D2 dissection in laparoscopic and open gastrectomy for gastric cancer

AIM: To evaluate the radicalness and safety of laparoscopic D2 dissection for gastric cancer. METHODS: Clinicopathological data from 209 patients with gastric cancer, who underwent radical gastrectomy with D2 dissection between January 2007 and February 2011, were analyzed retrospectively. Among these patients, 131 patients underwent laparoscopyassisted gastrectomy (LAG) and 78 underwent open gastrectomy (OG). The parameters analyzed included operative time, blood loss, blood transfusion, morbidity, mortality, the number of harvested lymph nodes (HLNs), and pathological stage.RESULTS: There were no significant differences in sex, age, types of radical resection [radical proximal gastrectomy (PG + D2), radical distal gastrectomy (DG + D2) and radical total gastrectomy (TG + D2)], and stages between the LAG and OG groups (P > 0.05). Among the two groups, 127 cases (96.9%) and 76 cases (97.4%) had 15 or more HLNs, respectively. The average number of HLNs was 26.1 ± 11.4 in the LAG group and 24.2 ± 9.3 in the OG group (P = 0.233). In the same type of radical resection, there were no signifi cant differences in the number of HLNs between the two groups (PG + D2: 21.7 ± 7.5 vs 22.4 ± 9.3; DG + D2: 25.7 ± 11.0 vs 22.3 ± 7.9; TG + D2: 30.9 ± 13.4 vs 29.3 ± 10.4; P > 0.05 for all comparisons). Tumor free margins were obtained in all cases. Compared with OG group, the LAG group had signifi cantly less blood loss, but a longer operation time (P < 0.001). The morbidity of the LAG group was 9.9%, which was not signifi cantly different from the OG group (7.7%) (P = 0.587). The mortality was zero in both groups. CONCLUSION: Laparoscopic D2 dissection is equivalent to OG in the number of HLNs, regardless of tumor location. Thus, this procedure can achieve the same radicalness as OG.

Current Status of Diagnosis And Treatment of Primary Breast Cancerin Beijing,2008

Objective：To investigate the status of diagnosis and treatment of primary breast cancer in Beijing,2008.Methods：All the patients who were diagnosed as primary breast cancer in Beijing in 2008 were enrolled in this study.Information of these patients,including the features of tumors,clinical diagnosis and treatment was collected,and filled in the well-designed questionnaire forms by trained surveyors.The missing data were partly complemented through telephone interviews.Results：A total of 3473 Beijing citizens were diagnosed as primary breast cancer（25 patients with synchronal bilateral breast cancer） in Beijing,2008.Of them 82.09% were symptomatic.19.02% and 34.11% were diagnosed using fine needle aspiration biopsy（FNAB） and core needle biopsy（CNB）,respectively.15.92% received sentinel lymph node biopsy（SLNB） and 24.27% received breast conserving surgery（BCS）.Among 476 cases with Her-2 positive,only 96 received anti-Her-2 therapy.We found that the standardization level varied in hospitals of different grades,with higher level in Grade-III hospitals.Of note,some breast cancer patients received non-standard primary tumor therapy：65.63% of the patients with ductal carcinoma in situ（DCIS） received axillary lymph node dissection and 36.88% received chemotherapy;25.89% of the patients underwent breast conserving surgery without margin status;12.10% of the patients received chemotherapy less than 4 cycles.Conclusion：Although most breast cancer patients received basic medical care,the mode of diagnosis and treatment should be improved and should be standardized in the future in Beijing.

Over-expression of Metastasis-associated in Colon Cancer-1 (MACC1) Associates with Better Prognosis of Gastric Cancer Patients

Objective： The aim of this study was to detect metastasis-associated in colon cancer-1 （MACC1） expression in Chinese gastric cancer and analyze the relationship between MACC1 expression and postoperative survival. Methods： The expression of MACC1 and c-MET protein in a sample of 128 gastric cancer tissues was detected by immunohistochemistry. A retrospective cohort study on the prognosis was carried out and data were collected from medical records. Results： The positive rate of MACC1 protein expression in gastric cancer was 47.66%, higher than that in adjacent noncancerous mucosa （P0.001）. MACC1 protein expression was not related to the clinicopathological variables involved. Kaplan-Meier analysis revealed that the survival of MACC1 positive group tended to be better than that of MACC1 negative group, particularly in patients with stage III carcinoma （P=0.032）. Cox regression analysis revealed that MACC1 protein over-expression in gastric cancer tended to be a protective factor with hazard ratio of 0.621 （P=0.057）. Immunohistochemical analysis showed that the positive rate of c-MET protein expression was much higher in cases with positive MACC1 expression in gastric cancer （P=0.002）, but P53 expression was not associated with MACC1 expression. Conclusion： MACC1 over-expression implies better survival and may be an independent prognostic factor for gastric cancer in Chinese patients.

Time Trends of Cancer Incidence in Urban Beijing,1998-2007

Objective：To report the time trends of cancer incidence in urban Beijing from 1998 to 2007.Methods：All data were obtained from Beijing Cancer Registry from 1998-2007 in urban Beijing.Time trends of incidence rate of cancer were assessed by annual percentage change（APC） of age-standardized incidence rate（ASR） of world standard population during this 10-year period.Results：For all 156851 cancer cases combined,the incidence rate rose in both males and females,with an APC of 2.23% and 3.74%,respectively.The incidence rate of upper gastrointestinal cancers declined significantly,with an APC of-2.83% in esophageal cancer and-1.37% in male gastric cancer,while lower gastrointestinal cancer,such as colorectal cancer,increased with an APC of 4.08%.The rates of kidney and bladder cancer increased with an APC of 7.93% and 5.57%,respectively.For women,the APC continued to rise in breast cancer（4.98%）,ovary cancer（6.16%）,cervix uteri cancer（11.74%）,corpus uteri cancer（6.96%） and thyroid gland cancer（13.39%）.The rate of prostate cancer among men increased with an APC of 8.58%;the rate of lymphoma and leukemia increased with APC of 5.48% and 5.44%,respectively.Conclusion：Because of population aging and urban modernization,the cancer burden in Beijing has become more and more severe and similar to the western developed countries.

Effects of Radiofrequency Ablation on Lymphocyte Subsets and Type 1/Type 2 T Cell Subpopulations in Patients with Hepatocellular Carcinoma

Objective： To evaluate whether radiofrequency ablation （RFA） might have an influence on immune status in hepatocellular carcinoma （HCC） patients. Methods： We measured the T lymphocytes, B lymphocyte and NK cells, and determined the population of Thl, Th2, Tcl and Tc2 of peripheral blood samples taken from 26 HCC patients before and after RFA. Results： The proportion of Typel cells （Thl and Tcl） and NK cells were significantly increased after RFA, especially in patients of the following subgroups： male, age〉55 years, pathological grade Ⅰ-Ⅱ tumor, clinical stage Ⅰ-Ⅱ or Child-Pugh A and B. Conclusion： TypeⅠ cells and NK cells in HCC patients were increased in a short period after RFA.

Breast Cancer Subtypes and Survival in Chinese Women with Operable Primary Breast Cancer

Objective： To investigate the associations between the different breast cancer subtypes and survival in Chinese women with operable primary breast cancer. Methods： A total of 1538 Chinese women with operable primary breast cancer were analyzed in this study, the median follow-up was 77 months. Estrogen receptor （ER）, progesterone receptor （PR）, and HER2 status were available for these patients. Results： Luminal A （ER＋ and/or PR＋, HER2-） had a favorable disease-free survival （DFS） and overall survival （OS） compared with other subtypes in the entire cohort. Using the luminal A as a reference, among the patients with lymph node positive disease, HER2＋ （ER-, PR-, HER2＋） had the worst DFS （hazard ratio, HR=1.80, 95% CI 1.11 to 2.91, P=0.017） and luminal B （ER＋ and/or PR＋, HER2＋） had the worst OS （HR=2.27, 95% CI 1.50 to 3.45, P0.001）; among the patients with lymph node negative disease, triple-negative （ER-, PR-, HER2-） had the worst DFS （HR=2.21, 95% CI 1.43 to 3.41, P0.001）, whereas no significant difference in DFS between HER2＋ and luminal B or luminal A was observed. Conclusion： As compared with luminal A, luminal B and HER2＋ have the worst survival in patients with lymph node positive disease, but this is not the case in patients with lymph node negative disease; triple-negative subtype has a worse survival in both lymph node positive and lymph node negative patients.

长期结果一胃癌患者在中国大型系列

Objective：The outcome of gastric cancer treatment in China is relatively poor compared with those in Japan and Korea.Relevant factors are not quite clear till now.The aim of this study is to present data on gastric cancer patients from a single high volume cancer center of China and to illuminate relevant factors regarding unsatisfactory outcome.Methods：A total of 2312 consecutive pathologically proven gastric carcinoma patients were treated in Beijing Cancer Hospital from January 1995 to December 2005.Clinical information including demographic information,tumor characteristics,therapeutic experience and survival was retrieved from the Database specially designed for Gastric Cancer Collaborative Group,Beijing Cancer Hospital.Results：There were 1633 males and 679 females with a median age of 58.8 years（range 19-89）.Merely 181 patients were in the early stage（7.8%）.Curative resection was performed in less than 72% of the patients.The number of lymph nodes harvested varied from 0 to 71（average 9） while the median number of positive lymph node was 2（0-37）.Only in 650 patients the number of lymph nodes harvested was more than 14.At the end of follow-up,874 patients were still alive while 1132 died.The 1,2,5,10-year overall survival were 68.50%,51.88%,36.83%,and 30.49%,respectively.Multivariate analysis demonstrated that TNM stage,tumor location,tumor size,surgery,and vascular invasion were independent prognostic factors.Conclusion：The outcome of gastric cancer in China is not as good as expected.Early detection and standardized curative resection should be prompted at present to improve the outcome.

Phase I Study to Determine MTD of Docetaxel and Cisplatin with Concurrent Radiation Therapy for Stage Ⅲ Non-Small Cell Lung Cancer

Objective： To evaluate the maximum tolerated dose （MTD） of docetaxel （DCT） and cisplatin （DDP） concurrently with three dimensional （3D） conformal radiotherapy or IMRT for patients with locally advanced non-small cell lung cancer （stage IIIa and IIIb） after 2–4 cycles of induction chemotherapy. Methods： Fourteen patients with histological/cytological proven stage III non–small-cell lung cancer were eligible. 3D or IMRT radiotherapy （60-70Gy in 30-35 fractions, 6-7weeks, 2 Gy/fraction） was delivered concurrently with cisplatin and docetaxel, 2 cycles during concurrent chemoradiotherapy （CCRT）. The level I dosage was composed of 56 mg/m2 DCT, on day 1 and 28mg/m2 DDP, on day 1 and day 2. The level II was composed of 60 mg/m2 DCT, on day 1 and 30 mg/ m2 DDP, on day 1 and day 2. The level III was composed of 64 mg/m2 DCT, on day 1 and 32 mg/ m2 DDP, on day 1 and day 2. Results： Fourteen patients were allocated and finished concurrent chemoradiotherapy. The dose-limiting neutropenia was at the dose Level III （64 mg/m2） and occurred in 2 of 5 patients. No dose limiting non-hematologic or hematologic toxicity occurred in the other patients. Conclusions： Patients with locally advanced non-small cell lung cancer may tolerate 60mg/m2 docetaxel and 60mg/m2 cisplatin for 2 cycles during concurrent radiotherapy after 2-3 cycles of induction chemotherapy.

Methylation and Demethylation of Ink4 Locus in Cancer Development

The Ink4 locus at chromosome 9p21 encodes P15Ink4b, P14Arf, P16Ink4a, MTAP, ncRNA ANRIL/p15AS and p16AS, which play an important role in regulation of stem cell self-renewal. Loss of functions of these genes promotes cell proliferation through bypassing checkpoint between the G1 and S phase of the cell cycle. Transcriptional silence by methylation of CpG island around transcription starting site （TSS） is a frequent event in the early stage of carcinogenesis. Chronic inflammation is a strong initiator for methylation of CpG island of the Ink4a gene. Combination of transcriptional silencers such as Polycomb group （PcG） proteins with gene-specific ncRNA could result in histone modifications including trimethylation at H3K27 firstly, and then at H3K9 epigenetically. In the case of long-term silence of transcription, methylation of CpG sites initiates and spreads progressively within the full CpG islands of the target gene. The methylation status of Ink4a CpG island is very stable even if its host cells are fused with Ink4a active cells.

Determination of PDCD5 in Peripheral Blood Serum of Cancer Patients

Objective：Programmed cell death 5 （PDCD5） is an apoptosis related gene and plays an important role in the pathogenesis and development of cancer.Whether PDCD5 is present in peripheral blood serum has not been reported.The aim of this study is to determine the contents of PDCD5 protein in peripheral blood serum of cancer patients,as well as normal subjects.Methods：ELISA was used to detect the serum PDCD5 concentrations in 100 normal persons,83 patients with breast cancer,74 patients with gastrointestinal tract cancer and 41 patients with lung cancer.The results were statistically analyzed and discussed.Results：PDCD5 could be detected in peripheral blood serum in both normal subjects and cancer patients.The serum PDCD5 contents in normal persons ranged from 3.8 to 6.1 ng/ml with a median of 4.70±0.68 ng/ml.For cancer patients the PDCD5 levels were 4.59±0.90,4.79±1.14 and 10.43±22.34 ng/ml for breast cancer,gastrointestinal cancer and lung cancer patients respectively.There was no statistically significant difference between the serum PDCD5 concentrations of normal persons and cancer patients.Conclusion：PDCD5 is present in peripheral blood.The PDCD5 levels in cancer patients are not statistically different from that of normal persons,though decreased expression of PDCD5 in malignant tissues has been found.

High Expression of ERCC1 Is a Poor Prognostic Factor in Chinese Patients with Non-small Cell Lung Cancer Receiving Cisplatin-based Therapy

Objective： to determine the role of excision repair cross-complementing group 1 gene （ERCC1） and ribonucleotide reductase subunit M1 （RRM1） expression in predicting response and survival in Chinese patients with advanced stage non-small cell lung cancer （NSCLC） treated with platinum-based chemotherapy. Methods： Formalin-fixed, paraffin-embedded biopsy tissues were retrospectively obtained from 160 advanced NSCLC patients. mRNA expression levels of ERCC1 and RRM1 were determined by real-time PCR. Results： Associations between mRNA expression level of ERCC1 and RRM1 and clinic-pathologic parameters were analyzed. One handred and forty two （88.75%） specimens were successfully amplified. mRNA expression level of ERCC1 and RRM1 was negatively associated with tumor response. ERCC1 expression levels ranged from 0.01 to 78.79 [median 0.63, mean 4.25 and standard deviation （SD） 9.23] and RRM1 from 0.00 to 30.91 （median 0.63, mean 0.87 and SD 3.36）. By adopting cut-off values according to median expression levels, we found that MST in patients with low ERCC1 mRNA levels was significantly longer in overall population than in patients with higher levels （18.63 versus 13.69 months, log-rank 5.73, P=0.017）, but we did not found the survival benefit of the patients with low expression level of RRM1. （19.07 versus 14.88, log-rank 1.66, P=0.197）. Further, in the multivariable Cox regression model analysis we found that low level of ERCC1 expression, the presence of weight loss and target therapy, were significant prognostic factors for survival. Conclusion： ERCC1 expression is associated with patients’ survival in Chinese advanced NSCLC patients treated with platinum-based regimen and may serve as a biomarker in predicting tumor response and clinical outcome in the patient population.

Combination of Recombinant Adenovirus-p53 with Radiochemotherapy in Unresectable Pancreatic Carcinoma

Objective：To assess the safety and efficacy of the combination of recombinant adenovirus-p53 （rAd-p53） with radiochemotherapy for treating unresectable pancreatic carcinoma.Methods：The eligible patients received concurrent rAd-p53 intratumoral injection and radiochemotherapy.Intratumoral injection of rAd-p53 was guided by B ultrasound.Radiochemotherapy consisted of intensity-modulated radiotherapy （IMRT） at two dose levels and intravenous gemcitabine （Gem）.For radiotherapy,gross target volume （GTV） and clinical target volume （CTV） were 55-60 Gy and 45-55 Gy in 25-30 fractions,respectively.Concurrent intravenous gemcitabine was administered at 350 mg/m2,weekly,for 6 weeks.The primary end points included toxicity,clinical benefit response （CBR） and disease control rate （DCR）.The secondary end points included progression-free survival （PFS） and overall survival （OS）.Results：Fifteen eligible patients were enrolled.Eight patients （53.3%） were evaluated as CBR and 12 （80%） achieved DCR.The median PFS and OS were 6.7 and 13.8 months,respectively.One-year PFS and OS were 40.0% and 51.1%,respectively.There were 8 （53.3%） patients reported grade 3 toxicities including neutropenia （6 patients,40%）,fever （1 patient,6.7%） and fatigue （1 patient,6.7%）.There was no grade 4 toxicity reported.Conclusion：Combination of rAd-p53 in unresectable pancreatic carcinoma showed encouraging efficacious benefit and was well tolerated.Long-term follow-up is needed to confirm the improvement of PFS and OS.

Neoadjuvant Therapy for Advanced Rectal Carcinoma in China:Whether Radiochemotherapy Is Superior to Radiotherapy?

Objective： To verify whether the 30 Gy preoperative radiotherapy regimen is effective to advanced rectal cancer, and whether the preoperative chemoradiation offers an advantage in sphincter preservation and tumor control compared with irradiation alone. Methods： A total of 141 patients administered neoadjuvant treatment with resectable lower rectal carcinoma from 2002 to 2006 were collected retrospectively. The patients were divided into two groups： preoperative radiotherapy alone （30Gy by 10 fractions） （PRT group） and preoperative chemoradiotherapy （PCRT group）. All patients underwent radical surgery after neoadjuvant treatment. Results： The overall sphincter-preservation rate was 68.8% （97/141）, with no significant difference between the two groups. The overall downstaging rate was 48.2% （68/141）, including 4 patients completely response （2.8%）. The T and N downstaging rate were 30.5% （43/141） and 53.8% （57/106） respectively, showing no statistically difference between the two groups. The 2-year overall survival rate was 93.6%; no survival benefit were observed in PCRT group. The 2-year cumulative local recurrence rates were similar as well （4.2% vs 6.7%, P=0.63）. Two patients with severe marrow suppression higher than grade 3 and 1 patient with severe perineum ulcer was observed in PCRT group, which did not occur in PRT group. Conclusion： The preoperative adjuvant treatment of 30Gy radiotherapy alone may be an optional treatment for Chinese lower rectal carcinoma. Preoperative chemoradiotherapy does not show actual superiority compared with radiotherapy alone.

Long-Term Chinese Herbs Decoction Administration for Management of Hot Flashes Associated with Endocrine Therapy in Breast Cancer Patients

Objective：To evaluate the effect of Chinese herbs decoction Shu-Gan-Liang-Xue on endocrine therapy-associated hot flashes symptom in breast cancer patients.Methods：Sixty-six patients with breast cancer receiving adjuvant endocrine therapy were categorized to two groups,the control group received endocrine therapy alone,the other group is administered with Chinese herbs decoction Shu-Gan-Liang-Xue besides the endocrine therapy：Shu-Gan-Liang-Xue decoction was administered above 6 months per year for more than 2 years.Frequency of hot flashes per day was recorded,and the effect of Shu-Gan-Liang-Xue decoction on hot flashes symptom being assessed with Kupperman Scoring Index.Results：Sixty cases were analyzed,32 cases in endocrine therapy combining Chinese herbs decoction group,28 cases in mere endocrine therapy group.For hot flashes symptom,in Chinese herbs decoction administration group,7 cases（21.9%） reported symptom disappeared,22 cases（68.7%） reported symptom alleviated,3 cases（9.4%） reported symptom not changed;in endocrine therapy alone group,5 cases（17.9%） reported symptom disappeared,13 cases（46.4%） reported symptom alleviated,10 cases（10/28,35.7%） reported symptom not changed.The difference between two groups was statistically significant（P=0.013）.For sleeping disorder,in Chinese herbs decoction administration group,27 cases（84.4%） reported symptom improved,5 cases（15.6%） reported no change;in endocrine therapy alone group,16 cases（57.1%） symptom improved,12 cases（42.9%） reported no change in sleeping disorder（P=0.019）,the difference was also of significance statistically.Conclusion：Long-term Chinese herbs decoction administration remarkably improved hot flashes symptom and sleeping disorder associated with endocrine therapy,meanwhile without definite toxicity and influence on the risk of recurrence of tumor.

心理社会肿瘤学在中国的发展现状——机会与挑战(英文)

Objective:In China over the past decade,psychosocial oncology has emerged as a new program. Development of this program requires attention to current opportunities,obstacles and cultural concerns. Methods: A selected literature review of academic papers in Chinese and English language journals and web sites was analyzed for themes regarding the current status,challenges,and opportunities for psychosocial oncology in China. Results: China’s national cancer strategy (2004-2010),based on WHO guidelines,is focused on cancer prevention and treatment,as well as quality of life among cancer patients and their families. The Chinese Anti-Cancer Association is now funding research,training and international collaboration in psychosocial oncology. The newly organized Chinese Psychosocial Oncology Society,founded in 2006,aims to provide a national forum for psychosocial oncology research. Cultural and systemic challenges to establishing psychosocial oncology as a core discipline in China include: (1) the family’s desire to ‘protect’ cancer patients by with-holding cancer-related information; (2) stigma and privacy regarding mental health issues; (3) biomedical practitioners’ claims that psychosocial on-cology is not sufficiently evidence-based; and (4) limited funding for psychosocial oncology care and research. Conclusion: The International Psycho-Oncology Society (IPOS) is considered a valuable resource towards China’s interest in partnering with the international psychosocial oncology community to enhance the discipline globally.

Long-term Follow-up Study on Gastric Intestinal Metaplasia Subtype and Its Relation to Expression of P53,Bcl-2 and PCNA

Objective： To investigate the correlation of typies of gastric intestinal metaplasia（IM）, expression of p53, bcl-2 and the proliferating cell nuclear antigen（PCNA）, with the lesion＇s evolution. Methods： A total of 80 patients with IM（53 male and 27 female, 35-64 years old） from an area with high-risk of gastric cancer（GC） in China were enrolled into this prospective study, including 28 cases of type Ⅰ （complete）, 25 cases of type Ⅱ （incomplete） , and 27 cases of type Ⅲ （incomplete）. Of the 80 cases, 62 cases including 19 cases of type Ⅰ, 22 type Ⅱ and 21 type Ⅲ, were followed up for 5-14 years（49 cases for 14 years, 6 for 10 years, and 7 for 5 years）. All of the 80 cases were studied immunohistochemically for the expression of p53, bcl-2 and PCNA. Results： The rate of p53-expressing cases was higher in type Ⅲ（25.9%） than in type Ⅰ（10.7%） and type Ⅱ （12.0%）, but without statistical significance（P=0.3070）. The positive rate of bcl-2 was obviously lower in type Ⅰ （21.4%） and type Ⅱ （24.0%） than in type Ⅲ（37.0%）, but not statistically significant（P=0.4223）. We observed difference in PCNA labelling index （LI） between type Ⅱ and type Ⅲ（P=0.0037）, and the difference was particularly significant in type Ⅰ as compared with type Ⅲ（P〈0.0001）. There was no statistical significance between type I and type II （P=0.0616）. Evolution into GC was detected in 0%, 4.5%, and 14.3% of type Ⅰ, type Ⅱ, and type Ⅲ IM cases, respectively. Progression to dysplasia was detected in 31.6%, 18.2%, and 14.3% of type Ⅰ, type Ⅱ, and type Ⅲ IM cases, respectively. Persistence of IM was documented in 31.6%, 45.5%, and 42.9% of type Ⅰ, type Ⅱ, and type Ⅲ IM cases, respectively. Regression of IM was documented in 36.8%, 31.8%, and 28.6% of type Ⅰ, type Ⅱ, and type ⅢIM cases, respectively. In progressive, persistent and regressive groups, the positive rates of p53 were 17.6%, 16.0% and 15.0%, bcl-2 were 29.4%, 36.0% and 25.0%, and PCNA LIs were 24.953±14.477, 23.752±12.934 and 25.105±10.055, respectively. There were no significant differences between the groups. Conclusion： The present follow-up study indicated that type Ⅲ had a higher risk for development of cancer than type Ⅰ or Ⅱ. PCNA LI was significantly higher in type Ⅲthan in type Ⅰ and Ⅱ, suggesting that cell proliferation in type Ⅲwas more active. Our data also indicated that the expression of p53 and bcl-2 had no apparent association with the particular type and the expression of p53, bcl-2 and PCNA had no apparent correlation with evolution of IM. Further studies with a larger sample size are needed to verify present observation.

Pericryptal Fibroblast Sheath in Intestinal Metaplasia,Dysplasia and Carcinoma of the Stomach

Objective： To investigate the existence of pericryptal fibroblasts sheath （PCFS） in normal gastric mucosa, intestinal metaplasia （IM）, indefinite for dysplasia （I-Dys）, low grade dysplasia （L-Dys）, high grade dysplasia （H-Dys） and gastric cancer （GC）, and its association with gastric carcinogenesis. Methods： In this study, we examined the existence of PCFS in normal gastric mucosa （N=10）, IM （N=26）, I-Dys （N=16）, L-Dys （N=13）, H-Dys （N=21） and GC （N=145） using immunohistochemical staining for two smooth muscle markers, alpha smooth muscle actin（α-SMA） and high molecular weight caldesmon （h-CD）. The significance of PCFS was discussed, especially in association with gastric carcinogenesis. Results： The PCFS was recognized in 65.4%（17/26） of IM, 62.5%（10/16） of I-Dys and 23.1% （3/13） of L-Dys respectively. No PCFS was detected in H-Dys and GC. The PCFS was gradually reduced in IM, Dys and GC in sequence （P〈0.0001）. Conclusion： The PCFS is associated with the differentiation of epithelium and involved in gastric carcinogenesis via epithelial-mesenchymal interaction.

Association of Lysosome Associated Protein Transmembrane 4 Beta Gene Polymorphism with the Risk of Pancreatic Cancer

Objective： Lysosome associated protein transmembrane 4 beta （LAPTM4B） was originally identified as a gene in human hepatocellular carcinoma （HCC）. It was successfully cloned by fluorescence differential display, rapid amplification of cDNA ends （RACE） and reverse transcription polymerase chain reaction （RT-PCR）. Previous study showed that the novel gene played an important role in the occurrence, development, migration and prognosis of tumors. Pancreatic cancer is an aggressive malignancy with the majority of patients dying within one year after diagnosis. This study tries to find out the relationship between lysosome associated protein transmembrane 4 beta gene polymorphism and the susceptibility of pancreatic cancer. Methods： A case-control study was conducted in China, including 58 pancreatic cancer cases and 156 healthy controls. Human genomic DNA was used as the template, polymerase chain reaction （PCR） was used to detect the distribution of LAPTM4B genotype. Analyses Odds ratio （OR） and corresponding 95% confidence interval （95%CI） with logistic regression were performed. Results： Two alleles of LAPTM4B generated three kinds of genotypes in population, ＊1/1, ＊1/2, and ＊2/2. The genotype frequency of ＊1/1, ＊1/2 and ＊2/2 in the pancreatic cancer group were 41.4%, 44.8% and 13.8% respectively, which were not significantly different from those of healthy group （47.4%, 42.9%, 9.6%） （P=0.773, P=0.291）. Also the ＊2 allele frequency of LAPTM4B among pancreatic cancer had no significantly difference with the controls （P=0.354）. When compared to the ＊1 allele, the people with ＊2 allele had no increased risk of pancreatic cancer. Conclusion： The gene polymorphism of LAPTM4B may not influence the susceptibility of pancreatic cancer.

Decrease of Peripheral Blood CD8+/CD28- Suppressor T Cell Followed by Dentritic Cells Immunomodulation among Metastatic Breast Cancer Patients

Objective： To explore the effects of dentritic cells on the peripheral blood lymphocyte subpopulations of metastatic breast cancer patients treated with chemotherapy. Methods： The current study involved 44 metastatic breast cancer patients treated with docetaxel-based chemotherapy. Among them, 25 cases were treated with dendritic cells derived from CD34＋ hematopoietic stem cells enriched autologous peripheral mononuclear cells after chemotherapy, and 19 cases received chemotherapy alone. Peripheral blood samples were collected from each patient before and after treatment, and lymphocyte subpopulations including CD3＋, CD3＋/CD4＋, CD3＋/CD8＋, CD3-/CD16＋56＋, CD3＋/CD16＋56＋, CD4＋/CD25＋, CD8＋/CD28-, CD8＋/CD28＋, CD4/CD8, DC1, DC2 and DC1/DC2 were analysed by a 3-color flow cytometric analysis. Results： The two treatment groups were well matched with regard to demographic and baseline disease characteristics. Comparing the changes of lymphocyte subpopulations between the two groups, it showed that the difference of the change of CD8＋/CD28-lymphocyte had statistic significance. The percentage of CD8＋/CD28-lymphocyte was lower in the chemotherapy＋DC group, but higher in the chemotherapy-alone group. Conclusion： As CD8＋/CD28-lymphocyte represent a kind of suppressive T lymphocyte, we conclude that dentritic cell therapy can relieve immunosuppression to some extent.

Phenotypic Classification of Well-Differentiated Gastric Adenocarcinoma

Objective： To investigate the genotypes of well-differentiated non-cardiac gastric adenocarcinoma and their clinicopathological significance. Methods： Sixty-four cases of well-differentiated non-cardiac gastric adenocarcinoma were included in this study. The expressions of intestinal phenotypic markers including CDX2, MUC2, Li-cadherin, CD10, Hepatocyte（Hep） and Villin, and gastric phenotypic markers including MUC5AC and pS2 were detected immunohistochemically. Based on the expressions of phenotypic markers, 64 cases can be divided into four phenotypes. Cases only expressing intestinal phenotypic markers were classified as intestinal phenotype; cases only expressing gastric phenotypic markers as gastric phenotype; cases expressing both intestinal and gastric phenotypic markers as gastrointestinal phenotype; and cases expressing neither intestinal nor gastric phenotypic marker as null phenotype. The association of phenotype and clinic-pathological parameters was analyzed. We also detected the expressions of markers related to the development and progression of cancer, including Rb, P53, c-Met, MIF, TGF-β-RII, β-catenin, CD44v6 and E-cadherin. Results： Of 64 cases, 33（51.6%） were intestinal type, 3（4.7%） were gastric type, 25（39.1%） were gastrointestinal type and 3（4.7%） were null type. Fifty-eight cases were either intestinal or gastrointestinal type, which accounted for 90.6% of all the cases. In addition, there was an association between phenotype and biological behaviors （invasion or metastasis）. The biological behaviors of intestinal and gastrointestinal type were better than gastric type. Compared with intestinal, gastric and gastrointestinal types, the biological behaviors of null type were the most aggressive. The biological behaviors of gastric carcinoma tended to be better as the number of expression of intestinal markers increased. Expression of markers related to the development and progression of cancer was not significantly correlated with phenotypes and biological behaviors of well-differentiated gastric carcinoma. Conclusion： Well-differentiated gastric adenocarcinomas are heterogeneous phenotypically. They can be divided into four phenotypes, namely intestinal, gastric, gastrointestinal and null types. Present findings show that well-differentiated gastric adenocarcinoma in the WHO classification is highly consistent with intestinal type gastric cancer in the Lauren classification. Expression of phenotypic marker is of certain clinic-pathologic significance.