Amputation in patients with extremity soft tissue sarcoma: the experience of an East Asian referral center.

BACKGROUND: This study aimed to investigate the characteristics and clinical outcomes in a series of patients with extremity soft tissue sarcoma (STS) who underwent amputation at a large East Asian referral center. PATIENTS AND METHODS: Of the 652 patients who underwent surgery for extremity STS, data of 37 consecutive patients who underwent amputation were reviewed retrospectively. The median follow-up period was 96.0 months (range, 15-216). The patients were classified in to three cohorts. The primary localized (PL) group included patients who underwent amputation as a primary surgical procedure with curative intent. The recurrent localized (RL) group included patients who underwent amputation as a revision procedure after failure of previous limb sparing surgeries. The metastatic group included patients who underwent amputation as a palliative procedure. RESULTS: There were 22 cases of amputation in 596 STS patients and the amputation rate was 3.6% (22/596). Further, 1.8% (9/490) of patients with primary localized STS underwent amputation. Patients with localized STS who underwent amputation had a 5-year disease-specific survival (DSS) rate of 89.9% (95% Confidence Interval (CI), 87.1-92.7%), a local-recurrence-free survival (LRFS) of 84.1% (95% CI, 80.5-87.6%), and a metastasis-free survival (MFS) of 84.6%. (95% CI, 81.1-88.0%) Compared with previous studies, our results showed higher DSS and MFS rates with similar LRFS. CONCLUSIONS: The amputation rate of extremity STS in our institute in East Asia was similar but slightly lower than that reported in Western studies. The oncologic outcome of amputation reported in this study was higher than that indicated in Western studies and oncologic outcome of amputation was not statistically different from those of limb salvage surgery. However, considering the small cohort in single institute study, there is a possibility of selection bias and future multi-center study is necessary. From our results, amputation is still a feasible option for appropriately selected patients unsuitable for limb-conserving surgery.

Whole-Genome Sequencing Reveals Mutational Signatures Related to Radiation-Induced Sarcomas and DNA-Damage-Repair Pathways.

Radiation-induced sarcoma (RIS) is a rare but serious late complication arising from radiotherapy. Despite unfavorable clinical outcomes, the genomic footprints of ionizing radiation in RIS development remain largely unknown. Hence, this study aimed to characterize RIS genomes and the genomic alterations in them. We analyzed whole-genome sequencing in 11 RIS genomes matched with normal genomes to identify somatic alterations potentially associated with RIS development. Furthermore, the abundance of mutations, mutation signatures, and structural variants in RIS were compared with those in radiation-naïve spontaneous sarcomas. The mutation abundance in RIS genomes, including one hypermutated genome, was variable. Cancer-related genes might show different types of genomic alterations. For instance, NF1, NF2, NOTCH1, NOTCH2, PIK3CA, RB1, and TP53 showed singleton somatic mutations; MYC, CDKN2A, RB1, and NF1 showed recurrent copy number alterations; and NF2, ARID1B, and RAD51B showed recurrent structural variations. The genomic footprints of nonhomologous end joining are prevalent at indels of RIS genomes compared with those in spontaneous sarcoma genomes, representing the genomic hallmark of RIS genomes. In addition, frequent chromothripsis was identified along with predisposing germline variants in the DNA-damage-repair pathways in RIS genomes. The characterization of RIS genomes on a whole-genome sequencing scale highlighted that the nonhomologous end joining pathway was associated with tumorigenesis, and it might pave the way for the development of advanced diagnostic and therapeutic strategies for RIS.

Does the Clinical Presentation of Secondary Osteosarcoma in Patients Who Survive Retinoblastoma Differ From That of Conventional Osteosarcoma and How Do We Detect Them?

BACKGROUND: Osteosarcoma is the most common secondary malignancy among survivors of retinoblastoma. Most previous reports on secondary malignancy of retinoblastoma included all types of secondary malignancies without a focus on osteosarcoma, owing to its rarity. In addition, there are few studies suggesting tools for regular surveillance for early detection. QUESTIONS/PURPOSES: (1) What are the radiologic and clinical characteristics of secondary osteosarcoma after retinoblastoma? (2) What is the clinical survivorship? (3) Is a radionuclide bone scan a reasonable imaging modality for early detection in patients with retinoblastoma? METHODS: Between February 2000 and December 2019, we treated 540 patients for retinoblastoma. Twelve patients (six male, six female) subsequently developed an osteosarcoma in the extremities; two of these patients had two sites of osteosarcoma (10 femurs, four tibiae) . A Technetium-99m bone scan image was examined annually in all patients for regular surveillance after the treatment of retinoblastoma as per our hospital's policy. All patients were treated with the same strategy as that used for primary conventional osteosarcoma, namely neoadjuvant chemotherapy, wide excision, and adjuvant chemotherapy. The median follow-up period was 12 years (range 8 to 21 years). The median age at the time of diagnosis of osteosarcoma was 9 years (range 5 to 15 years), and the median interval from retinoblastoma diagnosis to osteosarcoma diagnosis was 8 years (range 5 to 15 years). Radiologic characteristics were assessed with plain radiographs and MRI, while clinical characteristics were assessed through a retrospective review of medical records. For clinical survivorship, we evaluated overall survival, local recurrence-free survival, and metastasis-free survival. We reviewed the results of bone scans and clinical symptoms at the time of diagnosis for osteosarcoma after retinoblastoma. RESULTS: In nine of 14 patients, the tumor had a diaphyseal center, and five of the tumors were located at the metaphysis. The femur was the most common site (n = 10), followed by the tibia (n = 4). The median tumor size was 9 cm (range 5 to 13 cm). There was no local recurrence after surgical resection of the osteosarcoma, and the 5-year overall survival rate after the diagnosis of osteosarcoma was 86% (95% CI 68% to 100%). In all 14 tumors, the Technetium bone scan showed increased uptake in the lesions. Ten of 14 tumors were examined in clinic because of patient complaints of pain in the affected limb. Four patients showed no clinical symptoms detected by abnormal uptake on bone scan. CONCLUSION: For unclear reasons, secondary osteosarcomas in patients who were alive after the treatment of retinoblastoma had a slight predilection for the diaphysis of the long bone compared with patients with spontaneous osteosarcoma in other reports. The clinical survivorship of osteosarcoma as a secondary malignancy after retinoblastoma may not be inferior to that of conventional osteosarcoma. Close follow-up with at least yearly clinical assessment and bone scans or other imaging modalities appears to be helpful in detecting secondary osteosarcoma after the treatment of patients with retinoblastoma. Larger multi-institutional studies will be needed to substantiate these observations.Level of Evidenc e Level IV, therapeutic study.

Design of a Novel Sericite-Phosphoric Acid Framework for Enhancement of Pb(II) Adsorption.

In this study, phosphoric acid was used to attach anions to the weak interlayer structure of sericite, one of the clay minerals composed of a tetrahedral structure of silicate, to increase the adsorption capacity of cations. Natural sericite beads (NSB) and activated sericite beads with phosphoric acid (PSB) were prepared as beads in order to increase reusability and facilitate the separation of adsorbates and adsorbents. Using this, lead (Pb(II)) removal efficiency from an aqueous solution was comparatively analyzed. The pHpzc was 6.43 in NSB but lowered to 3.96 in PSB, confirming that more acidic functional groups were attached to the PSB surface. According to FT-IR analysis, P=O, P-O-C, P=OOH and P-O-P bonds appeared on the surface of the PSB adsorbent, and the peaks of carboxyl groups and OH-groups were large and broad. The maximum adsorption capacity of Langmuir was 52.08 mg/g for NSB and 163.93 mg/g for PSB. The adsorption process was close to physical adsorption for NSB and chemical adsorption for PSB, and both adsorbents were endothermic reactions in nature in that the higher the temperature, the higher the adsorption efficiency. The adsorption mechanism of Pb(II) to PSB was achieved by ion exchange, electrostatic interaction, hydrogen bonding, and complexation. The adsorption of Pb(II) using PSB was not significantly affected by the adsorption of competing ions and showed a high adsorption efficiency of 94% in reuse up to 6 times. This confirms the favorable feasibility of removing Pb(II) from industrial wastewater using PSB.

Percutaneous Cementoplasty for the Pelvis in Bone Metastasis: 12-Year Experience.

BACKGROUND: In advanced cancer patients, pelvic bone metastasis often causes pain and gait disturbance. The use of percutaneous bone cement [polymethylmethacrylate (PMMA)] injection for pain management and strengthening in pelvic bone metastasis has rarely been reported. To evaluate this method, we aimed to determine surgical outcomes and complications over a long-term follow-up period using a large patient group. PATIENTS AND METHODS: We retrospectively collected data from 178 patients who underwent percutaneous cementoplasty for pelvic metastatic lesions, 201 in total. Surgical outcomes evaluated included pain reduction and improvement of ambulation. Mortality within 1 month after procedure and pulmonary embolism caused by thrombus, fat, tumor emboli, or bone cement were investigated as surgical complications. For long-term survivors, pain relapse and mechanical failure were analyzed. The mean follow-up period was 12.6 months, and there were 159 fatalities at last follow-up. RESULTS: The mean regional pain numerical rating scale scores decreased from 6.1 preoperatively to 2.4 1 month after procedure (p < 0.01). Gait function was maintained, worsened, and uncheckable in 68%, 24%, and 8% of patients, respectively, 1 month after procedure. Of long-term survivors followed up for > 12 months (n = 53), there were no significant changes in serial plain radiographs, and regional pain aggravation was observed in 9%. Pulmonary cement embolism and bone cement implantation syndrome was observed in 11% and 10%, respectively. However, all patients with these complications were asymptomatic. CONCLUSIONS: Percutaneous cement injection into the pelvis is a feasible and safe palliative surgical option for patients with advanced malignancy in terms of pain reduction and maintenance of ambulatory function under regional anesthesia.

A Small Molecule That Promotes Cellular Senescence Prevents Fibrogenesis and Tumorigenesis.

Uncontrolled proliferative diseases, such as fibrosis or cancer, can be fatal. We previously found that a compound containing the chromone scaffold (CS), ONG41008, had potent antifibrogenic effects associated with EMT or cell-cycle control resembling tumorigenesis. We investigated the effects of ONG41008 on tumor cells and compared these effects with those in pathogenic myofibroblasts. Stimulation of A549 (lung carcinoma epithelial cells) or PANC1 (pancreatic ductal carcinoma cells) with ONG41008 resulted in robust cellular senescence, indicating that dysregulated cell proliferation is common to fibrotic cells and tumor cells. The senescence was followed by multinucleation, a manifestation of mitotic slippage. There was significant upregulation of expression and rapid nuclear translocation of p-TP53 and p16 in the treated cancer cells, which thereafter died after 72 h confirmed by 6 day live imaging. ONG41008 exhibited a comparable senogenic potential to that of dasatinib. Interestingly, ONG41008 was only able to activate caspase-3, 7 in comparison with quercetin and fisetin, also containing CS in PANC1. ONG41008 did not seem to be essentially toxic to normal human lung fibroblasts or primary prostate epithelial cells, suggesting ONG41008 can distinguish the intracellular microenvironment between normal cells and aged or diseased cells. This effect might occur as a result of the increased NAD/NADH ratio, because ONG41008 restored this important metabolic ratio in cancer cells. Taken together, this is the first study to demonstrate that a small molecule can arrest uncontrolled proliferation during fibrogenesis or tumorigenesis via both senogenic and senolytic potential. ONG41008 could be a potential drug for a broad range of fibrotic or tumorigenic diseases.

Conditioned Medium of Human Pluripotent Stem Cell-Derived Neural Precursor Cells Exerts Neurorestorative Effects against Ischemic Stroke Model.

Previous studies have shown that early therapeutic events of neural precursor cells (NPCs) transplantation to animals with acute ischemic stroke readily protected neuronal cell damage and improved behavioral recovery through paracrine mechanisms. In this study, we tested the hypothesis that administration of conditioned medium from NPCs (NPC-CMs) could recapitulate the beneficial effects of cell transplantation. Rats with permanent middle cerebral artery occlusion (pMCAO) were randomly assigned to one of the following groups: PBS control, Vehicle (medium) controls, single (NPC-CM(S)) or multiple injections of NPC-CM(NPC-CM(M)) groups. A single intravenous injection of NPC-CM exhibited strong neuroregenerative potential to induce behavioral recovery, and multiple injections enhanced this activity further by suppressing inflammatory damage and inducing endogenous neurogenesis leading to histopathological and functional recovery. Proteome analysis of NPC-CM identified a number of proteins that are known to be associated with nervous system development, neurogenesis, and angiogenesis. In addition, transcriptome analysis revealed the importance of the inflammatory response during stroke recovery and some of the key hub genes in the interaction network were validated. Thus, our findings demonstrated that NPC-CM promoted functional recovery and reduced cerebral infarct and inflammation with enhanced endogenous neurogenesis, and the results highlighted the potency of NPC-CM in stroke therapy.

Actual long-term survival after resection of stage III soft tissue sarcoma.

BACKGROUND: Actuarial survival based on the Kaplan-Meier method can overestimate actual long-term survival, especially among those with factors of poor prognosis. Patients with American Joint Committee on Cancer stage III soft tissue sarcoma (STS) represent a subset with a high risk of STS-specific mortality. Therefore, we aimed to characterize the clinicopathological characteristics associated with actual long-term survival in patients with stage III STS. METHODS: We retrospectively reviewed 116 patients who underwent surgical resection for stage III STS with curative intent between March 2000 and December 2013. Long-term survivors (n = 61), defined as those who survived beyond 5 years, were compared with short-term survivors (n = 36), who died of STS within 5 years. RESULTS: Multivariate logistic regression analyses showed that a tumor size < 10 cm [odds ratio (OR) 3.95, p = 0.047], histological grade of 2 (OR 8.12, p = 0.004), and American Society of Anesthesiologists (ASA) score of 1 (OR 11.25, p = 0.001) were independently associated with actual 5-year survival. However, 66% of the long-term survivors exhibited factors of poor prognosis: 36% had a tumor size > 10 cm and 48% had a histological grade of 3. Leiomyosarcoma (3 of 10) was negatively associated with actual long-term survival. CONCLUSIONS: Actual 5-year survival after resection of stage III STS was associated with tumor size, histological grade, and ASA score. However, majority of the actual 5-year survivors exhibit factors of poor prognosis, suggesting that aggressive treatment should be offered for a chance of long-term survival in these patients.

EMMPRIN expression is associated with metastatic progression in osteosarcoma.

BACKGROUND: Extracellular matrix metalloproteinase inducer (EMMPRIN), a cell-surface glycoprotein, is overexpressed in several cancer types. EMMPRIN induces a metastatic phenotype by triggering the production of matrix metalloproteinase proteins (MMPs) such as MMP1 and MMP2, and vascular endothelial growth factor (VEGF) in cancer cells and the surrounding stromal cells. The purpose of this study was to investigate the expression and role of EMMPRIN in osteosarcoma. METHODS: The level of EMMPRIN expression was evaluated using reverse transcriptase polymerase chain reaction (RT-PCR) in 6 tumor-derived osteosarcoma cell lines and compared with that in normal osteoblasts. To study the prognostic significance of EMMPRIN expression, immunohistochemistry was carried out in prechemotherapy biopsies of 54 patients. siRNA knockdown of EMMPRIN in SaOS-2 cells was conducted to explore the role of EMMPRIN. To study the role of EMMPRIN in tumor-stromal interaction in MMP production and invasion, co-culture of SaOS-2 cells with osteoblasts and fibroblasts was performed. Osteosarcoma 143B cells were injected into the tail vein of BALB/c mice and lung metastasis was analyzed. RESULTS: EMMRIN mRNA expression was significantly higher in 5 of 6 (83%) tumor-derived cells than in MG63 cells. 90% of specimens (50/54) stained positive for EMMPRIN by immunohistochemistry, and higher expression of EMMPRIN was associated with shorter metastasis-free survival (p = 0.023). Co-culture of SaOS-2 with osteoblasts resulted in increased production of pro-MMP2 and VEGF expression, which was inhibited by EMMPRIN-targeting siRNA. siRNA knockdown of EMMPRIN resulted in decreased invasion. EMMPRIN shRNA-transfected 143B cells showed decreased lung metastasis in vivo. CONCLUSIONS: Our data suggest that EMMPRIN acts as a mediator of osteosarcoma metastasis by regulating MMP and VEGF production in cancer cells as well as stromal cells. EMMPRIN could serve as a therapeutic target in osteosarcoma.

The application of 3D-printing technology in pelvic bone tumor surgery.

BACKGROUND: Three-dimensional (3D)-printing technology provides an advanced approach to pelvic bone tumor resection and reconstruction. However, only a few cases of pelvic bone tumor surgery using 3D-printing have been reported due to limited time since the introduction of the new implant. This study introduces pelvic bone tumor surgeries using 3D-printed bone-cutting guides and implants. METHODS: This single-center retrospective review included 12 patients who underwent malignant pelvic bone tumor surgeries using a 3D-printed bone-cutting guide and/or implant. Clinical information was collected regarding patient demographics, tumor characteristics, pathologic diagnosis, surgery details, and functional recovery. RESULTS: Type I internal hemipelvectomy was performed using 3D-printed bone-cutting guides for 4 patients that underwent cavitary bone tumor resection of the ilium. For 3 of these 4 patients, cavitary bone defects were filled with structural allobone graft precisely trimmed by the 3D-printed allograft-shaping guide (n = 1) and 3D-printed mesh-style titanium spacer (n = 2). For type II and III areas, one and two patients, respectively, underwent 3D-printing-assisted surgery. Five patients underwent type I, II, and III pelvic resection using 3D-printed cutting guides and reconstruction with 3D-printed implants. In all patients, independent gait was recovered except for a patient who underwent hindquarter amputation 4 months postoperatively because of local recurrence. CONCLUSIONS: This study provides preliminary, short-term data on the efficacy and safety of pelvic bone tumor surgery using 3D-printing.

Ambulation Recovery After Surgery for Metastases to the Femur.

BACKGROUND: Postoperative ambulation recovery after surgery for femur metastases has significant implications for not only the patient's quality of life but also administration of further cancer treatment. Thus, identification of preoperative predictors of ambulation recovery is necessary to set appropriate expectations and guide treatment. This study aimed to assess ambulation recovery rate and identify predictors of ambulation recovery in patients undergoing surgery for femur metastases. MATERIALS AND METHODS: A total of 244 patients who underwent surgery for femur metastases at our institution were reviewed. Patients were considered ambulatory if they were able to walk independently or walk with aids and nonambulatory if they were wheelchair bound or bedridden. The following potential clinicopathologic factors that might predict postoperative ambulation recovery were evaluated: premorbid general status, cancer burden, and local factors. RESULTS: A total of 165 patients (68%) regained ambulatory status postoperatively. A multivariate analysis revealed poor Eastern Cooperative Oncology Group (ECOG) performance status (odds ratio [OR], 5.327; p < .001) and nonambulatory premorbid ambulatory status (OR, 7.459; p < .001) as independent predictors of poor ambulation recovery after surgery for femur metastases. Postoperative ambulatory status was significantly associated with postoperative survival time (p < .001). CONCLUSION: Postoperative ambulation recovery rate in our cohort was 68%. Premorbid ambulatory status and ECOG performance status are predictors of ambulation recovery in patients undergoing surgery for femur metastases. IMPLICATIONS FOR PRACTICE: Postoperative ambulation recovery rate in this cohort was 68%. Premorbid ambulatory status and Eastern Cooperative Oncology Group performance status are predictors of ambulation recovery in patients undergoing surgery for femur metastases.

Changing odds of survival over time among patients undergoing surgical resection of extremity soft tissue sarcoma.

BACKGROUND: While survival after surgical treatment of extremity soft tissue sarcoma (STS) is traditionally reported as actuarial survival, conditional survival (CS) may be more clinically relevant as it accounts for time already survived. We compared actuarial survival and CS of STS patients. MATERIALS AND METHODS: We analyzed 567 patients who underwent surgery for localized extremity STS. Actuarial survival was estimated using the Kaplan-Meier method. Cox proportional hazards model was used to evaluate factors associated with disease-specific survival. Five-year CS (CS5) estimates at "χ" year(s) after surgery were calculated as CS5 = S(χ + 5)/S(χ). RESULTS: Whereas actuarial survival decreased over time, CS5 increased. The postsurgical 1-, 3-, and 5-year CS5 values were 84.5%, 90.0%, and 93.8%, respectively, whereas the 6-, 8-, and 10-year actuarial survival rates were 82.0%, 79.4%, and 78.5%, respectively. The calculated CS5 exceeded actuarial survival especially in patients with risk factors such as large tumor size and Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) grades 2 and 3 tumors. Patients with tumor size ≥5 cm had an actuarial survival of 73.9% at 10 years compared to a CS5 of 95.4% in patients alive at 5 years. Likewise, patients with FNCLCC grade 3 tumors had an actuarial survival of 71.1% at 10 years compared to a CS5 of 96.0% in patients alive at 5 years. CONCLUSIONS: Survival estimation by determination of CS can be dynamic and accurate especially in high-risk patients. CS can be useful for survival prediction and clinical decision making in extremity STS patients.

Gender difference in the relationship between uric acid and pulse pressure among Korean adults.

Hyperuricemia is associated with cardiovascular disease, but the relationship between uric acid (UA) and pulse pressure (PP) is unclear. Therefore, the present study assesses the relationship between UA and PP among Korean adults. Data from 6,310 subjects (2,800 men and 3,510 women) in the seventh Korean National Health and Nutrition Examination Survey (2016) were analyzed. After adjusting for related variables, the odds ratios (ORs) of hyperuricemia (UA ≥ 7.0 mg/dL in men or ≥ 6.0 mg/dL in women) in the high PP group (PP > 65.0 mmHg) in overall populations (OR, 1.563; 95% confidence interval [CI], 1.144-2.136) and women (OR, 1.631; 95% CI, 1.046-2.544) were significantly higher than those in normal PP, but not in men (OR, 1.309; 95% CI, 0.840-2.040). In conclusion, uric acid was positively associated with pulse pressure in women, but not in men.

Preliminary results: use of multi-hole injection nails for intramedullary nailing with simultaneous bone cement injection in long-bone metastasis.

OBJECTIVE: For symptomatic metastasis of the long bones, intramedullary nailing has been the most accepted fixation method. Intramedullary nailing has effective control of pain, perioperative bleeding, and local tumor progression by augmentation with bone cement around the nail. Here, we report the preliminary results of a new surgical implant that allows for simultaneous injection of bone cement while inserting a percutaneous, flexible intramedullary nail. MATERIALS AND METHODS: We performed palliative surgeries for long-bone metastasis using a multi-hole injection nail (MIN) with multiple side holes in the distal one third. When the nail tip entered the metastatic cancer lesion, the bone cement injection was started, and continued until the nail was completely seated. Ten patients with advanced cancer underwent palliative surgery using the new implant with simultaneous bone cement injection for humeral (n = 4), femoral (n = 4), and tibial (n = 2) metastases. RESULTS: The mean operative time was 42 min (range, 36-52 min). The mean length of the injection nail was 23.0 cm (range, 18.0-33.0 cm), and the mean volume of cement was 28.0 ml (range, 14.0-40.0 ml). Marked pain palliation (p < 0.001) and functional recovery (p = 0.01) were verified. The mean Musculoskeletal Tumor Society (MSTS) functional score improved significantly from 12.5 at 6 weeks preoperatively, to 24.9 postoperatively. No acute postoperative complications, including cement embolism, occurred. CONCLUSION: This minimally invasive surgical method with MIN could be useful for stabilization of long-bone metastases in patients with advanced cancer.

Deep learning approach for survival prediction for patients with synovial sarcoma.

Synovial sarcoma is a rare disease with diverse progression characteristics. We developed a novel deep-learning-based prediction algorithm for survival rates of synovial sarcoma patients. The purpose of this study is to evaluate the performance of the proposed prediction model and demonstrate its clinical usage. The study involved 242 patients who were diagnosed with synovial sarcoma in three institutions between March 2001 and February 2013. The patients were randomly divided into a training set (80%) and a testing set (20%). Fivefold cross validation was performed utilizing the training set. The test set was retained for the final testing. A Cox proportional hazard model, simple neural network, and the proposed survival neural network were all trained utilizing the same training set, and fivefold cross validation was performed. The final testing was performed utilizing the isolated test data to determine the best prediction model. The multivariate Cox proportional hazard regression analysis revealed that size, initial metastasis, and margin were independent prognostic factors. In fivefold cross validation, the median value of the receiver-operating characteristic curve (area under the curve) was 0.87 in the survival neural network, which is significantly higher compared to the area under the curve of 0.792 for the simple neural network (p = 0.043). In the final test, survival neural network model showed the better performance (area under the curve: 0.814) compared to the Cox proportional hazard model (area under the curve: 0.629; p = 0.0001). The survival neural network model predicted survival of synovial sarcoma patients more accurately compared to Cox proportional hazard model.

Bone tumor resection guide using three-dimensional printing for limb salvage surgery.

BACKGROUND AND OBJECTIVES: The three-dimensional (3D)-printed bone tumor resection guide can be personalized for a specific patient and utilized for bone tumor surgery. It is noninvasive, eidetic, and easy to use. We aimed to categorize the use of the 3D-printed guide and establish in vivo accuracy data. METHODS: We retrospectively reviewed 12 patients, who underwent limb salvage surgery using the 3D-printed guide at a single institution. To confirm the achievement of a safe bone margin, we compared the actual and planned distances between the cutting surface and tumor, which were reported in the final pathological report and measured from the same virtual cutting plane using graphical data of the cutting guide design, respectively. RESULTS: The use of the 3D-printed guide was categorized as follows: (a) wide excision only, (b) wide excision and biological reconstruction with a structural bone allograft shaped in accordance with the 3D-printed guide, and (c) wide excision and reconstruction with a 3D-printed personalized implant. The maximal cutting error was 3 mm. CONCLUSIONS: The 3D-printed resection guide is easy to use and shows promise in the field of orthopedic oncology, with its application in bone tumor resection and reconstruction with a structural bone allograft or 3D-printed implant.

Postmetastasis survival in high-grade extremity osteosarcoma: A retrospective analysis of prognostic factors in 126 patients.

BACKGROUND AND OBJECTIVES: Prognostic factors predictive of postmetastasis survival (PMS) in metastatic osteosarcoma are poorly understood. Our aims were to evaluate PMS in patients with high-grade osteosarcoma in extremities, and to identify prognostic factors related to PMS. METHODS: A retrospective review of data for 126 patients with metastatic osteosarcoma was conducted. The study population consisted of 70 men and 56 women, with a mean age of 21 years (range: 4-75 years). The mean postmetastasis follow-up period was 37 months (range: 1-245 months). RESULTS: The 5-year PMS rate was 31% and median PMS duration was 22 months. In the multivariate analyses, no metastasectomy (P < 0.001), local recurrence prior to metastasis (P = 0.016), extrapulmonary metastasis (P = 0.006), and poor histologic response to preoperative chemotherapy (P = 0.047) were significant poor prognostic factors. The 5-year PMS without any negative prognostic factor was 60.2%; with one factor, 31.6%; and with more than two factors, 3.6%. CONCLUSIONS: PMS in osteosarcoma patients was influenced by primary tumor-related factors such as histologic response to chemotherapy, as well as metastasis-related factors such as complete metastasectomy and metastasis site. A certain group of patients without such poor prognostic factors could be cured even after the development of metastasis.

Factors associated with local recurrence after surgery for bone metastasis to the extremities.

BACKGROUND AND OBJECTIVES: With increasing life expectancy of patients with bone metastasis, durable surgical stabilization of bone metastasis is necessary. Local recurrence (LR) can compromise surgical stabilization and necessitate retreatment. We analyzed LR rate and factors associated with LR in patients undergoing surgery for bone metastasis. METHODS: Patients (n = 301) who underwent surgery for bone metastasis to the extremities were reviewed. Possible factors that might be associated with LR were investigated. RESULTS: LR rate was 16% (49/301). Surgical margin was associated with LR, as patients with en-bloc resection had significantly less LR than patients who underwent curettage (5/66 vs 44/235, P = 0.03). Prostate cancer had lowest rate (0%) of LR and colon cancer had highest rate (31%). Interval from surgery to LR differed among primary cancer types (4.5 ± 3.9 months [lung cancer], vs 12.3 ± 12.9 months [other cancers], P = 0.041). In multivariate analysis, en-bloc surgical margins (HR = 0.372, P = 0.036) and primary cancers of breast or prostate (HR = 0.391, P = 0.049) were independent factors associated with longer LR-free survival. CONCLUSIONS: LR after surgery for bone metastasis to extremities is affected by surgical margin and primary cancer type. These factors, along with expected patient survival, need to be considered when planning surgery for bone metastasis to extremities.

Does fluid collection impact radiotherapy outcomes after wide excision of lower extremity soft tissue sarcoma?

BACKGROUND: Fluid collection (FC) of lymph or blood may accumulate at the site of excision after surgery for soft tissue sarcoma, with reported incidence rates from 10% to 36%. The purpose of this study is to analyze the impact of FC on local recurrence (LR) and wound complication rates after adjuvant postoperative radiotherapy (PORT) in lower extremity soft tissue sarcoma (LE-STS). METHODS: Eighty-eight patients diagnosed with LE-STS were curatively treated with wide excision and PORT. FC developed in 51.1% of patients. Full FC volumes were included in the irradiation field throughout the full course of PORT for 36 patients (80.0%). A median of 61.2 and 63 Gy was prescribed for patients with and without FC, respectively. RESULTS: After a median follow-up of 4.3 years, patients with and without FC had 5-year local control rates of 77.7% and 90.8% (P = 0.105). Eight patients with FC had LR, of which six patients had recurrent tumors at or within 4 cm of the FC wall and three of these patients had out-of-field LR. Wound complication occurred after RT in 3 (6.7%) of 45 patients with FC and 1 (2.3%) of 43 patients without FC. CONCLUSIONS: FC presents a potential risk for increased LR, particularly near the FC wall. Based on reasonable wound complication rates, we suggest the need and feasibility of fully including FC volumes in the irradiation field.