AIM： To investigate alternative or subordinate pathways involved in colorectal tumorigenesis and tumor growth, possibly determining at-risk populations and predicting responses to treatment. METHODS： Using microarra...AIM： To investigate alternative or subordinate pathways involved in colorectal tumorigenesis and tumor growth, possibly determining at-risk populations and predicting responses to treatment. METHODS： Using microarray gene-expression analysis, we analyzed patterns of gene expression relative to canonical molecular changes and clinicopathological features in 84 sporadic colorectal cancer patients, standardized by tumor location. Subsets of differentially expressed genes were confirmed by real-time reverse-transcript polymerase chain reaction （RT-PCR）. RESULTS： The largest number of genes identified as being differentially expressed was by tumor location, and the next largest number by lymphovascular or neural invasion of tumor cells and by mismatch repair （NMR） defects. Amongst biological processes, the immune response was significantly implicated in entire molecular changes observed during colorectal tumorigenesis （P 〈 0.001）. Amongst 47 differentially expressed genes, seven （PISD, NIBP, BAI2, STOML1, MRPL21, MRPL16, and MKKS） were newly found to correlate with tumorigenesis and tumor growth. Most location-associated molecular changes had distinct effects on gene expression, but the effects of the latter were sometimes contradictory. CONCLUSION： We show that several differentially expressed genes were associated with canonical molecular changes in sporadic colorectal cancers, possibly constituting alternative or subordinate pathways of tumorigenesis. As tumor location was the dominant factor influencing differential gene expression, location-specific analysis may identify location-associated pathways and enhance the accuracy of class prediction.展开更多
Based on Siewert classification, adenocarcinomas of the esophagogastric junction （AEGs） have different behaviors of perigastric-mediastinal nodal metastasis. Siewert type I AEGs have higher incidence of mediastinal ...Based on Siewert classification, adenocarcinomas of the esophagogastric junction （AEGs） have different behaviors of perigastric-mediastinal nodal metastasis. Siewert type I AEGs have higher incidence of mediastinal nodal metastasis than those of type H or III, especially at middle-upper mediastinum. With regard to the necessity of mediastinal lymphadenectomy, theoretically, transthoracic esophagogastrectomy with complete mediastinal lymphadenectomy is suggested for Siewert type I AEGs, while transhiatal total gastrectomy with lower mediastinal and D2 perigastric lymphadenectomy is a standard surgery for type II-III AEGs. Nevertheless, the mediastinal nodal metastasis is an independent factor of poor prognosis for any type of AEG.展开更多
Background: Changes in lung cancer has been characterized by the increase of cases among women and the increase in adenocarcinomas among other histological subtypes.Methods: Descriptive analysis of cases diagnosed wit...Background: Changes in lung cancer has been characterized by the increase of cases among women and the increase in adenocarcinomas among other histological subtypes.Methods: Descriptive analysis of cases diagnosed with lung cancer in Hospital Virgen de las Nieves(Spain) from 1990 to 2010,based on five variables(age, sex, smoking, histology and pathological anatomy). The study establishes associations between these variables and compares the results with the literature.Results: 2,026 patients were diagnosed with lung cancer in this period; 1,838 were males(90.7%) and 188 women(9.3%); 1,892 patients(93.4%) were smokers or ex-smokers and 134(6.6%) had never smoked; the most frequent non-small cell histology types were squamous cell carcinoma and adenocarcinoma and it was the most frequent neoplasia in women and were associated with a lower tobacco consumption.Conclusion: The large majority of lung cancer cases is associated with a history of smoking tobacco and there are histopathological differences according to gender and cumulative tobacco smoke load.展开更多
Objective:We aim to investigate radiomic imaging features extracted in computed tomography(CT)images to differentiate invasive pulmonary adenocarcinomas(IPAs)from non-IPAs appearing as part-solid ground-glass nodules(...Objective:We aim to investigate radiomic imaging features extracted in computed tomography(CT)images to differentiate invasive pulmonary adenocarcinomas(IPAs)from non-IPAs appearing as part-solid ground-glass nodules(GGNs),and to incorporate significant radiomic features with other clinically-assessed features to develop a diagnostic nomogram model for IPAs.Methods:This retrospective study was performed,with Institutional Review Board approval,on 88 patients with a total of 100 part-solid nodules(56 IPAs and 44 non-IPAs)that were surgically confirmed between February 2014and November 2016 in the First Affiliated Hospital of China Medical University.Quantitative radiomic features were computed automatically on 3D nodule volume segmented from arterial-phase contrast-enhanced CT images.A set of regular risk factors and visually-assessed qualitative CT imaging features were compared with the radiomic features using logistic regression analysis.Three diagnostic models,i.e.,a basis model using the clinical factors and qualitative CT features,a radiomics model using significant radiomic features,and a nomogram model combining all significant features,were built and compared in terms of receiver operating characteristic(ROC)curves.Decision curve analysis was performed for the nomogram model to explore its potential clinical benefit.Results:In addition to three visually-assessed qualitative imaging features,another three quantitative features selected from hundreds of radiomic features were found to be significantly(all P<0.05)associated with IPAs.The diagnostic nomogram model showed a significantly higher performance[area under the ROC curve(AUC)=0.903]in differentiating IPAs from non-IPAs than either the basis model(AUC=0.853,P=0.0009)or the radiomics model(AUC=0.769,P<0.0001).Decision curve analysis indicates a potential benefit of using such a nomogram model in clinical diagnosis.Conclusions:Quantitative radiomic features provide additional information over clinically-assessed qualitative features for differentiating 展开更多
AIM： To determine the role of Sonic hedgehog （Shh） pathway in colorectal adenocarcinomas through analysis of the expression of Shh pathway-related molecules, Shh, Ptchl, hedgehog-interacting protein （Hip）, Gil1, ...AIM： To determine the role of Sonic hedgehog （Shh） pathway in colorectal adenocarcinomas through analysis of the expression of Shh pathway-related molecules, Shh, Ptchl, hedgehog-interacting protein （Hip）, Gil1, Gli3 and PDGFRα. METHODS： Expression of Shh in 25 colorectal adenocarcinomas was detected by RT-PCR,in situ hybridization and immunohistochemistry. Expression of Ptchl was observed by in situ hybridization and immunohistochemistry. Expression of Hip, Gil1, Gli3 and PDGFRα was analyzed by in situ hybridization. RESULTS： Expression of cytokeratin AE1/AE3 was observed in the cytoplasm of colorectal crypts. Members of the Hh signaling pathway were expressed in colorectal epithelium. Shh was expressed in cytoplasm of dysplastic epithelial cells, while expression of Ptchl, Hip and Gill were mainly detected in the malignant crypts of adenocarcinomas. In contrast, PDGFRα was expressed highly in aberrant crypts and moderately in the stroma. Expression of Gli3 could not be detected in colorectal adenocarcinomas. CONCLUSION： These data suggest that Shh-Ptchl-Gli1 signaling pathway may play a role in the progression of colorectal tumor.展开更多
AIM: To detect the presence of inducible nitric oxide synthase (iNOS), nitrotyrosine (NT) and apoptosis in gastric adenocarcinomas and their possible correlations with the clinicopathological characteristics and progn...AIM: To detect the presence of inducible nitric oxide synthase (iNOS), nitrotyrosine (NT) and apoptosis in gastric adenocarcinomas and their possible correlations with the clinicopathological characteristics and prognosis of gastric adenocarcinoma.METHODS: Sixty-six specimens of gastric adenocarcinoma and corresponding adjacent normal gastric tissues were studied. Immunohistochemistry was employed to localize iNOS and NT protein and an immunohistochemical scoring system was used. The occurrence of apoptotic cell death (apoptotic index [AI]) was analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL) method. RESULTS: Results showed that iNOS expression wasdetected at an intermediate or high level in 41 of 66 (62%) specimens of gastric adenocarcinoma. NT expression was 58%. Neither of them was found in the normal gastric tissues; there were significant positive correlations among iNOSexpression, NT expression and AI. Many clinicopathologic characteristics of gastric adenocarcinoma, such as tumor size, depth of invasion, lymph node metastasis and TNM staging, were related to iNOS and NT expressions (P＜0.05). In 66 surviving patients, the 5-year survival rate of 41 patients who had tumors with intermediate or high iNOS expressions and high Ais (4.09%; 19.96%) was significantly lower than that of 25 patients who had tumors with negative or low iNOS expressions and low Ais (0.79%; 47.14%) (P= 0.001). COX's multivariate analysis revealed that the iNOS expression was identified as one of the significant independent prognostic factors predictive of a poor survival (relative risk [RR] = 2.69).CONCLUSION: NO produced by iNOS may play a stronger role in promoting gastric adenocarcinoma growth than in suppressing its growth. iNOS and NT expressions by gastric adenocarcinoma may correlate with a poor survival.展开更多
AIM:To investigate three isoforms of survivin in colorectal adenocarcinomas.METHODS:We used the LightCycler Technology(Roche),along with a common forward primer and reverse primers specific for the splice variants and...AIM:To investigate three isoforms of survivin in colorectal adenocarcinomas.METHODS:We used the LightCycler Technology(Roche),along with a common forward primer and reverse primers specific for the splice variants and two common hybridization probes labeled with fluorescein and LightCycler-Red fluorophore(LC-Red 640).Real time quantitative polymerase chain reaction(PCR) was performed on cDNAs from 52 tumor specimens from colorectal cancer patients and 10 unrelated normal colorectal tissues.In the patients group,carcinoembryonic antigen(CEA) and CA19-9 tumor markers were also measured immunochemically.RESULTS:Wild type survivin mRNA isoform was expressed in 48%of the 52 tumor samples,survivin-2b in 38%and survivin-ΔΕx3 in 29%,while no expression was found in normal tissues.The mRNA expression of wild type survivin presented a significant correlation with the expression of the ratio of survivin-2b,survivin-ΔΕx3,survivin-2b/wild type survivin and survivin-ΔΕx3/wild type survivin(P<0.001).The mRNA expression of wildsurvivin and survivin-ΔΕx3 was related with tumor size and invasion(P=0.006 and P<0.005,respectively).A significant difference was found between survivin-2b and morphologic cancer type.Also,the ratio of survivin-ΔEx3/ wild-survivin was significantly associated with prognosis.No association was observed between the three isoforms and grade,metastasis,Dukes stage and gender.The three isoforms were not correlated with CEA and CA19-9.CONCLUSION:Survivin isoforms may play a role in cell apoptosis and their quantification could provide information about clinical management of patients suffering from colorectal cancer.展开更多
Familial adenomatous polyposis (FAP) is an autosomal dominant inherited syndrome characterized by multiple adenomatous polyps (predisposing to colorectal cancer development) and numerous extracolonic manifestations. T...Familial adenomatous polyposis (FAP) is an autosomal dominant inherited syndrome characterized by multiple adenomatous polyps (predisposing to colorectal cancer development) and numerous extracolonic manifestations. The underlying genetic burden generates variable clinical features that may influence operative management. As a precancerous hereditary condition, the rationale of performing a prophylactic surgery is a mainstay of FAP management. The purpose of the present paper is to bring up many controversial aspects regarding surgical treatment for FAP, and to discuss the results and perspectives of the operative choices and approaches. Preferably, the decision-making process should not be limited to the conventional confrontation of pros and cons of ileorectal anastomosis or restorative proctocolectomy. A wide discussion with the patient may evaluate issues such as age, genotype, family history, sphincter function, the presence or risk of desmoid disease, potential complications of each procedure and chances of postoperative surveillance. Therefore, the definition of the best moment and the choice of appropriate procedure constitute an individual decision that must take into consideration patient’s preferences and full information about the complex nature of the disease. All these facts reinforce the idea that FAP patients should be managed by experienced surgeons working in specialized centers to achieve the best immediate and long-term results.展开更多
AIM TO correlate Helicobacter pylori （H. pylorli）, EpsteinBarr virus （EBV） and human papillomavirus （HPV） with gastric cancer （GC） cases in Para State, Brazil.METHODS Tissue samples were obtained from 302 gast...AIM TO correlate Helicobacter pylori （H. pylorli）, EpsteinBarr virus （EBV） and human papillomavirus （HPV） with gastric cancer （GC） cases in Para State, Brazil.METHODS Tissue samples were obtained from 302 gastric adenocarcinomas. A rapid urease test was used to detect the presence of H. pylori, and the presence of the cagA gene in the HP-positive samples was confirmed by PCR. An RNA in situ hybridization test designed to complement Eberl RNA was used to detect the presence of EBV in the samples, and the L1 region of HPV was detected using nested PCR. Positive HPV samples were genotyped and analyzed for E6 and E7 viral gene expression. Infections were also correlated with the clinical and pathological characteristics of the patients.RESULTS The majority of the 302 samples analyzed were obtained from men （65%） aged 55 years or older （67%） and were classified as the intestinal subtype （55%）. All three pathogens were found in the samples analyzed in the present study （H. pylori： 87%, EBV： 20%, HPV： 3%）. Overall, 78% of the H. pylori-positive （H. pylorl＋） samples were cagA＋ （H. pylori-cagA＋）, and there was an association between the cytotoxic product of this gene and EBV. Coinfections of H. pylori-cagA＋ and EBV were correlated with the most advanced tumor stages. Although only 20% of the tumors were positive for EBV, infection with this virus was associated with distant metastasis. Only the HPV 16 and 18 strains were found in the samples, although no expression of the E6 and E7 oncoproteins was detected. The fundus of the stomach was the region least affected by the pathogens.CONCLUSION HPV was not involved in gastric tumorigenesis. Prophy- lactic and therapeutic measures against H. pylori and EBV may prevent the development of GC, especially the more aggressive forms.展开更多
研究一：Takahashi T，Sonobe M，Kobayashi M，et al．Clinicopathologic features of non—small-cell lung cancer with EML4-ALK fusion gene[J]．Ann Surg Oncol，2010，17（3）：889—897．
BACKGROUND Colorectal polyps refer to all neoplasms that protrude into the intestinal cavity.Researchers believe that 50%-70%of colorectal cancers originate from adenomatous polyps.AIM To investigate the endoscopic mo...BACKGROUND Colorectal polyps refer to all neoplasms that protrude into the intestinal cavity.Researchers believe that 50%-70%of colorectal cancers originate from adenomatous polyps.AIM To investigate the endoscopic morphologic features,pathologic types,and clinical situation;evaluate the efficacy and safety of endoscopic mucosal resection(EMR);and guide clinicians in their daily practice.METHODS Two hundred thirty-four patients who underwent EMR in our hospital from January 1,2018 to December 31,2019 were recruited.Data including sex,age,endoscopic morphology of the polyps,and pathological characteristics were analyzed among groups.RESULTS A total of 295 polyps were resected from the 234 subjects enrolled in the study,of which 4(1.36%)were Yamada type I.There were 75(25.42%)type II,101(34.24%)type III,and 115(38.98%)type IV adenomas.Among them,41 were nonadenomas,110 were low-risk adenomas,139 were high-risk adenomas,and 5 were carcinomas.The differences in distribution were not statistically significant,with P values greater than 0.05.The risk of cancer significantly increased for polyps≥1 cm in diameter(c2=199.825,P=0.00).Regarding the endoscopic morphological features,congestion,erosion,and lobulation were more common on the surface morphology of high-risk adenomas and cancerous polyps(c2=75.257,P=0.00),and most of them were Yamada types III and IV.In all,6 of the 295 polyps could not be removed completely,with a one-time resection rate of 97.97%.There were two cases of postoperative bleeding and no cases of perforation,with an overall complication rate of 0.09%.CONCLUSION Colorectal polyps ranging from non-adenomatous polyps,low-risk adenomas,and high-risk adenomas to adenocarcinomas each has their own endoscopic features,while EMR,as a mature intervention,has good safety and operability and should be promoted clinically,especially at the primary care level.展开更多
The evaluation of therapeutic efficacy is necessary to predict the outcome of patients with metastatic colorectal cancer(CRC). In these patients, there is a critical need for predictive chemosensitivity assays and bio...The evaluation of therapeutic efficacy is necessary to predict the outcome of patients with metastatic colorectal cancer(CRC). In these patients, there is a critical need for predictive chemosensitivity assays and biomarkers to optimize efficacy and minimize toxicity. The introduction of targeted agents has improved the progression-free survival and overall survival of patients with metastatic disease. However, approximately 50% of patients do not show a positive response to chemotherapy and the selection of patients likely to respond to a specific regimen remains challenging. Cell culturebased chemosensitivity tests use autologous viable tumor cells to evaluate susceptibility to specific agents in vitro and predict their direct effects. Adenosine triphosphate-based assays and methyl thiazolyl-diphenyltetrazolium bromide-based assays are used widely as sensitivity tests because of their short assay period, technical simplicity, and the requirement of small amount of specimen. Among protein- and gene-based chemosensitivity assays, assessment of KRAS mutation status predicts the response to epidermal growth factor receptor-targeted therapy in CRC patients. The validation of predictive and prognostic markers enables the selection of therapeutic regimens with optimal efficacy and minimal toxicity for each patient, which has been termed personalized treatment. This review summarizes currently available predictive and prognostic chemosensitivity tests for metastatic CRC.展开更多
Background： Ovarian serous adenocarcinoma can be divided into low- and high-grade tumors, which exhibit substantial differences in pathogenesis, clinicopathology, and prognosis. This study aimed to investigate the d...Background： Ovarian serous adenocarcinoma can be divided into low- and high-grade tumors, which exhibit substantial differences in pathogenesis, clinicopathology, and prognosis. This study aimed to investigate the difl＇erences in the PH domain leucine-rich repeat protein phosphatase （PHLPP）, tbrkhead llomeobox type O3a （FoxO3a）, and RAD51 protein expressions, and their associations with prognosis in patients with low- and high-grade ovarian serous adenocarcinomas. Methods： The PH LPP, FoxO3a, and RA D51 protein expressions were examined in 94 high- and 26 low-grade ovarian serous adenocarcinomas by immunohistochemistry. The differences in expression and their relationships with pathological features and prognosis were analyzed. Results： In high-grade serous adenocarcinomas, the positive rates of PHLPP and goxO3a were 24.5% and 26.6%, while in low-grade tumors, they were 23.1% and 26.9%, respectively （P 〈 0.05 vs. the control specimens; low- vs. high-grade： P 〉 0.（15）. The positive rates of RAD51 were 70.2% and 65.4% in high- and low-grade serous adenocarcinomas, respectively （P 〈 0.（15 vs. the control specimens; low- vs. high-grade： P 〉 0.05）. Meanwhile, in high-grade tumors, Stage Ⅲ/Ⅳ tumors and lymph node and omental metastases were significantly associated with lower PHLPP and FoxO3a and higher RAD51 expression. The 5-year survival rates of patients with PHLPP- and FoxO3a-positive high-grade tumors （43.5% and 36.0%） were significantly higher than in patients with PHLPP-negative tumors （5.6% and 7.2%, respectively; P 〈 0.05）. Similarly, the 5-year survival rate of RAD5 l-positive patients （3.0%） was significantly lower than in negative patients （42.9%： P〈 0.05）. In low-grade tumors, the PHLPP, FoxO3a, and RAD51 expressions were not significantly correlated with lymph node metastasis, omental metastasis, Federation of Gynecology and Obstetrics stage, or prognosis. Conclusions： Abnormal PHLPP, FoxO3a, and RAD51 protein expressions may be involved展开更多
AIM To evaluate the incidence of lymph node metastasis （LNM） and its risk factors in patients with Siewert type Ⅰ and type Ⅱ pT1 adenocarcinomas.METHODS We enrolled 85 patients [69 men, 16 women; median age （ra...AIM To evaluate the incidence of lymph node metastasis （LNM） and its risk factors in patients with Siewert type Ⅰ and type Ⅱ pT1 adenocarcinomas.METHODS We enrolled 85 patients [69 men, 16 women; median age （range）, 67 （38-84） years] who had undergone esophagectomy or proximal gastrectomy for Siewert type Ⅰ and type Ⅱ pT1 adenocarcinomas. Predictive risk factors of LNM included age, sex, location of the tumor center, confirmed Barrett’s esophageal adenocarcinoma, tumor size, macroscopic tumor type, pathology, invasion depth, presence of ulceration, and lymphovascular invasion. Multivariate logistic regression analysis was used to identify factors predicting LNM. We also evaluated the frequencies of LNM for Siewert type Ⅰ and type Ⅱ pT1 adenocarcinomas in meta-data analysis.RESULTSLNMs were found in 11 out of 85 patients （12.9%, 95%CI： 5.8-20.0）. Only 1 of the 15 patients （6.6%, 95%CI： 0.0-19.2） who had a final diagnosis of pT1a adenocarcinoma had a positive LNM, whereas 10 of the 70 patients （14.2%, 95%CI： 6.0-22.4） with a final diagnosis of pT1b adenocarcinoma had positive LNM. Furthermore, only one of the 30 patients （3.3%, 95%CI： 0.0-9.7） with a tumor invasion depth within 500 μm from muscularis mucosae had positive LNM. Poor differentiation and lymphovascular invasion were independently associated with a risk of LNM. In meta-data analysis, 12 of the 355 patients （3.3%, 95%CI： 1.5-5.2） who had a final diagnosis of pT1a adenocarcinoma had a positive LNM, whereas 91 of the 438 patients （20.7%, 95%CI： 16.9-24.5） with a fnal diagnosis of pT1b adenocarcinoma had positive LNM.CONCLUSIONWe consider endoscopic submucosal dissection （ESD） is suitable for patients with Siewert type Ⅰ and type Ⅱ T1a adenocarcinomas. For patients with T1b adenocarcinoma, especially invasion depth is within 500 μm from muscularis mucosae with no other risk factor for LNM, diagnostic ESD could be a treatment option according to the overall status of patients and the展开更多
基金Supported by The Basic Research Program of the Korea Science & Engineering Foundation,No.R01-2006-000-10021-0the Korea Health 21 R&D Project,Ministry of Health & Welfare No.A062254
文摘AIM： To investigate alternative or subordinate pathways involved in colorectal tumorigenesis and tumor growth, possibly determining at-risk populations and predicting responses to treatment. METHODS： Using microarray gene-expression analysis, we analyzed patterns of gene expression relative to canonical molecular changes and clinicopathological features in 84 sporadic colorectal cancer patients, standardized by tumor location. Subsets of differentially expressed genes were confirmed by real-time reverse-transcript polymerase chain reaction （RT-PCR）. RESULTS： The largest number of genes identified as being differentially expressed was by tumor location, and the next largest number by lymphovascular or neural invasion of tumor cells and by mismatch repair （NMR） defects. Amongst biological processes, the immune response was significantly implicated in entire molecular changes observed during colorectal tumorigenesis （P 〈 0.001）. Amongst 47 differentially expressed genes, seven （PISD, NIBP, BAI2, STOML1, MRPL21, MRPL16, and MKKS） were newly found to correlate with tumorigenesis and tumor growth. Most location-associated molecular changes had distinct effects on gene expression, but the effects of the latter were sometimes contradictory. CONCLUSION： We show that several differentially expressed genes were associated with canonical molecular changes in sporadic colorectal cancers, possibly constituting alternative or subordinate pathways of tumorigenesis. As tumor location was the dominant factor influencing differential gene expression, location-specific analysis may identify location-associated pathways and enhance the accuracy of class prediction.
基金National Natural Science Foundation of China (No. 81372344 and 81301866)New Century Excellent Talents in University support program, Ministry of Education of China (2012SCU-NCET-11-0343)
文摘Based on Siewert classification, adenocarcinomas of the esophagogastric junction （AEGs） have different behaviors of perigastric-mediastinal nodal metastasis. Siewert type I AEGs have higher incidence of mediastinal nodal metastasis than those of type H or III, especially at middle-upper mediastinum. With regard to the necessity of mediastinal lymphadenectomy, theoretically, transthoracic esophagogastrectomy with complete mediastinal lymphadenectomy is suggested for Siewert type I AEGs, while transhiatal total gastrectomy with lower mediastinal and D2 perigastric lymphadenectomy is a standard surgery for type II-III AEGs. Nevertheless, the mediastinal nodal metastasis is an independent factor of poor prognosis for any type of AEG.
文摘Background: Changes in lung cancer has been characterized by the increase of cases among women and the increase in adenocarcinomas among other histological subtypes.Methods: Descriptive analysis of cases diagnosed with lung cancer in Hospital Virgen de las Nieves(Spain) from 1990 to 2010,based on five variables(age, sex, smoking, histology and pathological anatomy). The study establishes associations between these variables and compares the results with the literature.Results: 2,026 patients were diagnosed with lung cancer in this period; 1,838 were males(90.7%) and 188 women(9.3%); 1,892 patients(93.4%) were smokers or ex-smokers and 134(6.6%) had never smoked; the most frequent non-small cell histology types were squamous cell carcinoma and adenocarcinoma and it was the most frequent neoplasia in women and were associated with a lower tobacco consumption.Conclusion: The large majority of lung cancer cases is associated with a history of smoking tobacco and there are histopathological differences according to gender and cumulative tobacco smoke load.
基金supported by the National Natural Science Foundation of China (No. 81301222)the Special Research Grant for Non-profit Public Service (No. 201402013)the Science and Technology Department Project of Liaoning province (No. 2012020073-302)
文摘Objective:We aim to investigate radiomic imaging features extracted in computed tomography(CT)images to differentiate invasive pulmonary adenocarcinomas(IPAs)from non-IPAs appearing as part-solid ground-glass nodules(GGNs),and to incorporate significant radiomic features with other clinically-assessed features to develop a diagnostic nomogram model for IPAs.Methods:This retrospective study was performed,with Institutional Review Board approval,on 88 patients with a total of 100 part-solid nodules(56 IPAs and 44 non-IPAs)that were surgically confirmed between February 2014and November 2016 in the First Affiliated Hospital of China Medical University.Quantitative radiomic features were computed automatically on 3D nodule volume segmented from arterial-phase contrast-enhanced CT images.A set of regular risk factors and visually-assessed qualitative CT imaging features were compared with the radiomic features using logistic regression analysis.Three diagnostic models,i.e.,a basis model using the clinical factors and qualitative CT features,a radiomics model using significant radiomic features,and a nomogram model combining all significant features,were built and compared in terms of receiver operating characteristic(ROC)curves.Decision curve analysis was performed for the nomogram model to explore its potential clinical benefit.Results:In addition to three visually-assessed qualitative imaging features,another three quantitative features selected from hundreds of radiomic features were found to be significantly(all P<0.05)associated with IPAs.The diagnostic nomogram model showed a significantly higher performance[area under the ROC curve(AUC)=0.903]in differentiating IPAs from non-IPAs than either the basis model(AUC=0.853,P=0.0009)or the radiomics model(AUC=0.769,P<0.0001).Decision curve analysis indicates a potential benefit of using such a nomogram model in clinical diagnosis.Conclusions:Quantitative radiomic features provide additional information over clinically-assessed qualitative features for differentiating
基金grants from National Natural Science Foundation of China, No. 30228031, No. 30671072
文摘AIM： To determine the role of Sonic hedgehog （Shh） pathway in colorectal adenocarcinomas through analysis of the expression of Shh pathway-related molecules, Shh, Ptchl, hedgehog-interacting protein （Hip）, Gil1, Gli3 and PDGFRα. METHODS： Expression of Shh in 25 colorectal adenocarcinomas was detected by RT-PCR,in situ hybridization and immunohistochemistry. Expression of Ptchl was observed by in situ hybridization and immunohistochemistry. Expression of Hip, Gil1, Gli3 and PDGFRα was analyzed by in situ hybridization. RESULTS： Expression of cytokeratin AE1/AE3 was observed in the cytoplasm of colorectal crypts. Members of the Hh signaling pathway were expressed in colorectal epithelium. Shh was expressed in cytoplasm of dysplastic epithelial cells, while expression of Ptchl, Hip and Gill were mainly detected in the malignant crypts of adenocarcinomas. In contrast, PDGFRα was expressed highly in aberrant crypts and moderately in the stroma. Expression of Gli3 could not be detected in colorectal adenocarcinomas. CONCLUSION： These data suggest that Shh-Ptchl-Gli1 signaling pathway may play a role in the progression of colorectal tumor.
文摘AIM: To detect the presence of inducible nitric oxide synthase (iNOS), nitrotyrosine (NT) and apoptosis in gastric adenocarcinomas and their possible correlations with the clinicopathological characteristics and prognosis of gastric adenocarcinoma.METHODS: Sixty-six specimens of gastric adenocarcinoma and corresponding adjacent normal gastric tissues were studied. Immunohistochemistry was employed to localize iNOS and NT protein and an immunohistochemical scoring system was used. The occurrence of apoptotic cell death (apoptotic index [AI]) was analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL) method. RESULTS: Results showed that iNOS expression wasdetected at an intermediate or high level in 41 of 66 (62%) specimens of gastric adenocarcinoma. NT expression was 58%. Neither of them was found in the normal gastric tissues; there were significant positive correlations among iNOSexpression, NT expression and AI. Many clinicopathologic characteristics of gastric adenocarcinoma, such as tumor size, depth of invasion, lymph node metastasis and TNM staging, were related to iNOS and NT expressions (P＜0.05). In 66 surviving patients, the 5-year survival rate of 41 patients who had tumors with intermediate or high iNOS expressions and high Ais (4.09%; 19.96%) was significantly lower than that of 25 patients who had tumors with negative or low iNOS expressions and low Ais (0.79%; 47.14%) (P= 0.001). COX's multivariate analysis revealed that the iNOS expression was identified as one of the significant independent prognostic factors predictive of a poor survival (relative risk [RR] = 2.69).CONCLUSION: NO produced by iNOS may play a stronger role in promoting gastric adenocarcinoma growth than in suppressing its growth. iNOS and NT expressions by gastric adenocarcinoma may correlate with a poor survival.
文摘AIM:To investigate three isoforms of survivin in colorectal adenocarcinomas.METHODS:We used the LightCycler Technology(Roche),along with a common forward primer and reverse primers specific for the splice variants and two common hybridization probes labeled with fluorescein and LightCycler-Red fluorophore(LC-Red 640).Real time quantitative polymerase chain reaction(PCR) was performed on cDNAs from 52 tumor specimens from colorectal cancer patients and 10 unrelated normal colorectal tissues.In the patients group,carcinoembryonic antigen(CEA) and CA19-9 tumor markers were also measured immunochemically.RESULTS:Wild type survivin mRNA isoform was expressed in 48%of the 52 tumor samples,survivin-2b in 38%and survivin-ΔΕx3 in 29%,while no expression was found in normal tissues.The mRNA expression of wild type survivin presented a significant correlation with the expression of the ratio of survivin-2b,survivin-ΔΕx3,survivin-2b/wild type survivin and survivin-ΔΕx3/wild type survivin(P<0.001).The mRNA expression of wildsurvivin and survivin-ΔΕx3 was related with tumor size and invasion(P=0.006 and P<0.005,respectively).A significant difference was found between survivin-2b and morphologic cancer type.Also,the ratio of survivin-ΔEx3/ wild-survivin was significantly associated with prognosis.No association was observed between the three isoforms and grade,metastasis,Dukes stage and gender.The three isoforms were not correlated with CEA and CA19-9.CONCLUSION:Survivin isoforms may play a role in cell apoptosis and their quantification could provide information about clinical management of patients suffering from colorectal cancer.
文摘Familial adenomatous polyposis (FAP) is an autosomal dominant inherited syndrome characterized by multiple adenomatous polyps (predisposing to colorectal cancer development) and numerous extracolonic manifestations. The underlying genetic burden generates variable clinical features that may influence operative management. As a precancerous hereditary condition, the rationale of performing a prophylactic surgery is a mainstay of FAP management. The purpose of the present paper is to bring up many controversial aspects regarding surgical treatment for FAP, and to discuss the results and perspectives of the operative choices and approaches. Preferably, the decision-making process should not be limited to the conventional confrontation of pros and cons of ileorectal anastomosis or restorative proctocolectomy. A wide discussion with the patient may evaluate issues such as age, genotype, family history, sphincter function, the presence or risk of desmoid disease, potential complications of each procedure and chances of postoperative surveillance. Therefore, the definition of the best moment and the choice of appropriate procedure constitute an individual decision that must take into consideration patient’s preferences and full information about the complex nature of the disease. All these facts reinforce the idea that FAP patients should be managed by experienced surgeons working in specialized centers to achieve the best immediate and long-term results.
基金the National Council for scientific and technological development,No.(CNPq)402283/2013-9
文摘AIM TO correlate Helicobacter pylori （H. pylorli）, EpsteinBarr virus （EBV） and human papillomavirus （HPV） with gastric cancer （GC） cases in Para State, Brazil.METHODS Tissue samples were obtained from 302 gastric adenocarcinomas. A rapid urease test was used to detect the presence of H. pylori, and the presence of the cagA gene in the HP-positive samples was confirmed by PCR. An RNA in situ hybridization test designed to complement Eberl RNA was used to detect the presence of EBV in the samples, and the L1 region of HPV was detected using nested PCR. Positive HPV samples were genotyped and analyzed for E6 and E7 viral gene expression. Infections were also correlated with the clinical and pathological characteristics of the patients.RESULTS The majority of the 302 samples analyzed were obtained from men （65%） aged 55 years or older （67%） and were classified as the intestinal subtype （55%）. All three pathogens were found in the samples analyzed in the present study （H. pylori： 87%, EBV： 20%, HPV： 3%）. Overall, 78% of the H. pylori-positive （H. pylorl＋） samples were cagA＋ （H. pylori-cagA＋）, and there was an association between the cytotoxic product of this gene and EBV. Coinfections of H. pylori-cagA＋ and EBV were correlated with the most advanced tumor stages. Although only 20% of the tumors were positive for EBV, infection with this virus was associated with distant metastasis. Only the HPV 16 and 18 strains were found in the samples, although no expression of the E6 and E7 oncoproteins was detected. The fundus of the stomach was the region least affected by the pathogens.CONCLUSION HPV was not involved in gastric tumorigenesis. Prophy- lactic and therapeutic measures against H. pylori and EBV may prevent the development of GC, especially the more aggressive forms.
文摘研究一：Takahashi T，Sonobe M，Kobayashi M，et al．Clinicopathologic features of non—small-cell lung cancer with EML4-ALK fusion gene[J]．Ann Surg Oncol，2010，17（3）：889—897．
文摘BACKGROUND Colorectal polyps refer to all neoplasms that protrude into the intestinal cavity.Researchers believe that 50%-70%of colorectal cancers originate from adenomatous polyps.AIM To investigate the endoscopic morphologic features,pathologic types,and clinical situation;evaluate the efficacy and safety of endoscopic mucosal resection(EMR);and guide clinicians in their daily practice.METHODS Two hundred thirty-four patients who underwent EMR in our hospital from January 1,2018 to December 31,2019 were recruited.Data including sex,age,endoscopic morphology of the polyps,and pathological characteristics were analyzed among groups.RESULTS A total of 295 polyps were resected from the 234 subjects enrolled in the study,of which 4(1.36%)were Yamada type I.There were 75(25.42%)type II,101(34.24%)type III,and 115(38.98%)type IV adenomas.Among them,41 were nonadenomas,110 were low-risk adenomas,139 were high-risk adenomas,and 5 were carcinomas.The differences in distribution were not statistically significant,with P values greater than 0.05.The risk of cancer significantly increased for polyps≥1 cm in diameter(c2=199.825,P=0.00).Regarding the endoscopic morphological features,congestion,erosion,and lobulation were more common on the surface morphology of high-risk adenomas and cancerous polyps(c2=75.257,P=0.00),and most of them were Yamada types III and IV.In all,6 of the 295 polyps could not be removed completely,with a one-time resection rate of 97.97%.There were two cases of postoperative bleeding and no cases of perforation,with an overall complication rate of 0.09%.CONCLUSION Colorectal polyps ranging from non-adenomatous polyps,low-risk adenomas,and high-risk adenomas to adenocarcinomas each has their own endoscopic features,while EMR,as a mature intervention,has good safety and operability and should be promoted clinically,especially at the primary care level.
基金Supported by Grants from Asan Institute for Life Sciences,No.2014-69the National Research Foundation,No.NRF-2013R1A2A1A03070986+1 种基金Ministry of Science,ICT,and Future Planning,the Korea Health 21 RD Project,No.HI06C0868 and No.HI13C1750the Center for Development and Commer-cialization of Anti-Cancer Therapeutics,No.HI10C2014,Ministry of Health and Welfare,South Korea
文摘The evaluation of therapeutic efficacy is necessary to predict the outcome of patients with metastatic colorectal cancer(CRC). In these patients, there is a critical need for predictive chemosensitivity assays and biomarkers to optimize efficacy and minimize toxicity. The introduction of targeted agents has improved the progression-free survival and overall survival of patients with metastatic disease. However, approximately 50% of patients do not show a positive response to chemotherapy and the selection of patients likely to respond to a specific regimen remains challenging. Cell culturebased chemosensitivity tests use autologous viable tumor cells to evaluate susceptibility to specific agents in vitro and predict their direct effects. Adenosine triphosphate-based assays and methyl thiazolyl-diphenyltetrazolium bromide-based assays are used widely as sensitivity tests because of their short assay period, technical simplicity, and the requirement of small amount of specimen. Among protein- and gene-based chemosensitivity assays, assessment of KRAS mutation status predicts the response to epidermal growth factor receptor-targeted therapy in CRC patients. The validation of predictive and prognostic markers enables the selection of therapeutic regimens with optimal efficacy and minimal toxicity for each patient, which has been termed personalized treatment. This review summarizes currently available predictive and prognostic chemosensitivity tests for metastatic CRC.
文摘Background： Ovarian serous adenocarcinoma can be divided into low- and high-grade tumors, which exhibit substantial differences in pathogenesis, clinicopathology, and prognosis. This study aimed to investigate the difl＇erences in the PH domain leucine-rich repeat protein phosphatase （PHLPP）, tbrkhead llomeobox type O3a （FoxO3a）, and RAD51 protein expressions, and their associations with prognosis in patients with low- and high-grade ovarian serous adenocarcinomas. Methods： The PH LPP, FoxO3a, and RA D51 protein expressions were examined in 94 high- and 26 low-grade ovarian serous adenocarcinomas by immunohistochemistry. The differences in expression and their relationships with pathological features and prognosis were analyzed. Results： In high-grade serous adenocarcinomas, the positive rates of PHLPP and goxO3a were 24.5% and 26.6%, while in low-grade tumors, they were 23.1% and 26.9%, respectively （P 〈 0.05 vs. the control specimens; low- vs. high-grade： P 〉 0.（15）. The positive rates of RAD51 were 70.2% and 65.4% in high- and low-grade serous adenocarcinomas, respectively （P 〈 0.（15 vs. the control specimens; low- vs. high-grade： P 〉 0.05）. Meanwhile, in high-grade tumors, Stage Ⅲ/Ⅳ tumors and lymph node and omental metastases were significantly associated with lower PHLPP and FoxO3a and higher RAD51 expression. The 5-year survival rates of patients with PHLPP- and FoxO3a-positive high-grade tumors （43.5% and 36.0%） were significantly higher than in patients with PHLPP-negative tumors （5.6% and 7.2%, respectively; P 〈 0.05）. Similarly, the 5-year survival rate of RAD5 l-positive patients （3.0%） was significantly lower than in negative patients （42.9%： P〈 0.05）. In low-grade tumors, the PHLPP, FoxO3a, and RAD51 expressions were not significantly correlated with lymph node metastasis, omental metastasis, Federation of Gynecology and Obstetrics stage, or prognosis. Conclusions： Abnormal PHLPP, FoxO3a, and RAD51 protein expressions may be involved
文摘AIM To evaluate the incidence of lymph node metastasis （LNM） and its risk factors in patients with Siewert type Ⅰ and type Ⅱ pT1 adenocarcinomas.METHODS We enrolled 85 patients [69 men, 16 women; median age （range）, 67 （38-84） years] who had undergone esophagectomy or proximal gastrectomy for Siewert type Ⅰ and type Ⅱ pT1 adenocarcinomas. Predictive risk factors of LNM included age, sex, location of the tumor center, confirmed Barrett’s esophageal adenocarcinoma, tumor size, macroscopic tumor type, pathology, invasion depth, presence of ulceration, and lymphovascular invasion. Multivariate logistic regression analysis was used to identify factors predicting LNM. We also evaluated the frequencies of LNM for Siewert type Ⅰ and type Ⅱ pT1 adenocarcinomas in meta-data analysis.RESULTSLNMs were found in 11 out of 85 patients （12.9%, 95%CI： 5.8-20.0）. Only 1 of the 15 patients （6.6%, 95%CI： 0.0-19.2） who had a final diagnosis of pT1a adenocarcinoma had a positive LNM, whereas 10 of the 70 patients （14.2%, 95%CI： 6.0-22.4） with a final diagnosis of pT1b adenocarcinoma had positive LNM. Furthermore, only one of the 30 patients （3.3%, 95%CI： 0.0-9.7） with a tumor invasion depth within 500 μm from muscularis mucosae had positive LNM. Poor differentiation and lymphovascular invasion were independently associated with a risk of LNM. In meta-data analysis, 12 of the 355 patients （3.3%, 95%CI： 1.5-5.2） who had a final diagnosis of pT1a adenocarcinoma had a positive LNM, whereas 91 of the 438 patients （20.7%, 95%CI： 16.9-24.5） with a fnal diagnosis of pT1b adenocarcinoma had positive LNM.CONCLUSIONWe consider endoscopic submucosal dissection （ESD） is suitable for patients with Siewert type Ⅰ and type Ⅱ T1a adenocarcinomas. For patients with T1b adenocarcinoma, especially invasion depth is within 500 μm from muscularis mucosae with no other risk factor for LNM, diagnostic ESD could be a treatment option according to the overall status of patients and the
