摘要:Pancreatic neuroendocrine tumor is a common pancreatic tumor with high heterogeneity and multiple management modalities. A standard and practical staging system for pancreatic neuroendocrine tumors will be beneficial to clinical management and research. At present, there are two staging systems (ENETS and AJCC). Both of them have shortcomings which limit their clinical application. In addition, the coexistence of two staging systems is confusing to clinicians. We proposed a modified ENETS staging system by keeping the ENETS TNM definition and adopting the AJCC staging definition. The modified staging system can successfully distinguish patients with different prognosis and is helpful in establishing clinical standard. This study has been published in Journal of Clinical Oncology (JCO) and was selected as “2017 Best of JCO: Gastrointestinal edition”. This paper was aimed to interpret the modified staging system in clinical practice.
关键词:Pancreatic neuroendocrine tumor;Staging;Prognosis;European Neuroendocrine Tumor Society System;American Joint Committee on Cancer
摘要:Background and purpose: The incidence and mortality of lung cancer ranked first in China. This study aimed to describe lung cancer survival in Shanghai, and provide background information for cancer prevention and treatment evaluation. Methods: Data of lung cancer cases diagnosed during 2002-2006, follow-up information and death report were collected from Shanghai Cancer Registry. Life table method and Ederer Ⅱ were used to calculate observed survival (OS) and relative survival (RS) respectively. Related demographic characteristics and status were also analyzed to present the survival situations of the lung cancer survivors in Shanghai. Results: In this study, 41 802 lung cancer cases were included in analysis. The 5-year OS and RS for lung cancer were 13.75% and 20.23% respectively, and median survival time was 318 days. Survival rate was higher among females than males, with the 5-year OS of 15.49% and 13.00% respectively. The 5-year OS was higher among suburban residents (14.25%) than urban residents (13.23%). Survival rates decreased with increasing age and advanced stage. Patients aged 0-34 had a 5-year OS of 38.21%, while patients aged above 75 had a 5-year OS of 5.48%. Patients diagnosed with stage Ⅰ had a 5-year OS of 55.47%, while patients diagnosed with stage Ⅳ had a 5-year OS of 5.27%. Survival of lung cancer patients differed by tumor histological subtype. The 5-year OS of squamous lung cancer (24.40%) was higher than other histological types, followed by adenocarcinoma (22.26%), large cell (20.27%) and small cell lung cancer (12.22%). From 1972-1976 to 2002-2006, the 5-year OS of urban male patients increased from 6.8% to 12.4%, and 5-year OS of urban female patients increased from 7.3% to 14.9%. Analysis of RS gave the similar results. Conclusion: During the past 30 years, survival rate of lung cancer patients in Shanghai improved steadily, and the survival condition is above average among different countries and areas. However, survival rate of lung cancer is still low compared with other types of cancer. Future focus should be placed on the control of tobacco smoking, early detection by low-dose helical computed tomography and targeted therapy to further improve lung cancer survival.
摘要:Background and purpose: Primary pulmonary myxoid sarcoma (PPMS) is a very rare lung tumor that has recently been shown to harbor EWSR1-CREB1 translocation. This study aimed to investigate the clinicopathological characteristics and differential diagnosis of PPMS. Methods: The clinical and pathological features of 6 cases of PPMS with EWSR1 gene rearrangement were reviewed. Immunohistochemistry and fluorescence in situ hybridization (FISH) study were performed. Results: Six patients were enrolled in this study, including 4 male patients and 2 female patients with an age range of 23 to 64 years (median age, 44 years). All tumors involved pulmonary parenchyma, with a predominant endobronchial component in 1 and adjacent to bronchus in 5 patients. Microscopically, the tumor was lobulated and composed of cords of polygonal, spindle cells within myxoid stroma. Tumors were immunoreactive for only Vimentin and weakly focal for epithelial membrane antigen (EMA). All tumors were shown to harbor EWSR1 gene rearrangement by FISH. Follow-up of all patients showed that 1 patient developed a pleura and bone metastasis but was still alive and 5 were disease-free after 4-29 months. Conclusion: PPMS is an extremely rare sarcoma with low- grade malignant potential. This is characterized by distinct histological features and EWSR1 gene rearrangement. It is important that understanding tumor spectrum and genetic feature can contribute to diagnosis and differential diagnosis of PPMS.
关键词:EWSR1 gene;Primary pulmonary myxoid sarcoma;Fluorescence in situ hybridization
摘要:Background and purpose: Epithelial ovarian carcinoma is the most malignant tumor in female reproductive system because of its resistance to chemotherapy. Fructose-1, 6-bisphosphatase (FBP1) is a rate-limiting enzyme in gluconeogenesis used to catalyze the hydrolysis of fructose-1, 6-bisphosphate to fructose-6-phosphate and inorganic phosphate, thereby inhibiting the effect of glycolysis in tumor cells. This study aimed to investigate the association between the expression of FBP1 and chemosensitivity. Methods: The expression level of FBP1 in ovarian cancer patients was measured by immunohistochemistry. Results: According to the results of immunohistochemistry in 209 ovarian carcinoma specimens, the percentage of positive FBP1 expression was about 49.3% (103/209). Loss of FBP1 was a negative factor of survival (42.6 months vs 62.1 months, P=0.003). Besides, patients who were sensitive to chemotherapy displayed significantly higher scores of FBP1 expression than patients who were resistant to therapy (P=0.007). Conclusion: The rate-limiting enzyme FBP1 in gluconeogenesis can be used as a biomarker for predicting the chemoresistance and prognosis of ovarian cancer patients.
摘要:Background and purpose: Previous studies have confirmed that the expression of leucine-rich repeat-containing 3B (CLRRC3B) was significantly decreased in different human cancers, which was also associated with the migration and invasion of cancer cells. The aim of this study was to explore the potential mechanism of LRRC3B in the development of esophageal cancer. Methods: The LRRC3B expression was detected in 60 cancer tissues and 60 adjacent non-neoplastic tissues by immunohistochemistry. The mRNA and protein expression of LRRC3B in Eca109 and HEECs were detected using real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot, respectively. Eca109 cells with different treatments were divided into three groups: normal group, negative control group (transfected with pCMV6 plasmid), overexpression LRRC3B group (transfected with pCMV6-LRRC3B plasmid). Transwell assay was used to measure the migration and invasion of Eca109 cells in different groups. The protein levels of E-cadherin, N-cadherin, Vimentin and p-Akt were determined by Western blot. Results: The expression of LRRC3B in esophageal cancer tissues was lower than that of non-cancerous tissues, as well as the expression of LRRC3B in Eca109 was decreased compared with that of normal esophageal epithelial cell line HEEC. Overexpression of LRRC3B significantly inhibited Eca109 cells migration and invasion, upregulated the expression of E-cadherin and decreased the expression of N-cadherin and Vimentin. Moreover, overexpression of LRRC3B significantly inhibited the phosphorylation of Akt in Eca109 cells. Conclusion: The expression of LRRC3B was decreased in esophageal cancer. Overexpression of LRRC3B can efficiently inhibit the EMT progression in esophageal cancer cells by suppressing PI3K/Akt signaling pathway.
摘要:Background and purpose: Short tandem repeats (STR) multiplex PCR fluorescence detection technology is the most widely used DNA technology in individual identity and genetic identification. It’s the most direct method to obtain accurate conclusions. However, some studies have indicated that the rate of STR mutations in tumor tissue is significantly higher than that in normal tissues or blood. This study aimed to investigate the tendency of genetic instability in 20 STR loci on autosomal and Amel loci in tumor tissue samples from lung cancer. Methods: This study, collected 75 cases of human lung cancer tissues and the adjacent normal tissues. DNA samples were extracted by tissue DNA extraction kit, amplified using MicroreaderTM 21 Direct ID System PCR amplification kit. Capillary electrophoresis was performed using API 3130 analyzer, and results were analyzed by genetic analysis software (Gene Mapper ID V3.2). Results: STR alterations were detected in 24 specimens from 75 lung cancer tissues (32%). Fifty-five alterations were detected in the frequntly used 21 STR loci in total, including additional alleles 10 times, loss of heterozygosity 10 times, partial loss of heterozygosity 35 times. Partial loss of heterozygosity was the most common genetic alteration types accounting for 63.64% of the total alteration frequency. And multiple genetic alteration types could occur in the same lung cancer tissue. Among them, the highest alteration frequency occurred on D5S818 (7 times), secondly on D3S1358 and D12S391 (both 5 times), and no alterations on D2S441 and Penta E. Combining the experimental results and analysis on clinical data, this study found the statistical differences between the staging of lung cancer and the age of the patients with the STR loci alterations (P<0.05). However, the alterations did have much relationship with the classification of lung cancer and the patient's gender (P>0.05). Conclusion: STR loci of the lung cancer tissue were not stable, and the alteration occurred in the aged or high malignant degree lung cancer tissue more frequently. Meanwhile, no alteration was detected on D2S441 and Penta E. In the future research the two STR loci should be verified to determine whether they can be used as the stable STR loci in such cases by increasing the sample size.
关键词:Forensic biological evidence;Lung cancer;Short tandem repeats;Genetic alteration;Locus
摘要:Background and purpose: Diallyl disulfide (DADS) could inhibit the growth of cancer cells. This study aimed to investigate the effect of DADS and overexpression of RORα on EMT in human gastric cancer MGC803 cells with upregulation of RORα by DADS. Methods: The morphological effect on MGC803 cells was observed by phase-contrast microscope. The correlative molecules with EMT were detected by RT-PCR, Western blot, immunofluorescence and immunohistochemistry. The influence on xenograft tumor growth in nude mice was observed in MGC803 cells. Results: Phase-contrast microscope showed that MGC803 cells were of identical size, round or oval with decreased spindle cells and lower level of heteromorphism in DADS group and RORα/MGC803 group. The above-mentioned alterations were more obvious in RORα/MGC803+DADS group. Western blot exhibited obviously the downregulation of Snail protein in DADS group and RORα/MGC803 group (P<0.05). RT-PCR and Western blot disclosed that the expression of Vimentin was downregulated notably and E-cadherin was upregulated in DADS group, RORα/MGC803 group, and RORα/MGC803+DADS group more obviously (P<0.05). Immunofluorescence revealed that the positive expression of Snail and Vimentin protein was attenuate, while E-cadherin was strengthened in DADS group, RORα/MGC803 group and RORα/MGC803+DADS group compared with MGC803 cells. Moreover, the xenograft tumor growth was markedly decreased, and body weight of transplanted tumor was visibly reduced with the inhibition ratio of 15.07%, 26.55 % and 49.27%, respectively (P<0.05). The positive expression of Ki-67, CD34 and Vimentin were obviously decreased, while the positive expression of E-cadherin was increased. Conclusion: Overexpression of RORα can remarkably enhance inhibition of EMT in MGC803 cells by DADS in vivo and in vivo.
关键词:Diallyl disulfide;RORα;Human gastric cancer MGC803 cells;Epithelial-mesenchymal transformation;Snail;Vimentin;E-cadherin
摘要:Background and purpose: When patients have positive sentinel lymph node (SLN), axillary lymph node dissection (ALND) is usually performed, but most of them have no metastasis in the non-sentinel lymph node (nSLN). It is of great significance to predict metastasis of nSLN precisely. The aim of the study was to establish a nomogram for the intraoperative prediction of nSLN metastasis in breast cancer patients using one-step nucleic acid amplification (OSNA) techniques and to direct the subsequent therapy for breast cancer effectively. Methods: Of 552 breast cancer patients who underwent SLN biopsy in the 2010 OSNA clinical trial, 103 with SLN metastasis treated with ALND were assessed to establish a nomogram for intraoperative prediction of nSLN based on the molecular diagnosis. A validation cohort of 61 patients who met the similar criteria in the 2015 OSNA clinical trial subsequently validated it. Results: Primary tumor size, total tumor load, the number of positive SLNs and negative SLNs were associated with the presence of nSLN metastasis based on the multivariable logistic regression results, and a nomogram was established with these variables. Its area under the ROC curve was 0.814 for the predictive model and it was 0.842 in the re-validation cohort. The tumor size assessed by the postoperative histological examination was replaced by the size evaluated by the imaging examination, and the area under the ROC curve was 0.838. There was no statistically significant difference in the accuracy compared with the former validation data (P=0.740 6). Conclusion: The predictive nomogram based on the molecular diagnosis can predict the nSLN metastases intra/post-operatively. It appears to be obviously superior to other predictive models and may help to guide the axillary management and to make decisions about radiation target region.
摘要:Background and purpose: Natural killer/T-cell lymphoma (NKTCL) is a scarce subtype of malignant lymphoma, and it has heterogeneous clinical manifestation and treatment effect. Currently, no precise risk stratification is used to guide prognosis. This study aimed to evaluate the prognostic impact of pre-treatment peripheral blood absolute monocyte count (AMC) and platelet-lymphocyte ratio (PLR) in patients with primary nasal NKTCL, and provide more precise information for better risk stratification to select appropriate treatment and improve survival. Methods: Clinical data of 132 patients newly diagnosed with primary nasal NKTCL was collected in the Tianjin Medical University Cancer Institute and Hospital from Jan. 2008 to Dec. 2013. The relationship between AMC and PLR in pre-treatment peripheral blood and 5-year overall survival (OS) and progression-free survival (PFS) of patients was analyzed retrospectively. Independent prognostic factors of patients were determined by univariate analysis and Cox regression analysis. Results: Pre-treatment peripheral blood AMC and PLR play important roles in the prognosis stratification of patients with primary nasal NKTCL. The prognosis in patients of AMC<0.5×109/L were higher than those of AMC≥0.5×109/L, The prognosis in patients of PLR<150 were higher than those of PLR≥150 (P<0.05). Based on the four independent risk factors of staging, ECOG scoring, AMC and PLR, we tried to establish a new prognostic model, dividing all patients into three different risk groups and found that the 5-year OS and PFS of three groups had significant statistical differences. Conclusion: Peripheral blood AMC and PLR were significantly correlated with the prognosis of patients with primary nasal NKTCL. The new prognostic patterns based on the four independent risk factors, such as staging, ECOG scoring, AMC and PLR may be more convenient and more economical than IPI (International Prognostic Index, IPI) and KPI (Korean Prognostic Index, KPI).
摘要:Background and purpose: The prognosis of completely resected stage ⅢA(N2) non-small cell lung cancer (NSCLC) remains a significant concern. The 5-year overall survival (OS) rates range from 10% to 30%. This study aimed to analyze the patterns of first failure in completely resected stage ⅢA(N2) NSCLC and to assess the actuarial risk of developing metastasis at different sites and to guild standard clinical practice. Methods: Patients with ⅢA(N2) NSCLC who had undergone radical surgery in our hospital from Jan. 2005 to Jul. 2012 were retrospectively reviewed. The progression-free survival (PFS), the OS, patterns of first failure, the actuarial risk were analyzed. The cumulative incidence of first failure was determined using the Kaplan-Meier analysis. Results: Among 357 patients who met the eligibility criteria with completely resected stage ⅢA(N2) NSCLC, 5-year OS was 36.9%. There were 284 (77.6%) patients experiencing disease failure: 61 with local failure, 197 with local and distant failures, and 26 patients with local recurrence as the first failure. Brain, bone and lung were the main sites of distant failure as the first failure, while brain was the most common site. There were 67 patients developing brain metastases (BM) as the first site of failure. The median time of local failure as the first site of failure was 13.6 months, and the time to develop distant recurrence was 15.1 months. 92.5% BM developed in 3 years after the complete resection. Conclusion: As the first failure, the rate of distant failure was much higher than that of local failure in completely resected stage ⅢA(N2) NSCLC. Brain was the most common site of distant failure as the first failure. These results can be helpful in guiding standard clinical practice and evaluating the outcome of comprehensive treatment.
关键词:Non-small cell lung cancer;Stage ⅢA(N2);Patterns of first failure;Distant failure;Brain metastases
摘要:Background and purpose: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is of advantage in treating non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, their clinical effects vary individually. This study aimed to evaluate whether the EGFR ligand, plasma transforming growth factor α (TGF-α), could act as a predictor for the EGFR-TKI treatment efficiency in NSCLC patients with EGFR mutations and the association between TGF-α and prognosis in these patients. Methods: Seventy-five NSCLC patients with EGFR gene positive mutation were included in the current study from May 2012 to Jul. 2014 in Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine. Plasma TGF-α was measured using enzyme-linked immunosorbent assay (ELISA) in all of the patients before EGFR-TKI treatment. The radiographic evaluation was performed 2 months after the therapy. The association between TGF-α and clinical outcome and its prediction efficiency were determined, followed by the further analysis of the association between TGF-α and overall survival (OS) as well as progression-free survival (PFS). Results: After EGFR-TKI treatment, there were 20 patients with partial response (PR), 25 with stable disease (SD) and 30 with progression disease (PD) in all 75 NSCLC patients harboring EGFR positive mutation. The disease control (DC) rate reached 60%. Patients in PD group presented statistically significant higher plasma TGF-α than patients in the DC group (P<0.01). Multivariate COX model indicated that smoking status, lymph node metastasis and plasma TGF-α levels were independent risk factors for prognosis in these patients. The ROC analysis revealed that baseline plasma TGF-α showed good prediction efficiency [area under the curve (AUC)=0.926] and the cut-off point of TGF-α was 16.75 pg/mL. Higher level of TGF-α (≥16.75 pg/mL) was associated with smoking history, clinical stage, lymph node metastasis and clinical outcome of the patients (P<0.05). In comparison to patients with low TGF-α, the patients with high TGF-α concentration presented significantly reduced median OS and PFS (log-rank P<0.05). Conclusion: Higher plasma TGF-α (≥16.75 pg/mL) had a predictive role in EGFR-TKI resistance and poor prognosis.
摘要:Background and purpose: Radiation therapy has entered the era of precise radiotherapy. Setup error becomes important factor affecting the effects of radiotherapy. The aim of this study was to analyze the setup accuracy of the in-house developed technique of body plate with vacuum cushion and thermoplastic mask (Group A) and the conventional technique of arm support (Group B) in thoracic tumor radiotherapy. Methods: A total of 19 patients with thoracic tumor were enrolled in this study and randomly separated into Group A and Group B. The patients of Group A underwent the secondary set-up: align the marker on vacuum cushion and patient’s body to the room laser, cover the patient’s body with thermoplastic mask and align the marker on the mask to the room laser. The patients of Group B were directly setup by aligning the marker on the patient’s body to the room laser. The kilo-voltage cone beam computed tomography (KV-CBCT) was performed on each patient to collect the pre- and post-treatment CBCT images. The CBCT images were registered to the planning CT to analyze the translational error of Group A and Group B. Results: The pre-treatment set-up errors of Group A vs Group B were (1.06±0.58) vs (1.82±0.82) mm in left and right (LR) direction, (1.31±0.40) vs (2.18±1.20) mm in superior and inferior (SI) direction, and (1.28±0.66) vs (2.94±1.81) mm in anterior and posterior (AP) direction. The post-treatment set-up errors of Group A vs Group B were (0.86±0.54) vs (1.29±0.58) mm in LR direction, (1.07±0.58) vs (1.08±0.45) mm in SI direction, and (0.98±0.53) vs (1.56±0.63) mm in AP direction.Conclusion: The in-house developed immobilization technique of body plate with vacuum cushion and thermoplastic mask was more accurate and reproducible than the conventional immobilization technique of arm support in thoracic tumor radiotherapy.
关键词:Body position immobilization;Set-up error;Thoracic tumor;Image guided radiation therapy