Prognostic Factors after Surgical Treatment for Spinal Metastases.

Study Design: A retrospective multicenter case series was conducted. Purpose: This study aimed to investigate survival and prognostic factors after surgery for a metastatic spinal tumor. Overview of Literature: Prognostic factors after spinal metastasis surgery remain controversial. Methods: A retrospective multicenter study was conducted. The study participants included 345 patients who underwent surgery for spinal metastases from 2010 to 2020 at nine referral spine centers in Japan. Data for each patient were extracted from medical records. To identify the factors predicting survival prognosis after surgery, univariate analyses were performed using a Cox proportional hazards model. Results: The mean age was 65.9 years. Common primary tumors were lung (n=72), prostate (n=61), and breast (n=39), and 67.8% (n=234) presented with osteolytic lesions. The epidural spinal cord compression scale score 2 or 3 was recognized in 79.0% (n=271). Frankel grade A paralysis accounted for 1.4% (n=5), and 73.3% (n=253) were categorized as intermediate or high risk according to the new Katagiri score. The overall survival rates were -71.0% at 6 months, 57.4% at 12, and 43.3% at 24. In the univariate analysis, Frankel grade A (hazard ratio [HR], 3.59; 95% confidence interval [CI], 1.23-10.50; p<0.05), intermediate risk (HR, 3.34; 95% CI, 2.10-5.32; p<0.01), and high risk (HR, 7.77; 95% CI, 4.72-12.8; p<0.01) in the new Katagiri score were significantly associated with poor survival. On the contrary, postoperative chemotherapy (HR, 0.23; 95% CI, 0.15-0.36; p<0.01), radiation therapy (HR, 0.43; 95% CI, 0.26-0.70; p<0.01), and both adjuvant therapy (HR, 0.21; 95% CI, 0.14-0.32; p<0.01) were suggested to improve survival. Conclusions: Surgical indications for patients with Frankel grade A or intermediate or high risk in the new Katagiri score should be carefully considered because of poor survival. Chemotherapy or radiation therapy should be considered after surgery for better survival.

Malawer type I/V proximal humerus reconstruction after tumor resection: a systematic review.

BACKGROUND: Several reconstruction methods exist for Malawer type I/V proximal humerus reconstruction after bone tumor resection; however, no consensus has been reached regarding the preferred methods. METHODS: We conducted a literature search on various types of proximal humerus oncologic reconstruction methods. We collected data on postoperative functional outcomes assessed based on Musculoskeletal Tumor Society (MSTS) scores, 5-year reconstruction survival rates, and complications. We calculated each reconstruction's weighted mean based on the sample size and standard errors. Complications were categorized based on the Henderson classification. Based on these integrated data, our primary objective is to propose an optimal strategy for proximal humerus reconstruction after bone tumor resection. RESULTS: We examined various reconstruction techniques, including modular prosthesis (752 patients in 21 articles), osteoarticular allograft (142 patients in six articles), allograft prosthesis composites (236 patients in 12 articles), reverse shoulder total arthroplasty (141 patients in 10 articles), composite reverse shoulder total arthroplasty (33 patients in four articles), claviculo-pro-humero technique (51 patients in six articles), and cement spacer (207 patients in four articles). Weighted mean MSTS scores were: modular prosthesis (73.8%), osteoarticular allograft (74.4%), allograft prosthesis composites (79.2%), reverse shoulder total arthroplasty (77.0%), composite reverse shoulder total arthroplasty (76.1%), claviculo-pro-humero technique (75.1%), and cement spacer (69.1%). Weighted 5-year reconstruction survival rates were modular prosthesis (85.4%), osteoarticular allograft (67.6%), allograft prosthesis composites (85.2%), reverse shoulder total arthroplasty (84.1%), and cement spacer (88.0%). Reconstruction survival data was unavailable for composite reverse shoulder total arthroplasty and claviculo-pro-humero technique. Major complications included shoulder joint instability: modular prosthesis (26.2%), osteoarticular allograft (41.5%), allograft prosthesis composites (33.9%), reverse shoulder total arthroplasty (17%), composite reverse shoulder total arthroplasty (6.1%), claviculo-pro-humero technique (2.0%), and cement spacer (8.7%). Aseptic loosening of the prosthesis occurred: modular prosthesis (3.9%) and reverse shoulder total arthroplasty (5.7%). Allograft fracture was observed in 54.9% of patients with osteoarticular allograft. CONCLUSION: The complication profiles differed among reconstruction methods. Weighted mean MSTS scores exceeded 70% in all methods except cement spacer, and the 5-year reconstruction survival rate surpassed 80% for all methods except osteoarticular allograft. Proximal humerus reconstruction after bone tumor resection should consider potential complications and patients' individual factors.

Incidence of skeletal-related events in patients with Ewing sarcoma: An observational retrospective study in Japan.

BACKGROUND: Skeletal-related events (SREs), including the pathological fracture, surgical treatment or radiation of bone lesions, malignant spinal cord compression, hypercalcemia, are important considerations when managing metastatic bone tumors; however, owing to their rarity, the incidence of SREs in patients with Ewing sarcoma remains unknown. METHODS: We retrospectively reviewed the clinical data from 146 patients with Ewing sarcoma treated at a single institution from 2005 to 2019. The median age at diagnosis was 22.7 years. Fifty patients (34.2%) had metastatic disease at diagnosis. The primary outcome was the SRE-free rate among patients with Ewing sarcoma. Moreover, we identified the risk factors for SREs using univariate or multivariate analyses. RESULTS: During the observational period (median, 2.6 years), SREs occurred in 23 patients. Radiation to the bone, malignant spinal cord compression, and hypercalcemia were documented as the initial SREs in 12 patients (52.2%), 10 patients (43.5%), and one patient (4.3%), respectively. The SRE-free rate was 94.2 ± 2.0, 87.3 ± 3.0, and 79.6 ± 3.8% at 1, 2, and 3 years after the initial visit, respectively. Multivariate analysis revealed bone metastasis at diagnosis (hazard ratio [HR] = 4.41, p = 0.007), bone marrow invasion (HR = 34.08, p < 0.001), and local progression or recurrence after definitive treatment (HR = 3.98, p = 0.012) as independent risk factors for SREs. CONCLUSIONS: SREs are non-rare events that can occur during the treatment course for Ewing sarcoma, with an especially high incidence of malignant spinal cord compression. Patients with metastatic disease at diagnosis, especially in the bone or bone marrow, or with local progression or recurrence after definitive treatment, should be carefully monitored for the occurrence of SREs. The most effective methods to monitor the occurrence of SREs and new preventative therapies for SREs should be investigated in the future.

Extensive Synergy Between Recombinant Methioninase and Eribulin Against Fibrosarcoma Cells But Not Normal Fibroblasts.

BACKGROUND/AIM: The aim of the present study was to determine the synergy of recombinant methioninase (rMETase) and the anti-tubulin agent eribulin on fibrosarcoma cells, in comparison to normal fibroblasts, in vitro. MATERIALS AND METHODS: HT1080 human fibrosarcoma cells and HS27 human fibroblasts were used for in vitro experiments. Four groups were analyzed in vitro: No-treatment control; eribulin; rMETase; eribulin plus rMETase. Dual-color HT1080 cells which express red fluorescent protein (RFP) in the cytoplasm and green fluorescent protein (GFP) in the nuclei were used to visualize cytoplasmic and nuclear dynamics during treatment. RESULTS: Eribulin combined with rMETase greatly decreased the viability of HT 1080 cells. In contrast, eribulin combined with rMETase did not show synergy on Hs27 normal fibroblasts. Eribulin combined with rMETase also caused more fragmentation of the nucleus than all other treatments. CONCLUSION: The combination treatment of eribulin plus rMETase demonstrated efficacy on fibrosarcoma cells in vitro. In contrast, normal fibroblasts were resistant to this combination, indicating the potential clinical applicability of the treatment.

Ten-Year Clinical Outcomes of Endoscope-Assisted Minimally Invasive Surgical Decompression for Lumbar Spinal Stenosis with Degenerative Spondylolisthesis and Comparison with Conservative Treatment.

Introduction: This study aimed to evaluate the 10-year clinical outcomes of endoscope-assisted, minimally invasive surgical (MIS) decompression for lumbar spinal canal stenosis (LSS) with lumbar degenerative spondylolisthesis (DS) and to compare the radiographic changes in patients who underwent this procedure with those who underwent conservative therapy at 10-year follow-up. Methods: Between April 2007 and April 2010, 347 consecutive patients with DS and evidence of LSS underwent conservative treatment first from 2 to 4 weeks. The 114 patients who failed conservative treatment were then treated surgically by endoscope-assisted MIS decompression. Of them, 91 patients were followed for more than 10 years (group S), and 146 of the 233 patients treated conservatively were followed for more than 10 years (group C). Clinical outcomes of endoscope-assisted MIS decompression were assessed using the Short Form Health Survey-36 score (SF-36), the Roland Morris Disability Questionnaire (RDQ), and the neurological leg symptoms of the Japanese Orthopaedic Association Score (JOA score). Radiographic changes of the two groups were assessed by %slip, dynamic %slip, range of motion (ROM), and the height of the disc (DH) on plain radiographs. Results: Significant improvements in clinical outcomes on the SF-36, RDQ, and neurological leg symptoms of the JOA were observed. Radiographic assessment did not show significant differences in the assessed items between the two groups at baseline and after last treatment. Both groups had significantly decreased ROM and DH. Conclusions: The 10-year clinical outcomes of endoscope-assisted MIS decompression for DS were generally good. Furthermore, on radiographic comparison, the progress of spondylolisthesis after this procedure was virtually the same as in the natural course of the disease at 10-year follow-up.

What Is the Revision-free Survival of Resurfaced Allograft-prosthesis Composites for Proximal Humerus Reconstruction in Children With Bone Tumors?

BACKGROUND: Reconstruction of the proximal humerus in children who undergo bone tumor resection is challenging because of patients' small bone size and possible limb length discrepancy at the end of skeletal growth due to loss of the physis. There are several options for proximal humerus reconstruction in children, such as clavicula pro humero, free vascularized fibula grafting, massive bone osteoarticular allografting, endoprostheses, and allograft-prosthesis composites, but no consensus exists on the best method for reconstruction. Resurfaced allograft-prosthesis composites could be an alternative surgical option, but little is known about the results of this surgical technique. QUESTIONS/PURPOSES: (1) What are the complications and what is the survivorship free from reconstruction failure associated with resurfaced allograft-prosthesis composites in a small, single-center case series? (2) What Musculoskeletal Tumor Society scores do patients achieve after reconstructions with resurfaced allograft-prosthesis composites? METHODS: This study was a retrospective, single-arm case analysis in a single institution. We generally considered resurfaced allograft-prosthesis composites in children with malignant bone tumors involving the metaepiphysis of the proximal humerus in whom there was no evidence of joint contamination and in whom axillary nerve preservation was possible. Between 2003 and 2021, we treated 100 children (younger than 15 years) with bone tumors of the humerus. Thirty children (30%) with diaphyseal tumors (21 children) or distal tumors (9 children) were excluded. Among the potentially eligible children, 52 were not analyzed because they were treated with other procedures such as amputation, modular prostheses, cement spacers, free vascularized fibula grafting, and massive bone osteoarticular allografts. We included 18 children (26% of the potentially eligible children) who were treated with resurfaced allograft-prosthesis composites. There were 9 boys and 9 girls, with a median age of 10 years (range 4 to 15 years) at the time of diagnosis. A long stem (≥ 6 cm) in the resurfaced allograft-prosthesis composite was used in 9 children and a short stem (< 6 cm) was used in the remaining 9. One of the 18 children had a follow-up of less than 2 years. The median follow-up of the remaining 17 children was 4.7 years (range 2 to 19 years). The children' medical records were reviewed for clinical and functional outcomes. We performed a competing risk analysis to calculate the reconstruction failure-free survival of resurfaced allograft-prosthesis composites. Reconstruction failure was defined as removal of the implant or allograft because of implant loosening or breakage and allograft fracture or resorption. We analyzed the children's postoperative complications and functional outcomes at the end of the follow-up period using the Musculoskeletal Tumor Society functional scoring system. RESULTS: The competing risk analysis revealed that reconstruction failure was 25% (95% confidence interval 7% to 40%) at 3 years, reaching a plateau. Four of 18 children underwent surgical revision with a new reconstruction. The reasons for reconstruction revision were resorption of the allograft at the proximal part (2 children) and fracture of the allograft (2 children). Reconstruction revision was performed in 3 of 9 children who underwent reconstruction with a short stem and in 1 of 9 children who underwent reconstruction with a long stem. Several children had other complications that did not result in removal of the allograft. Allograft resorption was observed in 4 of 18 children, but no additional surgical treatment was performed. Shoulder instability or subluxation was observed in 4 of 18 children, but only 1 child underwent surgery with a reverse shoulder arthroplasty without removal of the resurfaced allograft-prosthesis composite. Limited elbow motion because of plate impingement was observed in 1 child who underwent surgical cutting of the protruding distal part of the plate. Incomplete radial nerve palsy after surgery occurred in 1 child, with spontaneous resolution after 2 months. Screw loosening occurred in 2 children who underwent surgery with removal of loose screws. Two children had a nonunion at the graft-host bone junction; 1 child underwent surgery with bone grafting and refixation of the graft-host bone junction, and the other child with both nonunion and plate breakage was treated with bone grafting and refixation of the graft-host bone junction with a new plate. Among 17 children who had a follow-up longer than 2 years, the median Musculoskeletal Tumor Society functional score at the last follow-up interval was 23 of 30 (range 20 to 26); 1 child was considered to have an excellent result (functional score ≥ 26), 15 children were considered to have a good result (functional score 21 to 25), and 1 child was considered to have a fair result (functional score ≤ 20). The Musculoskeletal Tumor Society functional score did not change after excluding 4 children who underwent replacement of resurfaced allograft-prosthesis composites (24 of 30 [range 20 to 26]). The median angle of flexion of the shoulder was 40° (range 20º to 90°), and the median angle of abduction was 30° (range 20º to 90°). CONCLUSION: Resurfaced allograft-prosthesis composites showed a high risk of complications, but not all complications resulted in removal of the reconstructed allograft. We used this technique mainly for very young children with small bones and for older children who underwent axillary nerve preservation. Although its success may be limited owing to a high risk of complications, a resurfaced allograft-prosthesis composite could be an alternative surgical option in order to preserve the bone stock and achieve good functional outcomes in very young children. We recommend using a long-stem resurfaced allograft-prosthesis composite, which may reduce the risk of complications. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Postpartum hemorrhage with associated placenta previa in a kidney transplant recipient: A case report.

INTRODUCTION: The efficacy and safety of uterine artery embolization (UAE) and prophylactic resuscitative endovascular balloon occlusion of the aorta (REBOA) against postpartum hemorrhage (PPH) in pregnant women after kidney transplantation have not been reported. Here, we describe a case of PPH associated with placenta previa in pregnancy following kidney transplantation, which was managed with UAE and prophylactic REBOA. CASE PRESENTATION: A 35-year-old, gravida 2, para 1 woman with total placenta previa presented with vaginal bleeding (460 mL) at 33 weeks and 3 days of gestation. Previously, she underwent a living-donor kidney transplantation for IgA nephropathy, and the renal artery of the transplanted kidney was anastomosed with the right internal iliac artery. An emergency cesarean section with prophylactic REBOA was performed under general anesthesia. A balloon catheter was introduced via the left femoral artery and positioned above the aortic bifurcation (Aortic zone 3). Upon confirming fetal delivery, the balloon was immediately inflated, and the total aortic occlusion time was 20 min. However, following aortic balloon deflation, atonic bleeding continued despite Bakri balloon usage and uterotonic drug administration. Subsequently, UAE was performed for the refractory PPH, the left uterine artery was embolized using a gelatin sponge, and hemostasis was successfully achieved. The patient recovered uneventfully and was discharged on postoperative day 7. DISCUSSION AND CONCLUSION: In pregnancies following kidney transplantation, prophylactic REBOA controls bleeding; however, it decreases blood flow to the transplanted kidney. Furthermore, uterine nutrient vasculature alterations are observed, necessitating a thorough understanding of the uterine artery supply pathways during UAE.

Clinical characteristics of motor functional neurological disorder manifesting as limb weakness after vaccination against coronavirus disease 2019: A case series.

Background: The characteristics of functional limb weakness (FLW) as one of the manifestations of functional neurological disorder after vaccination against coronavirus disease 2019 (COVID-19) remain controversial. Methods: In this descriptive case series, we aimed to elucidate the characteristics of Japanese patients with FLW who claimed muscle weakness after COVID-19 vaccination among patients who visited our outpatient clinic between 1 June 2021 and 31 December 2022. Results: Nine patients were diagnosed with FLW (mean age: 30.8 years), including two men and seven women. Seven patients were vaccinated with the BioNTech/Pfizer vaccine and two with the mRNA-1273 Moderna vaccine. All patients demonstrated various positive signs for FLW. Magnetic resonance imaging or computed tomography indicated no abnormality that could explain their symptoms. At the time of the clinic visit, five patients were treated for psychiatric disorders, including depression, insomnia, attention-deficit hyperactivity disorder, and Asperger's syndrome. Muscle weakness spread to the limbs beyond the vaccinated arm in seven patients. Conclusions: We describe the basic characteristics of FLW in Japanese patients after COVID-19 vaccination. Further recognition of these characteristics could aid the diagnosis of FLW by physicians allowing them to support these patients effectively.

Clinical Outcome in Patients With High-grade Soft-tissue Sarcoma Receiving Prosthetic Replacement After Tumor Resection of the Lower Extremities: Tokai Musculoskeletal Oncology Consortium Study.

AIM: This multicenter retrospective study aimed to clarify the surgical and oncological outcomes of patients with high-grade soft tissue sarcoma (STS) who underwent prosthetic replacement reconstruction after lower extremity tumor resection. PATIENTS AND METHODS: We retrospectively collected the data of 27 patients with high-grade STS. The mean follow-up duration after prosthetic replacement was 44.7 months. RESULTS: The mean age at surgery was 63 years. The mean tumor size was 16 cm. For reconstruction, proximal femur replacement was performed in 15 patients, distal femur replacement in six, and total femur replacement in six. The major complications were infections in nine patients and aseptic loosening in four. Nine patients developed local recurrence. The cause of revision surgery was infection in five patients, aseptic loosening in three, and metal allergy in one. The 5-year prosthetic survival rate was 51.1%. At the final follow-up, amputation was performed in five patients. The 5-year limb salvage rate was 76.8%. The mean functional score of the 25 patients who could be assessed was 16.0 (53%). Of the 27 patients, five were excluded from the survival analysis because they underwent prosthetic replacement for local recurrence. The 5-year overall survival rate in the remaining 22 patients was 45.3%. CONCLUSION: We identified a high rate of surgical complications and poor survival in patients with high-grade STS who underwent tumor resection and reconstruction using prosthetic replacement of the lower extremities, although limb salvage was achieved in 81.5% of the patients. Careful follow-up is needed for surgical complications and oncological events after surgery.

Special Issue: "Pediatric Orthopedic Malignancy: Types, Symptoms, and Treatment".

Pediatric orthopedic malignancies are extremely rare and require appropriate diagnosis and treatment by a multidisciplinary team [...].

Functional Neurological Disorder Overlapping Paroxysmal Kinesigenic Dyskinesia Confirmed by Genetic Diagnosis.

Functional neurological disorder (FND) may mimic various kinds of neurologic diseases and may coexist with other neurologic disorders. In cases overlapped by FND, it might be challenging to distinguish symptoms induced by FND and those induced by other underlying neurological disorders, especially when patients show no positive signs indicative of FND. Here, we present the case of a patient who was genetically diagnosed with paroxysmal kinesigenic dyskinesia (PKD). However, most of the patient's symptoms were considered to indicate FND. To our knowledge, there are no reports of FND overlapping PKD. This case illustrates the possibility that FND can coexist with and mimic symptoms of other diseases. It is necessary to rule out coexisting FND symptoms that may modify clinical presentations that cannot simply be explained by a recognized neurological disease.

Influence of time from injury to surgery on knee biomechanics during walking in patients with anterior cruciate ligament reconstruction.

The pilot study aimed to determine whether the time from injury to surgery influences on postoperative knee biomechanics during walking in patients with anterior cruciate ligament reconstruction (ACLR). Thirty-two patients with unilateral ACLR (early, 10 patients; delayed, 22 patients) and 30 control subjects participated in this study. All examinations for patients with ACLR were performed preoperatively and at 12 months postoperatively and comprised passive knee joint laxity, knee muscle strength, and knee kinematics and kinetics during walking. At both time points, there were no significant differences in passive knee joint laxity and knee muscle strength between the early ACLR and delayed ACLR groups. Preoperatively, both the early ACLR and delayed ACLR patients exhibited significantly reduced knee extension movement from midstance to terminal stance compared to the control subjects. Moreover, the delayed ACLR patients exhibited significantly decreased peak external knee flexion moment compared to the control subjects. At 12 months postoperatively, the early ACLR patients showed significant improvement in knee extension movement from midstance to terminal stance compared to pre-ACLR, while the delayed ACLR patients did not show significant improvement in this knee extension movement. It can be concluded that early ACLR may be more beneficial to improve knee biomechanics during walking.

Safety evaluation of immune-cell therapy for malignant tumor in the Cancer Immune-cell Therapy Evaluation Group (CITEG).

BACKGROUND AIMS: With the aim of strengthening the scientific evidence of immune-cell therapy for cancer and further examining its safety, in October 2015, our hospital jointly established the Cancer Immune-Cell Therapy Evaluation Group (CITEG) with 39 medical facilities nationwide. METHODS: Medical information, such as patients' background characteristics, clinical efficacy and therapeutic cell types obtained from each facility, has been accumulated, analyzed and evaluated by CITEG. In this prospective study, we analyzed the adverse events associated with immune-cell therapy until the end of September 2022, and we presented our interim safety evaluation. RESULTS: A total of 3839 patients with malignant tumor were treated with immune-cell therapy, with a median age of 64 years (range, 13-97 years) and a male-to-female ratio of 1:1.08 (1846:1993). Most patients' performance status was 0 or 1 (86.8%) at the first visit, and 3234 cases (84.2%) were advanced or recurrent cases, which accounted for the majority. The total number of administrations reported in CITEG was 31890, of which 960 (3.0%) showed adverse events. The numbers of adverse events caused by treatment were 363 (1.8%) of 19661 administrations of αßT cell therapy, 9 of 845 administrations of γδT-cell therapy (1.1%) and 10 of 626 administrations of natural killer cell therapy (1.6%). The number of adverse events caused by dendritic cell (DC) vaccine therapy was 578 of 10748 administrations (5.4%), which was significantly larger than those for other treatments. Multivariate analysis revealed that αßT cell therapy had a significantly greater risk of adverse events at performance status 1 or higher, and patients younger than 64 years, women or adjuvant immune-cell therapy had a greater risk of adverse events in DC vaccine therapy. Injection-site reactions were the most frequently reported adverse events, with 449 events, the majority of which were associated with DC vaccine therapy. Among all other adverse events, fever (228 events), fatigue (141 events) and itching (131 events) were frequently reported. In contrast, three patients had adverse events (fever, abdominal pain and interstitial pneumonia) that required hospitalization, although they were weakly related to this therapy; rather, it was considered to be the effect of treatment for the primary disease. CONCLUSIONS: Immune-cell therapy for cancer was considered to be a safe treatment without serious adverse events.

Recurrence rate after posterior percutaneous screw fixation without anterior debridement for pyogenic spondylitis compared with conservative treatment: a propensity score-matched analysis.

PURPOSE: Previous studies have shown that percutaneous pedicle screw (PPS) posterior fixation without anterior debridement for pyogenic spondylitis can improve patient quality of life compared with conservative treatment. However, data on the risk of recurrence after PPS posterior fixation compared with conservative treatment is lacking. The aim of this study was to compare the recurrence rate of pyogenic spondylitis after PPS posterior fixation without anterior debridement and conservative treatment. METHODS: The study was conducted under a retrospective cohort design in patients hospitalized for pyogenic spondylitis between January 2016 and December 2020 at 10 affiliated institutions. We used propensity score matching to adjust for confounding factors, including patient demographics, radiographic findings, and isolated microorganisms. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence of pyogenic spondylitis during the follow-up period in the matched cohort. RESULTS: 148 patients (41 in the PPS group and 107 in the conservative group) were included. After propensity score matching, 37 patients were retained in each group. PPS posterior fixation without anterior debridement was not associated with an increased risk of recurrence compared with conservative treatment with orthosis (HR, 0.80; 95% CI, 0.18-3.59; P = 0.77). CONCLUSIONS: In this multi-center retrospective cohort study of adults hospitalized for pyogenic spondylitis, we found no association in the incidence of recurrence between PPS posterior fixation without anterior debridement and conservative treatment.

Outcomes of Window Therapy with Carboplatin and Ifosfamide for Pediatric Osteosarcoma: A Case Series.

For the treatment of osteosarcoma, cisplatin (CDDP) can be substituted by carboplatin (CBDCA) to reduce toxicity. We report a single institution experience of CBDCA-based regimen. Two to three cycles of CBDCA + ifosfamide (IFO) therapy (window therapy) were administered as neoadjuvant therapy for osteosarcoma. Depending on the response of window therapy, the subsequent protocols were determined; for good responders, surgery is performed, and postoperative therapies with CBDCA + IFO, adriamycin (ADM) and high-dose methotrexate (MTX) were administered; for stable disease, the postoperative regimens were advanced before surgery, and the remaining amount of postoperative chemotherapy is deduced; for progressive disease, CBDCA-based regimen is changed to CDDP-based regimen. From 2009 to 2019, seven patients were treated with this protocol. During the window therapy, two patients (28.6%) were assessed as good responders and completed the regimen as planned. Four patients (57.1%) had stable disease, and the chemotherapy schedules were modified. One patient (14.2%) with progressive disease was shifted to the CDDP-based regimen. At final follow-up, four patients showed no evidence of disease and three patients died of the disease. Since the efficacy during window therapy was limited, a CBDCA-based regimen in the neoadjuvant setting was considered insufficient for performing adequate surgery.

Current Concepts in the Resection of Bone Tumors Using a Patient-Specific Three-Dimensional Printed Cutting Guide.

Orthopedic oncology has begun to use three-dimensional-printing technology, which is expected to improve the accuracy of osteotomies, ensure a safe margin, and facilitate precise surgery. However, several difficulties should be considered. Cadaver and clinical studies have reported more accurate osteotomies for bone-tumor resection using patient-specific cutting guides, especially in challenging areas such as the sacrum and pelvis, compared to manual osteotomies. Patient-specific cutting guides can help surgeons achieve resection with negative margins and reduce blood loss and operating time. Furthermore, this patient-specific cutting guide could be combined with more precise reconstruction using patient-specific implants or massive bone allografts. This review provides an overview of the basic technologies used in the production of patient-specific cutting guides and discusses their current status, advantages, and limitations. Moreover, we summarize cadaveric and clinical studies on the use of these guides in orthopedic oncology.

Amino acid polymorphisms in human histocompatibility leukocyte antigen class II and proinsulin epitope have impacts on type 1 diabetes mellitus induced by immune-checkpoint inhibitors.

Introduction: Immune-checkpoint inhibitors are effective in various advanced cancers. Type 1 diabetes mellitus induced by them (ICI-T1DM) is a serious complication requiring prompt insulin treatment, but the immunological mechanism behind it is unclear. Methods: We examined amino acid polymorphisms in human histocompatibility leukocyte antigen (HLA) molecules and investigated proinsulin epitope binding affinities to HLA molecules. Results and Discussion: Twelve patients with ICI-T1DM and 35 patients in a control group without ICI-T1DM were enrolled in the study. Allele and haplotype frequencies of HLA-DRB1*04:05, DQB1*04:01, and most importantly DPB1*05:01 were significantly increased in patients with ICI-T1DM. In addition, novel amino acid polymorphisms in HLA-DR (4 polymorphisms), in DQ (12 polymorphisms), and in DP molecules (9 polymorphisms) were identified. These amino acid polymorphisms might be associated with the development of ICI-T1DM. Moreover, novel human proinsulin epitope clusters in insulin A and B chains were discovered in silico and in vitro peptide binding assays to HLA-DP5. In conclusion, significant amino acid polymorphisms in HLA-class II molecules, and conformational alterations in the peptide-binding groove of the HLA-DP molecules were considered likely to influence the immunogenicity of proinsulin epitopes in ICI-T1DM. These amino acid polymorphisms and HLA-DP5 may be predictive genetic factors for ICI-T1DM.

Clinical characteristics of primary cutaneous and subcutaneous Ewing sarcoma.

OBJECTIVE: Given the rarity of cutaneous/subcutaneous Ewing sarcoma, their clinical characteristics remain poorly understood. In this study, we aimed to analyse the clinical characteristics of patients with cutaneous/subcutaneous Ewing sarcoma and review the treatment strategy. METHODS: We reviewed the clinical data of 154 patients with Ewing sarcoma who were treated at our hospital between 2005 and 2019. Amongst these patients, 21 patients with cutaneous/subcutaneous Ewing sarcoma were analysed. As a basic strategy, patients with localized disease received intensive chemotherapy (vincristine-doxorubicin-cyclophosphamide/ifosfamide-etoposide), followed by definitive surgery with or without radiotherapy. In total, 15 patients underwent pre-diagnostic resection with macroscopic residue (seven patients) or non-macroscopic residue (eight patients) before intensive chemotherapy. RESULTS: The median tumour length of the measurable lesions was 3.2 cm, and the ratio of metastasis was significantly lower than the Ewing sarcoma of other anatomical sites (10% vs. 37%, P = 0.013). Despite the pre-diagnostic resection, local recurrence after additional resection and/or adjuvant radiotherapy did not occur in any of the patients with localized disease. Overall survival was significantly higher in patients with cutaneous/subcutaneous Ewing sarcoma than in patients with Ewing sarcoma of other anatomical sites (hazard ratio = 0.33, P = 0.013). The event-free survival rate of cutaneous/subcutaneous Ewing sarcoma was also superior to that of Ewing sarcoma of other anatomical sites (hazard ratio = 0.35, P = 0.01). CONCLUSIONS: Patients with cutaneous/subcutaneous Ewing sarcoma may have better prognosis than those with Ewing sarcoma at other anatomical sites. Although pre-diagnostic resection without appropriate investigations is not recommended, local control may be recovered by using a combination of additional resection, chemotherapy and radiotherapy.

Risk Factors for Cage Migration Following Lateral Lumbar Interbody Fusion Combined With Posterior Instrumentation: A Multicenter Retrospective Study of 983 Cases.

STUDY DESIGN: A multicenter retrospective study. OBJECTIVE: This study aimed to elucidate the incidence and risk factors of lateral cage migration (LCM) after lateral lumbar interbody fusion (LLIF) combined with posterior instrumentation. SUMMARY OF BACKGROUND DATA: LLIF has recently become a widely accepted procedure for the treatment of lumbar degenerative diseases. Although LLIF complications include vascular, nerve, and abdominal organ injuries, few studies have identified specific risk factors for LCM after LLIF. MATERIALS AND METHODS: Between January 2015 and December 2020, 983 patients with lumbar degenerative diseases or osteoporotic vertebral fractures underwent LLIF combined with posterior instrumentation. The fusion sites were located within the lumbosacral lesions. LCM was defined as a change of >3 mm in the movement of the radiopaque marker on radiographs. The patients were classified into LCM and non-LCM groups. Medical records and preoperative radiographs were also reviewed. The 1:5 nearest-neighbor propensity score matching technique was used to compare both groups, and radiologic parameters, including preoperative disk height (DH), preoperative sagittal disk angle, disk geometry, height variance (cage height minus DH), and endplate injury, were analyzed to identify the factors influencing LCM incidence. RESULTS: There were 16 patients (1.6%) with LCM (10 men and 6 women; mean age 70.1 yr). The Cochran-Armitage trend test showed a linear trend toward an increased rating of LCM with an increasing number of fused segments ( P =0.003), and LCM occurred at the terminal cage-inserted disk level in all patients in the LCM group. After propensity-matched analysis, we identified high DH ( P <0.001), large sagittal disk angle ( P =0.009), round-type disk ( P =0.008), and undersized cage selection ( P <0.001) as risk factors for LCM. CONCLUSION: We identified risk factors for LCM after LLIF combined with posterior instrumentation. To avoid this complication, it is important to select the appropriate cage sizes and enhance posterior fixation for at-risk patients.

Association of two-staged surgery with systemic perioperative complications in lateral lumbar interbody fusion for adult spinal deformity: a propensity score-weighted study.

PURPOSE: Adult spinal deformity (ASD) surgery carries a higher risk of perioperative systemic complications. However, evidence for the effect of planned two-staged surgery on the incidence of perioperative systemic complications is scarce. Here, we evaluated the effect of two-staged surgery on perioperative complications following ASD surgery using lateral lumbar interbody fusion (LLIF). METHODS: The study was conducted under a retrospective multi-center cohort design. Data on 293 consecutive ASD patients (107 in the two-staged group and 186 in the one-day group) receiving corrective surgery using LLIF between 2012 and 2021 were collected. Clinical outcomes included occurrence of perioperative systemic complications, reoperation, and intraoperative complications, operation time, intraoperative blood loss, transfusion, and length of hospital stay. The analysis was conducted using propensity score (PS)-stabilized inverse probability treatment weighting to adjust for confounding factors. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in a PS-weighted cohort. RESULTS: In this cohort, 19 (18.4%) patients in the two-staged group and 43 (23.1%) patients in the one-day group experienced any systemic perioperative complication within 30 days following ASD surgery. In the PS-weighted cohort, compared with the patients undergoing one-day surgery, no association with the risk of systemic perioperative complications was seen in patients undergoing two-staged surgery (PS-weighted OR 0.78, 95% CI 0.37-1.63; p = 0.51). CONCLUSION: Our study suggested that two-staged surgery was not associated with risk for perioperative systemic complications following ASD surgery using LLIF.