Sujia Wu

A liquid biopsy-based method for the detection and quantification of circulating tumor cells in surgical osteosarcoma patients

A method for the enumeration and quantification of osteosarcoma (OS) circulating tumor cells (CTCs) is currently not available. A correlation between the number of CTCs and progression-free survival (PFS) has been established for other cancers, but not for OS CTCs. A method was therefore developed for CTC quantification in OS and validated in a prospective cohort of surgical patients with primary and recurrent/metastatic OS (N=23). Human OS cells, acting as CTCs, were enumerated from spiked human peripheral blood (PB) following erythrocyte and leukocyte depletion. The OS cells were quantified microscopically based on aneuploidy and a CK18−/CD45− phenotype. Aneuploidy was assayed by fluorescence in situ hybridization (FISH) using fluorescence-labeled alpha-satellite probes for the centromeres of chromosome (CEP 8). CK18 and CD45 phenotyping was performed with immunocytochemistry. HOS cells in spiked PB could be effectively retrieved with the FISH-based enumeration method, which was subsequently employed in an OS patient cohort. PB of recurrent/metastatic OS patients contained more CTCs than the PB of primary OS patients. OS patients with ≥2 CTCs per 7.5 ml of PB had worse PFS than patients whose PB contained <2 CTCs. In 2 cases, CTCs were present in PB of OS patients with negative X-ray and chest CT scans. In conclusion, our method was able to quantitate CTCs in liquid biopsies of OS patients. The number of CTCs has diagnostic and prognostic value.

The epidemiological and clinical features of primary giant cell tumor around the knee: A report from the multicenter retrospective study in china.

Objectives We aimed to determine the demographic characteristics of giant cell tumor around the knee in China. Methods Between March 2000 and June 2014, patients with primary giant cell tumor around the knee were recruited from 6 institutions located in different regions of China, and were reviewed retrospectively the clinical features according to gender and age. Results 334 qualified patients were included in this study. The sex ratio was 1.14:1 (178/156), with mean ages of 36.9 years in men and 33.1 years in women, constituting a significant difference (P=0.007). The prevalence of pathological fracture was 32.9% overall (28.7% in men and 37.8% in women). The prevalence of simple fracture was significantly higher in women (26.3%) than in men (15.2%), P=0.042. Tumor location and staging did not differ significantly according to sex (P>0.05). However, comparing with >40 years old, those patients aged ≤40 were more likely to have a right knee tumor (56.7% vs. 44.7%, P=0.042), less likely to have Enneking stage 3 disease (18.6% vs. 35.0%, P=0.005), and less likely to have both soft-tissue extension and a mass (18.6% vs. 34.0%, P=0.009). Conclusions Giant cell tumor around the knee was more common in men than in women, although female patients were younger on average. Further, cases among patients ≤40 years old were observed to be milder than cases among older patients. The results suggest that efficient treatment and preservation of function should both be valued for young patients with giant cell tumor around the knee.

Giant Cell Tumor of the Pelvis: a Systematic Review

This is a systematic review of articles concerning the morbidity, recurrence rate, treatment and treatment complications of pelvic giant cell tumors (GCTs). The key words “giant cell tumor, pelvis” were used to identify articles which included data on patients with pelvic GCTs in English and Chinese databases of published reports from 1949–2012. The articles were filtered by title, abstract and full text. Thirty‐eight articles and 165 patients were identified for this review. Data on all identified patients were studies; data in different articles on the same patients was not used repeatedly. The following patient data were collected where possible and subjected to systematic analysis; age, location of GCT, treatment, follow‐up, complications, recurrence and whether alive or dead. The mean age of onset was 33.2 years (range, 14–73 years), the peak ages of onset being between 21 and 40 years. A pronounced sex difference was identified, the male : female ratio being 1:1.7. The acetabulum was the commonest area for pelvic GCTs. Forty‐eight tumors were primarily located in the iliac, 60 in the acetabular and 31 in the ischiopubic area. Twenty‐seven patients experienced complications of treatment. Patients who had been treated by wide resection had the most complications; these included incisional infection and delayed healing of incisions. Local recurrence was common, having occurred in 39/158 patients (24.6%), comprising 24/72 (33.3%) who had undergone intralesional surgery only; 9/20 (45.0%) who had undergone radiotherapy only; 1/51 (2.0%) who had undergone wide resection; and 5/14 patients (35.7%) who had undergone radiation therapy or cryotherapy plus intralesional surgery. Mortality was low (3.2%, 5/158). Pelvic GCT is not common, the acetabular area appears to the most frequent site and the peak age is the third and fourth decades. Although the recurrence rate is high for all pelvic GCTs, the mortality is low. Treatment has a critical influence on recurrence. In spite of the associated complications, the lower local recurrence rate makes wide resection a reasonable option for patients with extensive and/or aggressive GCTs.

Recurrence Rates and Risk Factors for Primary Giant Cell Tumors around the Knee: A Multicentre Retrospective Study in China

Giant cell tumors of the bone (GCTBs) are commonly diagnosed in Asian populations, usually around the knee. Herein, we aimed to determine the clinical characteristics, local recurrence rates, and relevant risk factors of primary GCTB around the knee. Univariate and multivariate survival analyses were used to identify the risk factors for local recurrence. Four hundred ten patients with primary GCTB around the knee, treated between March 2000 and June 2014, were recruited from 7 institutions in China. The overall local recurrence rate was 23.4%, but was higher in patients aged 20–39 years (28.5%; P = 0.039). The local recurrence rate was the highest in patients treated with intralesional curettage (53.4%), and the lowest in those treated with resection (4.9%). We found a higher risk of tumor recurrence in the proximal fibula compared to the distal femur (hazard ratio: 28.52, 95% confidence interval: 5.88–138.39; P < 0.0001), and in patients treated with curettage compared to those treated with resection (hazard ratio: 12.07, 95% confidence interval: 4.99–29.18; P < 0.0001). Thus, the tumor location must be considered when selecting the optimal surgical treatment approach to reduce the risk of local recurrence and preserve joint function, especially in young patients.

Sex Differences in the Recurrence Rate and Risk Factors for Primary Giant Cell Tumors Around the Knee in China.

Although giant cell tumor of bone (GCTB) is more common in women in Western countries, it tends to be more common in men in Asian countries. We aimed to determine the sex differences in clinical characteristics, local recurrence rate, and relevant risk factors for local recurrence in primary GCTB around the knee. Between March 2000 and June 2014, patients with primary GCTB around the knee were recruited from 7 institutions in China, and 410 patients were included. The age at diagnosis was younger in women than in men (34.0 vs 37.2 years). The local recurrence rates were 23.4% overall, 25.8% in men, and 20.7% in women. Lower local recurrence rates were observed with en-bloc marginal resection in both men (6.9%) and women (3.1%). With tumors located in the distal femur, the local recurrence rate was higher for men than for women (29.1% vs 14.3%, P = 0.025). Local recurrence was significantly associated with the tumor location and surgical operation in men and only surgical operation in women. These findings suggest that more aggressive operations should be considered in men with GCTB in the proximal fibula.

Development and proposal of a scoring system for giant cell tumour of the bone around the knee

PurposeThe purpose of this study was to provide the surgeons with effective and reliable guidelines for surgical decision-making by establishing a scoring system for giant cell tumour (GCTSS) based on evidence and expert opinion.MethodsThe modified Delphi technique and analytic hierarchy process were used to establish the GCTSS. The GCTSS was defined and classified based on different surgical methods using data from 207 patients collected retrospectively between October 2003 and December 2014. Finally, prospective data of 40 patients between December 2014 and October 2015 were used to analyze concordance between score categorization and experts’ consensus on surgical procedure.ResultsA novel GCTSS included pathological fracture, cortical bone destruction, tumour size, and articular surface involved. The total scores ranged from 1 to 12 points. The strategy for each patient was decided: a total score of 1–4 suggested intralesional curettage alone for excellent post-operative function; 5–9 points indicated intralesional curettage with internal fixation for less surgery-related complications; and 10–12 points indicated prosthesis replacement for long-term local control. The κ-statistic for the predictive validity of total score was 0.611. The κ coefficient of each group represented moderate or substantial agreement, which was acceptable. The intraclass correlation coefficient for inter- and intra-observer reliability of total score was 0.831 and 0.740, respectively.ConclusionsThe novel GCTSS is a comprehensive scoring system with content validity that can aid surgeons in assessing the aggressiveness or severity of giant cell tumour and might become a prognostic tool for surgical decision-making.

Epidemiological and Clinical Features of Primary Giant Cell Tumors of the Distal Radium: A Multicenter Retrospective Study in China

Giant cell tumors of the distal radius are challenging for surgeons because they are associated with high recurrence rates and poor functional outcomes. Between June 2005 and October 2015, patients with primary giant cell tumors of the distal radius were recruited from seven orthopedic centers in China. The patients’ clinical features and demographic characteristics were obtained from medical records and reviewed retrospectively. Overall, 48 cases of giant cell tumors of the distal radius were assessed in this study. These patients were more likely to be between 20 and 40 years of age, to have a Campanacci grade of III, and to undergo a surgical style of resection. The prevalence of pathological fractures was 12.5% overall (20.0% in men and 4.3% in women). The prevalence of local recurrence was 30.0% overall (38.1% in men and 21.1% in women) during the average follow-up period of 62.5 months, with a pulmonary metastasis rate of 5.0%. Giant cell tumors of the distal radius were predominant in men and were more likely to recur locally than around the knee. These findings suggest that it is crucial to evaluate the optimal surgical approach for balancing local recurrence control and functional outcomes to reduce the disease burden.

How to Fill the Cavity after Curettage of Giant Cell Tumors around the Knee? A Multicenter Analysis

Background: Intralesional excision with curettage is the standard method of giant cell tumor (GCT) treatment, but the ideal filling material after curettage remains controversial. The purpose of this study was to compare the oncological and functional outcomes which underwent cementation or bone grafting after GCT curettage around the knee. Methods: We reported 136 cases with GCTs in distal femur or proximal tibia who accepted curettage from five clinical centers during the last 15 years. All patients were divided into two groups according to filling materials. Recurrence-free survival proportions were used to evaluate oncological outcomes while the Musculoskeletal Tumor Society (MSTS) 93 functional score was used to evaluate functional outcomes. Other parameters including surgical complication, general condition, and radiological classification had been analyzed. The valid statisitical data was analyzed using SPSS 13.0 software. Results: After GCT curettage, 86 patients (63.2%) accepted bone grafting while 50 patients (36.8%) accepted cementation. There was no statistical difference in age, gender, tumor location, radiological classification, fixation, follow-up time, and MSTS 93 functional score between cementation group and bone grafting group. The recurrence-free survival proportions showed that the recurrence rate in bone grafting group was higher than it in cementation group (P = 0.034). Surgical complication was lower in cementation group than that in bone grafting group but without statistically significant difference (P = 0.141). Conclusions: Parameters including patients’ age, gender, tumor location, and radiological classification did not affect surgeons’ treatments in cavity filling after GCT curettage. Cementation should be recommended because of easy usage, the similar postoperative knee function with bone grafting, and the better local tumor control than bone grafting.