Functional analysis of a rice 12-oxo-phytodienoic acid reductase gene (OsOPR1) involved in Cd stress tolerance.

BACKGROUND: The accumulation of cadmium (Cd) in plants may compromise the growth and development of plants, thereby endangering human health through the food chain. Understanding how plants respond to Cd is important for breeding low-Cd rice cultivars. METHODS: In this study, the functions of 12-oxo-phytodienoic acid reductase 1 (OsOPR1) were predicted through bioinformatics analysis. The expression levels of OsOPR1 under Cd stress were analyzed by using qRT-PCR. Then, the role that OsOPR1 gene plays in Cd tolerance was studied in Cd-sensitive yeast strain (ycf1), and the Cd concentration of transgenic yeast was analyzed using inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Bioinformatics analysis revealed that OsOPR1 was a protein with an Old yellow enzyme-like FMN (OYE_like_FMN) domain, and the cis-acting elements which regulate hormone synthesis or responding abiotic stress were abundant in the promoter region, which suggested that OsOPR1 may exhibit multifaceted biological functions. The expression pattern analysis showed that the expression levels of OsOPR1 were induced by Cd stress both in roots and roots of rice plants. However, the induced expression of OsOPR1 by Cd was more significant in the roots compared to that in roots. In addition, the overexpression of OsOPR1 improved the Cd tolerance of yeast cells by affecting the expression of antioxidant enzyme related genes and reducing Cd content in yeast cells. CONCLUSION: Overall, these results suggested that OsOPR1 is a Cd-responsive gene and may has a potential for breeding low-Cd or Cd-tolerant rice cultivars and for phytoremediation of Cd-contaminated in farmland.

Two-step osteotomy/discectomy through cannulated screw (TOCS) technique for en bloc resection of spine tumor: surgical technique and preliminary results.

PURPOSE: We have developed a novel technique for osteotomy/discectomy during en bloc resection of spine tumors named two-step osteotomy/discectomy through cannulated screw (TOCS). This study aims at describing the procedure of TOCS technique and assessing its efficiency and safety. METHODS: We retrospectively reviewed fourteen patients who underwent en bloc resection for spine tumors using TOCS technique in our center between August 2018 and September 2022. The technique was based on a specially designed "slotted" cannulated screw which was a cannulated screw with a longitudinal slot to provide the accessibility of T-saw. During osteotomy/discectomy, the "slotted" cannulated screw was inserted obliquely along the plane between the dura and the posterior wall of spine in light of the planned osteotomy/discectomy plane under routine fluoroscopic imaging guidance. The T-saw was introduced through the screw, and the osteotomy/discectomy was performed sequentially in two steps under the guidance of the screw by turning the slot away and toward the dura. The intra-/perioperative complication, neurological function (determined by Frankel grading), surgical margin (determined by a pathologist using AJCC R system), follow-up details were documented. RESULTS: The mean duration of surgery was 599.3 (360-890) min with a mean volume of intra-operative hemorrhage of 2021.4 (800-5000) mL. The intra-/perioperative complications were found in four patients (28.6%). R0 and R1 resections were achieved in nine and five patients, respectively. There was no R2 resection. After a mean follow-up period of 30.6 (10-67) months, all patients were alive except one patient died ten months after surgery due to unrelated cause. No recurrence and implant failure were found. Thirteen patients (92.9%) exhibited completely normal neurological function same as their preoperative neurological status. CONCLUSION: Using TOCS technique can facilitate a precise, complete and safe osteotomy/discectomy procedure during en bloc resection for spine tumor without the aid of intra-operative navigation.

Bioinformatic and functional analysis of OsDHN2 under cadmium stress.

As a toxic heavy metal, cadmium (Cd) is one of the principal pollutants influencing rice productivity and food security. Despite several studies, the underlying mechanism of Cd response in plants remains largely unclear. Dehydrins are part of the late embryogenesis abundant (LEA) family which protect plants against abiotic stresses. In this study, a Cd-responsive LEA gene, OsDHN2, was functionally characterized. The chromosome localization results indicated that OsDHN2 was located on chromosome 2 of rice. Meanwhile, cis-acting elements, such as MBS (MYB binding site involved in drought-inducibility), ARE (anaerobic induction), and ABRE (abscisic acid), were present in the OsDHN2 promoter region. Expression pattern analysis also showed that OsDHN2 expression was induced in both roots and shoots under Cd stress. Overexpression of OsDHN2 improved Cd tolerance and reduced Cd concentration in yeast. Moreover, increased expression levels of SOD1, CTA1, GSH1, or CTT1 were found in transgenic yeast under Cd stress, suggesting the increased antioxidant enzymatic activities. These results suggested that OsDHN2 is a Cd-responsive gene that has the potential to improve resistance to Cd in rice.

Expression of OsHARBI1-1 enhances the tolerance of Arabidopsis thaliana to cadmium.

BACKGROUND: As one of the major food crops in the world, rice is vulnerable to cadmium (Cd) pollution. Understanding of the molecular mechanisms of Cd uptake, transport and detoxification in rice is essential for the breeding of low-Cd rice. However, the molecular mechanisms underlying the response of rice to Cd stress remains to be further clarified. RESULTS: In this study, a novel Cd-responsive gene OsHARBI1-1 was identified in the rice genome and its expression pattern and function were characterized. Bioinformatics analysis showed that the promoter region of OsHARBI1-1 had multiple cis-acting elements in response to phytohormones and stress, and the expression of OsHARBI1-1 was induced by phytohormones. OsHARBI1-1 protein was targeted to the nucleus. qRT-PCR analysis results showed that the expression of OsHARBI1-1 in the roots was repressed while the expression in the shoots was increased under Cd stress. Heterologous expression of OsHARBI1-1 in yeast conferred tolerance to Cd and reduced Cd content in the cells. Meanwhile, the expression of OsHARBI1-1 in Arabidopsis thaliana (A. thaliana) enhanced the tolerance of A. thaliana to Cd stress. In addition, compared with the wild type plants, the POD activity of transgenic plants was increased, while the SOD and CAT activities were decreased. Interestingly, the accumulation of Cd in the roots of A. thaliana expressing OsHARBI1-1 was significantly increased, whereas the Cd accumulation in the shoots was slightly decreased. Compared to the WT plants, the expression of genes related to Cd absorption and chelation was upregulated in transgenic A. thaliana under Cd stress, while the expression of genes responsible for the translocation of Cd from the roots to the shoots was downregulated. Moreover, the expression of phytohormone-related genes was significantly influenced by the expression of OsHARBI1-1 with and without Cd treatment. CONCLUSIONS: Findings of this study suggest that OsHARBI1-1 might play a role in the response of plants to Cd response by affecting antioxidant enzyme activities, Cd chelation, absorption and transport, and phytohormone homeostasis and signaling.

Analysis for clinical feature and outcome of chondroblastoma after surgical treatment: A single center experience of 92 cases.

BACKGROUND: Chondroblastoma is a rare, benign, cartilaginous bone tumor derived from epiphyseal chondrocytes. Although the clinical characteristics and experience of surgical treatment of the smaller number of patients has been reported in the literature, it is difficult to draw conclusions about the clinical and radiographic features and the outcome for surgical treatment of this disease due to the rarity of chondroblastoma. This study was aiming to review the epidemiologic characteristics and outcome of surgical management for patients with chondroblastoma. METHODS: We performed a retrospective analysis of 92 patients with chondroblastoma. Clinical data, radiographic images, surgical treatment and outcome were analyzed. Eighty-two patients received the extensive intralesional curettage and ten cases had the En-block resection. RESULTS: The most common site of disease was proximal femur (20.7%, 19/92), followed by distal femur (18.5%, 17/92) and proximal tibia (16.3%, 15/92). The secondary aneurysmal bone cyst component was most common for chondroblastoma of the small irregular bones, such as patella and foot. Four (4.3%, 4/92) cases receiving the extensive intralesional curettage developed the local recurrence, respectively two at the proximal tibia, one at the pelvis and one at the calcaneus. Time to local recurrence were respectively 14.5, 8.8, 27.0 and 5.6 months, with the average 14 months. Kaplan-Meier estimated survivorship curve of local recurrence-free survival rates of one, two and five years were respectively 97.7%, 96.2% and 93.9%. The mean Musculoskeletal Tumor Society (MSTS) score was 29.4. At the last follow-up, no one had the pulmonary metastasis and death associated with the disease. CONCLUSION: Intralesional curettage plus local adjuvants can obtain satisfactory outcome for chondroblastoma. LEVEL OF EVIDENCE: Level IV.

Surgical Strategy of Pediatric Benign Sacral Tumors.

BACKGROUND: Primary benign osseous tumors and tumor-like lesions at the sacrum are rare in the pediatric population and exact surgical strategy is still unclear. In this study, we evaluate the outcome for pediatric patients with benign tumors and tumor-like lesions at the sacrum who were receiving surgical treatment according to our proposed surgical strategy and classification. METHODS: We analyzed 49 pediatric patients with sacral benign tumors or tumor-like lesions aged 18 years and below from 2005 to 2018. There were 23 men and 26 women with a mean age of 14.0±3.8 years. Nineteen patients had giant cell tumors (GCTs), 9 aneurysmal bone cysts, 5 osteoblastomas, 5 neurogenic tumors, 3 hemangiomas, 3 teratomas, 2 Langerhans cell histiocytosis, 1 chondroblastoma, 1 fibrous dysplasia, and 1 GCT of tendon sheath. We proposed our surgical plan and surgical classification for pediatric patients with sacral benign tumors or tumor-like lesions. RESULTS: The mean follow-up duration was 6.2 years (range, 1.0 to 18.9 y). GCTs (39%, 19/49) and primary aneurysmal bone cysts (18%, 9/49) are the top 2 common histologic types. Preoperative selective arterial embolization (SAE) was performed in 12 cases and 24 patients received intraoperative aortic balloon occlusion (ABO) as the preoperative surgical plan. Furthermore, according to tumor location at the sacrum, we classified surgical excision of sacral benign tumors and tumor-like lesions into 3 types. Fourteen cases were classified as type I, 27 as type II, 3 as type III, and 5 patients with neurogenic tumors cannot be classified into this surgical classification. Ten patients had wound complications. Two had femoral artery thrombosis because of ABO application. One had mechanical failure. Rate of local recurrence was 16%. Seven patients with GCTs and 1 with neurogenic tumor had local recurrence. No patient died of disease at the last follow-up. For the assessment of neurological function, the rate of neurological dysfunction was 12% (6/49). Four cases had urinary incontinence, 3 fecal incontinence, and 3 had bowel obstruction. Next, univariate analysis for influence of preoperative SAE and intraoperative ABO on complications demonstrated that both of them exerted no significant influence on the occurrence of oncological and nononcological complications. CONCLUSIONS: The proposed surgical strategy can provide an excellent therapeutic effect for pediatric benign tumors and tumor-like lesions at the sacrum. Preoperative SAE and intraoperative ABO can safeguard pediatric patients with high vascularity of benign tumor at the sacrum during the operation. LEVEL OF EVIDENCE: Level IV.

Lateral malleolus en bloc resection for the distal fibula osteosarcoma based on a new classification and proposed reconstruction choice: Analysis of 6 cases prognosis and literature review.

BACKGROUND: Amputation has been regarded as the standard surgical treatment for distal fibula osteosarcoma. With the advances in surgery and adjuvant chemotherapy, it have made limb salvage possible. However, the choice of a specific reconstruction procedure is frequently based on the surgeon's preference and it lacks of guidelines and high quality studies with the objective result on the subject. MATERIALS AND METHODS: Six patients with the distal fibular osteosarcoma which were received biological reconstruction were retrospectively reviewed at our bone tumor center from November 2003 to November 2015. There were 6 male with a mean age of 24.2 years (range, 12-47 years). The minimum follow-up duration was 53.3 months (median, 96.3 months; average, 108.4 months; range, 53.3-204.1 months). No patient was lost at the last follow-up. All data were obtained from the clinical and radiograph records. Furthermore, the literature review was based on the Google Scholar, Medline, EMBASE and Pubmed databases. The search was performed using the terms "distal fibula", "lower limb tumour", "sarcoma", "fibular metastasis" and "limb-salvage surgery" for the literature review from 1979 to 2017. RESULTS: Of the six patients with the final follow-up in the present study, four cases (83.3%, 4/6) achieved excellent prognosis without oncologic complications. A second surgical procedure was performed in two patients, one to treat local recurrence and one to receive metastasectomy due to the pulmonary metastasis. Case 6 received the below knee amputation due to recurrence. All the cases available for functional evaluation at the final follow-up had a mean functional MSTS score of 29.6 (range, 28-30) except case 6 receiving the amputation below the knee. Meanwhile, the VAS evaluation had a mean functional score of 0.2 points (range, 0-1 points). The results of our cohort and literature review illustrated that the patient with the malignant tumor of lateral malleolus could obtain excellent oncological prognosis and ankle function. CONCLUSIONS: We have provided treatment recommendations depending on the tumor volume and associated extent and proposed the primary ankle arthrodesis was performed after en bloc resection of Type II and III lateral malleolus osteosarcoma, based on the proposed classification. Furthermore, the patient with the malignant tumor of lateral malleolus could obtain excellent oncological prognosis.

Assessment of patient experiences following total sacrectomy for primary malignant sacral tumors: A qualitative study.

BACKGROUND AND OBJECTIVES: Few reports have investigated patient experiences following total en bloc sacrectomy. The aims of this study were to obtain a deeper understanding of patients' personal experiences, needs, and satisfaction with the treatment to reveal areas in which perioperative and long-term patient care can be improved. METHODS: A qualitative design was applied to examine patient experiences and supportive care needs. Patients treated between 2007 and 2017 were identified from our institutional database. RESULTS: A total of 28 survivors were interviewed (13 females, age 13-75 years). Eight themes were identified: the effect of surgery on patients' (a) daily lives, (b) social activities, (c) work or school activities, (d) and family lives; (e) acceptance of ostomy surgery; (f) need for guidance regarding long-term rehabilitation; (g) satisfaction with the medical services provided in the hospital; and (h) satisfaction with the treatment outcomes. CONCLUSION: Total en bloc sacrectomy can yield satisfactory oncological outcomes; however, the procedure is a life-changing event for patients and their families. Physicians must provide long-term support and guidance after surgery to enable patients to fully understand and cope with the changes in their lives.

Use of an Artificial Ligament Decreases Hip Dislocation and Improves Limb Function After Total Femoral Prosthetic Replacement Following Femoral Tumor Resection.

BACKGROUND: Hip dislocation is a major complication of total femoral prosthetic reconstruction (TFR) after femoral tumor resection. Hip dislocation can occur because of inadequate functional abductor musculature, inadequate hip capsule repair, or a long lever arm after total femur replacement. To eliminate the negative effects of these factors on the risk of hip dislocation, the use of artificial ligaments may help to increase the stability of the hip joint. We aimed to determine whether application of an artificial ligament would improve limb function and active range of movement (ROM) after TFR. METHODS: Fifty-eight patients who underwent femoral tumor resection and TFR were included. A band-shaped artificial ligament was wrapped spirally around the proximal site of the total femur prosthesis for periacetabular soft tissue reconstruction in 12 patients. The other 46 patients did not consent to receiving the artificial ligament. Complications including hip dislocation and infection, limb function, and active hip ROM were compared between patients who did and did not receive the artificial ligament. RESULTS: The hip dislocation rate was lower in the patients who received the artificial ligament. The risk of deep infection did not differ between groups. The group that received the ligament also achieved better limb function and active ROM on flexion and abduction. CONCLUSION: Patients treated with total femur resection and endoprosthetic replacement with an artificial ligament for periacetabular soft tissue reconstruction had a more stable hip joint, better limb function, and greater active hip ROM than did patients who did not receive an artificial ligament.

Preservation of the contralateral sacral nerves during hemisacrectomy for sacral malignancies.

PURPOSE: This study aimed to evaluate the oncologic and functional outcome of the cases treated with hemisacrectomy through a sagittal plane in the sacrum and simultaneous en bloc resection together with the ipsilateral sacroiliac joint without sacrificing the contralateral sacral nerves and summarize tumor resection techniques and reconstruction strategy. METHODS: En bloc resection of a sacral malignancy with ipsilateral sacroiliac joint and preservation of the contralateral sacral nerves by sagittal hemisacrectomy had been performed in 15 patients. An intra-abdominal aortic balloon was used in all these cases and a combined posterior-anterior approach was adopted. A modified Galveston technique was used to reestablish spinopelvic stability and a nonvascularized fibula autograft was used in selected cases. RESULTS: Contralateral sacral nerves were preserved in all 15 patients. Adequate margins (wide and marginal margin) were accomplished in 10 patients. Local recurrence occurred in seven (47%) patients, and four of these had an inadequate margin. There was no perioperative death. Four (27%) patients had wound problems. No mechanical breakdown occurred until the last follow-up. All the patients were able to walk without the use of a walking aid. Sphincter function was partially preserved in all these patients. At the last follow-up, seven (47%) patients survived without evidence of disease, two (13%) patients lived with disease, and six (40%) patients had died of disease. CONCLUSIONS: This procedure has an oncologic outcome that is similar to that of other high sacrectomy and a much better function outcome. Although demanding, it is indicated in selected patients.

Intentional Dural Resection during en bloc Spinal Resection Could Provide a Secure Surgical Margin for Patients with Recurrent Spinal Tumors.

OBJECTIVE: It is always difficult to obtain a comfortable surgical margin for patients with recurrent malignant or invasive benign spinal tumors. Tumor intraspinal invasion and dural adhesion are the essential reasons. There are always residual tumor cells maintained at the edge of dura. Dural resection is a key point to obtain a comfortable surgical margin for such cases. Whether such patients benefit from this risky surgical procedure is unknown. This study aims to understand better the oncological results, associated risks, and neurological function of this risky surgical procedure. METHODS: We retrospectively reviewed clinical data from six consecutive patients who registered spinal tumors in our institute and underwent dural resection during en bloc spinal resection from June 2013 to May 2020. The demographic and perioperative data, oncological outcomes, complications, and neurological status were collected and analyzed. RESULTS: All six patients were followed up for 24 to 46 months (mean follow-up time: 32.8 months). Local recurrence was detected in one patient (1/6, 16.7%) at 36 months postoperatively and in five patients with no evidence of disease at the last follow up (survival rate 83.3%). Eleven complications occurred in four patients (66.7%), and the dural resection-related complications included only four cases of cerebrospinal fluid leakage (CSFL), which accounted for 36.4% (4/11) of all complications. Neurologic status evaluated by the Frankel grade showed improvement of one grade in one case and deterioration of one to two grades in five patients immediately after surgery. All deterioration cases recovered to the preoperative level 6 months after the operation. CONCLUSION: Dural resection is significant for patients with dura matter invaded by recurrent primary malignant or invasive benign spinal tumors with the purpose of clinical cure. This study demonstrated that in strictly selected cases, intentional dural resection could provide satisfying local control and long-term disease-free survival with acceptable complications and satisfying neurological function.

[Surgical treatment for long bone giant cell tumor of extremity with pathologic fracture].

OBJECTIVE: To identify the clinical features of patients with giant cell tumors (GCT) of long bones in extremities presented with pathological fracture (PF), and discuss the surgical strategy with retrospective analysis and literature review. METHODS: We searched medical electronic records from January 1999 to December 2011 in our hospital to identify patients with definite diagnosis of extremity GCT presented with PF. Clinical data including gender, tumor site, age, surgical treatment option, postoperative complication, limb function, local recurrence and pulmonary metastasis were collected and analyzed statistically. The t-test and chi-square test were used for continuous and dichotomous variables, respectively. RESULTS: Between 1999 and 2011 we treated 201 patients with GCT in extremities (long bone only: femur, tibia, fibula, humerus, ulna, and radius), 33 of whom presented with a PF. The gender ratio was 1.06 for a male predominance. The median age was 33 (15-62), and the most common site of pathologic fractures was distal femur (n=17), followed by proximal tibia (n=5), proximal femur (n=5), proximal humerus (n=4), and distal radius (n=2). Nine fractures were intra-articular. The tumors were treated by extended curettage (n=11) or en bloc excision (n=22), and the fractures were reconstructed by endoprosthesis (n=20), autologous iliums graft combined with synthetic bone substitutes (n=7), acrylic cementing (n=3), autologous fibula graft (n=2), or allograft (n=1). Ten operations were followed by complications of any kind, where implant failure and recurrence were the commonest, and re-operation rate was 27.3%. The mean functional score according to the scoring system of the Musculoskeletal Tumor Society (MSTS) was 81% in patients who received endoprosthesis replacement and 82% in other reconstruction options. CONCLUSION: Extended curettage and en bloc resection were all considered to be the effective treatment options for patients with extremity GCT presented with PF. However, local recurrence and implant related complication were the major concern for joint reservation and prosthetic replacement, respectively.

Metallochaperone protein OsHIPP17 regulates the absorption and translocation of cadmium in rice (Oryza sativa L.).

Heavy metal-associated isoprenylated plant proteins (HIPPs) play vital roles in regulating heavy metal responding activities in plants. Yet only a handful of studies have characterized the functions of HIPPs. In this study, a novel HIPP member OsHIPP17 was functionally characterized, which was involved in the tolerance of yeast and plants to cadmium (Cd). The Cd accumulation in yeast cells was increased due to the overexpression of OsHIPP17. Nevertheless, the overexpression of OsHIPP17 in Arabidopsis thaliana resulted in compromised growth under Cd stress. Meanwhile, the mutation of OsHIPP17 resulted in 38.9-40.9 % increase of Cd concentration in rice roots as well as 14.3-20.0 % decrease of Cd translocation factor. Further investigation of the genes responsible for Cd absorption and transporter indicated that the expression levels of these genes were also perturbed. In addition, two OsHIPP17-interacting proteins, OsHIPP24 and OsLOL3 were identified in a yeast two hybrid assay. Further analysis of their functions revealed that OsHIPP24 or OsLOL3 may be involved in the regulation of Cd tolerance by OsHIPP17 in rice. All above results implied that OsHIPP17 may affect Cd resistance by regulating the absorption and translocation of Cd in rice.

OsHIPP17 is involved in regulating the tolerance of rice to copper stress.

Introduction: Heavy metal-associated isoprenylated plant proteins (HIPPs) play vital roles in metal absorption, transport and accumulation in plants. However, so far, only several plant HIPPs have been functionally analyzed. In this study, a novel HIPP member OsHIPP17, which was involved in the tolerance to copper (Cu) was functionally characterized. Methods: In this study, qRT-PCR, Yeast transgenic technology, Plant transgenic technology, ICP-MS and so on were used for research. Results: OsHIPP17 protein was targeted to the nucleus. The Cu concentration reached 0.45 mg/g dry weight due to the overexpression of OsHIPP17 in yeast cells. Meanwhile, the overexpression of OsHIPP17 resulted in the compromised growth of Arabidopsis thaliana (Arabidopsis) under Cu stress. The root length of Oshipp17 mutant lines was also significantly reduced by 16.74- 24.36% under 25 mM Cu stress. The roots of Oshipp17 rice mutant showed increased Cu concentration by 7.25%-23.32%. Meanwhile, knockout of OsHIPP17 decreased the expression levels of OsATX1, OsZIP1, OsCOPT5 or OsHMA5, and increased the expression levels of OsCOPT1 or OsHMA4. Antioxidant enzyme activity was also reduced in rice due to the knockout of OsHIPP17. Moreover, the expression levels of cytokinin-related genes in plants under Cu stress were also affected by overexpression or knockout of OsHIPP17. Discussion: These results implied that OsHIPP17 might play a role in plant Cu toxic response by affecting the expression of Cu transport genes or cytokinin-related genes. Simultaneously, our work may shed light on the underlying mechanism of how heavy metals affect the plant growth and provide a novel rice genetic source for phytoremediation of heavy metal-contaminated soil.

Distinct genomic features between osteosarcomas firstly metastasing to bone and to lung.

Background: Osteosarcoma initially metastasing to bone only shows distinct biological features compared to osteosarcoma that firstly metastasizes to the lung, which suggests us underlying different genomic pathogenetic mechanism. Methods: We analyzed whole-exome sequencing (WES) data for 38 osteosarcoma with paired samples in different relapse patterns. We also sought to redefine disease subclassifications for osteosarcoma based on genetic alterations and correlate these genetic profiles with clinical treatment courses to elucidate potential evolving cladograms. Results: We investigated WES of 12/38 patients with high-grade osteosarcoma (31.6%) with initial bone metastasis (group A) and 26/38 (68.4%) with initial pulmonary metastasis (group B), of whom 15/38 (39.5%) had paired samples of primary lesions and metastatic lesions. We found that osteosarcoma in group A mainly carries single-nucleotide variations displaying higher tumor mutation burden and neoantigen load and more tertiary lymphoid structures, while those in group B mainly exhibits structural variants. High conservation of reported genetic sequencing over time in their evolving cladograms. Conclusions: Osteosarcoma with mainly single-nucleotide variations other than structural variants might exhibit biological behavior predisposing toward bone metastases as well as better immunogenicity in tumor microenvironment.

Analysis of mechanical complications for patients with extremity sarcoma after biological reconstruction.

BACKGROUND: Biological reconstruction after tumor resection is significant for restoration of limb integrality. However, it is unclear what risk factors influence mechanical complications of patients after extremity sarcoma resection and biological reconstruction. The objective of study was (1) to compare complications between patients receiving inactivated autograft and allograft, (2) to analyze influence of graft type, nonunion and fixation method on mechanical complications for patients after biological reconstruction. HYPOTHESIS: We hypothesized allograft, nonunion and fixation method influence occurrence of mechanical complications after biological reconstruction. MATERIALS AND METHODS: We retrospectively reviewed 71 patients with sarcomas at the extremity receiving biological reconstruction from January 1999 to November 2015. Eight patients were lost at last follow-up. Sixty-three patients with complete clinical data were recruited into the present study. There were 32 males and 31 females with a mean age of 20.5±14.9 years (median, 17 years; range, 2-72 years). Sixty-one cases had tumors at lower extremity and two at upper extremity. Histological diagnosis was confirmed as forty-five with osteosarcoma, thirteen with Ewing sarcoma and five with chondrosarcoma. RESULTS: Forty-four patients were free of disease, sixteen died of disease and three lived with pulmonary metastasis at last follow-up. Twenty-one out of 63 patients (33.3%) had local recurrence requiring surgical treatment. Reconstruction choice (mechanical complications rates were 38.9% for allograft (14/36) versus 14.8% for inactivated autograft (4/27)) and nonunion occurrence (yes 58.8% (10/17); no 17.4% (8/46)) had the close relationship with mechanical complication in the univariate analysis. The multivariate analysis revealed fixation method (p=0.041) and nonunion (p=0.008) were prognostic factors for mechanical complication of sarcoma resection and biological reconstruction at the extremity. Fourteen of 36 patients receiving massive allograft had a second surgery due to mechanical complication compared to 4 of 27 patients with massive inactivated autograft (38.9%, 14/36 vs. 14.8%, 4/27 (p=0.05)). Time to union for diaphysis and metaphysis was not significantly different between allograft and inactivated autograft groups. DISCUSSION: Patients receiving massive allograft are prone to suffer from the mechanical complications. Extramedullary plate and nonunion have the tendency of increasing occurrence of mechanical complications of biological reconstruction. LEVEL OF EVIDENCE: IV; retrospective study.

Elbow hemiarthroplasty with a 3D-printed megaprosthesis for defects of the distal humerus or proximal ulna after tumour resection : a preliminary report.

AIMS: The aim of this study was to investigate the feasibility of application of a 3D-printed megaprosthesis with hemiarthroplasty design for defects of the distal humerus or proximal ulna following tumour resection. METHODS: From June 2018 to January 2020, 13 patients with aggressive or malignant tumours involving the distal humerus (n = 8) or proximal ulna (n = 5) were treated by en bloc resection and reconstruction with a 3D-printed megaprosthesis with hemiarthroplasty, designed in our centre. In this paper, we summarize the baseline and operative data, oncological outcome, complication profiles, and functional status of these patients. RESULTS: Preparation of the prosthesis was a mean of 8.0 days (SD 1.5), during which time no patients experienced tumour progression. The mean operating time and intraoperative blood loss were 158.1 minutes (SD 67.6) and 176.9 ml (SD 187.8), respectively. All of the prostheses were implanted successfully. During a mean follow-up of 25.7 months (SD 7.8), no patients died, but four had complications (two superficial wound problems, one temporary palsy of radial nerve, and one dislocation). No aseptic loosening, structural failure, infection, heterotopic ossification, or degenerative arthritis was seen in this study. The mean flexion of the elbow was 119.6° (SD 15.9°) and the mean extension lag was 11.9° (SD 13.8°). The mean Musculoskeletal Tumor Society 93 score and Mayo Elbow Performance Score were 28.4 (SD 0.9) and 97.7 (SD 4.4), respectively. CONCLUSION: The custom-made, 3D-printed megaprosthesis with hemiarthroplasty is a feasible option for functional reconstruction after resection of a tumour in the distal humerus or proximal ulna. Cite this article: Bone Joint J 2022;104-B(6):747-757.

Reconstruction With a 3D-Printed Megaprosthesis With Ankle Arthrodesis After Distal Tibial Tumor Resection.

BACKGROUND: Reconstruction after en bloc resection of the distal tibia has remained an unsettled issue despite many attempts with bone grafts or prostheses in the past. Failures of the previous methods have been attributed to inadequate mechanical strength, poor articular stability, failed osseointegration, and poor soft tissue coverage. To overcome these shortcomings, we designed and applied a 3D-printed megaprosthesis with ankle arthrodesis. METHODS: A total of 13 patients underwent resection of a distal tibial tumor and reconstruction with a 3D-printed distal tibial megaprosthesis between January 2017 and November 2020. Mean age was 14.9±6.5 years. Diagnoses included 11 cases of osteosarcoma and 1 case each of low-grade phosphaturic mesenchymal tumor and rhabdomyosarcoma. Baseline characteristics, operative data, complication profiles, and oncologic, and functional outcomes were reviewed and analyzed. RESULTS: All 13 cases attained a wide or marginal resection. During a mean follow-up of 26.8±10.6 months, 1 patient experienced local recurrence and distant metastasis, whereas 3 other patients only developed distant metastasis. Periprosthetic infection subsequent to paronychia occurred in 1 patient 24 months after the operation. No other complications were observed. By the last follow-up, the mean MSTS-93 score was 28.0±1.5. CONCLUSION: In this relatively small cohort with short-term follow-up, reconstruction with the 3D-printed megaprosthesis with ankle arthrodesis was found to be a safe and efficacious method after resection of a distal tibial malignancy.

Ultra-Short Course of Neo-Adjuvant Denosumab for Nerve-Sparing Surgery for Giant Cell Tumor of Bone in Sacrum.

STUDY DEIGN: This was a retrospective study about sacral giant cell tumor of bone (GCTB). OBJECTIVE: This study aimed to investigate whether ultra-short course of neo-adjuvant denosumab treatment for sacral GCTB could (1) induce radiological and histological response? (2) Facilitate nerve-sparing surgery? (3) Achieve satisfactory oncological and functional outcomes? SUMMARY OF BACKGROUND DATA: Previous reports on long course of neo-adjuvant denosumab treatment for GCTB showed significant tumor response and a relatively high recurrent rate after curettage. METHODS: Sixty-six patients with sacral GCTB treated with neoadjuvant denosumab and nerve-sparing surgery were categorized into ultra-short course group (≤3 doses and operation within D21 since 1st dose, 41 patients) or conventional group (>3 doses or operation after D21 since 1st dose, 25 patients). The radiological and histological response, operative data, oncological and functional outcomes were compared. RESULTS: The ultra-short course group demonstrated fewer doses of neo-adjuvant denosumab (mean: 2.1 vs. 4.8, P  < 0.001) and shorter time to surgery (12.2 days vs. 72.3 days, P < 0.001). Similar patterns of radiological and histological response were observed in the two groups with less fibrosis and ossification in the ultra-short course group. The operative duration (199.9 min vs. 187.8 min, P = 0.364) and estimated blood loss (1552.4 mL vs. 1474.0 mL, P = 0.740) were comparable. Most (94.8%) of the patients received adjuvant denosumab. After a mean follow-up of 29.4 months, three cases (8.8%) and five cases (20.8%) showed local recurrence in each group (P = 0.255). The estimated recurrence-free survival (56.2 vs. 51.2 months, P = 0.210) and the functional status [Motor-Urination-Defecation scores: 25.9 vs. 25.7, P = 0.762] did not differ between the two groups. CONCLUSION: Ultra-short course of neo-adjuvant denosumab for sacral GCTB could elicit radiological and histological responses as conventional course did. The less degree of fibrosis and ossification might facilitate nerve-sparing surgery and help to achieve satisfactory local control and functional status.Level of Evidence: 4.

[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.