[Clinicopathological features of the primary gastric neuroendocrine neoplasms].

OBJECTIVE: The aim of this study was to investigate the clinicopathological features of different histological types of primary gastric neuroendocrine neoplasms (including the esophagogastric junction), and to analyze the characteristics and difficulties in diagnosis of all the subtypes of this disease. METHODS: 75 cases of primary gastric neuroendocrine neoplasms (including the esophagogastric junction) were included in this study. The expressions of several markers including somatostatin, synaptophysin, chromogranin A, CD56, S-100, neuron-specific enolase and CD57 were assayed in all the specimens by immunohistochemical staining, and their significance in the diagnosis and prognosis of gastric neuroendocrine neoplasms were assessed. In addition, the relationship between various clinical parameters such as tumor location, histological types, depth of invasion and metastasis was also analyzed. RESULTS: The incidence of gastric neuroendocrine neoplasms accounted for 1.5% of gastric cancer in the same period, and the proportion of each subtype was 53.3% (40/75) in G3, 29.3% (22/75) in MANEC, 16.0% in G1(12/75), and 1.3% (1/75) in G2, respectively. 41.7% (5/12) of the G1 showed multifocal lesions, accompanyied with neuroendocrine cell hyperplasia in the gastric mucosa. 54.67% (41/75) of the NEN located in the esophagogastric junction. The lymph node metastasis of MANEC is unique. The coincidence rate in diagnosis of preoperative biopsies and postoperative specimen was 75.0% (9/12) in G1, 72.7% (16/22) in MANEC, and 25.0% (10/40) in G3, respectively. CONCLUSIONS: Gastric neuroendocrine neoplasms occur mainly in the esophagogastric junction, and most of them were highly malignant. The coincidence rate of preoperative and postoperative pathological diagnosis for primary gastric neuroendocrine neoplasms is low. Therefore, it should be very cautious when diagnosis of this disease is made in a preoperative biopsy.

[Detection and clinical implication of aneuploidy of chromosomes 11 and 20 in gastric adenocarcinoma].

OBJECTIVE: The aim of this study was to find out the value of chromosome aneuploidy in early diagnosis and prediction of postoperative recurrence of gastric adenocarcinoma (GAC). METHODS: Tissue samples, including 49 GAC, pairing pericancerous mucosa and normal gastric mucosa from the distant cutting margin were use in this study. Two centromere probes, Cen11 and Cen20 specific for chromosomes 11 and 20 were analyzed by FISH . The clinicopathological data were summarized. RESULTS: The incidence of aneuploidy of chromosome 11 in the tumors, pericancerous mucosa and normal gastric mucosa from the distant cutting margin were 83.7%, 40.8%, and 16.3%, respectively (P < 0.001), and those of chromosome 20 were 87.8%, 53.1%, and 16.3%, respectively (P < 0.001). The aneuploidy of Cen 11 displayed a significant correlation with Lauren's claasification, and lymph node metastasis (P < 0.05 for both). The pericancerous mucosa and normal gastric mucosa from the distant cutting margin displayed mainly chronic inflammatory changes, intestinal metaplasia and dysplasia. CONCLUSIONS: Aneuploidy of Cen11 and Cen20 in pericancerous mucosa may be used as a candidate marker for early diagnosis of gastric adenocarcinoma and may have a predictive value of postoperative recurrence.

[Prognostic factor analysis of surgical treatment in patients with rectal neuroendocrine neoplasms].

OBJECTIVE: To analyze the prognostic factors and long-term surgical efficacies of rectal neuroendocrine neoplasm (NEN). METHODS: The clinical and pathological data of 141 patients with rectal NENs treated between January 1999 and November 2012 were retrospectively analyzed. The Kaplan-Meier method was used to calculate survival time and Cox regression to analyze the clinicopathological factors correlating with patient prognosis. RESULTS: The overall 1, 3 and 5-year survival rates were 95.4%, 87.0% and 82.8% respectively. According to the criteria of WHO classification (2010) and staging system about rectal NEN, there were grade 1 (G1) (n = 76, 79.2%), grade 2 (G2) (n = 12, 12.5%), neuroendocrine carcinoma (NEC) (n = 7, 7.3%) and mixed adenoneuroendocrine carcinoma (n = 1, 1.0%), the 1, 3 and 5-year survival rates were 98.6%, 43.7%,0% and 100.0% respectively. There were stage I (n = 71, 74.0%) , stage II (n = 5, 5.2%), stage III (n = 12, 12.5%) and stage IV (n = 8, 8.3%) . The 1, 3 and 5-year survival rates were 97.7%, 75.0%, 57.1% and 25.0% respectively.Univariate analysis showed that tumor diameter, histological grade, lymph node metastasis, distant metastasis, radical surgery and muscular layer invasion significantly affected the postoperative survival. And Cox multivariate analysis indicated that tumor diameter and histological grade were independent prognostic factors. CONCLUSIONS: Rectal NENs vary significantly in their prognoses.However, radical surgery offers satisfactory long-term survival rates. An optimal surgical approach should be selected based on tumor size. And more radical surgery should be performed for neuroendocrine tumors >2 cm.

[Analysis of clinicopathological features of intestinal neuroendocrine neoplasms].

OBJECTIVE: To analyze the clinicopathological features of intestinal neuroendocrine neoplasms. METHODS: The clinicopathological features of 114 patients with intestinal neuroendocrine neoplasms treated in our hospital from April 1999 to March 2011 were retrospectively reviewed, including tumor location, histological classification, muscle invasion, metastasis and clinical data. Immunohistochemical SP staining was applied to examine the expression of 15 markers in the tumor specimens. RESULTS: The male:female ratio of the patients was 1.33, and most of the tumors were located in the rectum of polypoid type. The positive rate of immunohistochemical staining of Syn expression was 97.4%, NSE 95.6%, PGP9.5 84.2%, CD56 75.4%, CD57 72.8%, CgA 43.0%, S100 36.0%, Syn combined with CgA 99.1%, and the two marker Syn and CgA combined with any one of CD56, CD57 or PGP9.5 reached to 100%. The 5-years survival rates of G1, G2 were 98.9% and 76.9%, respectively, and the overall 5-year survival rate of intestinal neuroendocrine neoplasms was 92.9%. Two of the 7 cases of poor differentiated neuroendocrine carcinoma died after operation, another 2 of them lost to follow up. Others were still alive during the follow-up. Among the 3 patients with small cell carcinoma, two survived for 8 to 24 months after operation, and one lost to follow up. Two cases of mixed adenoneuroendocrine carcinoma (MANEC) were still surviving during the follow-up. Different histological types of intestinal neuroendocrine neoplasms were significantly different in sex, primary tumor site, pathological type, tumor size, types of combined tumors, pT stage, aggressive nervous and vascular invasion, and metastasis (all P < 0.05). Single factor analysis of the intestinal neuroendocrine neoplasms indicated that tumor size (Z = -6.334, P < 0.001), histological classification (χ(2) = 31.175, P < 0.001) and muscle invasion (χ(2) = 63.567, P < 0.001) were associated with metastasis of intestinal neuroendocrine neoplasms. Logistic analysis showed that muscle invasion was the main behavior risk factor of this tumor (OR = 1.827, P < 0.05). CONCLUSIONS: Intestinal neuroendocrine neoplasms usually occur in males, and the most common involved organ is the rectum. Their histological types are related to the prognosis, and the depth of invasion is an important metastasis factor of intestinal neuroendocrine neoplasms. Of the neuroendocrine makers, the combination of CgA and Syn shows a higher diagnostic sensitivity.

Oncolytic Herpes Simplex Virus Type 2 Can Effectively Inhibit Colorectal Cancer Liver Metastasis by Modulating the Immune Status in the Tumor Microenvironment and Inducing Specific Antitumor Immunity.

Although colorectal cancer is the leading cause of death in patients with liver metastases, there are no efficient treatments available. Oncolytic virus therapy, a new type of tumor therapy, has become a potential solution. With the goal of improving the treatment of advanced colorectal cancer, we applied oncolytic herpes simplex virus type 2 (oHSV2) in a mouse model of colorectal cancer with liver metastasis. Compared with the control, oHSV2 effectively inhibited the growth of subcutaneous primary tumors, significantly reduced the number and size of liver metastases, and prolonged the median survival time of the mice. In addition, neutrophils, natural killer (NK) cells, T cells, B cells, and cytokines in the tumor microenvironment and the body were all activated, and their frequencies increased significantly. Moreover, the proportion of immunosuppressive myeloid-derived suppressor cells decreased. oHSV2 treatment, which establishes an effective long-term antitumor immune response, is strongly resistant to rechallenge by the same tumor. Our data show that oHSV2 can effectively kill the primary tumor and attack distal and metastatic tumors by inducing immune responses, resulting in lasting antitumor efficacy and preventing tumor recurrence. It is believed that oHSV2 has good clinical application prospects.

Correlation between electrical characteristics and biomarkers in breast cancer cells.

Both electrical properties and biomarkers of biological tissues can be used to distinguish between normal and diseased tissues, and the correlations between them are critical for clinical applications of conductivity (σ) and permittivity (ε); however, these correlations remain unknown. This study aimed to investigate potential correlations between electrical characteristics and biomarkers of breast cancer cells (BCC). Changes in σ and ε of different components in suspensions of normal cells and BCC were analyzed in the range of 200 kHz-5 MHz. Pearson's correlation coefficient heatmap was used to investigate the correlation between σ and ε of the cell suspensions at different stages and biomarkers of cell growth and microenvironment. σ and ε of the cell suspensions closely resembled those of tissues. Further, the correlations between Na+/H+ exchanger 1 and ε and σ of cell suspensions were extremely significant among all biomarkers (pε < 0.001; pσ < 0.001). There were significant positive correlations between cell proliferation biomarkers and ε and σ of cell suspensions (pε/σ < 0.05). The microenvironment may be crucial in the testing of cellular electrical properties. ε and σ are potential parameters to characterize the development of breast cancer.

[Clinical and pathological analysis of 114 cases with non-ductal pancreatic adenocarcinoma occupying lesions].

OBJECTIVE: To improve the diagnosis and treatment of non-ductal pancreatic adenocarcinoma-occupying lesions. METHODS: A retrospective analysis was made for 114 cases of pancreatic non-ductal adenocarcinoma-occupying pathologically confirmed lesions. RESULTS: (1) There were 36 males (31.6%) and 78 females (68.42%); (2) presenting symptoms and signs were abdominal pain (n = 56, 49.1%), back pain (n = 24, 21.1%), weight loss (n = 18, 15.8%) and obstructive jaundice (n = 8, 0.07%); (3) the positive rates of CA19-9, CA242 and CEA were 21.1%, 19.7% and 5.6% respectively; (4) pancreaticoduodenectomy was performed in 26 patients, distal pancreatectomy in 53, tumor enucleation in 15, segmental pancreatectomy in 9, partial resection in 3, duodenum-preserving pancreatic head resection in 1 and palliative surgery (either cholecystojejunostomy anastomosis or gastrojejunostomy) in 7; (5) pathologic analysis revealed 35 solid pseudopapillary neoplasm of pancreas, 28 pancreatic endocrine tumors, 18 focal chronic pancreatitis, 11 serous cystic neoplasms, 9 mucinous cystic neoplasms, 4 pancreatic cysts, 3 acinar cell carcinomas, 2 pancreatic cavernous hemangiomas, 1 sarcoma of pancreas, 1 sarcomatoid carcinoma of pancreas, 1 pancreatic schwannoma and 1 pancreatic neuroblastoma. CONCLUSION: The non-ductal pancreatic adenocarcinoma-occupying lesions have no specific clinical presentation or serum tumor marker. An understanding of the natural history of these lesions is important for optimal management.

oHSV2 Can Target Murine Colon Carcinoma by Altering the Immune Status of the Tumor Microenvironment and Inducing Antitumor Immunity.

Oncolytic viruses are promising immunoreagents. Numerous studies have shown that oncolytic virotherapy is effective for many tumors. Herein, we investigated the therapeutic effect of oHSV2, an oncolytic type 2 herpes simplex virus, on mouse colon carcinoma. The in vivo antitumor efficacy of oHSV2 was observed in both unilateral and bilateral colon cancer models. oHSV2 effectively eliminated tumors and prolonged the survival of mice without side effects. Additionally, treatment with oHSV2 effectively prevented the growth of rechallenged tumors and distant implanted tumors. The specific killing ability of splenic immune cells to tumor cells was enhanced. oHSV2 treatment effectively reduced the content of inhibitory immune cells (regulatory T cells [Tregs] and myeloid-derived suppressor cells [MDSCs]) and increased the content of positive immune cells (natural killer [NK], CD8+ T, and dendritic cells [DCs]) in the spleen. Moreover, treatment with oHSV2 remodeled the tumor immune microenvironment. In summary, treatment with oHSV2 can effectively eliminate primary tumors, generate tumor-specific immunity, and elicit immune memory to inhibit tumor recurrence and metastasis. Furthermore, this virotherapy can reshape the immune status of the spleen and tumor microenvironment in mice, which can further improve the therapeutic antitumor effect.

Changes and Influential Factors of Chemotherapy Usage for Non-Small Cell Lung Cancer Patients in China: A Multicenter 10-Year (2005-2014) Retrospective Study.

BACKGROUND: Chemotherapy has improved the survival of non-small cell lung cancer (NSCLC) patients over the past few decades. However, there have not been any epidemiological studies on chemotherapy for Chinese NSCLC patients. PATIENTS AND METHODS: The patients diagnosed as primary lung cancer between January 1, 2005, and December 31, 2014, in eight hospitals from eight provinces in China were retrospectively reviewed. Demographic and clinical data were extracted from medical history systems. Chi-square test and logistic regression were used to analyze the changes of chemotherapy usage and influential factors. RESULTS: A total of 7184 lung cancer cases were eligible, among which 6481 NSCLC cases were included in this analysis. Among stage I/II patients, the percentages of receiving adjuvant chemotherapy did not change significantly between the earlier (28.5%) and the latter five years (25.7%) (p = 0.1288). Among stage IIIA patients, the percentages of chemotherapy usage did not change significantly between the earlier and the latter five years in neo-adjuvant (7.5% vs 5.6%, p = 0.1478) and adjuvant (23.1% vs 26.8%, p = 0.1129) treatment. The proportions of first-line platinum-based doublets for stage IIIB/IV patients changed significantly over the 10 years (p < 0.0001). Patients from provinces with inferior gross domestic product, with lower medical reimbursement rates and without smoking history were more likely to use the docetaxel/paclitaxel doublets, comparing with the gemcitabine doublets. CONCLUSION: From 2005 to 2014, there was no significant change in the chemotherapy pattern of early NSCLC. Economic factors mainly contributed to the significant changes in the first-line chemotherapy regimen selection for advanced patients.

[Clinicopathological features of uterine neoplasms with perivascular epithelioid cell differentiation].

OBJECTIVE: To study the neoplasm with perivascular epithelioid cell differentiation (PEComa) with respect to their morphologic, immunohistochemical and clinical phenotypes. METHODS: Three PEComas were included in this study, one located at the left uterine horn, and two presented as a mass in the uterine corpus. The tumors were examined by histopathology and immunohistochemistry. RESULTS: The lesions were composed of spindle, blunt epithelioid cells, with foci of, or scattered, cells showing adipose differentiation in two cases. The myomelanocytic differentiation was demonstrated, proving the diagnosis as PEComa. Mild nuclear atypia and focal necrosis was observed in one lesion, and the rest two showed malignant morphologic phenotypes including moderate nuclear atypia and coagulative necrosis. The mitotic and Ki67-labelling indices ranged from 0.5/10 HPF to 14/10 HPF and 0.6% to 7.0%, respectively. All of the three patients remain alive. Malignant nature of the two lesions with worrisome morphology was confirmed by occurrence of metastases after hysterectomy. CONCLUSION: PEComa is a rare tumor, occurring preferentially in the uterus. It is regarded as a tumor with uncertain malignant potential, but a minority of them shows malignant clinical behaviors. Some pathologic parameters including large tumor size, sheet-like necrosis, marked nuclear atypia, elevated mitotic index (> or = 10/10 HPF), aberrant mitotic figure and vascular invasion may help to establish a diagnosis of malignant PEComa.

[Correlation between aneuploidy of chromosome 17, over-expression of TP53 and TOPIIalpha, and the clinicopathological features and diagnosis of gastric adenocarcinoma].

OBJECTIVE: The purpose of this study was to investigate the markers which can be used in auxiliary diagnosis of gastric adenocarcinoma (GAC), and their correlation with their clinicopathological features. METHODS: 122 surgical specimens including 99 gastric adenocarcinoma (GAC), 18 adjacent mucosa and 5 distal normal mucosa were collected, and analyzed by in situ hybridization (FISH). The centromere probe cen17, specific for chromosome 17, which was reported to be frequently amplified in GAC, was selected for the FISH analysis. The clinicopathological features of the 99 GAC cases were reviewed, and the level of TP53 and TOPIIalpha gene expression, located in chromosome 17, was detected using tissue micro-array (TMA), compared with that of corresponding adjacent normal mucosa. Data were analyzed with SPSS 11.5 for Windows. RESULTS: The statistical results of FISH and TMA showed that 58.6% of cen17 in tumor tissues were aneuploid, and 45.5% of TP53 and 84.7% of TOPIIalpha were over-expressed in GAC samples, significantly higher than those in non-tumor gastric mucosa (0, 12.1% and 14.1%, respectively) (P = 0.000). 58 GAC tissues were aneuploid of cen17, including 26 cases TP53-positive and 49 cases TOPIIalpha-positive. The expression of TP53 in non-tumor gastric mucosa with dysplasia was significantly higher than that in the mucosa without dysplasia (P = 0.009). Aneuploidy of cen17 was more frequent in grade 1 or 2 than in grade 3 GAC (P < 0.05). Higher frequency of aneuploidy of cen17 was also observed in the gastric cardia than in pylorus (P < 0.05), while no correlation was found between aneuploidy of cen17 and age, sex of patients, lymph node metastasis, and clinical stage of tumors. Over-expression of TP53 protein was associated with the size of tumors (P < 0.05). In addition, a negative correlation was observed between over-expression of TOPIIalpha and lymph node metastasis (LNM) as well as TNM classification (P < 0.05). CONCLUSION: Detection of aneuploidy of cen17 as well as over-expression of TP53 and TOPIIalpha may be helpful in the diagnosis and prognostic prediction of gastric adenocarcinoma.

Inhibition of colorectal cancer liver metastasis in BALB/c mice following intratumoral injection of oncolytic herpes simplex virus type 2 for the induction of specific antitumor immunity.

Liver metastasis represents the most prominent metastasis of colorectal cancer (CRC) and is the leading cause of CRC mortality, making the early prevention of this event very important. While current CRC therapies include surgery, radiotherapy and chemotherapy, no effective treatment option for CRC liver metastasis (CRLM) exists. Furthermore, the effects of currently available metastatic CRC drugs are frequently limited by their toxicity and side effects. Oncolytic herpes simplex virus type 2 (oHSV2) selectively infects tumor cells and also induces an antitumor immune response. The present study investigated the cytopathic effects of oHSV2 on CT-26 cells in vitro and tested its inhibitory effect on CRLM. In vitro experimental data demonstrated that oHSV2 effectively inhibited the growth of CT-26 cells. In vivo study data demonstrated that treatment with oHSV2 alone slowed the growth of subcutaneous xenograft tumors without inducing weight loss and also inhibited CRLM by increasing the numbers of cluster of differentiation (CD)4+ T, CD8+ T and natural killer cells. In summary, oHSV2 shows potential as a safe and effective therapeutic agent for inhibiting the metastasis of CT-26 CRC cells to the liver.

Trends of Postoperative Radiotherapy for Completely Resected Non-small Cell Lung Cancer in China: A Hospital-Based Multicenter 10-Year (2005-2014) Retrospective Clinical Epidemiological Study.

Objectives: The role of postoperative radiotherapy (PORT) in the treatment of patients with completely resected non-small cell lung cancer (NSCLC) is not clear. Few study explored the trends of the PORT use. In this study, we examine the status of PORT use of completely resected NSCLC in mainland China. Methods: From 2005 to 2014, patients with primary lung cancer from eight hospitals across seven geographic regions of mainland China were selected. Then patients with staged I-IIIA NSCLC receiving radical surgery were enrolled in this study. The chi-square test was used to compare differences in the use of PORT among the groups of different age, regions and stages. The Cochran-Armitage trend test was used to identify the trend in the PORT use from 2005 to 2014. Results: Totally, 2,253 out of 7,184 patients were with staged I-IIIA NSCLC receiving completely resection. Only 122 patients (5.42%) received PORT. During this decade, the use of PORT declined significantly (p = 0.0002). In high socio-economic areas, the percentage of PORT use was 7.43%, which was significantly higher than 1.34% in the low socio-economic areas (p < 0.0001). Age was also associated with PORT use (p = 0.0747). For N0-1 and N2 NSCLC, the proportions of PORT use were 4.01 and 10.22%, respectively (p < 0.0001). And in N0-1 or N2 NSCLC, the proportions both decreased significantly during this decade (p = 0.009 and 0.026, respectively). For stage I, IIA, IIB and IIIA, the proportions who received PORT were 2.59, 4.65, 5.49, and 10.29%, respectively (p < 0.0001). Modern radiation techniques were widely used, but the volumes and doses varied widely. The proportions of using IMRT and EPID/IGRT increased after 2012. Conclusions: In China, the use of PORT was less than developed countries and had a declined trend. The use of PORT was related to disease stages, patients' age and geographic location. Both in N0-1 and N2 diseases, the use of PORT declined. Proper education of radiation doctors was urgently needed.

What are the clinical symptoms and physical signs for non-small cell lung cancer before diagnosis is made? A nation-wide multicenter 10-year retrospective study in China.

BACKGROUND: Most lung cancer patients are diagnosed after the onset of symptoms. However, whether the symptoms of lung cancer were independently associated with the diagnosis of lung cancer is unknown, especially in the Chinese population. METHODS: We conducted a 10 years (2005-2014) nationwide multicenter retrospective clinical epidemiology study of lung cancer patients diagnosed in China. As such, this study focused on nonsmall cell lung cancer (NSCLC). We calculated the odds ratios (ORs) for variables associated with the symptoms and physical signs using multivariate unconditional logistic regressions. RESULTS: A total of 7184 lung cancer patients were surveyed; finally, 6398 NSCLC patients with available information about their symptoms and physical signs were included in this analysis. The most common initial symptom and physical sign was chronic cough (4156, 65.0%), followed by sputum with blood (2110, 33.0%), chest pain (1146, 17.9%), shortness of breath (1090, 17.0%), neck and supraclavicular lymphadenectasis (629, 9.8%), weight loss (529, 8.3%), metastases pain (378, 5.9%), fatigue (307, 4.8%), fever (272, 4.3%), and dyspnea (270, 4.2%). Patients with squamous carcinoma and stage III disease were more likely to present with chronic cough (P < 0.0001) and sputum with blood (P < 0.0001) than patients with other pathological types and clinical stages, respectively. Metastases pain (P < 0.0001) and neck and supraclavicular lymphadenectasis (P = 0.0006) were more likely to occur in patients with nonsquamous carcinoma than in patients with other carcinomas. Additionally, patients with stage IV disease had a higher percentage of chest pain, shortness of breath, dyspnea, weight loss, and fatigue than patients with other stages of disease. In multivariable logistic analyses, compared with patients with adenocarcinoma, patients with squamous carcinoma were more likely to experience symptoms (OR = 2.885, 95% confidence interval [CI] 2.477-3.359) but were less likely to present physical signs (OR = 0.844, 95% CI 0.721-0.989). The odds of having both symptoms and physical signs were higher in patients with late-stage disease than in those with early-stage disease (P < 0.0001). CONCLUSIONS: The symptoms and physical signs of lung cancer were associated with the stage and pathological diagnosis of NSCLC. Patients with squamous carcinoma were more likely to develop symptoms, but not signs, than patients with adenocarcinoma. The more advanced the stage at diagnosis, the more likely that symptoms or physical signs are to develop. Further prospective cohort studies are needed to explore these results.

Clinical characteristics and medical service utilization of lung cancer in China, 2005-2014: Overall design and results from a multicenter retrospective epidemiologic survey.

OBJECTIVES: This study aimed to explore the clinical profile and its trajectory of lung cancer on clinicopathological characteristics and medical service utilization in China. METHODS: Patients diagnosed with primary lung cancer in tertiary hospitals during 2005-14 were selected from seven geographic regions of China. Data on clinical characteristics and medical service utilization was extracted from medical record, and the ten-year trends were explored. RESULTS: A total of 7184 patients were included, the mean age was 58.3 years and the male-to-female-ratio was 2.7. From 2005 to 2014, the proportion of ≥60 year-old patients increased from 41.2% to 56.2% (p < 0.001). The smoking rate decreased from 62.9% to 51.1% (p < 0.001) and the proportion of females increased from 23.5% to 31.9% (p < 0.001). The proportion of advanced stage increased from 41.9% to 47.4% (p < 0.001). Adenocarcinoma's proportion increased from 36.4% to 53.5% (p < 0.001) while that of squamous carcinoma decreased from 45.4% to 34.4% (p < 0.001). The application of chest X-ray dropped from 50.2% to 31.0% (p < 0.001) but that of chest CT increased from 65.8% to 81.4% (p < 0.001). As two main treatment options, chemotherapy (p = 0.290) and surgery (p = 0.497) remained stable. The medical expenditure per patient increased from 40,508 to 66,020 Chinese Yuan (p < 0.001). CONCLUSIONS: The sustaining high smoking exposure, increasing proportion of female patients, advancing clinical stage, shifting of predominant pathology and increasing medical expenditure demonstrate potential challenges and directions on lung cancer prevention and control in China. Despite substantial changes of clinical characteristics, main treatment options remained unchanged, which needs further investigation.

The ubiquitin-proteasome pathway mediates gelsolin protein downregulation in pancreatic cancer.

A well-known observation with respect to cancer biology is that transformed cells display a disturbed cytoskeleton. The underlying mechanisms, however, remain only partly understood. In an effort to identify possible mechanisms, we compared the proteome of pancreatic cancer with matched normal pancreas and observed diminished protein levels of gelsolin--an actin filament severing and capping protein of crucial importance for maintaining cytoskeletal integrity--in pancreatic cancer. Additionally, pancreatic ductal adenocarcinomas displayed substantially decreased levels of gelsolin as judged by Western blot and immunohistochemical analyses of tissue micoarrays, when compared with cancerous and untransformed tissue from the same patients (P < 0.05). Importantly, no marked downregulation of gelsolin mRNA was observed (P > 0.05), suggesting that post-transcriptional mechanisms mediate low gelsolin protein levels. In apparent agreement, high activity ubiquitin-proteasome pathway in both patient samples and the BxPC-3 pancreatic cancer cell line was detected, and inhibition of the 26s proteasome system quickly restored gelsolin protein levels in the latter cell line. The status of ubiquitinated gelsolin is related to lymph node metastasis of pancreatic cancer. In conclusion, gelsolin levels are actively downregulated in pancreatic cancer and enhanced targeting of gelsolin to the ubiquitin-proteasome pathway is an important contributing factor for this effect.

Pathologic characteristics of primary primitive neuroectodermal tumor in the cervix: a small round cell malignant tumor with glial and epithelial differentiation after neoadjuvant chemotherapy.

Primary primitive neuroectodermal tumor (PNET) of the cervix is extremely rare. Only few previous researches have reported on morphologic descriptions in frozen sections or changes in this tumor after radiotherapy or chemotherapy treatments. In the following study we investigated two cases of PNET in cervix. One of which had taken frozen exam and the other experienced neoadjuvant chemotherapy. Briefly, the morphological analysis in intraoperative frozen indicated small round cell malignant tumor with Homer-Wright rosettes, which similar to that in paraffin sections. The morphological changes after chemotherapy showed glial and epithelial differentiation as well as other common reaction. Immunochemistry test of neural and neuroendocrine markers and the detection of EWSR1 gene rearrangement may show positive in this disease in cervix. In conclusion, the obtained data may be useful for further examination, detection and diagnosis of PNET in clinical practice. Also, to the best of our knowledge, this was the first time that morphological and pathological changes were examined in PNET post-chemotherapy. However, the exact mechanisms of these changes require further exploration.

Effect of socioeconomic status on stage at diagnosis of lung cancer in a hospital-based multicenter retrospective clinical epidemiological study in China, 2005-2014.

There is inconsistent evidence of associations between socioeconomic status (SES) and lung cancer stage in non-Chinese populations up to now. We set out to determine how SES affects stage at diagnosis at both individual and area levels, from a hospital-based multicenter 10-year (2005-2014) retrospective clinical epidemiological study of 7184 primary lung cancer patients in mainland China. Individual-level SES data were measured based on two indicators from case report forms of the study: an individual's education and occupation. Seven census indicator variables were used as surrogates for the area-level SES with principal component analysis (PCA). Multivariate analysis was undertaken using binary logistic regressions and multinomial logit model to describe the association and explore the effect across tertiles on stage after adjusting for demographic variables. There was a significant stepwise gradient of effect across different stages in the highest tertile of area-level SES, comparing with the lowest tertile of area-level SES (ORs, 0.77, 0.67, and 0.29 for stage II, III, and IV). Patients with higher education were less likely to have stage IV lung cancer, comparing with the illiterate group (ORs, 0.52, 0.63, 0.71, 0.64 for primary school, middle school, high school, college degree or above subgroup, respectively). Findings suggest that the most socioeconomically deprived areas may be associated with a higher risk of advanced-stage lung cancer, and increasing educational level may be correlated with a lower risk to be diagnosed at advanced stage in both men and women.

Overexpression of annexin 1 in pancreatic cancer and its clinical significance.

AIM: To investigate the expression of annexin I in pancreatic cancer and its relationship with the clinicopathologic factors, and to evaluate its potential clinical significance. METHODS: Annexin I expression was analyzed by Western blot and immunohistochemical staining in pancreatic adenocarcinoma and multi-tissue microarrays (MTAs). RESULTS: Western blot analysis showed that annexin I was overexpressed in 84.6% (11/13) pancreatic ductal adenocarcinomas. Immunohistochemistry analysis of pancreatic cancer in MTAs showed that annexin I protein was 71.4%(30/42) positive which was markedly increased compared with that in the tumor matched normal pancreas tissues 18.4%(7/38) (P<0.01). In the meantime, the high expression of annexin 1 was correlated with the poor differentiation of pancreatic adenocarcinoma. CONCLUSION: Annexin 1 overexpression is a frequent biological marker and correlates with the differentiation of pancreatic cancer during tumorigenesis.

[Primary gastric endocrine tumors].

OBJECTIVE: To study the clinicopathological features of gastric neuroendocrine tumors. METHODS: Twenty cases were reviewed. The specimens were formalin-fixed, paraffin-embedded and immunostained by S-P method. RESULTS: Among the twenty cases, one case was carcinoid, three were malignant carcinoids, six had small cell carcinomas and ten had mixed extocrine--endocrine carcinomas. Immunohistological examination of tumor cells found 80% positive for S-100, NSE (85%), CgA (50%), SY (50%), gastrin (30%), serotonin (65%), AE1/AE3 (50%), and CEA (80%). CONCLUSIONS: In the WHO classification, there are five histological types in endocrine tumors of gastrointestinal tract. They are carcinoid, malignant carcinoid, small cell carcinoma, mixed exocrine--endocrine carcinoma and tumor-like lesions. But some cases in our paper were so different that they could not be classified. The gastric endocrine tumors are different from intestinal endocrine tumors and in classification, treatment and prognosis.