Analysis of immunohistochemistry staining,neuronspecific enolase level and somatostatin receptor scintigraphy of 77 cases with digestive neuroendocrine neoplasm

Objective: To assess the value of biomarkers and somatostatin receptor scintigraphy in the diagnosis of gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). Methods: 77 GEP-NEN patients were included. The neuroendocrine properties of the tumors were determined by immunohistochemistry staining of neuroendocrine markers Syn and CgA. Plasma neuronspecific enolase (NSE) levels were measured, and all the patients had 99Tcm-HYNIC-TOC somatostatin receptor scintigraphy results. Results: Immunohistochemistry staining positive rates of Syn and CgA were 90.4% (66/73) and 65.7% (44/67), and the former was statistical higher than the latter (χ2= 12.7, P < 0.01). Plasma NSE levels were significantly higher in GEP-NEN patients (16.02 ng/ml-5713.00 ng/ml). 64.9% (50/77) GEP-NEN represented avid uptake in somatostatin receptor scintigraphy. Poorly differentiated GEP-NEN had lower imaging positive rate (χ2 = 8.23, P < 0.01). Conclusion: Immunohistochemistry staining positive rate of Syn is higher than CgA. Origins from stomach, small intestine and pancreas have relatively high CgA expression. Plasma NSE level maybe became another useful marker in the diagnosis of GEP-NEN. Somatostatin receptor scintigraphy results are correlated with differentiation. Well differentiated GEP-NEN has higher somatostatin receptor expression.     

Predictive factors of lymph node metastasis in early mucinous adenocarcinoma

OBJECTIVE To identify clinicopathologic factors which predict lymph node metastases （LNM） in early mucinous adenocarcinoma patients, and to further explore the possibility of using minimally invasive treatment for patients with the disease. METHODS Data was collected from 38 patients with early mucinous adenocarcinoma who were surgically treated, and the association between clinicopathologic factors and the presence of LNM was retrospectively analyzed using univariate and multivariate logistic regression analysis. RESULTS Tumor size greater than 2.0 cm, the development of submucosal invasion, and the presence of lymphatic vessel involvement （LVI） were confirmed through univariate analysis as having a significant association with LNM and were considered to be significant and independent risk factors for LNM through multivariate analysis. CONCLUSION Tumor size 〉 2.0 cm, the development of submucosal invasion, and the presence of LVI are independent predictive factors for LNM in early mucinous adenocarcinoma. Minimally invasive treatment may be an effective treatment for intramucosal early mucinous adenocarcinoma when the tumor size is 2.0 cm or less, and if LVI has not occurred, as confirmed by postoperative histologic examination.     

Prognostic significance of ERCC1 expression in postoperative patients with gastric cancer

Aim： This study explored the correlation between the expression of excision repair cross-complementation group 1 （ERCC1） and the prognosis of gastric cancer patients. Methods： From January 2005 to December 2008, 605 patients who underwent radical surgery in The First Affiliated Hospital of Nanjing Medical University were enrolled. We conducted the follow-up every 6 months and its contents included a comprehensive medical history, tumor markers and abdominal ultrasound or CT and other imaging findings. Deadline was April 30, 2013 and follow-up time between 51 to 91 months. Survival time is calculated from the date of diagnosis to death or last follow-up date. Immunohistochemistry （IHC） was used to assess the expression of ERCCI in resected samples. The relationship between ERCCI expression and survival of patients was investigated. The comparison of count data were analyzed by Chi-square test. Median survival time （MST） and the 5-year survival rate were calculated by life table analysis. The Kaplan-Meier curves were used for survival analysis. Results： ERCC1 expression was positive in 412 patients （68.1%）. There is no significant difference between ERCCl-positive group and ERCCl-negative group in terms of the MST and 5-year survival rate （P=0.455）. The MST and 5-year survival rate have no significant difference （P=0.162） between group with chemotherapy and group with no chemotherapy in patients with ERCCl-positive expression. However, the MST and 5-year survival rate in patients with ERCCl-negative expression benefited more from with chemotherapy （P=0.019）. The ERCCl-positive patients survived longer than those ERCCl-negative patients （P=0.183） in subgroup with no adjuvant chemotherapy. In the subgroup analysis, ERCC 1 expression had no significant relationship with overall survival in patients with stage II or llI gastric cancer （P〉0.05）. Conclusions： ERCC1 might be a good prognostic factor for the patients of gastric cancer after radical resection. Patients with ERCC     

Synergistic action of clonorchiasis, HBV infection and alcohol consumption on primary hepatocellular carcinoma

OBJECTIVE It has been recognized that HBV infection and alcohol consumption are two important risk factors for primary hepatocellular carcinoma （HCC）. Recently, the role of clonorchiasis as a risk factor for HCC is controversial. We aimed to investigate whether these factors increase the risk of HCC in Guangxi, China.
METHODS A hospital-based, case-control study of HCC was conducted from July 2005 to July 2007. We enrolled 500 consecutive patients with HCC as an experimental group and 500 patients without tumor in liver as a control group. The risk factors that the patients were exposed to were assessed.
RESULTS Comparing the risks of developing the HCC, we found out the following results. The risk of developing HCC for the patients with clonorchiasis was 5 folds of that for the patients without clonorchiasis （OR = 5.0; 95% CI： 3.1-8.1）, and the risk for the patients with alcohol consumption was 3 folds of that for the patients without drinking alcohol （OR = 3.4; 95% CI： 2.3-4.9）, and similarly, the risk for the patients with HBV infection was 21 times of that for the patients without HBV infection （OR = 20.6; 95% CI： 14.3-29.7）. According to crossover analysis, there was significant interaction among clonorchiasis, HBV infection and alcohol consumption, with synergistic indices greater than 1. The etiologic fractions attributed to these interactions [EF （A × B）] are 0.7465, 0.5789 and 0.5506, respectively. CONCLUSION Clonorchiasis, HBV infection and heavy alcohol consumption are independent risk factors for developing HCC in our population in Guangxi, and as they can interact synergistically, the risk of developing HCC is increased. Data from this study may indicate new prevention strategies of developing HCC in high-risk individuals.     

Risk factors of intra-abdominal bacterial infection after liver transplantation in patients with hepatocellular carcinoma

Objective： To explore the risk factors of intra-abdominal bacterial infection （IAI） after liver transplantation （LT） in patients with hepatocellular carcinoma （HCC）. Methods： A series of 82 HCC patients who received LT surgeries in our department between March 2004 and April 2010 was recruited in this study. Then we collected and analyzed the clinical data retrospectively. Statistical analysis system （SPSS） software was adopted to perform statistical analysis. Chi-square test, t-test and Wilcoxon rank sum test were used to analyze the clinical data and compute the significance of the incidences of early-stage IAI after LT for HCC patients. Binary logistic regression was performed to screen out the risk factors, and multiple logistic regression analyses were performed to compute the independent risk factors. Results： A series of 13 patients （13/82, 15.9%） had postoperative IAI. The independent risk factors of postoperative intra-abdominal bacterial infections after LT for HCC patients were preoperative anemia [Hemoglobin （HGB） 〈90 g/L] and postoperative abdominal hemorrhage （72 hours 〉400 mL）, with the odds ratios at 8.121 （95% CI, 1.417 to 46.550, P=0.019） and 5.911 （95% CI, 1.112 to 31.432, P=0.037）. Conclusions： Postoperative IAI after LT in patients with HCC was a common complication. Preoperative moderate to severe anemia, as well as postoperative intra-abdominal hemorrhage more than 400 mL within the first 72 hours might independently indicate high risk of IAI for these patients.     

Prognostic Value of Ki67 and VEGF Expression in Laryngeal Squamous Cell Carcinoma

OBJECTIVE To investigate the prognostic value of measuring Ki67 and VEGF expression in laryngeal squamous cell carcinoma （LSCC）. METHODS The expression of Ki67 and VEGF in 32 LSCC tissues was studied by immunohistochemical staining. Of these cases, 5 recurred （recurrent group）, 3 cases metastasized （metastatic group）, 8 cases died （deceased group） and 24 cased survived （survival group） over a 3 year period of follow-up after their operation. RESULTS The expression of Ki67 and VEGF in the deceased group was higher compared to that in the survival group （P〈0.01）. Overexpression of Ki67 was found in the recurrent group and in the metastatic group （P〈0.05）. VEGF expression was higher in the recurrent group than in the non recurrent group （P〈0.05）. With Cox-regression of multivariate analysis, Ki67 （RR：3.236; P=0.001）, the clinical T stage （RR：1.382; P=0.029） and metastasis in lymph nodes （RR：0.316; P=0.033） were shown to be independent prognostic factors for survival of LSCC patients. CONCLUSION Ki67 and VEGF expression is related to the prognosis of LSCC. Overexpression of the 2 markers indicated poor prognosis of the disease, a finding which might be helpful for the treatment of laryngocarcinoma.     

Locoregional radiotherapy in patients with distant metastases of nasopharyngeal carcinoma at diagnosis

Systemic chemotherapy is the basic palliative treatment for metastatic nasopharyngeal carcinoma （NPC）; however, it is not known whether Iocoregional radiotherapy targeting the primary tumor and regional lymph nodes affects the survival of patients with metastatic NPC. Therefore, we aimed to retrospectively evaluate the benefits of Iocoregional radiotherapy. A total of 408 patients with metastatic NPC were included in this study. The mortality risks of the patients undergoing supportive treatment and those undergoing chemotherapy were compared with that of patients undergoing Iocoregional radiotherapy delivered alone or in combination with chemotherapy. Univariate and multivariate analyses were conducted. The contributions of independent factors were assessed after adjustment for covariates with significant prognostic associations （P 〈 0.05）. Both Iocoregional radiotherapy and systemic chemotherapy were identified as significant independent prognostic factors of overall survival （OS）. The mortality risk was similar in the group undergoing Iocoregional radiotherapy alone and the group undergoing systemic chemotherapy alone [multi-adjusted hazard ratio （HR） = 0.9, P = 0.529]; this risk was 60% lower than that of the group undergoing supportive treatment （HR = 0.4, P = 0.004） and 130% higher than that of the group undergoing both systemic chemotherapy and Iocoregional radiotherapy （HR = 2.3, P 〈 0.001）. In conclusion, Iocoregional radiotherapy, particularly when combined with systemic chemotherapy, is associated with improved survival of patients with metastatic NPC.     

Response and long-term effect of patients with triple-negative breast cancer receiving neo-adjuvant anthracycline-based chemotherapy

OBJECTIVE The breast cancer lack of expression of estrogen receptor （ER）, progesterone receptor （PR）, and human epidermal growth factor receptor 2 （HER-2） is defined as the Triple-negative breast cancer （TNBC）. Our purpose is to compare the response and long-term effect of the TNBC and non-TNBC patients receiving neo-adjuvant anthracycline-based chemotherapy, and to investigate the mechanisms of TNBC affecting the survivals. METHODS Data of long-term follow-up （median, 5.4 years） of 326 patients who received neo-adjuvant chemotherapy with anthracycline-based regimen, during a period from 2000 to 2003, were analyzed. Expressions of ER, PR, HER-2, P53, Ki-67 and E-cadherin were determined using immunohistochemical staining method. A multivariate Cox regression analysis was used to analyze independent prognostic factors affecting the relapse-free survival （RFS） and overall survival （OS） rates. Clinical effects of the neo-adjuvant anthracycline-based chemotherapeutic regimen and the RFS and OS rates were compared between the patients with TNBC and non-TNBC, and the correlations among the triplenegative phenotype （TNP）, tumor grading and the expressions of P53, Ki-67 and E-cadherins were analyzed. RESULTS TNP, TNM staging, histological grades, clinical response of the neo-adjuvant chemotherapy and pathological complete remission （pCR） rate were the independent prognostic factors affecting the survival rates. Furthermore, 70 （21.5%） of the 326 patients suffered TNBC. Compared with the subjects in non-TNBC group, the patients with TNBC had a significantly higher pCR rate （P = 0.046） and clinical response rate （P = 0.037）, but also decreased 5-year RFS （P = 0.001） and OS （P = 0.004） rates. The RFS and OS rates were not improved in the TNBC patients who achieved a clinical remission after the neo-adjuvant chemotherapy. The triple-negative phenotype was positively correlated with the level of P53, Ki-67 expression （P = 0.007, P = 0.028）, but negatively correlated with level of E-cadherin （P = 0.034）. CONCLUSION Both clinical remission rate and pCR rate of the TNBC patients receiving neo-adjuvant anthracycline-based chemotherapy are high, however, the long-term effect is poor. The mechanism may relate to a strong potential of proliferation and invasive metastasis, as well as lack of an effective therapeutic target in the TNBC patients.     

Meta-analysis:prognostic value of survivin in patients with pancreatic cancer

Objective： The aim of the study was to conduct a systematic review of the literature evaluating survivin expres- sion in pancreatic carcinoma as a prognostic indicator. Methods： The relevant literatures were searched using PubMed, EMBASE, and Chinese Biomedicine Databases. A meta-analysis of the association between survivin expression and overall survival in patients with pancreatic cancer was performed. Studies were pooled and summary hazard ratios （HRs） were calculated. Subgroup analysis according to the location of survivin expression was also performed. Results： Seven eligible studies with a total of 448 patients were included in this study. Combined HR suggested that survivin expression had an unfavorable impact on survival of pancreatic cancer patients （HR = 1.65, 95% CI： 1.02-2.68）. When stratified according to the location of survivin expression, the combined HR showed that expression in the cytoplasm was significantly associated with poor prog- nosis of pancreatic cancer patients （HR = 2.09, 95% CI： 1.29-3.40）. In contrast, survivin expression in the nucleus was not significantly associated with poor prognosis （HR = 0.83, 95% CI： 0.24-2.81）, and the heterogeneity was highly significant （I2 = 87.2%, P = 0.005）. Conclusien： Survivin expression was associated with a poor prognosis in patients with pancreatic cancer. Cytoplasmic expression of survivin may be a prognostic factor for pancreatic cancer patients. Based on the current obtained data, there was no evidence that survivin expression in the nucleus had a significant impact on patients＇ overall survival.     

Effect of EGFR-TKI retreatment following chemotherapy for advanced non-small cell lung cancer patients who underwent EGFR-TKI

Objective： Non-small cell lung cancer （NSCLC） patients with epidermal growth factor receptor （EGFR）-activating mutations have higher response rate and more prolonged survival following treatment with single-agent EGFR tyrosine kinase inhibitor （EGFR-TKI） compared with patients with wild-type EGFR. However, all patients treated with reversible inhibitors develop acquired resistance over time. The mechanisms of resistance are complicated. The lack of established therapeutic options for patients after a failed EGFR-TKI treatment poses a great challenge to physicians in managing this group of lung cancer patients. This study evaluates the influence of EGFR-TKI retreatment following chemotherapy after failure of initial EGFR-TKI within at least 6 months on NSCLC patients. Methods： ＇i-he data of 27 patients who experienced treatment failure from their initial use of EGFR-TKI within at least 6 months were analyzed. After chemotherapy, the patients were retreated with EGFR-TKI （gefitinib 250 mg qd or erlotinib 150 mg qd）, and the tumor progression was observed. The patients were assessed for adverse events and response to therapy. Targeted tumor lesions were assessed with CT scan. Results： Of the 27 patients who received EGFR-TKI retreatment~ 1 （3.7%） patient was observed in complete response （CR）, 8 （29.6%） patients in partial response （PR）, 14 （51.9%） patients in stable disease （SD）, and 4 （14.8%） patients in progressive disease （PD）. The disease control rate （DCR） was 85.2% （95% CI： 62%-94%）. The median progression-free survival （mPFS） was 6 months （95% CI： 1-29）. Of the 13 patients who received the same EGFR-TKI, 1 patient in CR, 3 patients in PR, 8 patients in SD, and 2 patients in PD were observed. The DCRwas 84.6%, and the mPFS was 5 months. Of the 14 patients who received another EGFR-TKI, no patient in CR~ 6 patients in PR, 6 patients in SD, and 2 patients in PD were observed. The DCRwas 85.7%, and the mPFS was 9.5 months. Significant di     

Recent advances in lymphatic targeted drug delivery system for tumor metastasis

The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.     

Therapy for non-small-cell lung cancer patients with brain metastasis

Brain metastasis is a major cause of poor prognosis and high mortality for non-small cell lung cancer patients. The prognosis of non-small-cell lung cancer（NSCLC） patients with brain metastasis is generally poor and more effective treatment is required to improve their prognosis. Whole-brain radiotherapy, surgery, stereotactic radiosurgery, chemotherapy and targeted therapy are the main treatment for brain metastasis. This review focuses on the five therapeutic strategy and in particular, on targeted therapy.     

分子靶向联合治疗非小细胞肺癌研究进展

肺癌是全世界最常见的恶性肿瘤之一,最新统计表明每年有超过一万的患者因肺癌死亡。尽管以铂类为基础的化疗方案仍处于一线地位,近年来也涌现出不少新的药物作为复发或远处转移NSCLC患者的二线或三线治疗。作用于表皮生长因子受体（ep iderm al growth factor receptor）/人表皮生长因子受体（hum an ep iderm al factor receptor）（EGFR/HER1）信号传导途径中不同靶点的一系列靶向药物治疗的开展,将肺癌的治疗提高到分子水平。     

颅内动脉瘤诊断和超早期显微手术治疗以及腰大池持续引流术应用的临床分析

<正>颅内动脉瘤是当今人类致死、致残率较高的一种常见的脑血管疾病[1]。急性自发性蛛网膜下腔出血(SSAH)发病的主要原因为动脉瘤自发性破裂,其可引起患者剧烈头痛、恶心呕吐或意识障碍等症状,为患者就诊的主要原因。动脉瘤自发性破裂为一种潜在致死性疾病,如未及时对患者进行处理或处理不当,可造成患者死亡,后果严重[2]。我们就13例临床资料总结如下。一、资料与方法1.一般资料:本组患者13例,其中男性7例,女性6例;     

宫颈炎性病变患者人乳头瘤病毒感染情况的临床分析

<正>子宫颈癌是女性三大恶性肿瘤之一,其发生发展经历了正常宫颈到宫颈上皮内瘤变到宫颈浸润癌的过程。近年来的研究结果显示,高危型人乳头瘤病毒(human papillomavirus,HPV)感染是宫颈上皮癌变的诱发因素。HPV的感染发生先于宫颈癌,其为宫颈癌前病变和宫颈癌发生的必要生物学条件[1]。大规模人群中HPV感染情况的调查可以清楚地了解HPV感染与宫颈上皮内瘤变(CIN)级别和宫颈癌之间     

Clinical value of cancer cells joint detection in peripheral blood plasma of thyroid cancer patients

We aimed to detect cytokeratin 19 （CK19） and polymorphic epithelial mucin 1 （MUC1） expression in peripheral blood of thyroid cancer patients, and investigate the clinical value of it as a diagnostic marker for circulating blood micrometastases. Methods： The flow cytometry （FCM） was used to detect and analyze CK19 and MUC1-expressing cells in peripheral blood of 491 thyroid cancer patients. Results： CK19 and MUC1 expression showed no statistically significant difference with gender and age in thyroid cancer patients （P 〉 0.05）, while had statistically significant difference with tumor size, lymph node stage and distant metastasis （P 〈 0.01）. The expression of CK19 and MUC1 were positively correlated （r = 0.628, P = 0.00）. Conclusion： CK19 is closely related to MUC1 expression, tumor size, extent of invasion and distant metastasis in peripheral blood of thyroid cancer patients. The circulating blood CK19 and MUC1 tests can help predict thyroid cancer micrometastases and prognosis.     

Effect of grape seed proanthocyanidins on tumor vasculogenic mimicry in liver cancer xenograft mode

Objective： As a novel blood supply pattern, vasculogenic mimicry （VM） has attracted increasingly attention in recent years, which may partly compensate for the absence of feeding and facilitate tumor perfusion. However, anti-angiogenic drugs have little effect on VM. The grape seed proanthocyanidins （GSPs）, a kind of promising bioactive phytochemical, has shown anti-carcinogenesis and anti-angiogenic in several tumor models. However, GSPs regulation of VM and its possible mechanisms in a H22 hepatoma carcinoma model remain not clear. The aim of this study was to examine the effects of GSPs on proliferation and VM in a H22 hepatoma carcinoma model and to investigate the underlying mechanism. Methods： Seventy-five mice were divided into the control group and experimental groups treated with different concentration of GSPs. CD34-PAS dual staining was employed to identify the VM structure. The immunohistochemical staining for investigating the expression of VEGF, EphA2 and MMP-2 protein was performed. Results： Treatment of the H22 model with Endostar （4 mg/kg）, 50, 100, 200 mg/kg of the GSPs resulted in 6.87%, 17.81%, 27.43%, 53.52% inhibition in tumor growth, respectively. The mean weight of tumors were significantly lower in GSPs （100 mg/kg） and GSPs （200 mg/kg） groups than in the control group （all P 〈 0.01）. Similarly, compared with the control group, the number of VM channels were significantly reduced in GSPs （100 mg/kg） and GSPs （200 mg/kg） groups （all P 〈 0.01）. Immunohistochemistry showed significant decreases in the expression levels of VEGF, EphA2 and MMP-2 protein in GSPs （100 mg/kg） and GSPs （200 mg/kg） groups when compared with control group （all P 〈 0.001）. Conclusion： This is the first report providing evidence that GSPs inhibit the VM structure by regulation of the VEGF/EphA2/MMPs signaling pathway. Therefore, we concluded that GSPs has the potential of being a clinical anti-VM inhibitor.     

急性早幼粒细胞性白血病的复发机制及微小残留病灶的监测

<正>急性早幼粒细胞性白血病(APL)是急性髓系白血病(AML)所有亚型中预后最好的一种,以骨髓及其他造血器官中异常早幼粒细胞浸润、异常染色体t(15;17)、PML-RARα融合基因为特征。目前,APL治疗策略包括全反式维甲酸(ATRA)联合蒽环类药物为基础的诱导治疗,2³个周期以蒽环类药物为基础的巩固治疗,13个周期以蒽环类药物为基础的巩固治疗,1²年包括ATRA伴或不伴     

The effect and significance on Akt and PTEN expression in melanoma B16 cells with chamaejasme extract

Objective： The aim of this study was to investigate the effect on Akt and PTEN expression and the mechanism of proliferation and apoptosis of melanoma B16 cells treated with chamaejasme extract. Methods： The expressions of Akt and PTEN of B16 cells treated with different concentrations of chamaejasme extract were detected with immunohistochemical method, cell apoptosis index （AI） was calculated with in situ labeling method. Results： Akt expressions of B16 cells treated with different concentrations of chamaejasme extract were significantly lower than the control group, while the PTEN expres- sions significantly up-regulated, and the effects appeared to be dose-related （P 〈 0.05）. The Akt/AI of B16 cells treated with different concentrations of chamaejasme extract was significantly lower than the control group, all the parameters had ex- tremely difference （F = 24.58, P 〈 0.05）. Conclusion： Chamaejasme extract can inhibit proliferation and induce apoptosis of malignant melanoma B 16 cells by down-regulating the expression of Akt and up-regulating the expression of PTEN.