A preliminary study on stereotactic ablative brachytherapy for lung metastases from cervical cancer / 中国辐射卫生

Objective To preliminarily study the effectiveness and safety of stereotactic ablative brachytherapy (SABT) for lung metastases from cervical cancer. Methods We analyzed the clinical data of 18 patients with cervical cancer with lung metastasis treated with SABT to compare gross tumor volume (VGTV) and squamous cell carcinoma (SCC) antigen before and after SABT. The clinical benefit rate (CBR) and adverse reactions were recorded. Results After SABT treatment, there were significant decreases in VGTV (t=1.708, P<0.05) and the SCC antigen level (t=1.704, P<0.05). CBR reached 94.4%. Adverse reactions of grades 3-4 did not occur in any patient. Fourteen patients had mild complications, including 1 case of bloody sputum and 1 case of a small pneumothorax. Ten cases developed mild radiation-induced lung injury, with grade 2 radiation pneumonitis in 4 cases. The Karnofsky performance status score and needle depth were not associated with the occurrence of adverse reactions, while the radius of GTV and interstitial lung disease were associated with the occurrence of adverse reactions. Conclusion SABT is a safe and effective alternative to the treatment of lung metastases from cervical cancer.

Analysis of prognostic factors in 135 patients with pulmonary metastasis from esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective:To investigate the prognostic factors of patients with esophageal squamous cell carcinoma with pulmonary metastasis.Methods:Clinical characteristics of 135 esophageal squamous cell carcinoma patients presenting with pulmonary metastasis after treatment in Zhejiang Cancer Hospital from 2008 to 2018 were retrospectively analyzed. Thesurvival rate was calculated by Kaplan-Meier method. Univariate analysis was performed by log-rank test. Multivariate prognostic analysis was conducted by Cox models.Results:The median follow-up time of 135 patients with esophageal squamous cell carcinoma was 94.2 months (19.5-258.9 months), and 109 patients died (80.7%). The 1-and 2-year overall survival rates were 47.4% and 25.1%, with the median survival time was 11.1 months (7.3-14.9 months). Univariate prognostic analysis showed that age, number of lung metastases, treatment of lung metastases, lymph node metastasis, distant organ metastasis, and the interval between the first treatment and lung metastasis were the prognostic factors of esophageal squamous cell carcinoma with lung metastasis (all P<0.05). Multivariate analysis demonstrated that age and number of lung metastases were the independent prognostic factors for patients with esophageal squamous cell carcinoma with lung metastases (all P<0.05). Conclusions:Age and number of lung metastases are the independent prognostic factors for patients with esophageal squamous cell carcinoma with lung metastases. Surgery or radiotherapy-based regional therapy can enhance clinical prognosis.

Application of dual-energy CT in differential diagnosis of lung metastases and benign nodules in breast cancer / 中华放射学杂志

Objective:To investigate the application value of dual-energy CT in the differential diagnosis of lung metastases and benign nodules in breast cancer.Methods:The data of 96 patients with pathology-confirmed breast cancer at the Fifth Affiliated Hospital of Wenzhou Medical University from March 2017 to June 2021 were analyzed retrospectively. All patients received dual-energy chest CT scans within 2 weeks before surgery. All 96 patients were female, aged 31-84 (56±12) years. A total of 207 pulmonary nodules from 96 patients were classified into 81 lung metastases and 126 benign nodules according to pathological findings. Conventional CT features [longest diameter, boundary, location and CT value difference between arterial and venous phases (ΔCT) of nodules] and dual-energy CT parameters [standardized iodine concentration (NIC), slope of energy spectrum (λ HU) and normalized effective atomic number (nZ eff) in arterial and venous phases] were analyzed and measured. The χ 2 test, independent samples t test and Kruskal-Wallis rank-sum test were used to analyze the differences of conventional CT features and dual-energy CT parameters between lung metastases and benign nodules. First, the least shrinkage and selection operator (LASSO) regression method was used to screen conventional CT features and dual-energy CT parameters, and then logistic regression analysis was performed to screen out independent risk factors for lung metastases. Receiver operating characteristic (ROC) curves were used to evaluate the efficacy of CT parameters alone and logistic model in differentiating lung metastases from benign lung nodules. Results:There were statistically significant differences between lung metastases and benign nodules in longest diameter, ?CT, NIC, λ HU and nZ eff in arterial and venous phases (all P<0.05). LASSO regression and binary logistic regression analysis showed that the venous phase λ HU (OR=59.413, 95%CI 14.233-248.002, P<0.001) and the venous phase nZ eff (OR=4.508, 95%CI 2.787-7.290, P<0.001) were independent risk factors for predicting lung metastases. Among them, the venous phase λ HU had the highest diagnostic efficiency, with an area under curve (AUC) of 0.794 and an accuracy of 74.88%. The AUC of the logistic model constructed by combining the venous phase λ HU and the venous phase nZ eff could reach 0.958, and the accuracy was improved to 92.27%, which was significantly higher than the efficacy of the two alone ( Z=6.02, 9.54, all P<0.001). Conclusion:Dual-energy CT has great application value in the identification of lung metastases and benign nodules in patients with breast cancer, especially when combined with venous phase λ HU and venous phase nZ eff, the diagnostic efficiency is further improved.

Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

Survival Analysis of 76 Cases of Head and Neck Adenoid Cystic Carcinoma with Lung Metastasis / 中国肺癌杂志

BACKGROUND@#Adenoid cystic carcinoma (ACC) of the head and neck often develops lung metastasis. At present, there are not many research reports on ACC lung metastasis, little is known about its exact clinical features and treatment results, and there is no consensus on the best treatment strategy. This study explored the effective treatment strategies, clinical outcomes and long-term prognosis of head and neck ACC lung metastases.@*METHODS@#The clinical and follow-up data of 76 patients with head and neck ACC lung metastases were retrospectively analyzed. According to the initial treatment of patients, they are divided into 4 groups: surgery, surgery+chemotherapy or radiotherapy, chemotherapy or radiotherapy and supportive treatment. The patients were staged according to the International Registry of Lung Metastases Staging System (IRLM). Kaplan-Meier method and Log-rank test were used to compare the statistical differences of overall survival (OS) and progression-free survival (PFS) of patients with different treatment methods and different IRLM stages.@*RESULTS@#The OS and PFS of patients undergoing surgery are better than those of supportive therapy or radiotherapy and/or chemotherapy (OS: P<0.000,1; PFS: P<0.000,1). The OS and PFS of patients with low stage IRLM are better than those with high stage (OS: P<0.000,1; PFS: P<0.000,1). Patients with single lung metastasis and without pleural effusion have better OS and PFS.@*CONCLUSIONS@#The long-term prognosis of patients with lung metastasis of head and neck ACC who undergo surgery is better than other treatments, which is related to higher OS and PFS. For patients with ACC lung metastases who are operationally eligible, the significance of complete surgical resection should be higher than other treatment options.

Stereotactic body radiation therapy for liver and lung oligometastases from colorectal cancer: safety, local efficacy and prognostic factors / 中华放射肿瘤学杂志

Oligometastasis is an intermediate status between the locally advanced and wide spread disease. Patients with oligometastasis may obtain long-term survival after local treatment. Stereotactic body radiation therapy (SBRT) can deliver radical ablative doses in a small number of fractions, which is a highly precise local ablation therapy. Approximately half of patients diagnosed with colorectal cancer (CRC) will develop metastases, with the liver and lung as the most common site of involvement. In this article, the safety, local efficacy and prognostic factors of SBRT for liver and lung oligometastases from CRC were illustrated. The highlights of SBRT implementation were also discussed. SBRT is safe and effective for oligometastases from CRC under respiratory motion management and robust quality assurance.

Analysis of influencing factors for lung metastasis of hepatocellular carcinoma after liver transplantation and application value of its nomogram prediction model / 中华消化外科杂志

Objective:To investigate the influencing factors for lung metastasis of hepato-cellular carcinoma after liver transplantation and application value of its nomogram prediction model.Methods:The retrospective cohort study was conducted. The clinicopathological data of 339 hepatocellular carcinoma patients with lung metastasis after liver transplantation who were admitted to Zhongshan Hospital of Fudan University from January 2015 to June 2019 were collected. There were 299 males and 40 females, aged from 23 to 73 years, with a median age of 54 years. According to the random numbers showed in the computer, all 339 patients were divided into training dataset consisting of 226 and validation dataset consisting of 113, with a ratio of 2:1. All patients underwent classic orthotopic liver transplantation. Observation indicators: (1) analysis of clinicopathological data of patients in the training dataset and validation dataset; (2) follow-up; (3) analysis of influencing factors for lung metastasis of hepatocellular carcinoma after liver transplanta-tion; (4) construction and evaluation of nomogram prediction model for lung metastasis of hepatocellular carcinoma after liver transplantation. Follow-up was conducted using outpatient examination and telephone interview to detect lung metastasis of patients up to November 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the paired t test. Measurement data with skewed distribution were represented as M( P25, P75) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute number or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate lung metastasis rate and draw lung metastasis curve. The Log-rank test was used for survival analysis. The COX proportional hazard model was used for univariate and multivariate analysis. Based on the results of multivariate analysis, the nomogram prediction model was constructed. The prediction accuracy of the nomogram model was evaluated using C-index and receiver operating characteristic (ROC) curve. The calibration curve was used to evaluate the prediction error of the model. Results:(1) Analysis of clinicopathological data of patients in the training dataset and validation dataset: there was no significant difference in general data between patients in the training dataset and validation dataset ( P>0.05). (2) Follow-up: 226 patients in training dataset and 113 patients in validation dataset were followed up. The follow-up time of training dataset was 5.2 to 69.0 months, with a median follow-up time of 29.3 months, and the follow-up time of validation dataset was 4.3 to 69.0 months, with a median follow-up time of 30.4 months. Up to the last follow-up, 48 cases of the training dataset and 22 cases of the validation dataset had lung metastasis, with the incidence and median time of lung metastasis were 21.24%(48/226), 19.47%(22/113) and 8.5 months, 7.8 months, respectively. There was no significant difference in lung metastasis between patients in the training dataset and validation dataset ( χ2=0.144, P>0.05). (3) Analysis of influencing factors for lung metastasis of hepatocellular carcinoma after liver transplantation: results of univariate analysis showed that age, alpha fetoprotein, tumor diameter, tumor differentiation degree, vascular invasion, systemic immune inflammation index and postoperative treatment were related factors for lung metastasis of hepatocellular carcinoma after liver transplantation ( hazard ratio=0.465, 3.413, 1.140, 3.791, 2.524, 2.053, 1.833, 95% confidence interval as 0.263?0.822, 1.740?6.695, 1.091?1.191, 1.763?8.154, 1.903?3.349, 1.047?4.027, 1.038?3.238, P<0.05) . Results of multivariate analysis showed that age, tumor diameter and vascular invasion were independent influencing factors for lung metastasis of hepatocellular carcinoma after liver transplantation ( hazard ratio=0.462, 1.076, 2.170, 95% confidence interval as 0.253?0.843, 1.013?1.143, 1.545?3.048, P<0.05). (4) Construction and evaluation of nomogram prediction model for lung metastasis of hepatocellular carcinoma after liver transplantation: the C-index was 0.810 (95% confidence interval as 0.758?0.863) and 0.802 (95% confidence interval as 0.723?0.881) of the nomogram prediction model for lung metastasis of hepatocellular carcinoma after liver transplanta-tion in the training dataset and validation dataset, respectively, showing good discrimination ability. The area under ROC of 0.5-, 1- and 2-year nomogram prediction model in the training dataset and the validation dataset were 0.815(95% confidence interval as 0.725?0.905), 0.863(95% confidence interval as 0.809?0.917), 0.835(95% confidence interval as 0.771?0.900)and 0.873(95% confidence interval as 0.801?0.945), 0.858(95% confidence interval as 0.760?0.956), 0.841(95% confidence interval as 0.737?0.945), respectively, which illustrated that the model had good predictive ability. The formula of nomogram prediction model=33.300 06+(?33.300 06)×age(≤50 years=0, >50 years=1)+2.857 14×tumor diameter (cm)+31.585 71×vascular invasion (M0 stage of microvascular invasion staging=0, M1 stage of microvascular invasion staging=1, M2 stage of microvascular invasion staging=2, visible tumor thrombus=3). The optimal threshold of nomogram risk score was 77.5. Patients with risk score ≥77.5 were assigned into high risk group, and patients with risk score <77.5 were assigned into low risk group. The 0.5-,1- and 2-year lung metastasis rate of patients in the high risk group and low risk group of the training dataset were 16.7%, 39.2%, 46.4% and 1.4%, 4.1%, 6.9%, respectively, showing a significant difference between the two groups ( χ2=54.86, P<0.05). The 0.5-,1- and 2-year lung metastasis rate of patients in the high risk group and low risk group of the validation dataset were 17.6%, 29.0%, 39.5% and 0, 3.1%, 4.8%, respectively, showing a significant difference between the two groups ( χ2=25.29, P<0.05). Conclusions:Age, tumor diameter and vascular invasion are independent influencing factors for lung metastasis of hepatocellular carcinoma after liver transplantation. The nomogram prediction model based on age, tumor diameter and vascular invasion can predict risk of lung metastasis for hepatocellular carcinoma patients after liver transplantation accurately.

Serum endothelin-1 level in children with osteosarcoma and its correlation with lung metastasis / 中华实用儿科临床杂志

Objective:To investigate the serum levels, diagnosis and prognosis value of endothelin-1(ET-1) in children suffering from lung metastasis of osteosarcoma.Methods:A total of 84 children with osteosarcoma, 67 children with lung metastasis of osteosarcoma and 35 healthy people from January 1, 2013 to January 1, 2018 in Second People′s Hospital of Nanyang were retrospectively included.The serum level of ET-1 was measured by performing enzyme linked immunosorbent assay(ELISA) methods and the influencing factors of serum ET-1 levels in children with lung metastasis of osteosarcoma were conducted by Logistic regression analysis.The clinical value of ET-1 in the prediction of the incidence of lung metastasis in children with osteosarcoma was analyzed by receiver operating characteristic (ROC) curve.Forty-five children with lung metastasis of osteosarcoma were followed up for 18 months and the prognosis value of serum ET-1 levels in children with lung metastasis of osteosarcoma was evaluated by Kaplan-Meier survival analysis. Results:The serum ET-1 level in children with lung metastasis of osteosarcoma was 97.23 (65.13, 134.98) ng/L and significantly higher than osteosarcoma group 60.21 (43.12, 74.63) ng/L and healthy control group 34.45 (12.01, 63.03) ng/L, respectively ( Z=-5.671, -4.92, all P<0.05), with significant differences. Logistic regression analysis proved that lung bilateral involvement ( OR=3.449), numbers of lung metastases (more than 3)( OR=3.449), average diameter of lung metastases (more than 5 cm) ( OR=6.501) and extrapulmonary metastasis ( OR=4.369) were independent risk factors for elevated serum ET-1 levels in children developing lung metastasis of osteosarcoma.The predictive value of ET-1 in the incidence of lung metastasis in children with osteosarcoma was significant (area under ROC curve: 0.841). When the cut-off value was 94.27 ng/L, the sensitivity and specificity were 88.5% and 92.6%, respectively.Survival analysis revealed that higher levels of ET-1 was correlated with poor prognosis ( OR=3.287, 95% CI: 1.119-9.547). Conclusions:The serum levels of ET-1 in children with lung metastasis of osteosarcoma are significantly elevated.ET-1 is a serological marker for the differential diagnosis of lung metastasis of osteosarcoma.Moreover, the higher levels of ET-1 are correlated with poor prognosis in children with lung metastasis of osteosarcoma.

One case of cervical ectopic thyroid carcinoma with lung metastasis / 中华内分泌外科杂志

Ectopic thyroid gland refers to the presence of thyroid tissue outside the normal position of the neck, which is relatively rare in clinical practice, and ectopic and cancer change is rare. This article focuses on a patient with "supraclavicular mass" as the first symptom admitted to the Thyroid Surgery Department of Binzhou People’s Hospital, After the operation, the pathology confirmed ectopic thyroid cancer with lymph node metastasis, and the imaging showed lung metastasis. This article summarizes the case data.

Pharmacological Mechanism of Wumeiwan in Treating Lung Metastasis of Breast Cancer / 中国实验方剂学杂志

Objective:To explore the potential target and mechanism of Wumeiwan in the treatment of lung metastasis of breast cancer by network pharmacological analysis and experimental verification. Method:The databases of active ingredients and targets of Wumeiwan were established through Traditional Chinese Medicine Systems Pharmacology（TCMSP） Database and Analysis Platform，and the targets of lung metastasis of breast cancer were established through the GeneCards database and Online Mendelian Inheritance in Man（OMIM） database，and the data of Chinese medicine targets and disease targets were matched. Cytoscape 3.6.0 software was used to establish the network analysis of traditional Chinese medicine-active ingredients-therapeutic targets，and the interaction relationship between key target proteins was analyzed by STRING database. Target gene ontology（GO） analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG） signal pathway enrichment analysis were performed by using the Biological Information Annotation Database. Result:A total of 108 possible important targets for Wumeiwan in the treatment of lung metastasis of breast cancer were found，including interleukin 6（IL6），cysteine aspartate-specific protease-3（CASP3），vascular endothelial growth factor A（VEGFA），epidermal growth factor receptor（EGFR），mitogen-activated protein kinase（MAPK8）， and others. GO enrichment analysis yielded 29 cell components（CC），1 218 biological processes（BP） and 125 molecular functions（MF） related to lung metastasis of breast cancer，and KEGG enrichment analysis yielded 118 pathways related to lung metastasis of breast cancer（<italic>P<</italic>0.05），including MAPK signaling pathway and apoptosis pathway. <italic>In vitro</italic> experiments showed that cinnamaldehyde， the active ingredient of Wumeiwan， could induce apoptosis，inhibit proliferation and migration of MCF7 cells，partially validating the predicted results of network pharmacology to a certain extent. Conclusion:The therapeutic effect of Wumeiwan on lung metastasis of breast cancer may be multi-target，multi-pathway and multi-mechanism. The results of this study provide more evidence for the clinical application of Wumeiwan.

Preparation and evaluation of schisandrin B-loaded F127 modified lipid-polymer nanoparticles for inhibition of breast cancer lung metastasis / 中国中药杂志

In the current study, schisandrin B(SchB)-loaded F127 modified lipid-polymer hybrid nanoparticles(SchB-F-LPNs) were developed to improve the inhibition of breast cancer lung metastasis. Modified nanoprecipitation method was used to prepare SchB-F-LPNs. The nanoparticles were spherical in shape with shell-core structure by TEM observation. SchB-F-LPNs showed a mean particle size of(234.60±6.11) nm with zeta potential of(-5.88±0.49) mV. XRD results indicated that SchB existed in the nanoparticles in an amorphous state. The apparent permeability coefficient through porcine mucus of F-LPNs was 1.43-fold of that of LPNs as shown in the in vitro mucus penetration study. The pharmacokinetics study showed that the C_(max) of SchB was(369.06±146.94) μg·L~(-1),(1 121.34±91.65) μg·L~(-1) and(2 951.91±360.53) μg·L~(-1) respectively in SchB suspensions group, SchB-LPNs group and SchB-F-LPNs group after oral administration in rats. With SchB suspensions as the reference formulation, the relative bioavailability of SchB-F-LPNs was 568.60%. SchB-F-LPNs inhibited the morphological change during transforming growth factor-β1(TGF-β1)-induced epithelial-mesenchymal transition. In addition, SchB-F-LPNs significantly decreased the number of metastatic pulmonary nodules in 4 T1 tumor-bearing mice, suggesting that SchB-F-LPNs may inhibit the metastasis of breast cancer. These results reveal the promising potential of SchB-F-LPNs in treatment of breast cancer lung metastasis.

Chemical genomics reveals inhibition of breast cancer lung metastasis by Ponatinib via c-Jun

Metastasis is the leading cause of human cancer deaths. Unfortunately, no approved drugs are available for anti-metastatic treatment. In our study, high-throughput sequencing-based high-throughput screening (HTS) and a breast cancer lung metastasis (BCLM)-associated gene signature were combined to discover anti-metastatic drugs. After screening of thousands of compounds, we identified Ponatinib as a BCLM inhibitor. Ponatinib significantly inhibited the migration and mammosphere formation of breast cancer cells in vitro and blocked BCLM in multiple mouse models. Mechanistically, Ponatinib represses the expression of BCLM-associated genes mainly through the ERK/c-Jun signaling pathway by inhibiting the transcription of JUN and accelerating the degradation of c-Jun protein. Notably, JUN expression levels were positively correlated with BCLM-associated gene expression and lung metastases in breast cancer patients. Collectively, we established a novel approach for the discovery of anti-metastatic drugs, identified Ponatinib as a new drug to inhibit BCLM and revealed c-Jun as a crucial factor and potential drug target for BCLM. Our study may facilitate the therapeutic treatment of BCLM as well as other metastases.

Research Progress and Application of Mouse Tumor Lung Metastasis Models / 中国实验方剂学杂志

Early diagnoses and treatment methods are being constantly improved, but cancer metastasis remains a main cause of mortality in malignant tumor patients. Lung is thought to be the organ most prone to distal metastasis among malignant tumors due to its unique physiological and pathological character. Tumor lung metastasis is unpredictable and may result in irreversible damages. Presently, no exact mechanism or specific targeting therapies are found. Depending on the unique theory system-treatment based on symptom differentiation, traditional Chinese medicine has made significant progress on controlling tumor lung metastasis, but its application methods and mechanism still need further study and exploration. More appropriate and idealized animal models are required as a studying medium. Therefore, the establishment of animal models to simulate lung metastasis of cancer patients has become the key to the study of tumor lung metastasis. In order to produce a better platform for investigating the pathogenesis, underlying mechanism, early diagnosis and therapeutics for tumor lung metastasis, and to provide reference for the selection and establishment of mouse lung metastasis model, this article would introduce the implementation, application and estimation of several common methods (tail vein injection, mammary fat pad orthotopic injection, tibia injection, tissue orthotopic implantation, transgenic mice and so on). Meanwhile, the development of mouse lung metastasis model still needs expanding of thoughts, rational and flexible utilization of existing models, and interdisciplinary cooperation to establish preferable animal models and make results more reliable.

Preliminary application of 192Ir high-dose rate brachytherapy in postoperative recurrent colorectal cancer with intrapulmonary oligometastases / 中华放射医学与防护杂志

Objective@#To investigate the efficacy and feasibility of 192Ir high-dose rate brachytherapy for recurrent intrapulmonary oligometastasis after colorectal cancer surgery.@*Methods@#Patients from May 2013 to October 2017 with intrapulmonary oligometastasisafter colorectal cancer surgery in Cangzhou Integrated Traditional Chinese and Western Medicine Hospital were enrolled. A total of 15 lesions were obtained from 10 patients, which were treated with CT-guided high dose rate of 192Ir. The implant needles were inserted into the tumor and were adjusted to appropriate positions under the guidance of CT. Then the images after transplanting were uploaded to the planning system to delineate the target area and the organ at risk volume. Patients underwent a single radiation dose of 20 Gy.@*Results@#All 10 patients were successfully treated. Grade 1 adverse events were observed for 30% of patients. Of the 10 patients, one patient had a mild cough, and two had bloody sputum. There was no serious adverse events occurred. The local control rate (LC) of the patients at 1 year after treatment was achieved in 93.3%. Only one developed local advancement after six months, who received the secondary brachytherapy. The median progression-free survival(PFS) was 8.5 months and the median overall survival(OS) was 14.7 months.@*Conclusions@#High dose rate brachytherapy is effective in terms of recurrent lung metastases after surgery for colorectal cancer, with a moderate rate of adverse reactions and a favorable local tumor control rate.

Relationship between the initial change of thyroglobulin and outcome in differentiated thyroid carcinoma patients with pulmonary metastases after 131I treatment / 中国医师进修杂志

Objective To investigate the relationship between the initial change of thyroglobulin (Tg) and clinical outcome in differentiated thyroid carcinoma (DTC) patients with pulmonary metastases after 131I treatment. Methods A total of 69 DTC patients with pulmonary metastases from January 2010 to December 2015 were retrospectively analyzed. Patients were divided into 3 groups according to the variation of Tg: groupⅠ(Tg declined≥ 50%), groupⅡ(Tg declined＜50% or Tg increased＜10%), and group Ⅲ (Tg increased ≥10% ). The follow-up time was (49.2 ± 9.3) months. Clinical outcomes were divided into remission, stable disease and progressive disease according to the serum test and imaging results. Results The percentage of group Ⅰ, Ⅱ, Ⅲ patients was 44.9% (31/69), 40.6% (28/69), and 14.5% (10/69) respectively. Results of follow-up showed 19.4% (6/31) patients achieved remission and 80.6% (25/31) had stable disease in groupⅠ. There were 10.7% (3/28) patients with remission, 60.7% (17/28) with stable disease and 28.6% (8/28) with progression disease in groupⅡ. All patients showed progressive disease in groupⅢ. The clinical outcome was related to the variation of Tg after 131I treatment (P＜0.01). Conclusions Initial Tg after 131I treatment could be a predictor to the outcome of patients. The increased Tg level indicates a high possibility of 131I refractory disease.

The Predictive Values of Lesion Size, F-18 FDG Avidity and I-131 Avidity for the Clinical Outcome of I-131 Treatment in Patients with Metastatic Differentiated Thyroid Carcinoma Only in the Lung / 대한핵의학회잡지

PURPOSE: We aimed to evaluate the prognostic values of radiography, F-18 FDG PET, and I-131 whole body scans in patients with lung-only metastasis from differentiated thyroid carcinoma (DTC).METHODS: Between 1998 and 2013, we included 31 patients (F: 26, M: 5) with lung-only metastasis from DTC who had been treated with I-131 and underwent PET. Lung metastasis was categorized according to the size (macronodular ≥1.0 cm vs. micronodular <1.0 cm), FDG avidity (avid vs. non-avid), and I-131 avidity (avid vs. non-avid). Progression-free survival (PFS) was evaluated for each patient.RESULTS: Among 31 patients, seven (23%) had macronodular lung metastasis, 26 (84%) had FDG avid lung metastasis, and 16 (52%) had I-131 avid lung metastasis. During the median follow-up period of 9.4 y, median PFS was 6.1 y. Based on Kaplan-Meier analysis, macronodular lung metastasis (p = 0.017) and I-131 non-avid lung metastasis (p = 0.059) were significantly associated with worse outcomes, but FDG avid lung metastasis was not (p = 0.135). Patients with FDG non-avid lung metastasis did not experience disease progression during follow-up, while 11 of 26 patients (42%) experienced disease progression. Based on univariate analysis, the hazard ratio for a poor prognosis was 3.78 (p = 0.029) for macronodular lung metastasis and 3.29 (p = 0.079) for I-131 non-avid lung metastasis.CONCLUSIONS: Macronodular and I-131 non-avid lung metastasis were associated with a poor prognosis in lung-only metastasis from DTC. Although FDG avid lung metastasis may be associated with a poor prognosis, a larger-scale study is needed.

Effect of atrial natriuretic peptide ( ANP) on pulmonary melanoma metastasis in ANP knockout mice and C57BL／6J mice / 中国比较医学杂志

Objective To investigate the role of atrial natriuretic peptide (ANP) in lung metastasis of melanoma. Methods Melanoma B16F10 cells were intravenously injected into ANP knockout mice and C57BL／6J mice. After three weeks, the mice were sacrificed, and the lungs were removed, embedded, and examined by pathology using HE staining. The numbers of metastatic foci on the lung surface and micrometastatic foci in the lung tissues were counted. Results The ANP knockout mice displayed fewer metastatic foci on the lung surface and less micrometastatic foci in the lung tissues of ANP knockout mice than in the C57BL／6J mice. Conclusions ANP deletion significantly suppresses the metastasis of melanoma in the lung of mice.

Establishment of a C57BL/6 J mouse model of metastatic melanoma in the lung / 中国实验动物学报

Objective To investigate the influencing factors involved in the establishment of a C57BL/6 J model of metastatic melanoma in the lung,including the way of tumor inoculation,the number of inoculated cells and the time of tumor formation. Methods Mouse melanoma B16F10 cells were cultured in vitro. 1)Eighteen healthy male C57BL/6 J mice were randomly divided into three groups. Mice in each group received 100 μL cell suspension(including 3 ×106 melanoma cells)via intravenous,intraperitoneal and subcutaneous injection,respectively. After two weeks,the mice were killed and dissected,and the tumor growth and metastasis were observed. 2)Eighteen male mice were randomly divided into three groups. Mice in each group were injected with 3 ×106cells,1 ×106cells, and 3 ×105cells through the tail vein,respectively. After two weeks,mice were killed and dissected,and the tumor growth and metastasis were observed. 3)Eighteen male mice were randomly divided into three groups. Mice in each group were injected with 1×106cells though the tail vein. Mice were killed and dissected after one week, two weeks and three weeks, respectively. The growth and metastasis of tumor were observed. Results 1)The success rate of lung metastasis was 100% in the mice with intravenous injection,but not in mice receiving intraperitoneal injection and subcutaneous injection. 2)The size of metastatic melanoma nodules were moderate in mice inoculated by 1 ×106cells. The number of melanoma metastatic foci was too high in the mice inoculated with 3 ×106cells,but too low in the mice inoculated with 3 ×105cells. 3)Significant metastatic melanoma foci were observed in the mice killed and dissected after two weeks with no death. The number of melanoma foci in the lung was too high in the mice killed after three weeks,while was too low in the mice killed at one week after tumor cell inoculation. Conclusions Intravenous injection of 1×106mouse melanoma cells into C57BL/6 J mice and killed after two weeks is an optimal method for establishment of a mouse model of metastatic melanoma in the lung, and is worth of recommendation.

Prevention and evaluation of tumor recurrence and metastasis after liver transplantation for hepatocellular carcinoma / 中华肝胆外科杂志

Liver transplantation is an important clinical treatment for primary liver cancer,but the high rate of recurrence and metastasis has a serious impact on the efficacy of HCC treatment,among which extrahepatic metastasis is the most common.Up to now,there is still lack of effective methods to prevent postoperative recurrence and metastasis.Therefore,how to prevent the recurrence and metastasis of liver cancer after liver transplantation is of great significance.This paper summarized the prevention and evaluation of recurrent lung metastasis after liver transplantation for liver cancer from three aspects:before transplantation,among transplantation and after transplantation.

Surgical resection of synchronous and metachronous lung and liver metastases of colorectal cancers

PURPOSE: Surgical resection of isolated hepatic or pulmonary metastases of colorectal cancer is an established procedure, with a 5-year survival rate of about 50%. However, the role of surgical resections in patients with both hepatic and pulmonary metastases is not well established. We aimed to analyze overall survival of these patients and associated factors. METHODS: Data retrospectively collected from 66 patients who underwent both hepatic and pulmonary metastasectomy after colorectal cancer surgery from August 2002 through August 2013 were analyzed. In univariate analysis, the log-rank test compared patient survival between groups. P < 0.1 was considered indicative of significance. Multivariate analysis of the significance data using a Cox proportional hazard model identified factors associated with overall survival. The synchronous group (n = 57) was defined as patients who had metastasectomy within 3 months from primary colorectal cancer surgery. The remaining nine patients constituted the metachronous group. RESULTS: Median follow-up was 126 months from the primary colorectal cancer surgery. The 5-year survival was 73.4%. There was no difference in overall survival between the synchronous and metachronous groups, consistent with previous studies. Distribution (involving one hemiliver or both, P = 0.010 in multivariate analysis) of liver metastases and multiplicity of the pulmonary metastasis (P = 0.039) were predictors of poor prognosis. CONCLUSION: Sequential or simultaneous resection of both hepatic and pulmonary metastasis of colorectal cancer resulted in good long-term survival in selected patients. Thus, an aggressive surgical approach and multidisciplinary decision making with surgeons seems to be justified.