Surgical Treatment and Proposed Modified Classification for Harrington Class III Periacetabular Metastases.

OBJECTIVES: This study aims to: (i) evaluate the outcome of patients with Harrington class III lesions who were treated according to Harrington classification; (ii) propose a modified surgical classification for Harrington class III lesions; and (iii) assess the efficiency of the proposed modified classification. METHODS: This study composes two phases. During phase 1 (2006 to 2011), the clinical data of 16 patients with Harrington class III lesions who were treated by intralesional excision followed by reconstruction of antegrade/retrograde Steinmann pins/screws with cemented total hip arthroplasty (Harrington/modified Harrington procedure) were retrospectively reviewed and further analyzed synthetically to design a modified surgical classification system. In phase 2 (2013 to 2019), 62 patients with Harrington class III lesions were classified and surgically treated according to our modified classification. Functional outcome was assessed using the Musculoskeletal Tumor Society (MSTS) 93 scoring system. The outcome of local control was described using 2-year recurrence-free survival (RFS). Owing to the limited sample size, we considered P < 0.1 as significant. RESULTS: In phase 1, the mean surgical time was 273.1 (180 to 390) min and the mean intraoperative hemorrhage was 2425.0 (400.0 to 8000.0) mL, respectively. The mean follow-up time was 18.5 (2 to 54) months. Recurrence was found in 4 patients and the 2-year RFS rate was 62.4% (95% confidence interval [CI] 31.6% to 93.2%). The mean postoperative MSTS93 score was 56.5% (20% to 90%). Based on the periacetabular bone destruction, we categorized the lesions into two subgroups: with the bone destruction distal to or around the inferior border of the sacroiliac joint (IIIa) and the bone destruction extended proximal to inferior border of the sacroiliac joint (IIIb). Six patients with IIIb lesions had significant prolonged surgical time (313.3 vs 249.0 min, P = 0.022), massive intraoperative hemorrhage (3533.3 vs 1760.0 mL, P = 0.093), poor functional outcome (46.7% vs 62.3%, P = 0.093), and unfavorable local control (31.3% vs 80.0%, P = 0.037) compared to the 10 patients with IIIa lesions. We then modified the surgical strategy for two subgroup of class III lesions: Harrington/modified Harrington procedure for IIIa lesions and en bloc resection followed by modular hemipelvic endoprosthesis replacement for IIIb lesions. Using the proposed modified surgical classification, 62 patients in the phase 2 study demonstrated improved surgical time (245.3 min, P = 0.086), intraoperative hemorrhage (1466.0 mL, P = 0.092), postoperative MSTS 93 scores (65.3%, P = 0.067), and 2-year RFS rate (91.3%, P = 0.002) during a mean follow-up time of 19.9 (1 to 60) months compared to those in the phase 1 study. CONCLUSION: The Harrington surgical classification is insufficient for class III lesions. We proposed modification of the classification for Harrington class III lesions by adding two subgroups and corresponding surgical strategies according to the involvement of bone destruction. Our proposed modified classification showed significant improvement in functional outcome and local control, along with acceptable surgical complexity in surgical management for Harrington class III lesions.

Malignant Pelvic Tumors Involving the Sacrum: Surgical Approaches and Procedures Based on a New Classification.

OBJECTIVE: To introduce a new classification of Enneking type IV pelvic tumors involving the sacrum and a corresponding system of standardized surgical approaches and procedures for resection of such tumors, and to investigate the feasibility and therapeutic effect of the new system. METHODS: Data on 59 patients treated between February 2003 and February 2013 by standardized surgical approaches and procedures were retrospectively reviewed. The study subjects comprised 28 male and 31 female patients with a mean age at diagnosis of 36 years (range, 2-72 years). There are four subtypes in the new classification: (i) subtype IVa, neoplasms invading the ipsilateral sacral wing; (ii) subtype IVb, neoplasms invading the ipsilateral sacral foramina; (iii) subtype IVc, neoplasms invading the contralateral sacral foramina; and (iv) subtype IVd, neoplasms invading the whole of the sacrum. Standardized surgical approaches and procedures were devised for en-bloc resection for each subtype with adequate margins. RESULTS: Adequate margins were achieved in 43/59 patients (72.9%). The mean operation time was 5.0 h and the mean intraoperative blood loss 2157 mL. At the final follow-up, 27/53 patients (50.9%) who had been followed up were alive and in complete remission. The mean Musculoskeletal Tumor Society 93 score was 17.4 (58%) of a possible 30 points. The mean functional score for patients who had undergone a pelvic zone II resection was 15.2, compared with 19.0 for those with an intact pelvic zone II. CONCLUSIONS: The proposed standardized protocols should help orthopaedic surgeons to achieve adequate margins, manage risk, achieve better oncologic and functional outcomes, and minimize perioperative complications when treating massive pelvic tumors involving the sacrum.

Endoprosthetic reconstruction for large extremity soft-tissue sarcoma with juxta-articular bone involvement: functional and survival outcome.

BACKGROUND: Large extracompartmental limb soft-tissue sarcoma with juxta-articular bone involvement poses major challenges in disease management. Radical resection of sarcoma frequently requires concomitant bone resection and reconstruction. We describe the clinical outcomes of endoprosthetic reconstruction and the complications associated with this procedure. METHODS: Thirty patients with soft-tissue sarcomas with local juxta-articular bone involvement in an extremity underwent surgery at our center between May 2004 and October 2011, 20 for primary sarcomas and 10 for local recurrences. Clinical data from those patients were analyzed retrospectively. The bone affected included the proximal femur (10 cases), the distal femur (nine cases), the proximal humerus (eight cases), the proximal tibia (two cases), or the total femur (one case). Wide excision of the tumor and the bone tissue involved was performed on every patient, followed by reconstruction of the subsequent defect using tumor endoprosthesis. All patients underwent regular follow-up for an average of 25 (range, 3-84) mo. RESULTS: Three patients had poor wound healing. Implant fractures leading to additional revisions occurred in two cases. Local tumor recurrence developed in four patients. There were 15 patients with lung metastases, and 11 patients died of disseminated metastases. In the latest follow-up, 14 patients survived free of disease and five were alive with tumors. The mean Musculoskeletal Tumor Society functional analysis for proximal femur, distal femur, proximal tibia, proximal humerus, and total femur were 90%, 82%, 73%, 71%, and 60%, respectively. The 2- and 5- y survival rates were 61.6% and 30.0%, respectively. CONCLUSIONS: Endoprosthetic reconstruction could yield satisfactory results as a wide excision and limb salvage therapeutic strategy for patients with large extracompartmental soft-tissue sarcomas with juxta-articular bone involvement. Acceptable complications occurred in the present report.

[Surgical managements for bone metastases in tibia of 16 cases].

OBJECTIVE: To investigate the different surgical options for tibia metastatic disease and to evaluate the survival prognostic factors, postoperation function and complications. METHODS: A retrospective evaluation of 16 patients treated for tibia metastatic disease between Jan. 2000 and Feb. 2013 was conducted at our center. The underlying histology of the lesions showed metastatic lung carcinoma (five),breast carcinoma (three), bladder carcinoma (two), unknown (two), renal cell carcinoma, colon carcinoma, hepatic cellular cancer and lymphoma (one each). The locations of these lesions were proximal in 11 patients (with one patient having two synchronous lesions in the proximal metaphysis on both sides), diaphyseal in 4 patients, and distal metaphyseal in two patients. One patient presented with a pathologic fracture,and the risk of impending pathologic fracture of the remainders was evaluated by Mirels scoring system. Of all the 16 patients, 15 were treated surgically (with 16 operations performed). Six of them were reconstructed with proximal tibial replacement, 9 underwent curettage and cementation (with or without inner-fixations), and 1 patient had lower third calf amputation. We employed VAS scoring system to evaluate the pain intensity of the lesions before and after operation.The post-operation function was assessed by MSTS scoring system. The survival rate was described by Kaplan-Meier survival curve. RESULTS: Fourteen of all the patients were followed-up and enrolled in the research. The median postoperative survival was 7 months (1-72 months).The mean half year survival rate and 2-year survival rate were 57.14% and 8.9% respectively.The mean Mirels score was 9.8 ± 1.0. The mean VAS score before the operation was 7.62 ± 1.03, which turned out to be 1.36 ± 0.86 after the operation. The mean MSTS score for the endoprosthesis and curettage was 21.0 ± 0.63 and 23.1 ± 1.25 respectively. CONCLUSION: The mobidity of tibia metastatic diseases is very low.Surgical intervention, combined with the application of bisphosphonate and postoperative radiotherapy, is absolutely necessary for the treatment of tibial metastatic disease, contributing to an improved quality of life and limb function.

[Surgical classification and therapeutic strategy for metastases of proximal femur].

OBJECTIVE: To establish a surgical classification system for metastases of proximal femur and discuss the therapeutic strategy with retrospective analysis and literature review. METHODS: The data of 99 patients who underwent a total of 102 operations for femoral metastatic lesions from January 2003 to December 2011 was analyzed. There were 50 males and 49 females, and the median age was 56 years (range 15-87 years). The most common diagnosis was lung cancer (30 cases), followed by breast cancer (17 cases). All femoral lesions were divided into 4 types (I-IV) with different anatomic site and biomechanic characteristic. The patients with various surgical reconstruction mode and postoperative follow-up data were recorded. RESULT: There were 65 side who received widely or marginal resection and 37 side who received intralesional resection. The patients were operated with bipolar hip prosthesis (n = 3), ordinary total hip replacement (THR) (n = 10), bipolar tumor prosthesis (n = 48), THR with tumor prosthesis (n = 8), intramedullary nailing (n = 21), and plate/screw (n = 12). The estimated survival for the 99 patients was 10.3 months. Type I, II, III and IV patients with postoperative American Society of bone and soft tissue tumors-93 rating were 86.5%, 77.3%, 81.3% and 69.1%. Patients with type IV were worse compared with the other 3 groups (t = 4.763, P = 0.031). The 10 operations were followed by complications of any kind. Complication rate of patients with type IV were 3/12, and it was significantly higher than the other 3 groups of patients (χ(2) = 4.018, P = 0.045). CONCLUSIONS: The classifications and corresponsive surgical methods for upper femur metastases had some superiority in hinting prognosis and guiding treatment.

[Evaluation of efficacy and safety of rivaroxaban in the prevention of postoperative venous thromboembolism in adult patients with primary bone tumor undergoing knee operation].

OBJECTIVE: To explore the incidence of postoperative venous thromboembolism (VTE) in adult patients with primary bone tumor undergoing knee operation and evaluate its efficacy and safety in the prevention of VTE. METHODS: For this prospective, randomized and negative-control single-center trial, a total of 100 eligible patients were selected and randomly divided into observation and control groups. Observation group (rivaroxaban): the first rivaroxaban tablet was taken in the first 24 hours after operation. Rivaroxaban was administered daily every 24 hours up to Day 14. CONTROL GROUP: no anticoagulant was taken postoperatively. RESULTS: Efficacy indictors: 6 cases of DVT (an incidence of 12%) occurred in the observation group versus 15 (30%) in the control group. Significant statistical difference existed between two groups (P < 0.05). Furthermore, neither pulmonary embolism nor death was found in either group. Safety indicators:a total of 3 bleeding (1 major and 2 non-major) cases occurred in observation group versus a total of 2 bleeding (no major and 2 non-major) cases in control group. No significant statistical difference existed in bleeding events (P > 0.05). The total incidence of adverse effect was 6% (3/50) in the observation group. The drainage volume of the observation group was a little more than that of the control group. But no significant statistical difference existed in drainage duration (P > 0.05). And there was almost no change in the coagulation system by laboratory examination after oral administration. CONCLUSION: With an excellent safety profile and a low incidence of adverse effects, Rivaroxaban is effective and safe in the prevention of VTE in adult patients with primary bone tumor undergoing knee operation.

[Evaluation of prognostic factors for synovial sarcoma].

OBJECTIVE: To determine the independent prognostic factors of primary synovial sarcoma. METHODS: The clinical data of 52 patients followed up from 66 patients with synovial sarcoma treated between September 1997 and September 2008 was analyzed retrospectively. There were 28 male and 24 female patients aged from 11 to 71 years old. Three and five-year overall survival (OS), recurrence rate and 9 prognostic factors were analyzed in this study. Univariate and multivariate analysis were performed to determine the prognostic factors of OS. RESULTS: Fifty-two patients were followed up with the follow-up time ranged from 6 to 88 months (median 32 months). The 3-, 5-year overall survival rate and local recurrence rate were 52.8%, 30.3% and 32.7% respectively. Univariate showed tumor size < 5 cm, tumor located at extremities, adequate surgical margin and radical resection combined with radiotherapy had better survival rate (P < 0.05). Multivariate analysis demonstrated that tumor size, primary site and adequate surgical margin were independent prognostic factors for OS. Patients received radical resection combined with radiotherapy have longer median relapse time (25 months) compared with marginal resection combined with radiotherapy (18 months) and single radical resection (12 months). Thirty-five (67%) patients were treated with chemotherapy and seventeen (33%) patients received no chemotherapy for the primary tumor. Treatment with chemotherapy was not associated with an improved OS (P = 0.52). CONCLUSIONS: The independent prognostic factors of synovial sarcoma are tumor size, primary site and adequate surgical margin. Doxorubicin and ifosfamide based chemotherapy was not associated with an improved OS in patients with synovial sarcoma. Radical resection combined with radiotherapy can best control local condition.

[The survival and functional outcome of primary bone sarcomas in distal lower extremity].

OBJECTIVE: To analyze the oncological and functional outcome of limb salvage in this location. METHODS: From November 2003 to January 2010, 20 patients with primary malignant bone tumors of the distal lower extremity were treated. There were 15 male and 5 female, the mean age was 20 years. Among 14 patients with malignant distal tibial sarcoma, 11 patients had ankle arthrodesis reconstructed by using allograft (7 patients) or autografts (4 patients), the other 3 patients underwent below-knee amputation. Three patients with osteosarcoma of distal fibula reconstructed with ipsilateral fibular head, 3 patients with calcaneus osteosarcoma underwent total calcanectomy and reconstructed with fibular segment and iliac crest. The mean follow-up was 36.4 months. RESULTS: Five of 7 (71.4%) patients with allograft reconstruction were associated with delayed wound healing, however, only 1 of 10 patients with autograft had this problem (P = 0.036). One local recurrence was observed, 2 osteosarcoma patients died of disseminated disease. The estimated 2-year and 5-year overall survival for the patients with malignant tibial sarcomas were 92.9% and 79.6% respectively, for the patients with distal tibial high-grade osteosarcoma were 87.5% and 70.0% respectively. The mean functional MSTS score was 82% for limb salvage patients. CONCLUSIONS: The survival of patients with primary malignant bone tumor of distal lower extremity seems to be better than that of other sites. Limb salvage can provide satisfactory local control and functional results.

(-)-Epigallocatechin-3-gallate induces apoptosis and suppresses proliferation by inhibiting the human Indian Hedgehog pathway in human chondrosarcoma cells.

PURPOSE: Chondrosarcoma is a soft tissue sarcoma with a poor prognosis that is unresponsive to conventional chemotherapy. The regulatory mechanisms for the rapid proliferation of chondrosarcoma cells and the particular aggressiveness of this sarcoma remain poorly understood. In this study, we investigate the effect of epigallocatechin-3-gallate (EGCG) on growth and apoptosis of chondrosarcoma cells. METHODS: The chondrosarcoma cell lines, SW1353 and CRL-7891, were cultured with and without EGCG. The MTT assay was used to test the cytotoxicity of EGCG. Flow cytometry and DAPI staining were used to observe cell apoptosis caused by EGCG. To explore the effect of EGCG on the Indian Hedgehog signaling pathway and apoptosis-related proteins, RT-PCR and Western blotting were used to detect the expression of PTCH and Gli-1 in the Indian Hedgehog signaling pathway. Meanwhile, expression of Bcl-2, Bax, and caspase-3 were also evaluated by Western blot analysis. RESULTS: EGCG effectively inhibited cellular proliferation and induced apoptosis of SW1353 and CRL-7891. EGCG inhibited the human Indian Hedgehog pathway, down-regulated PTCH and Gli-1 levels, and induced apoptosis as confirmed by DAPI staining followed by flow cytometry. Protein expression levels of caspase-3 were unchanged in response to EGCG treatment in chondrosarcoma cells; however, the expression levels of Bcl-2 were significantly decreased and the levels of Bax were significantly increased. CONCLUSIONS: Our findings demonstrate that EGCG is effective for growth inhibition of a chondrosarcoma cell lines in vitro, and suggest that EGCG may be a new therapeutic option for patients with chondrosarcoma.

[The surgical management of sacral chordoma].

OBJECTIVE: To analyze the surgical treatment results and experience of sacral chordoma. METHODS: The data of 51 cases of sacral chordoma surgically treated from July 1997 to July 2007 was retrospectively studied. The age of patients ranged from 21 to 75 years (mean 57 years), including 32 males and 19 females. Forty patients had the first surgery, while other 11 patients were referred to our hospital because of local recurrence from other hospital. Wide resection for all 17 S(3-5) tumors, and wide resection plus piece-meal excision for 34 tumors which involved S(3) above. Reconstruction was performed using pedicle screw and rod device to achieve the continuity between the lumbar spine and the pelvis. The oncologic and functional outcomes of 51 patients were reviewed. RESULTS: After a mean duration of follow-up of 3.5 years (range from 15 to 108 months), 5 of 51 patients died of disease. Seventeen of 40 (42.5%) patients who underwent first surgery recurred during follow-up, 18 of 28 patients (64.3%) got re-relapse after second or third surgeries. Postoperative wound complications were as high as 31.6%. CONCLUSIONS: Chordoma is a biologically aggressive low-grade malignant tumor. Wide resection is a prerequisite for curative treatment of sacrococcygeal chordoma, intralesional curettage causes the risk of high local recurrence for which curative resection in a second or third procedure is more difficult to achieve. In order to preserve near normal bowel and bladder function for the tumor which involves S(3) above, wide en-bloc resection plus piece-meal excision in the cephalad is performed.

Sorafenib induces growth inhibition and apoptosis in human synovial sarcoma cells via inhibiting the RAF/MEK/ERK signaling pathway.

Synovial sarcoma is a soft tissue sarcoma with poor prognosis and lack of response to conventional cytotoxic chemotherapy. The regulatory mechanisms for the rapid proliferation of synovial sarcoma cells and the particular aggressiveness of this sarcoma remain poorly understood. Mitogen-activated protein kinase (MAPK) cascades have been shown to play important roles in synovial sarcoma survival. Sorafenib (Nexavar, BAY 43-9006), a potent recombinant activated factor (RAF) inhibitor, inhibits the MAPK signaling pathway both in vitro and in vivo. In this study, we examined the inhibitory proliferation effects of sorafenib in synovial sarcoma growth and evaluated whether sorafenib modulates MAPK and tumor apoptosis cascades in human synovial sarcoma cell lines SW982 and HS-SY-II. Our results indicated that sorafenib effectively inhibited cellular proliferation and induces apoptosis of these two cells. Sorafenib inhibited the phosphorylation of MEK and ERK, downregulated cyclin D1 and Rb levels, caused G(1) arrest and S phase decrease, and induced apoptosis as confirmed by flow cytometry and the TUNEL assay. Furthermore, Bcl-xl and Mcl-1 levels significantly decreased, whereas expression levels of the proteins bcl-2 and bax were unchanged in response to sorafenib treatment in SW982 and HS-SY-II cells. In conclusion, our findings demonstrate that sorafenib is effective for growth inhibition of synovial sarcoma cell lines in vitro and suggest that sorafenib may be a new therapeutic option for patients with synovial sarcoma.

[Resection and reconstruction of upper thoracic tumor by high transthoracic approach].

OBJECTIVES: To define the role of high transthoracic approach in the treatment of cervicothoracic and high thoracic tumor, and analyze the problem encountered during tumor resection and reconstruction of this technique and oncological results of patients who received this type of surgery. METHODS: Twenty-one patients with cervicothoracic and high thoracic tumor (T(1 - 4)) were treated with high transthoracic approach. This series included metastatic tumor 11 patients, eosinophilic granuloma of bone 2 patients, osteosarcoma 1 patient, Ewing's sarcoma 2 patients, chondrosarcoma 2 patients, giant cell tumor 2 patients, lymphoma 1 patient. High transthoracic approach was applied to these patients for tumor resection and spinal cord decompression. Reconstruction method included artificial vertebrae implantation or bone graft implantation combined with anterior internal fixation. RESULTS: Chest-back pain of all patients relieved significantly after operation. Paraplegia of 3 patients was improved from grade A to grade D according to Frankel grading system, the other 2 patients recovered completely. Pulmonary infection and pulmonary atelectasis occurred in 2 patients; cerebrospinal fluid leakage happened in 1 patient; thoracic aorta rupture happened in 1 patient. The follow-up period was 11 - 58 months, 9 patients died, including 7 patients with metastatic cancer, 1 patient with Ewing's sarcoma, 1 patient with osteosarcoma. CONCLUSIONS: High transthoracic approach is a satisfactory method in dealing with the lesion of cervicothoracic and high thoracic vertebrae, especially with the lesion involving the vertebrae and single vertebral arch. The thoracic canal can be decompressed effectively by this approach.

[The clinical outcome of proximal fibular osteosarcoma with en-bloc resection].

OBJECTIVE: To evaluate the local recurrence and 5-year survival of proximal fibular osteosarcoma. METHODS: From October 1997 to July 2005, 12 patients with proximal fibular osteosarcoma were treated. There were 9 males and 3 females. The mean age at diagnosis was 16 (9-23) years old. Histopathological diagnosis were obtained by trut-cut biopsy, Enneking surgical stages of 12 lesions were as follows: 11 grade II B and 1 grade III. Induction chemotherapy was applied to all patients except one who left the hospital after the biopsy. Of 11 patients, 8 were performed Malawer type I resection, and 3 type II. All patients continued to get postoperative chemotherapy. RESULTS: Regular follow-up was applied. Only 1 patient was found local recurrence one year after operation and received re-resection, the others did not. Four patients died of lung metastases, including the one who did not get treated, one stage III and two II B patients. The range of follow up was 6 to 117 months. The evaluated 5 year disease-free survival of 11 patients who got treated was 72.7% by using Kaplan Meier survival analysis. CONCLUSIONS: The local recurrence is low, and 5 year disease-free survival is acceptable, in accordance with present point that marginal resection may not impact survival for fibular osteosarcoma. No knee instability is found in this group after great care is taken for proper reconstruction of lateral collateral ligament and reinsertion of biceps femoris tendon on the lateral condyle of tibia.

[A case of primary leiomyosarcoma of tibia with multiple skeletal metastases].

To describe the first case of leiomyosarcoma of the tibia with multiple skeletal metastases in China. A 31-year-old woman was referred to Peking University People's Hospital for evaluation of a lesion on the proximal left tibia. The radiographic examination showed the lesion had a moth-eaten destructive appearance with ill-defined border and soft tissue extension. The tumor is isointense to muscle on T1-weighed images and heterogeneous and of high signal on T2-weighed images. Technetium-99m bone scintigraphy demonstrated multiple markedly increased skeletal radioisotope uptake. The tibia lesion was surgically removed. Microscopically, tumor cells consisted of spindle shaped cells, arranged in bundles, with cigar-shaped and blunt-ended nuclei. Immunohistochemistry revealed that the tumor cells were positive for smooth muscle antigen (SMA) and caldesmon. It should be cautious to make the diagnosis of leiomyosarcoma arising in bone. After excluding metastasizing leiomyosarcoma of gastrointestinal tract, urinary system and uterus, the final diagnosis relies on immunohistochemical analysis, however, other spindle cell sarcomas have to be differentially diagnosed.

[Clinical study of solitary bone plasmacytoma].

OBJECTIVE: To study the clinical characteristics and the prognosis of solitary bone plasmacytoma (SBP). METHODS: From June 1997 to June 2002, ten SBP patients were treated in our department. Two lesions were in sacrum, two in pelvis, the other six lesions were in proximal femur, femoral diaphyseal, scapula, thoracic vertebra, proximal humus, and rib respectively. The preoperative laboratory tests were normal. Operation was performed on all patients. The pathologic diagnose was plasmacytoma and then they underwent further laboratory examination, urine Bence-Jone protein is positive in 3 patients, serous IgG value was higher than normal in 2 patients, abnormal M protein was found in electrophoresis in 2 patients. All patients received radiotherapy postoperatively. RESULTS: Four patients were excluded, whose follow-up were lessen than ten months, the other six patients's average follow-up is 28.2 months (from 18 to 48 months), one patient who developed multiple myeloma (MM) six months postoperatively received chemotherapy using M2 protocol and died 21 months after operation. The other five patients had disease-free survive and remain solitary bone lesion after the treatment of surgery and radiology. CONCLUSION: Compared with MM, SBP patients are younger, the therapeutic results and prognosis are better. The main prognostic factors include age, the size of lesion, the axial bone lesion, persistence of myeloma protein after radiotherapy, early diagnosis and treatment, and so on.