepatic biliary tract, 12 involving the middle third, and 19 involving the lower third. The diagnosis of bile duct cancer was confirmed histopathologically in 42 of the patients, with a clear predominance of adenocarcinoma (97.6%). Eleven (26.2%) of the patients received curative resection, 30 received palliative procedures (i.e. biliary-enteric bypass (n = 14) and external drainage (n = 16)), 6 received permanent percutaneous transhepatic cholangio-drainage (PTCD) alone, and 8 received exploratory laparotomy only or conservative treatment. Forty-eight patients (87.3%) were followed-up. The overall mean survival period was 10.8 ± 9.7 mo (¯x ± s); patients with curative resection had the longest survival period (21.4 ± 16.7 mo, P < 0.01) and highest survival rate (P < 0.05). A significant survival difference was observed for patients with biliary-enteric anastomosis as compared with those who had external drainage, etc. (P < 0.05), but there was no significant difference in survival period between patients who had preoperative PTCD (n = 23) and those who did not (n = 26) (P < 0.05). CONCLUSION: Curative resection is the treatment of choice for suitable patients with extrahepatic bile duct cancer; biliary-enteric anastomosis is preferable for those with unresectable tumor in order to improve prognosis and quality of life.     

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.     

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.     

肝细胞癌癌组织Hic-5和COL1A1表达及其对术后生存的预测价值*

目的 探讨肝细胞癌(HCC)组织氧化氢诱导的克隆基因-5(Hic-5)和I型胶原α1链(COL1A1)表达及其对HCC患者术后生存时间的预测价值。方法 2013年9月～2016年7月我院行肝癌切除术的HCC患者97例,术后取癌组织和癌旁肝组织。采用RT-PCR法和免疫组化法分别检测组织Hic-5和COL1A1 mRNA和蛋白表达。随访3年。结果 HCC患者癌组织Hic-5蛋白表达阳性率为53.6%,显著高于癌旁组织(16.5%,P＜0.05),其mRNA阳性率为66.0%,也显著高于癌旁组织(25.8%,P＜0.05);HCC患者癌组织COL1A1蛋白表达阳性率为71.1%,显著高于癌旁组织(25.8%,P＜0.05),其mRNA阳性率为78.4%,也显著高于癌旁组织(30.9%,P＜0.05);TNM Ⅰ～Ⅱ期患者癌组织Hic-5 mRNA阳性率为56.4%,显著低于Ⅲ～Ⅳ期者(78.6%,P＜0.05),COL1A1 mRNA阳性率为70.9%,也显著低于Ⅲ～Ⅳ期者(88.1%,P＜0.05),存在门静脉癌栓患者癌组织Hic-5 mRNA阳性率为82.5%,显著高于无门静脉癌栓者(54.4%,P＜0.05),COL1A1 mRNA阳性率为90.0%,显著高于无门静脉癌栓者(70.2%,P＜0.05);随访的87例患者生存时间为8.2~36.0个月,中位生存时间为36.0(14.6,36.0)个月;癌组织Hic-5阳性表达患者3 a生存时间为26.3(16.1,36.0)月,显著短于Hic-5阴性者【36.0(30.6,36.0),P＜0.05】,3 a无事件生存时间为21.4(11.7,36.0)月,也显著短于Hic-5阴性者【36.0(24.2,36.0),P＜0.05】。结论 HCC患者癌组织Hic-5阳性表达预示术后生存时间缩短,其原因可能与肿瘤分期差或门静脉存在癌栓有关。     

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.     

Transjugular intrahepatic portosystemic shunt vs endoscopic therapy in preventing variceal rebleeding

AIM:To compare early use of transjugular intrahepatic portosystemic shunt(TIPS) with endoscopic treatment(ET) for the prophylaxis of recurrent variceal bleeding.METHODS:In-patient data were collected from 190 patients between January 2007 and June 2010 who suffured from variceal bleeding.Patients who were older than 75 years;previously received surgical treatment or endoscopic therapy for variceal bleeding;and complicated with hepatic encephalopathy or hepatic cancer,were excluded from this research.Thirty-five cases lost to follow-up were also excluded.Retrospective analysis was done in 126 eligible cases.Among them,64 patients received TIPS(TIPS group) while 62 patients received endoscopic therapy(ET group).The relevant data were collected by patient review or telephone calls.The occurrence of rebleeding,hepatic encephalopathy or other complications,survival rateand cost of treatment were compared between the two groups.RESULTS:During the follow-up period(median,20.7 and 18.7 mo in TIPS and ET groups,respectively),rebleeding from any source occurred in 11 patients in the TIPS group as compared with 31 patients in the ET group(Kaplan-Meier analysis and log-rank test,P = 0.000).Rebleeding rates at any time point(6 wk,1 year and 2 year) in the TIPS group were lower than in the ET group(Bonferroni correction α' = α/3).Eight patients in the TIPS group and 16 in the ET group died with the cumulative survival rates of 80.6% and 64.9%(Kaplan-Meier analysis and log-rank test c2 = 4.864,P = 0.02),respectively.There was no significant difference between the two groups with respect to 6-wk survival rates(Bonferroni correction α' = α/3).However,significant differences were observed between the two groups in the 1-year survival rates(92% and 79%) and the 2-year survival rates(89% and 64.9%)(Bonferroni correction α' = α/3).No significant differences were observed between the two treatment groups in the occurrence of hepatic encephalopathy(12 patients in TIPS group and 5 in ET group,KaplanMeier analysis and log-rank test,c2 = 3.103,P = 0.08).The average total cost for the TIPS group was higher than for ET group(Wilcxon-Mann Whitney test,52 678 RMB vs 38 844 RMB,P 0.05),but hospitalization frequency and hospital stay during follow-up period were lower(Wilcxon-Mann Whitney test,0.4 d vs 1.3 d,P = 0.01;5 d vs 19 d,P 0.05).CONCLUSION:Early use of TIPS is more effective than endoscopic treatment in preventing variceal rebleeding and improving survival rate,and does not increase occurrence of hepatic encephalopathy.     

Prognostic and survival analysis of 837 Chinese colorectal cancer patients

AIM:To develop a prognostic model to predict survival of patients with colorectal cancer (CRC). METHODS:Survival data of 837 CRC patients undergoing surgery between 1996 and 2006 were collected and analyzed by univariate analysis and Cox proportional hazard regression model to reveal the prognostic factors for CRC. All data were recorded using a standard data form and analyzed using SPSS version 18.0 (SPSS, Chicago, IL, United States). Survival curves were calculated by the Kaplan-Meier method. The log rank test was used to assess differences in survival. Univariate hazard ratios and significant and independent predictors of disease-specific survival and were identified by Cox proportional hazard analysis. The stepwise procedure was set to a threshold of 0.05. Statistical significance was defined asP < 0.05. RESULTS:The survival rate was 74% at 3 years and 68% at 5 years. The results of univariate analysis suggested age, preoperative obstruction, serum carcinoembryonic antigen level at diagnosis, status of resection, tumor size, histological grade, pathological type, lymphovascular invasion, invasion of adjacent organs, and tumor node metastasis (TNM) staging were positive prognostic factors (P < 0.05). Lymph node ratio (LNR) was also a strong prognostic factor in stage Ⅲ CRC (P < 0.0001). We divided 341 stage Ⅲ patients into three groups according to LNR values (LNR1, LNR ≤ 0.33, n = 211; LNR2, LNR 0.34-0.66, n = 76; and LNR3, LNR ≥ 0.67, n = 54). Univariate analysis showed a significant statistical difference in 3-year survival among these groups:LNR1, 73%; LNR2, 55%; and LNR3, 42% (P < 0.0001). The multivariate analysis results showed that histological grade, depth of bowel wall invasion, and number of metastatic lymph nodes were the most important prognostic factors for CRC if we did not consider the interaction of the TNM staging system (P < 0.05). When the TNM staging was taken into account, histological grade lost its statistical significance, while the specific TNM staging system s     

Surgical management of patients with bowel obstructions secondary to gastric cancer

AIM: To assess whole-body fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the management of small bowel obstructions (SBOs) secondary to gastric cancer and its role in treatment strategies. METHODS: The medical records of all of the patients who were admitted for an intestinal obstruction after curative resection for gastric cancer were retrospectively reviewed. PET/CT was performed before a clinical treatment strategy was established for each patient. The patients were divided into 2 groups: patients with no evidence of a tumor recurrence and patients with evidence of a tumor recurrence. Tumor recurrences included a local recurrence, peritoneal carcinomatosis or distant metastases. The primary endpoint was the 1-year survival rate, and other variables included patient demographics, the length of hospital stay, complications, and mortality. RESULTS: The median time between a diagnosis of gastric cancer and the detection of a SBO was 1.4 years. Overall, 31 of 65 patients (47.7%) had evidence of a tumor recurrence on the PET/CT scan, which was the only factor that was associated with poor survival. Open and close surgery was the main type of surgical procedure reported for the patients with tumor recurrences. R0 resections were performed in 2 patients, including 1 who underwent combined adjacent organ resection. In the group with no evidence of a tumor recurrence on PET/CT, bowel resections were performed in 7 patients, adhesiolysis was performed in 7 patients, and a bypass was performed in 1 patient. The 1-year survival curves according to PET/CT evidence of a tumor recurrence vs no PET/CT evidence of a tumor recurrence were significantly different, and the 1-year survival rates were 8.8% vs 93.5%, respectively. There were no significant differences (P = 0.71) in the 1-year survival rates based on surgical vs nonsurgical management (0% with nonoperative treatment vs 20% after exploratory laparotomy). CONCLUSION: 18 F-FDG PET/CT can be used to identify the causes of bowel obst     

Correlation of postoperative survival and angiogenic growth factors in pancreatic carcinoma

BACKGROUND/AIMS: VEGF (vascular endothelial growth factor) and EGF (epidermal growth factor) are promoters of angiogenesis. It was the aim of this study to investigate a possible coexpression of both growth factors in tumor samples of pancreatic cancer patients in relation to survival after resection of the tumor. METHODOLOGY: We investigated the expression of VEGF165 and EGF in tumor specimen from 19 patients that underwent pancreaticoduodenectomy. Growth factor expression was determined using immunohistochemical methods. RESULTS: Coexpression of VEGF165 and EGF was observed in tumor samples of 9 (47%) patients. VEGF165 and EGF expression in the same tumor correlates significantly (P < 0.05, Fisher-test). UICC stage III pancreatic carcinoma patients with VEGF165 negative tumor cells had a significantly better outcome after surgery compared to UICC stage III patients with VEGF165-positive tumor cells (median survival time 19 months vs. 9 months respectively; P < 0.05, Wilcoxon-test). CONCLUSIONS: Antiangiogenic therapy after surgery for pancreatic cancer may be beneficial, especially for UICC III patients.