What Are the MSTS Scores and Complications Associated With the Use of Three-dimensional Printed, Custom-made Prostheses in Patients Who Had Resection of Tumors of the Hand and Foot?

BACKGROUND: There are a few good options for restoring bone defects in the hand and foot. 3D-printed implants have been used in the pelvis and elsewhere, but to our knowledge, they have not been evaluated in the hand and foot. The functional outcome, complications, and longevity of 3D-printed prostheses in small bones are not well known. QUESTIONS/PURPOSES: (1) What are the functional outcomes of patients with hand or foot tumors who were treated with tumor resection and reconstruction with a 3D-printed custom prosthesis? (2) What complications are associated with using these prostheses? (3) What is the 5-year Kaplan-Meier cumulative incidence of implant breakage and reoperation? METHODS: Between January 2017 and October 2020, we treated 276 patients who had tumors of the hands or feet. Of those, we considered as potentially eligible patients who might have extensive loss in their joint that could not be fixed with a bone graft, cement, or any prostheses available on the market. Based on this, 93 patients were eligible; a further 77 were excluded because they received nonoperative treatment such as chemoradiation, resection without reconstruction, reconstruction using other materials, or ray amputation; another three were lost before the minimum study follow-up of 2 years and two had incomplete datasets, leaving 11 for analysis in this retrospective study. There were seven women and four men. The median age was 29 years (range 11 to 71 years). There were five hand tumors and six tumors of the feet. Tumor types were giant cell tumor of bone (five), chondroblastoma (two), osteosarcoma (two), neuroendocrine tumor (one), and squamous cell carcinoma (one). Margin status after resection was ≥ 1 mm. All patients were followed for a minimum of 24 months. The median follow-up time was 47 months (range 25 to 67 months). Clinical data; function according to the Musculoskeletal Tumor Society, DASH, and American Orthopedic Foot and Ankle Society scores; complications; and survivorship of implants were recorded during follow-up in the clinic, or patients with complete charts and recorded data were interviewed on the telephone by our research associates, orthopaedic oncology fellows, or the surgeons who performed the surgery. The cumulative incidence of implant breakage and reoperation was assessed using a Kaplan-Meier analysis. RESULTS: The median Musculoskeletal Tumor Society score was 28 of 30 (range 21 to 30). Seven of 11 patients experienced postoperative complications, primarily including hyperextension deformity and joint stiffness (three patients), joint subluxation (two), aseptic loosening (one), broken stem (one), and broken plate (one), but no infection or local recurrence occurred. Subluxations of the metacarpophalangeal and proximal interphalangeal joints in two patients' hands were caused by the design of the prosthesis without a joint or stem. These prostheses were revised to a second-generation prosthesis with joint and stem, leading to improved dexterity. The cumulative incidence of implant breakage and reoperation in the Kaplan-Meier analysis was 35% (95% CI 6% to 69%) and 29% (95% CI 3% to 66%) at 5 years, respectively. CONCLUSION: These preliminary findings suggest that 3D implants may be an option for reconstruction after resections that leave large bone and joint defects in the hand and foot. Although the functional results generally appeared to be good to excellent, complications and reoperations were frequent; thus, we believe this approach could be considered when patients have few or no alternatives other than amputation. Future studies will need to compare this approach to bone grafting or bone cementation. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Anatomic 3D-Printed Endoprosthetic With Multiligament Reconstruction After En Bloc Resection in Giant Cell Tumor of Distal Radius.

A 34-year-old woman was diagnosed with a giant cell tumor of the right distal radius with extensive articular invasion. After en-bloc resection of 5.5 cm of the distal radius, reconstruction was done with three-dimensional printing custom-made distal radius prosthesis. In addition, a multiligament reconstruction was done to prevent postoperative radiocarpal subluxation and imitate the native distal radius. At 18 months, the range of motion was 20° dorsiflexion, 10° palmar flexion, 10° supination, and 60° pronation. Her grip strength was 60% compared with the contralateral side. No complications were seen during this 2-year follow-up. We present the combined 3-dimensional printed custom-made prosthetic with multiligament reconstruction as an innovative method without postoperative complication at 2 years.

Rotationplasty for Unplanned Fixation of Pathological Fracture Distal Femoral Osteosarcoma.

INTRODUCTION: Rotationplasty had been reported as a salvage procedure for many decades. However, this procedure has not been used for unplanned fixation for pathological fracture of osteosarcoma. Therefore, this is the first case report of rotationplasty for this particular indication. Case Presentation. We report a case of a 22-year-old Thai female patient who sustained a supracondylar fracture at the distal femur and underwent a surgical treatment by open reduction and internal fixation with a distal femoral locking plate and screws. Follow-up radiographic imaging revealed that there were abnormal osteolytic lesions, and conventional high-grade osteosarcoma was diagnosed by a pathological study. There were no distant metastases from Computed Tomography (CT) scan or Technitium-99m bone scintography. After discussing with the patient for treatment options, rotationplasty was chosen for her definitive treatment after 3 courses of neoadjuvant chemotherapy. All of the contaminated tissues were removed during the surgery. The neurovascular bundles were preserved. A standard rotationplasty type A-1 according to the Winkelmann Classification was performed. Postoperative imaging showed satisfactory outcomes, and the wound healed uneventfully. The patient was able to move her ankle as a knee, and external prosthetic fitting was made. Adjuvant chemotherapy was given after a free margin with good tumor necrosis which was achieved as shown in the pathological study. At the patient's 3-year follow-up visit, she has stable size of lung nodules. She can walk with external prosthesis, limping slightly. Her new knee could move as expected, and she was satisfied with the result of the treatment. CONCLUSION: Rotationplasty for unplanned fixation of pathological fracture is a complex procedure. Patients often do not select this type of treatment because of the cosmetic acceptance even though it yields a good functional result. Therefore, awareness of the pathological fracture should initially be taken into account to prevent inappropriate fixation which could result in an unnecessary amputation.

Relative telomere length and oxidative stress in musculoskeletal tumors.

Telomeres are capped at the end of the chromosome and gradually shorten when the cell divides. When there is an oxidative stress, it can cause the DNA to be damaged. Hence, 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been shown to be an indicator for oxidative DNA damage. This study aimed to determine the relative telomere length (RTL) and 8-OHdG levels in neoplastic tissues, adjacent non-neoplastic tissues, and blood leukocytes of musculoskeletal (MS) tumor patients. Neoplastic tissues were compared to adjacent non-neoplastic tissues in MS tumor patients (n = 46). Peripheral blood leukocytes (PBLs) of MS tumor subjects were compared to those of age-matched healthy controls (n = 107). RTL was evaluated by quantitative real-time polymerase chain reaction and 8-OHdG levels were quantified by enzyme-linked immunosorbent assay. The RTL in neoplastic tissues was significantly shorter than that in non-neoplastic tissues [1.12 (0.86-1.46) vs 1.45 (1.25-1.65), P = 0.001]. PBLs had lower RTL than non-neoplastic tissues in MS tumor patients [1.04 (0.85-1.13) vs 1.45 (1.25-1.65), P < 0.001]. However, there was no significant difference between RTL in PBLs and in neoplastic tissues. In addition, PBLs of MS tumor patients had higher RTL than those of the controls [1.04 (0.85-1.13) versus 0.78 (0.68-0.90), P < 0.001]. The 8-OHdG levels in neoplastic tissues were remarkably higher than those in non-neoplastic tissues [8.14 (6.81-11.37) nM/µg/µl vs. 3.79 (2.53-6.17) nM/µg/µl, P < 0.001]. Furthermore, plasma 8-OHdG levels in MS tumor patients were markedly greater than those in the controls [102.50 (73.16-133.50) nM vs. 41.09 (6.81-11.37) nM, P < 0.001]. Area under the curve (AUC) was 0.7536 (95% confident interval (CI) 0.6602-0.8469) when the cut-off value of RTL in PBLs was 0.97. Also, plasma 8-OHdG levels depicted that when the cut-off value was 38.67 nM, the AUC was 0.7723 (95% CI 0.6920-0.8527). Moreover, ROC curve analysis showed that both RTL and 8-OHdG appeared to improve the sensitivity (85.68%) and specificity (70.91%) with the AUC 0.8639 (95% CI 0.7500-0.9500). This study suggested that blood leukocyte RTL and plasma 8-OHdG could serve as promising non-invasive biomarkers to differentiate between MS tumor patients and healthy controls. Additionally, telomere attrition and increased oxidative DNA damage might play contributory roles in the pathogenesis of MS tumors.

Alu hypermethylation and high oxidative stress in patients with musculoskeletal tumors.

BACKGROUND: Alu is one of the non-autonomous element retrotransposons, constituting nearly 11% of the human DNA. Methylation changes of the Alu element can cause genomic instability, a hallmark of cancer development, ultimately leading to the development of cancer. Epigenetic factors may induce the aberrant methylation of Alu and also oxidative stress. However, current knowledge of Alu methylation and oxidative stress is limited. There are few studies that have evaluated Alu methylation and oxidative stress on musculoskeletal tumor progression. Therefore, the present study evaluated the status of Alu methylation in musculoskeletal (MS) tumor, adjacent tissues, and blood leukocytes from MS tumor subjects, as well as unaffected participants. Moreover, we also investigated the oxidative stress status in MS tumor subjects and the control participants and determined the correlation between Alu methylation in MS tumors and that in blood leukocytes. METHODS: Musculoskeletal tumors from musculoskeletal tumor patients (n = 40) were compared to adjacent tissues (n = 40). The blood leukocytes from musculoskeletal tumor patients were compared to the blood leukocytes from controls (n = 107). Alu methylation status was analyzed using quantitative combined bisulfite restriction analysis (COBRA). In addition, 8-hydroxy 2'-deoxyguanosine (8-OHdG) values were determined using enzyme-linked immunosorbent assay. RESULTS: Alu methylation values in MS tumors were statistically significantly higher than those in adjacent tissues (P = 0.035). Similarly, Alu methylation statuses in the blood leukocytes of MS tumor subjects were statistically greater than those of control participants (P < 0.001). Moreover, there was a positive association between Alu methylation levels in MS tumors and blood leukocytes (r = 0.765, P < 0.001). In addition, the highest tertile was significantly associated with the risk of MS tumors (OR = 14.17, 95% CI [5.08-39.51]; P < 0.001). The 8-OHdG values in MS tumors were statistically higher than in adjacent tissues (P < 0.001) and circulating 8-OHdG levels were substantially greater in MS tumor subjects than in the control participants (P < 0.001). DISCUSSION: These findings suggest that Alu methylation in blood leukocytes and plasma 8-OHdG might represent non-invasive biomarkers to help diagnose MS tumors. Therefore, Alu hypermethylation and high oxidative stress might be involved in the pathogenesis of the musculoskeletal tumors.