Search

The association between skeletal muscle status and gastric cancer (GC) prognosis remains unclear. Here, we investigated the impact of the skeletal muscle index (SMI) on overall survival (OS) in GC patients after radical gastrectomy.We divided 178 patients into four groups: adult men, adult women, elderly men and elderly women. The SMI, calculated using CT images, of patients was graded using cutoff values of group-specific tertiles. Age, body mass index, SMI grade, Charlson comorbidity index, surgical method (total vs distal gastrectomy), tumor stage, and histological type and differentiation were included in Cox regression models to assess the primary outcome parameter of OS. A new prognostic score for 3- year OS was established by combining the SMI grade and tumor stage, and receiver operating characteristic (ROC) curve analyses were used to determine its predictive reliability.For groups with high, medium, and low SMI grades, the 3-year OS rates were 94.04, 79.08 and 59.09% and 86.09, 70.11 and 49.11% (p0.001) in patients undergoing distal and total gastrectomy, respectively. In the multivariate analysis, low SMI (hazard ratio (HR) 1.82, 95% confidence interval (CI) 1.14-2.9), advanced stage (HR 2.89, 95% CI 1.43-5.83), and total gastrectomy (HR 1.69, 95% CI 0.95-3.01) were independent risk factors for OS (p0.010). The areas under the ROC curves for the prognostic score were 0.77 (range 0.61-0.93) and 0.76 (range 0.65-0.86) in patients undergoing distal and total gastrectomy, respectively.The preoperative SMI was an independent prognostic factor for long-term survival in GC patients after radical gastrectomy.

To explore the expressions of S100A8 and S100A9 in gastric cancer.A total of 176 patients with gastric cancer, including 124 males and 52 females, were recruit from 1998 to 2004, average age 57(26-80)years. The expressions of S100A8 (n = 125) , S100A9 (n = 176) and S100A8/A9 heterodimer (calprotectin) in gastric tissue samples were assessed by immunohistochemistry and immunofluorescence. The co-localization of S100A9 and its dimerization partner S100A8 and heterodimer S100A8/A9 were examined by laser confocal scanning.Receiver operator characteristic (ROC) curve was used in determining the cut-off value of S100A9 and S100A8-positive inflammatory cell counts in evaluating the pathological TNM stage. To obtain associations between S100A9 or S100A8 cell counts and clinicopathologic variables, the data were cross-tabulated and χ(2)-test was performed. Cumulative survival was estimated by the Kaplan-Meier method.ROC curves using the S100A9 and S100A8-positive inflammatory cell counts were 0.623 and 0.522 for pathological TNM stages respectively. The cutoff values were 200 and 65 per 200× magnification field with a sensitivity of 61.48% and 51.09% and a specificity of 64.29% and 51.52% respectively. Patients with S100A9 positive expression (n = 77) had better overall survival than negative expression(n = 99) ((35.1 ± 10.8) vs (20.3 ± 3.0) months, P = 0.021). There was no statistical significance between S100A8 positive expression(n = 62) and negative expression(n = 63) ((26.4 ± 2.8) vs (29.5 ± 2.9) months, P = 0.145).In gastric cancer tissues, both S100A9 and S100A8 proteins were detected in tumor-infiltrating inflammatory cells while no case of S100A8/A9 heterodimer was found. In addition, S100A9 and S100A8 proteins were detected in inflammatory cells in chronic gastritis. Distribution of these two proteins also partly overlapped.S100A9 positive expression in gastric cancer tissues is associated with an excellent prognosis. But S100A8 positive expression has no prognostic association. Calprotectin expression differs between gastric cancer and gastritis.Further explorations are warranted.

To evaluate the effect of perioperative imatinib mesylate (IM) therapy for patients with initial resectable primary local advanced gastrointestinal stromal tumor (GIST) at intermediate or high risk on R0 resection rate and the prognosis.Forty-eight above GIST patients between December 2001 and February 2012 were divided into 2 groups: neoadjuvant group (15 cases, pre- and post-operation IM therapy) and adjuvant group (33 cases, post-operative IM therapy). R0 resection rate, complication rate, disease-free survival (DFS) and overall survival (OS) were analyzed and compared between the two groups.The maximal tumor diameter and average tumor diameter were larger in neoadjuvant group as compared to adjuvant group (11.2 cm vs. 7.7 cm, P=0.005; 9.1 cm vs. 6.2 cm, P=0.014). The response rate of preoperative IM therapy was 93.3% (14/15). The R0 resection rate was 86.7% and 84.8% (P=1.000), and the complication rate was 13.3% and 9.1% (P=0.642) in neoadjuvant and adjuvant group respectively. The 3-year DFS was 55% and 41% (P=0.935), and 5-year OS was 83% and 75% (P=0.766) in neoadjuvant and adjuvant group respectively.Resectable primary local advanced GIST at intermediate or high risk with larger tumor diameter receiving perioperative IM therapy can achieve the same R0 resection rate, complication rate, DFS and OS as the GIST with smaller diameter receiving operation first. Perioperative IM therapy has potential advantage.

To explore the expression of CCAAT/enhancer binding protein beta (CEBPB) in gastric carcinoma tissues and its association with clinicopathological features and prognosis.CEBPB protein expression level was detected by immunohistochemistry method in resected gastric carcinomas and adjacent gastric mucosa tissues (n=81), and its association with clinicopathological features and prognosis was analyzed.The immunohistochemical staining of CEBPB was predominantly in the nucleus with some cytoplasmic staining. As a result, 16% (13/81) of the gastric carcinomas were stained positively, whereas there was hardly positive expression in adjacent gastric mucosa tissues. There was a significant association between the expression of CEBPB and distant metastasis on univariate analysis (P0.05). The median survival time in patients with positive CEBPB expression was significantly lower than those with negative CEBPB expression (19.4 months vs. 45.2 months, P=0.024). Multivariable analysis showed that CEBPB was independently associated with prognosis (HR=2.544, 95%CI:1.154-5.610, P=0.021).Up-regulation of CEBPB suggests poor prognosis in patients with gastric cancer.

The secreted phospholipase A2 type IIA (PLA2G2A) gene has been identified as a modifier of intestinal adenoma multiplicity in Apc(Min/+) mice. The aim of the present study was to analyse the clinical significance of PLA2G2A expression in human gastric cancer. Using immunohistochemistry, cytoplasmic immunoreactivity of PLA2G2A was observed in 27% (40 of 149) of gastric cancer tissues compared with negative staining in normal mucosa. The PLA2G2A expression rate in well-differentiated carcinoma was elevated significantly compared with that in poorly differentiated carcinoma (46% versus 19%, P = 0.001). Statistical analysis also revealed that PLA2G2A expression correlated negatively with depth of mural invasion, lymph node metastasis and tumour-node-metastasis (TNM) stage (P 0.05). Patients with positive PLA2G2A expression showed higher 5-year overall survival than those with negative expression (P = 0.0004). In intestinal metaplasia, PLA2G2A was found to be abundant in Paneth cells. The coexistence of PLA2G2A and lysozyme was observed in Paneth cell-rich gastric cancer (P 0.0001). PLA2G2A may predict survival and might be a potential biomarker for early detection and individualized therapy.

To study the status of splenic hilar lymph nodes(No.4sa, No.10 or No.11d lymph nodes) metastasis and to investigate the proper dissection technique in patients with advanced gastric cancer.A retrospective study was performed to investigate 590 patients who underwent D2 curative proximal or total gastrectomy for gastric carcinoma from January 2006 to December 2009. Clinicopathological factors such as sex, age, location of the primary tumor, tumor sizes, gross type, depth of invasion, microscopic classification, neoadjuvant chemotherapy and the metastasis of adjacent lymph node were analyzed with univariate and multivariate analysis. Influence of combined splenectomy or pancreatectomy on lymph node dissection was also investigated.The overall ratio of metastatic lymph node(positive lymph nodes/lymph nodes harvested) in the splenic hilum was 17.5%(99/565). The positive rates of No.4sa, No.10, No.11d lymph nodes were 17.8% (41/230), 13.9%(29/209), and 22.8%(29/127), respectively. A total of 7.1%(42/590) of the patients had lymph node metastasis in the splenic hilum. Multivariable logistic regression analysis showed that age, tumor size, depth of tumor invasion, positive metastasis of No.4sb lymph node were independent risk factors for lymph node metastasis in the splenic hilum region. When comparing patients undergoing combined splenectomy or pancreatectomy(n=23) and those who did not undergo combined organ resection (n=553), the ratios of metastatic lymph node in the splenic hilum were 14.8%(4/27) and 17.2%(91/527), respectively, and the difference was not statistically significant(P0.05). The postoperative complication rates were 26.1%(6/23) and 5.4%(30/553), respectively, and the difference was statistically significant(P0.05). The operative mortality rates were 4.3% and 0.9%, respectively, and the difference was not statistically significant(P0.05).Metastasis to lymph nodes in the splenic hilum region in patients with gastric cancer possesses a certain pattern, and it is associated with tumor location, size, depth of invasion, and metastasis in No.4sb. Combined resection of the spleen or pancreas does not result in increased number of harvested lymph nodes or positive lymph nodes, yet is associated with higher complication rate. Therefore, combined organ resection should be meticulous.

To observe the clinicopathological characteristics of gastric cancer with pathological complete response(pCR) following neoadjuvant chemotherapy.Data of gastric cancer patients who received neoadjuvant chemotherapy from 2002 to 2008 in the Beijing Cancer Hospital were reviewed. Five cases were found to have pCR. The slides were reviewed by two experienced pathologists independently. Histological structure, morphology of tumor cells, morphology and quantity of stromal cells were evaluated.Structure of the gastric wall was distinguishable in all the 5 cases, while distortion and rupture of muscular layer were found in 2 cases. Exudative inflammatory reaction was present in the whole gastric wall including the serosa layer. Three patients had ulcerative lesions with epithelial layer shedding, and atypical hyperplasia was found around the border of the ulcer, and vascular endothelial cells were swollen. Residual distorted necrotic tumor cells resided in 1 case only and no residual tumor cells was present in the other 4 patients. Significant hyperplasia of fibroblasts was present in 4 cases, large amount of lymphocytes infiltration in 3 cases including concurrent plasma cell infiltration in 1 case, multinucleated giant cell reaction in the muscular layer of 1 case, and foam cells aggregation in 1 case with mucinous adenocarcinoma. In addition, there were 2 cases with pCR had lymph node metastasis.For cases with pCR following neoadjuvant chemotherapy, heterogeneity of stromal cells reaction is found in previous tumor site. Furthermore, the response of primary tumor does not necessarily parallel to that of lymph nodes.

To compare the expression of human epidermal growth factor receptor 2 (HER2) under different scoring systems in gastroesophageal cancer and its relationship with clinicopathological features.Clinicopathological data were retrospectively reviewed of 127 patients with gastroesophageal cancer between January and December 2009 in the Department of Surgery at the Cancer Hospital of Peking University. Tumor specimens were collected. The expression of HER2 protein was detected by immunohistochemistry.HER2 positive rate(++/+++) in gastroesophageal cancer was 15.0%(19/127) with both new and traditional immunohistochemical scoring systems, while HER2 strong positive rate(+++) was 10.2%(13/127) and 6.3%(8/127), respectively(P=0.26). Univariate analysis showed that the expression rate of HER2 protein was associated with differentiation and Lauren classification of the tumor. Multivariable analysis showed that TNM staging and tumor differentiation were independently associated with the expression of HER2 protein(both P0.05).There is no change in HER2 positive rate in gastroesophageal cancer between the new and traditional immunohistochemical scoring systems. Expression of HER2 is associated with clinicopathological features in the gastroesophageal cancer.

To clarify the important clinicopathological and therapeutical factors affecting the prognosis of patients with gastroesophageal junction carcinoma.Data of 514 cases with gastroesophageal junction carcinoma who underwent surgical treatment from September 1995 to January 2007 was retrospectively analyzed. Relevant prognostic factors were studied with univariate and multivariate analysis.For all 514 cases (424 men and 90 women), the median age was 63 years. The 1-, 3- and 5-year survival rates of this group were 74.8%, 42.1% and 29.1%, respectively. Gross type, TNM classification, histological type, vascular invasion and extent of surgical resection affected patients' survival remarkably. There was no significant difference in survival between operative approaches (via laparotomy or left thoracotomy) (P0.05). Long-term survival was similar between proximal subtotal gastrectomy and total gastrectomy in advanced cases (P0.05). For stage II and III tumors, patients with neoadjuvant chemotherapy had better prognosis than those without (P0.05). Cox multivariate regression analysis revealed TNM classification and vascular invasion were independent prognostic factors.TNM classification and vascular invasion are independent prognostic factors for gastroesophageal junction carcinoma. Neoadjuvant chemotherapy may improve prognosis of the patients with stage II and III tumors. Radical resection should be achieved with rational surgical procedures tailored by tumor position, size, staging and so on.

Human epidermal growth factor 2 (HER2) is one of the most important prediction factors, but only 25% - 30% of breast cancer patients HER2 are positive. It is unknown whether there are other molecular markers that could be used to predict prognosis and recurrence in HER2 negative patients. This study investigated correlations of cyclin A2 and HER2 levels with clinical outcomes in 281 patients with invasive breast cancer in order to identify whether cyclin A2 can serve as a prognostic factor in HER2 negative patients.Immunohistochemical staining was used to detect cyclin A2 and HER2 expression in 281 patients. Cyclin A2 and HER2 gene amplifications were analyzed using gene analysis and RT-PCR in 12 patients. Risk and survival estimates were analyzed using Log-rank, Kaplan-Meier, and Cox regression analysis; cyclin A2 and HER2 consistency with survival were analyzed using Kappa analysis.Patients with higher cyclin A2 and HER2 expressions had significantly shorter disease-free survival periods (P = 0.047 and P = 0.05, respectively). Kappa analysis performed that cyclin A2 and HER2 showed a low Kappa index (kappa = 0.37), allowing us to conclude that cyclin A2 and HER2 detect different pathologies. Gene analysis and RT-PCR showed that cyclin A2 was upregulated in patients with early relapse; the average increase was 3.69 - 2.74 fold.Cyclin A2 and HER2 are associated with proliferation and high recurrence, particularly when combined. Cyclin A2 is easily detected by nuclear staining and might be a useful biomarker for recurrence risk in HER2 negative patients.

To explore the pattern of lymph node metastasis and its influence on the prognosis of early gastric cancer(EGC).The pattern of lymph node metastasis and the 3-,5-year survival rates in 157 EGC patients undergone surgery from October 1995 to October 2005 were analyzed retrospectively. The SPSS 11.5 statistics software was used to perform univariate and multivariate analysis.Twenty-two cases had lymph node metastasis among 157 EGC patients(14%). Two mucous cancers(2.4%) and 20 submucosal tumors(27.0%) had lymph node metastases (P0.01). Lymph node metastasis was not seen in minute gastric cancer(diameteror =0.5 cm). Lymph node metastasis rates were 6.4% in the cancers with diameter 1.1-2.0 cm and 21.5% in the cancers with the diameter2.0 cm(P0.01). Besides, lymph node metastasis rate of well-differentiated EGC was 0, of moderate differentiated EGC 11.1%, and poor-differentiated EGC 0.9%(P0.01). Of 9 cases with vascular cancer embolus, 4 had lymph node metastases. Logistic regression analysis showed that tumor size, vascular cancer embolus, histopathological type and depth of invasion were independent factors of lymph node metastasis in EGC. The 3- and 5-year survival rates of EGC patients with lymph node metastasis were 81.6 % and 79.5% respectively, which were much lower than those without lymph node metastasis(95.7% and 93.2%, P0.01).Lymph node metastasis in EGC is mainly correlated with depth of infiltration, tumor size, vascular cancer embolus and differentiation. For EGC treatment, choice should be made reasonably based on the risk of lymph node metastasis.

To explore the CT criteria for evaluating lymph node (LN) metastasis and preoperative N-staging of gastric cancer through the comparison of CT signs and surgical pathology.Eighty-nine patients with gastric cancer underwent CT examinations before radical resections. A soft-reading method on PACS workstation was employed to evaluate the detection of LNs. The size and number of LNs were registered, and the accumulated size of LNs was calculated in every case. The pathological N-staging (pN(0-3)) was considered on the basis of pathological examination of excised specimens according to UICC TNM-staging system (6th edition, 2002). The relationships between LN metastases and CT findings were analyzed by SPSS using t test and one-way ANOVA analysis.The distribution of maximal size, CT detection number and accumulated size were significantly different among different pN stages (P0.01). All these 3 indicators were significantly different between LN metastasis group and non-metastasis group (P0.01). There was no significant difference of maximal size among different pN stages in positive metastasis LNs (P0.05), while significant difference could be found in CT detection number between pN1 and pN3 (P0.01), pN2 and pN3 (P0.01), and in accumulated size between pN1 and pN3 (P0.01), pN1 and pN2 (P0.01).The involvement of LNs in gastric cancer and pN staging are associated with size, number, and accumulated size of CT detection. CT detection number is more valuable in the evaluation of N staging than LNs size. CT detection number combined with accumulated size of LNs can provide meaningful information for preoperative N-staging.

Survivin, a potential predictive marker to chemotherapeutic drugs, reduces the susceptibility of tumor cells to proapoptotic stimuli, thereby promoting tumor cell survival during tumor treatment with anticancer agents. In the present study, we examined the correlation between drug-response and expression of survivin in gastric cancer.Drug-response was performed by histoculture drug-response assay (HDRA) in 42 patients with advanced gastric cancer. Survivin variants was studied by real-time RT-PCR at mRNA levels.In our data, twenty-one cases (50%) were sensitive to at least one of drugs tested in the HDRA and 80% (16/20) were positively confirmed clinically, with 100% sensitivity and 83.3% specificity. The diagnostic efficacy of the HDRA were calculated as the area under the receiver operating characteristic (AUC-ROC) curve and showed a value of 0.917. More importantly, significant statistical differences (p=0.012) in chemoresponse to docetaxel were revealed depending on the mRNA level of wild-type survivin.These clinical data demonstrated, for the first time, that wild-type survivin is useful for evaluating the docetaxel-response in patients with gastric cancer. Moreover, the HDRA is an excellent clinical useful drug-response assay for patients to individualize their chemotherapy.

To assess the antitumor activity and safety of aromatase inhibitors in advanced breast cancer.Fifty-two advanced and female breast cancer patients with measurable and /or bone valuable tumor lesions were observed from June 2003 to September 2006. They were treated by aromatase inhibitors for at least 24 weeks, of whom 11 were treated less than 24 weeks because of disease progress; their age range was from 37 to 75 years (median 58); 8 patients were pre-menopausal, 6 with ovarian ablation and 2 with Goserelin to suppress ovarian function. Thirty-six patients were treated with exemestane, 13 with anastrozole and 3 with letrozole. Major items were observed including objective response rate (ORR=CR+PR), clinical benefit rate (CBR=CR+PR+SDor=24 weeks), time to progress (TTP), time to failure (TTF), safety and toxicity.CR were 6 cases (11.5%) , with 1 case going on for 152 weeks, 1 case for 96 weeks, and other 4 cases for longer than 60 weeks; PR were 19 cases (36.5%), lasting 32-96 weeks; 16 cases obtained SDor=24 weeks(30.8%); and 11 cases PD (progress of disease)+SD24 weeks (21.2%). ORR were 48%, CBR 78.8%, and TTP 78.87 weeks (95% CI 61.13%-96.61%); although the patients who did not achieve objective response (group B) were treated with chemotherapy, radiotherapy or another kind of aromatase inhibitor, but their survival time was significantly different from that of the patients who achieved objective response (group A) when defined by Kaplan-Meier survival estimate. The over survival was 92% in group A, and 81.5% in group B when patients follow up more than 24 weeks [Log Rank (Mantel-Cox) analysis, chi2=3.85, P=0.047]; side effects were observed such as arthralgia, sweating, hot flash, and 2 patients developed heart failure with uncertain related drug before recovery.The single agent effective rate of aromatase inhibitor was 48%. The patients had long term survival if they obtained CR or PR, and the side effects were well tolerated.

To elucidate the clinicopathological features of solid pseudopapillary tumor (SPT) of the pancreas.Eight patients with SPT of the pancreas admitted from August 1996 to March 2005 were retrospectively analyzed.All the 8 patients were female with an average age of 25.3 (13-41) years. The primary clinical manifestations included abdominal mass (n = 3), vague abdominal pain (n = 3), and duodenal obstruction (n = 1). SPT was occasionally found in one patient during physical examination. Six tumors located at the head and the other two in the body and tail of the pancreas. Pancreaticoduodenectomies were performed in 4 patients, tumor enucleations in 2, distal pancreatectomies in 1, and palliative internal drainage with a cystoenterotomy in the other one with an unresectable huge cystic lesion. All patients were alive on an average follow-up of 37.8 (8-103) months.SPT occurs mainly in adolescent and young females, and satisfactory outcome may be achieved with active and appropriate surgeries.

To investigate the feasibility and safety of spleen-preserving distal pancreatectomy with conservation of the splenic arteries and veins in treatment of benign neoplasms of distal pancreas.Four patients with solid-pseudopapillary neoplasm, 1 males and 3 females, aged 30 (17 - 37), underwent laparotomy. The distal pancreas with tumor was cut. The perforating branches between the splenic artery and vein and the distal pancreas were isolated, ligated, and cut. The splenic artery and vein and the short and left gastric vessels were all preserved. The spleen remained intact.The mean operation time was 208 minutes +/- 52 minutes, and the mean blood loss was 475 ml +/- 96 ml. Blood transfusion was not necessary. The mean post-operative hospital stay was 18 days +/- 13 days. No post-operative complications were found except for pancreatic leakage occurring in one patient that was cured by conservative treatment. No metastasis and recurrence was found.Safe and feasible, spleen-preserving distal pancreatectomy with conservation of the splenic arteries and veins is one of the best choices for treatment of benign and borderline tumors of pancreas.

To investigated p53 gene mutation in plasma of gastric cancer patients.DNA extracted from plasma and matched tumor and tumor-adjacent normal tissues of 96 gastric cancer patients, and DNA from 20 healthy people were studied. Exons 5, 6, 7, and 8 of p53 were amplified by PCR. The mutation status was analyzed by denaturing high-performance liquid chromatography (DHPLC), followed by direct sequencing of cases with aberrant chromatographic patterns.Heterozygous mutations of p53 gene were detected in 19.9% (19/96) of primary tumor tissues and 5.2% (5/96) of corresponding plasma. All p53 gene mutations detected in plasma DNA consisted with mutations in the matched primary tumor samples. Neither the tumor-adjacent gastric mucosa tissues nor control plasma from healthy volunteers showed p53 gene mutation. No correlation was found between p53 mutation status and clinicopathological features of gastric cancer patients.p53 gene mutation in plasma can be detected in tissues and plasma of gastric cancer patients, which could be applied in screening and surveillance of this disease.

To investigate the expression of metabolic enzymes of fluoropyrimidines in primary colorectal cancer.Sixty-one cases of pathological confirmed primary colorectal cancer were collected in Beijing Cancer Hospital from August 2003 to February 2004. The expressions of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT) were detected in paired tumor tissues and non-cancerous tissues by RT-PCR.Expression of each enzyme in tumor tissues was positively correlated with that in paired non-cancerous tissues respectively. Compared with the expression of each enzyme in cancer with that in non-cancer, OPRT was higher in cancer while that of DPD and TS was comparable. The expression of OPRT was approximately 4.38-folds higher in colorectal cancer tissues than that in non-cancerous tissues (P=0.000). The lowest expression of OPRT was found in mucinous carcinoma while the highest levels in poorly-differentiated adenocarcinoma. There were correlations between the ratio of tumor tissues/non-cancerous tissues OPRT expression (T/N) and metastasis to the lymph nodes (r=0.36; P=0.005), small vessel invasion (r=0.26; P=0.041) and differentiation (r=-0.33; P=0.009).The detection of three enzymes by means of RT-PCR is practical and can be used in clinical application. Our results also suggest that OPRT is a potential biomarker in predicting prognosis of colorectal cancer.