Correlation between Patient‐Derived Xenograft Modeling and Prognosis in Osteosarcoma

ObjectiveTo retrospectively analyze and compare the relationship between the success rate of patient‐derived xenograft (PDX) modeling of osteosarcoma and prognosis (3‐year overall survival rate and disease‐free survival rate) and incidence of lung metastasis.MethodsThe sample group consisted of 57 osteosarcoma patients with definite pathological diagnoses from Shanghai General Hospital from 2015–2017. PDX models in 57 patients were analyzed by retrospective analyses. Among the patients currently inoculated, 20 were tumorigenic in the PDX model, and 37 were nontumorigenic. According to the tumorigenicity of PDXs, the corresponding osteosarcoma patients were divided into two groups. The effects of clinically related indicators on the model were retrospectively compared. The patients were followed, and the 3‐year survival, 3‐year disease‐free survival (DFS), and lung metastasis rates were collected. The relationship between the modeling success and patient prognosis was investigated.ResultsIn the chemotherapy‐treated group, the PDX modeling success rate was 17.4%, and in the nonchemotherapy group, the success rate was 47.1%. The success of PDX modeling was related to whether patients received chemotherapy. The success rate of PDX modeling is significantly reduced after receiving chemotherapy. The 3‐year overall survival rate of the PDX‐grafted group was 49.23%, and that of the PDX‐nongrafted group was 65.71%. There was a significant difference between the two groups, showing a strong negative correlation between the 3‐year survival rate and the success rate of the PDX model. The 3‐year disease‐free survival rate of the PDX‐grafted group was 29.54%. The 3‐year DFS of the PDX‐nongrafted group was 50.34%. There was a significant difference between the two groups. Lower grafted rates indicate a higher DFS rate. The incidence of lung metastasis in the PDX‐grafted group was 32.4%, and that in the nongrafted group was 13.1%. There was a significant difference between the two groups. The successful establishment of the PDX model indicates that patients are more likely to have lung metastases.ConclusionsThe success of PDX modeling often indicates poor prognosis (low 3‐year overall survival rate and disease‐free survival rate) and a greater possibility of lung metastasis. Therefore, PDX modeling in osteosarcoma patients can accurately predict the prognosis of patients and the risk of lung metastasis in advance to help us develop better therapeutic strategies.     

ALP监测对判定骨肉瘤辅助化疗预后的意义

本文分析了５６例四肢骨肉瘤在治疗前测定ＡＬＰ水平对判定预后的意义。结果表明，ＡＬＰ水平高者，术后３年肺转移率明显增高，５年生存率亦明显降低；ＡＬＰ水平正常者，预后良好。作者建议，辅助化疗及手术时，分析ＡＬＰ水平对骨肉瘤有很好的预后判定价值，在计划或调整治疗方案时，此因素应该被考虑。     

血管内皮生长因子对骨肉瘤的血管生成及转移预后的影响

目的 :研究血管内皮生长因子 (VEGF)对骨肉瘤血管生成、生长、转移及预后的影响。方法 :对 69例骨肉瘤患者的临床病理资料进行回顾性研究 ,应用CD3 4、VEGF单克隆抗体对其组织切片分别进行免疫组化染色 ,应用地高辛标记的VEGF探针对 2 7例原发性骨肉瘤进行原位杂交染色。分析研究了VEGF表达与CD3 4染色阳性的血管密度的关系 ,所有上述临床病理资料及染色结果与患者预后情况进行统计学分析。结果 :在 3 9例 (5 6.5 % )VEGF表达阳性的标本中 ,CD3 4染色阳性的肿瘤微血管密度 (MVD)明显较 3 0例VEGF表达阴性的血管密度高 (P <0 .0 5 )。多元回归分析显示 ,血管密度 (MVD)增高及VEGF表达阳性与骨肉瘤患者的远隔转移发生、不良预后密切相关 (P <0 .0 5 )。临床病理资料中 ,外科手术边界微小病灶阳性情况、Enneking外科分期、肿瘤大小和患者年龄与患者预后相关 (P <0 .0 5 )。患者性别、手术方法分类以及病理亚型与预后无相关性。结论 :VEGF在骨肉瘤的血管生成和转移中起到重要作用 ,VEGF是骨肉瘤血管生成的决定性刺激因子 ,骨肉瘤微血管密度 (MVD)和骨肉瘤组织中VEGF表达情况是骨肉瘤患者的独立性预后因素。     

Clinicopathologic Prognostic Factors in Myxoid Liposarcoma: A Retrospective Study of 49 Patients With Long-Term Follow-Up

BACKGROUND: The main goal of this retrospective study was to investigate prognostic factors influencing the survival of myxoid liposarcoma (MLS) with emphasis on the role of transitional areas (TLS) and round cell morphology (RCLS). METHODS: From 1977 to 2004, 49 patients-28 men (57%) and 21 women (43%) with a median age of 44 years (range, 7-83 years)-were diagnosed with an MLS. In 42 patients, the histology could be reviewed, and tumors were classified as MLS, TLS, or RCLS. Clinicopathologic factors were analyzed for influence on survival by univariate and multivariate methods. RESULTS: The median follow-up of 49 patients was 101 months (range, 4-550 months). Of the 42 patients for whom histology was reviewed, 16 tumors were classified as MLS (38%), 19 as TLS (45%), and 7 as RCLS (17%). Sixteen patients (33%) developed a local recurrence after a median follow-up of 21 months (range, 2-108 months). Thirteen patients (27%) developed metastases. The median interval between diagnosis and metastasis was 41 months (range, 0-222 months). Median survival after metastasis was 18 months (range, 1-179 months). The 5- and 10-year disease-specific survival rates were 85% and 72%, whereas the 5- and 10-year overall survival rates were 83% and 68%, respectively. Age at presentation (P = .02), tumor grade (P = .01), and tumor size (P = .005) were significant prognostic factors associated with survival. Tumor grade was the only independent prognostic variable that remained significant with multivariate analysis. A TLS presentation had no negative influence on patient survival. CONCLUSIONS: Age at presentation, tumor grade, and tumor size had a negative influence on survival by univariate analysis, whereas tumor grade was the only independent prognostic factor by multivariate analysis. TLS was not associated with poor outcome.     

Risk of Fracture in Primary Aldosteronism: A Population‐Based Cohort Study

Primary aldosteronism (PA) is associated with increased urinary calcium excretion and osteoporosis prevalence. We studied the long‐term effect of hyperaldosterone on fracture risk and possible risk mitigation via treatments, by comparing PA patients and their essential hypertension (EH) counterparts extracted by propensity score match. We used a longitudinal population database from the Taiwan National Health Insurance, and used a validated algorithm to identify PA patients diagnosed in 1997–2010. Our sample included 2533 PA patients, including 921 patients with aldosterone‐producing adenoma (APA). Our methods for assessing excessive fracture risk included multivariable Cox regression and the competing risk regression. The incidence rate of fracture at any site was 14.4 per 1000 person‐years for PA, and 11.2 per 1000 person‐years for APA. In contrast, the incidence rate of fracture at any site was 8.3 per 1000 person‐years in EH controls for PA, and 6.5 per 1000 person‐years in EH controls for APA. Mineralocorticoid receptor antagonist (MRA) treatment might be associated with higher risk of osteoporotic fracture in the whole female PA cohort (subdistribution hazard ratio [SHR] = 2.12, p = 0.008) as well as female APA patients (SHR = 1.15, p = 0.049). As to fracture at any site, MRA treatment was also associated with higher risk; the SHR was 1.88 (p < 0.001) in the whole female PA cohort, and 2.17 (p = 0.019) in female APA patients. PA is tightly associated with higher risk of bone fracture, even in the case where the competing risk of death was controlled. Particularly, female PA patients treated with MRA were confronted with significantly higher risk in bone fracture than their EH controls. © 2017 American Society for Bone and Mineral Research.     

Risk Criteria and Prognostic Factors for Predicting Recurrences After Resection of Primary Gastrointestinal Stromal Tumor

Background The introduction of adjuvant imatinib in gastrointestinal stromal tumors (GISTs) raised debate over the accuracy of National Institutes of Health risk criteria and the significance of other prognostic factors in GIST. Methods Tumor aggressiveness and other clinicopathological factors influencing disease-free survival (DFS) were assessed in 335 patients with primary resectable CD117-immunopositive GISTs (median follow-up, 31 months after primary tumor resection) from a prospectively collected tumor registry. Results Overall median DFS was 37 months, and estimated 5-year DFS was 37.8 %. In univariate analysis, high or intermediate risk group (P < .000001), mitotic index >5/50 high-power field (P < .00001), primary tumor size >5 cm (P < .00001), nongastric primary location (P = .0001), male sex (P = .01), R1 resection/tumor rupture (P = .0003), and epithelioid cell or mixed cell pathological subtype (P = .05) negatively affected DFS. In multivariate analysis, statistically significant factors negatively influencing DFS for model 1 were mitotic index >5/50 high-power field (P = .004), primary tumor size >5 cm (P = .001), male sex (P = .003), R1 resection/tumor rupture (P = .04), and nongastric primary tumor location (P = .02), and for model 2 were high/intermediate risk primary tumor (P < .0001 and P = .008, respectively), male sex (P = .007), resection R1/tumor rupture (P = .01), and nongastric primary tumor location (P = .02). Five-year DFS for high, intermediate, and low/very low risk group was 20%, 54%, and 96%, respectively. Conclusions The risk criteria for assessing the natural course of primary GISTs were validated, but additional independent prognostic factors—primary tumor location and sex—were also identified.     

Expression and Clinical Significance of High‐Mobility Group AT‐hook 2 (HMGA2) in Osteosarcoma

ObjectiveAlthough high‐mobility group AT‐hook 2 (HMGA2) has been shown to have crucial roles in the pathogenesis and metastasis of various malignancies, its expression and significance in osteosarcoma remain unknown. Here we evaluate the expression, clinical prognostic value, and overall function of HMGA2 in osteosarcoma.MethodsSixty‐nine osteosarcoma patient specimens within a tissue microarray (TMA) were analyzed by immunohistochemistry for HMGA2 expression. Demographics and clinicopathological information including age, gender, tumor location, metastasis, recurrence, chemotherapy response, follow‐up time, and disease status were also collected. After validation of expression, we determined whether there was a correlation between HMGA2 expression and patient clinicopathology. HMGA2 expression was also evaluated in osteosarcoma cell lines and patient tissues by Western blot, we analyzed the expression of HMGA2 in the human osteosarcoma cell lines MG63, 143B, U2OS, Saos‐2, MNNG/HOS, and KHOS. HMGA2‐specific siRNA and clonogenic assays were then used to determine the effect of HMGA2 inhibition on osteosarcoma cell proliferation, growth, and chemosensitivity.ResultsHMGA2 expression was elevated in the osteosarcoma patient specimens and human osteosarcoma cell lines. HMGA2 was differentially expressed in human osteosarcoma cell lines. Specifically, a relatively high expression of HMGA2 was present in KHOS, MNNG/HOS, 143B and a relatively low expression was in MG63, U2OS as well as Saos‐2. HMGA2 expression is correlated with metastasis and shorter overall survival. High HMGA2 expression is an independent predictor of poor osteosarcoma prognosis. There was no significant correlation between HMGA2 expression and the age, gender, or tumor site of the patient. HMGA2 expression is predominantly within the nucleus. The expression of HMGA2 also directly correlated to neoadjuvant chemoresistance. There was a significant reduction of HMGA2 expression in the siRNA transfection group. After the use of siRNA, the proliferation of osteosarcoma cells is decreased and the chemosensitivity of osteosarcoma cells is significantly increased.ConclusionOur study supports HMGA2 as a potential prognostic biomarker and therapeutic target in osteosarcoma.     

Incomplete Ablation After Radiofrequency Ablation of Hepatocellular Carcinoma: Analysis of Risk Factors and Prognostic Factors

Background Complete ablation rates after a single session of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) vary from 48% to 97%. Limited data are available regarding risk factors and prognostic significance of incomplete ablation. Methods Between April 2001 and March 2006, 298 patients underwent RFA of 393 HCC nodules with an intent of complete ablation after a single session. Risk factors for incomplete ablation and its effect on overall survival were analyzed. Results Two hundred seventy-three (91.6%) underwent complete tumor ablation, whereas the other 25 (8.4%) underwent incomplete tumor ablation after a single session of RFA. By multivariate analysis, tumor size >3 cm (P = .049) was found to be the only independent risk factor for incomplete ablation. There was no statistically significant difference in overall survival between patients with complete and incomplete ablation. By univariate analysis, no previous transarterial chemoembolization (TACE), preoperative serum alfa-fetoprotein ≤100 μg/mL, and complete response after further treatment of incomplete ablation were associated with better overall survival in patients with incomplete ablation. Conclusions This study demonstrated that incomplete ablation after RFA of HCC was associated with tumor size >3 cm. Our data also suggest that aggressive further treatment of tumors with incomplete ablation aiming at complete tumor response improves overall survival.     

Role of Surgical Margin on Local Recurrence in High Risk Extremity Osteosarcoma: A Case-Controlled Study

Background

The relationship between surgical margin and local recurrence (LR) in osteosarcoma patients with poor responses to chemotherapy is unclear. Moreover, the incidences of LR according to three different resection planes (bone, soft tissue, and perineurovascular) are not commonly known.

Methods

We evaluated the incidence of LR in three areas. To assess whether there is a role of surgical margin on LR in patients resistant to preoperative chemotherapy, we designed a case (35 patients with LR) and control (70 patients without LR) study. Controls were matched for age, location, initial tumor volume, and tumor volume change during preoperative chemotherapy.

Results

LR occurred at the soft tissues in 18 cases (51.4%), at the perineurovascular tissues in 11 cases (31.4%), and at the bones in six cases (17.2%). The proportion of inadequate perineurovascular margin was higher in the case group than in the control group (p = 0.01). Within case-control group (105 patients), a correlation between each margin status and LR at corresponding area was found in the bone (p < 0.001) and perineurovascular area (p = 0.001).

Conclusions

LR is most common in soft tissues. In patients showing similar unfavorable responses to chemotherapy, the losses of perineurovascular fat plane on preoperative magnetic resonance imaging may be a valuable finding in predicting LR.     

Second Hepatectomy for Recurrent Colorectal Liver Metastasis: Analysis of Preoperative Prognostic Factors

Background Second hepatectomy is a potentially curative treatment for patients with hepatic recurrence of colorectal cancer. However, there is still no consensus about the patient selection criteria for second hepatectomy under these circumstances, and the factors affecting prognosis after second hepatectomy remain uncertain.Methods Clinicopathologic data for 111 consecutive patients with colorectal liver metastasis who underwent second hepatectomy at a single institution between 1985 and 2004, and for whom complete clinicopathologic reports were available, were subjected to univariate and multivariate analyses.Results The morbidity and mortality rates were 14% and 0%, respectively, and the overall 5-year survival rate was 41%. Multivariate analysis revealed that synchronous resection for the first liver metastasis (hazard ratio, 1.8), more than three tumors at the second hepatectomy (1.9), and histopathological involvement of the hepatic vein and/or portal vein by the first liver metastasis (1.7) were independently associated with poor survival. We used these three risk factors to devise a preoperative model for predicting survival. The 5-year survival rates of patients without any risk factors, and with one, two, or three risk factors, were 62%, 38%, 19%, and 0%, respectively.Conclusions Second hepatectomy is beneficial for patients without any risk factors. Before second hepatectomy, chemotherapy should be considered for patients with any of these risk factors, especially with two or three factors, in the adjuvant or neoadjuvant setting to prolong survival. These results need to be confirmed and validated in another data set or future prospective trial according to the scoring scheme we outline.     

Prognostic Factors of Survival among Women with Metastatic Breast Cancer and Impact of Primary or Secondary Nature of Disease on Survival: A French Population‐Based Study

We aim to determine whether differences in survival exist between two populations of women with metastatic breast cancer (MBC) and to identify prognostic factors of survival after metastasis diagnosis. Data on women with MBC diagnosed between 2000 and 2011 were provided by the Côte d'Or Breast cancer registry. Survival rates and median overall survival (OS) after metastasis diagnosis were determined using the Kaplan–Meier method and prognostic factors were determined in a Cox proportional hazard model. Overall, 282 women with primary MBC and 340 with secondary MBC were included. A 2‐year survival rate was significantly better in women with primary MBC (50.8% [95% CI: 47.8–53.8%] versus 44.5% [95% CI: 41.8–47.2%]). However, median OS did not differ between the two groups (p = 0.1). The prognostic factors associated with worst survival were a triple‐negative tumor type (p < 10^?4), multiple metastases sites (p < 10^?4), an older age at metastasis (p < 10^?4), and a SBR grade G3 (p = 0.007). OS between women with primary MBC and women with secondary MBC does not seem to differ significantly. This population‐based study provides original epidemiological data on French women without any selection bias inherent to hospital cohorts.     

Prognostic Analysis of Spinal Metastasis Secondary to Lung Cancer after Surgeries: A Unicentric,Large‐Cohort,Retrospective Study

Purpose Spinal metastases of lung cancer (SMLC) usually have high degree of malignancy and require surgical treatment. However, there are several controversies about the efficacy of surgery. This study aimed to investigate factors predicting prognosis of SMLC after surgery‐based comprehensive treatment.MethodsA cohort of 112 cases of SMLC who underwent surgical treatment between 2009 and 2020 were retrospectively reviewed and analyzed. The surgical strategies included total en‐bloc spondylectomy, debulking surgery, palliative decompression, and vertebral augmentation procedures. The patients were regularly followed‐up. Survival analysis was performed, as well as analysis of the patients'' neurological recovery, pain relief, and improvement of Karnosky performance score (KPS). Cox regression was used to analyze influencing factors of survival time, and Kaplan–Meier method was performed in survival analysis.ResultsThe cohort included 63 males and 49 females, with an average age of 60.6 ± 10.6 years. Median survival time was 16 months. A total of 86.7% of paralysis patients'' neurological function recovered and 83.9% of patients with low KPS score (10–40) improved. Surgical method was significantly correlated with improvement of neurological function (p < 0.001) and KPS (p < 0.001). The mean bleeding volume was 502 ml and operative time was 170 min. The survival rates at 3, 6, 12, 24, and 36 months were 92.0%, 80.4%, 63.4%, 63.4%, and 22.6%, respectively. Postoperative Frankel grade (p < 0.001), postoperative KPS score (p = 0.001), and application of molecular targeted drugs (p < 0.001) were significantly correlated with survival time in univariate analysis, while application of molecular targeted drugs was an independent predictor for a longer survival by a multivariate analysis.ConclusionSurgery‐based comprehensive treatment brought a fair outcome, with elongated survival time. Surgery can significantly improve patients'' neurological function and physical performance status. Adjuvant targeted therapy is an independent positive factor for patients'' survival.     

骨肉瘤患者延长生命保存肢体的临床研究(136例15年回顾)

作者１９８１～１９９６年共治疗骨肉瘤患者１３６例，随访５～１５年。２年生存率６１％，５年生存率２６．５％。作者首次在国内将大剂量顺铂全身化疗、双途径化疗以及ＤＳＡ介入化疗用于骨肉瘤术前化疗。在１３６例骨肉瘤患者中保肢手术８０例，其中开创放疗是国内首次开展。作者还对骨肉瘤的早期诊断、术前化疗、保肢手术以及肺转移瘤切除等问题提出了自己的看法。     

Risk Stratification for Early Esophageal Adenocarcinoma: Analysis of Lymphatic Spread and Prognostic Factors

Background  

Knowledge of factors related to outcome is vital for the selection of therapeutic alternatives for patients with early (T1) esophageal adenocarcinoma. This study was undertaken to determine predictors of lymphatic spread and prognostic factors for T1 esophageal adenocarcinoma following esophagectomy.