Fine hippocampal morphology analysis with a multi-dataset cross-sectional study on 2911 subjects.

CA1 subfield and subiculum of the hippocampus contain a series of dentate bulges, which are also called hippocampus dentation (HD). There have been several studies demonstrating an association between HD and brain disorders. Such as the number of hippocampal dentation correlates with temporal lobe epilepsy. And epileptic hippocampus have a lower number of dentation compared to contralateral hippocampus. However, most studies rely on subjective assessment by manual searching and counting in HD areas, which is time-consuming and labor-intensive to process large amounts of samples. And to date, only one objective method for quantifying HD has been proposed. Therefore, to fill this gap, we developed an automated and objective method to quantify HD and explore its relationship with neurodegenerative diseases. In this work, we performed a fine-scale morphological characterization of HD in 2911 subjects from four different cohorts of ADNI, PPMI, HCP, and IXI to quantify and explore differences between them in MR T1w images. The results showed that the degree of right hippocampal dentation are lower in patients with Alzheimer's disease than samples in mild cognitive impairment or cognitively normal, whereas this change is not significant in Parkinson's disease progression. The innovation of this paper that we propose a quantitative, robust, and fully automated method. These methodological innovation and corresponding results delineated above constitute the significance and novelty of our study. What's more, the proposed method breaks through the limitations of manual labeling and is the first to quantitatively measure and compare HD in four different brain populations including thousands of subjects. These findings revealed new morphological patterns in the hippocampal dentation, which can help with subsequent fine-scale hippocampal morphology research.

Fine scale hippocampus morphology variation cross 552 healthy subjects from age 20 to 80.

The cerebral cortex varies over the course of a person's life span: at birth, the surface is smooth, before becoming more bumpy (deeper sulci and thicker gyri) in middle age, and thinner in senior years. In this work, a similar phenomenon was observed on the hippocampus. It was previously believed the fine-scale morphology of the hippocampus could only be extracted only with high field scanners (7T, 9.4T); however, recent studies show that regular 3T MR scanners can be sufficient for this purpose. This finding opens the door for the study of fine hippocampal morphometry for a large amount of clinical data. In particular, a characteristic bumpy and subtle feature on the inferior aspect of the hippocampus, which we refer to as hippocampal dentation, presents a dramatic degree of variability between individuals from very smooth to highly dentated. In this report, we propose a combined method joining deep learning and sub-pixel level set evolution to efficiently obtain fine-scale hippocampal segmentation on 552 healthy subjects. Through non-linear dentation extraction and fitting, we reveal that the bumpiness of the inferior surface of the human hippocampus has a clear temporal trend. It is bumpiest between 40 and 50 years old. This observation should be aligned with neurodevelopmental and aging stages.

Reconstructing avascular necrotic femoral head through a bioactive ß-TCP system: From design to application.

A variety of techniques have been used for treating avascular necrosis of the femoral head (ANFH), but have frequently failed. In this study, we proposed a ß-TCP system for the treatment of ANFH by boosting revascularization and bone regeneration. The angio-conductive properties and concurrent osteogenesis of the highly interconnected porous ß-TCP scaffold were revealed and quantified through an in vivo model that simulated the ischemic environment of ANFH. Mechanical test and finite element analysis showed that the mechanical loss caused by tissue necrosis and surgery was immediately partially compensated after implantation, and the strength of the operated femoral head was adaptively increased and eventually returned to normal bone, along with continuous material degradation and bone regeneration. For translational application, we further conducted a multi-center open-label clinical trial to assess the efficacy of the ß-TCP system in treating ANFH. Two hundred fourteen patients with 246 hips were enrolled for evaluation, and 82.1% of the operated hips survived at a 42.79-month median follow-up. The imaging results, hip function, and pain scores were dramatically improved compared to preoperative levels. ARCO stage Ⅱ disease outperformed stage Ⅲ in terms of clinical effectiveness. Thus, bio-adaptive reconstruction using the ß-TCP system is a promising hip-preserving strategy for the treatment of ANFH.

Does joint-sparing tumor resection jeopardize oncologic and functional outcomes in non-metastatic high-grade osteosarcoma around the knee?

BACKGROUND: We previously reported joint-sparing tumor resection for osteosarcoma with epiphyseal involvement in which transepiphyseal osteotomy went through the in situ ablated epiphysis. However, we do not know whether this is a safe approach when compared with joint-sacrificed tumor resection. Our objective was to compare oncologic and functional outcomes between patients who underwent joint preservation (JP) and joint replacement (JR) tumor resection. Furthermore, we identified the risk factors of local recurrence, metastasis and survival. METHODS: Eighty-nine patients with non-metastatic high-grade osteosarcoma around the knee were treated with limb-salvage surgery (JP in 47 and JR in 42). Age, gender, tumor location, pathologic fracture, plain radiographic pattern, limb diameter change, perivascular space alteration, surgical margin, local recurrence, metastasis, death, and the Musculoskeletal Tumor Society (MSTS)-93 scores were extracted from the records. Univariate analysis was performed to compare oncologic and functional outcomes. Binary logistic and cox regression models were used to identify predicted factors for local recurrence, metastasis, and survival. RESULTS: Local recurrence, metastasis and overall survival were similar in the JP and JR group (p = 0.3; p = 0.211; p = 0.143). Major complications and limb survival were also similar in the JR and JP group (p = 0.14; p = 0.181). The MSTS score of 27.06 ± 1.77 in the JP group was higher than that of 25.88 ± 1.79 in the JR group (p = 0.005). The marginal margin of soft tissue compared with a wide margin was the only independent predictor of local recurrence (p = 0.006). Limb diameter increase and perivascular fat plane disappearance during neoadjuvant chemotherapy were independent predictors for metastasis (p = 0.002; p = 0.000) and worse survival (p = 0.000; p = 0.001). CONCLUSIONS: Joint-sparing tumor resection with the ablative bone margin offers advantage of native joint preservation with favorable functional outcomes while not jeopardizing oncologic outcomes compared with joint-sacrificed tumor resection. Surgeon should strive to obtain adequate soft tissue surgical margin decreasing risk of local recurrence. Novel drug regimens might be reasonable options for patients with obvious limb diameter increase and perivascular fat disappearance during chemotherapy.

Acceptor Engineering Produces Ultrafast Nonradiative Decay in NIR-II Aza-BODIPY Nanoparticles for Efficient Osteosarcoma Photothermal Therapy via Concurrent Apoptosis and Pyroptosis.

Small-molecule photothermal agents (PTAs) with intense second near-infrared (NIR-II, 1,000 to 1,700 nm) absorption and high photothermal conversion efficiencies (PCEs) are promising candidates for treating deep-seated tumors such as osteosarcoma. To date, the development of small-molecule NIR-II PTAs has largely relied on fabricating donor-acceptor-donor (D-A-D/D') structures and limited success has been achieved. Herein, through acceptor engineering, a donor-acceptor-acceptor (D-A-A')-structured NIR-II aza-boron-dipyrromethene (aza-BODIPY) PTA (SW8) was readily developed for the 1,064-nm laser-mediated phototheranostic treatment of osteosarcoma. Changing the donor groups to acceptor groups produced remarkable red-shifts of absorption maximums from first near-infrared (NIR-I) regions (~808 nm) to NIR-II ones (~1,064 nm) for aza-BODIPYs (SW1 to SW8). Furthermore, SW8 self-assembled into nanoparticles (SW8@NPs) with intense NIR-II absorption and an ultrahigh PCE (75%, 1,064 nm). This ultrahigh PCE primarily originated from an additional nonradiative decay pathway, which showed a 100-fold enhanced decay rate compared to that shown by conventional pathways such as internal conversion and vibrational relaxation. Eventually, SW8@NPs performed highly efficient 1,064-nm laser-mediated NIR-II photothermal therapy of osteosarcoma via concurrent apoptosis and pyroptosis. This work not only illustrates a remote approach for treating deep-seated tumors with high spatiotemporal control but also provides a new strategy for building high-performance small-molecule NIR-II PTAs.

Predicting chemosensitivity based on mini patient-derived xenografts in osteosarcoma patients: A retrospective study.

Context: The survival of patients diagnosed with osteosarcoma has not improved in the past three decades because of chemoresistance. Aim: This study aimed to improve the prognosis of patients with osteosarcoma. Settings and Design: From January 1, 2018, to June 30, 2019, a total of 14 patients with osteosarcoma were enrolled who underwent mini patient-derived xenograft (mini-PDX) assay in our hospital. Methods and Materials: We recruited 14 patients with osteosarcoma having acquirable lesions to establish PDX models and examine the sensitivity of nine drugs, including methotrexate (MTX), ifosfamide (IFO), epirubicin, and etoposide. Drug sensitivity was evaluated using the tumor relative proliferation rate (TRPR), and the patients' responses were assessed according to the RECIST 1.1 guidelines. Statistical Analysis Used: The difference in TRPR was analyzed using a paired t-test, while progression-free survival (PFS) was analyzed using the Kaplan-Meier method. Results: The mini-PDX results revealed that IFO had a lower tumor proliferation rate than MTX, indicating that IFO was more sensitive in patients with osteosarcoma (38.3% vs. 84.3%, P = 0.031). Thus, the regimen where IFO alternates with doxorubicin and cisplatin was recommended as adjuvant chemotherapy. MTX could replace IFO if the TRPR was better. Finally, 11 patients received adjuvant chemotherapy. A comparison of PFS revealed that sensitive patients with TRPR of <40% had a better prognosis (9.4 months vs. 3.7 months, P = 0.0324). Conclusions: Chemotherapy based on mini-PDX can improve the survival of patients with osteosarcoma whose TRPR was <40%, and that chemotherapy without MTX could be an alternative for osteosarcoma.

Evaluation of Anlotinib Combined with Adriamycin and Ifosfamide as Conversion Therapy for Unresectable Soft Tissue Sarcomas.

(1) Background: This study investigated the safety and efficiency of adriamycin and ifosfamide combined with anlotinib (AI/AN) as a neoadjuvant conversion therapy in uSTS. (2) Methods: Patients with uSTS were eligible to receive AI/An, including adriamycin (20 mg/m2/d) and ifosfamide (3 g/m2/d) for the first to the third day combined with anlotinib (12 mg/d) for 2 weeks on/1 week off, all of which combine to comprise one cycle. Surgery was recommended after four cycles of treatment. (3) Results: A total of 28 patients were enrolled from June 2018 to December 2020. The best tumor responses included eight patients with partial responses and 20 with a stable disease. Patients with synovial sarcoma and liposarcoma had a significant decrease in the number of tumors compared with fibrosarcoma (p = 0.012; p = 0.042). The overall response rate and disease control rate were 28.57% and 100%, respectively. In total, 24 patients received surgery, while the rates of limb salvage and R0 resection were 91.67% (n = 22/24) and 87.50% (n = 21/24), respectively. Until the last follow-up visit, the mean PFS and RFS were 21.70 and 23.97 months, respectively. During drug administration, 67.87% of patients had grade ≥3 AEs. No treatment-related death occurred. (4) Conclusions: AI/AN followed by surgery showed favorable efficiency and manageable safety in patients with uSTS. A randomized controlled study with a large cohort should be performed for further investigations.

A classification system of joint-salvage tumor resection in osteosarcoma of the knee: A retrospective cohort study.

BACKGROUND: Joint-preserving surgery is possible for patients with juxta-articular osteosarcoma of the knee, even when the tumor invades the epiphysis. Oncologic and functional outcomes may vary due to the extent of tumor invasion, the amount of epiphysis preservation, and reconstruction methods. We aimed to introduce a novel classification facilitating clinical evaluation of different surgical treatments. METHODS: We identified 52 patients with osteosarcoma of the knee undergoing joint-preserving tumor resection and intercalary reconstruction. We classified procedures into two types and six subtypes based on the tumor location and adjuvant treatment employed. Oncologic outcomes, limb function and complications were compared among different types. RESULTS: None of the patients had a local recurrence in the preserved epiphysis apart from three (5.7 %) who had local recurrence in soft tissue. Overall survival rate of the patients was 82.7 % at 5 and 10 years. There was no difference in survival rate (P = 0.909), local recurrence (P = 0.642) between type I (tumor not invading epiphysis) and type II (tumor invading epiphysis). In addition to one skin necrosis in the 3D-printed prosthesis reconstruction and one infection in Capanna reconstruction, all complications necessitating additional surgery occurred in allograft. The Musculoskeletal Tumor Society (MSTS) scores ranged from 21 to 30 with a median of 26. There were differences in the MSTS scores among six subgroups (P = 0.015), with the highest in type Ia and the lowest in type IIc. The less of the viable epiphysis retained, the worse the knee function was at long-term follow up. CONCLUSIONS: The suggested classification can guide surgical strategy and is convenient for comparison of the functional results.

An end-to-end multi-task system of automatic lesion detection and anatomical localization in whole-body bone scintigraphy by deep learning.

SUMMARY: Limited by spatial resolution and visual contrast, bone scintigraphy interpretation is susceptible to subjective factors, which considerably affects the accuracy and repeatability of lesion detection and anatomical localization. In this work, we design and implement an end-to-end multi-task deep learning model to perform automatic lesion detection and anatomical localization in whole-body bone scintigraphy. A total of 617 whole-body bone scintigraphy cases including anterior and posterior views were retrospectively analyzed. The proposed semi-supervised model consists of two task flows. The first one, the lesion segmentation flow, received image patches and was trained in a supervised way. The other one, skeleton segmentation flow, was trained on as few as five labeled images in conjunction with the multi-atlas approach, in a semi-supervised way. The two flows joint in their encoder layers so each flow can capture more generalized distribution of the sample space and extract more abstract deep features. The experimental results show that the architecture achieved the highest precision in the finest bone segmentation task in both anterior and posterior images of whole-body scintigraphy. Such an end-to-end approach with very few manual annotation requirement would be suitable for algorithm deployment. Moreover, the proposed approach reliably balances unsupervised labels construction and supervised learning, providing useful insight for weakly labeled image analysis. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Intercalary tibial reconstruction with frozen tumor-bearing autograft in combination with ipsilateral fibula in limb-salvage surgery.

PURPOSE: The purpose of this study was to examine whether the results of a reconstruction using frozen autograft in combination with vascularized fibula are comparable to other reconstructive methods in limb-salvage surgery for tibial sarcoma with regard to the functional outcome and complications. METHODS: Between 2008 and 2012, nine patients with bone sarcoma of the tibia underwent excision of the affected segment that was then frozen and reimplanted with an ipsilateral vascularized fibular graft within it. Patients were examined clinically and radiographically. RESULTS: The mean follow-up was 48.8 months. The mean time to full weight-bearing was 6.2 months and to complete radiological union 6.8 months at the conjunction. One patient required a mid-thigh amputation due to local recurrence in soft tissue. No local recurrence arising from the frozen autograft was detected. Complications included wound dehiscence in 1, clawed toes in 1, temporary peroneal nerve palsy in 1, and stress fracture in 1. The average musculoskeletal tumor society functional score was 94.5%. CONCLUSIONS: Combination of a frozen tumor-bearing autograft and ipsilateral pedicled fibula is an effective reconstruction for massive bone defect arising from resection of bone sarcoma in tibia. This approach has the advantage of combining the biological properties offered by the vascularized bone graft with the mechanical endurance of the frozen autograft. The method is best indicated for intercalary defects of the tibia for selected patients. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Effect of Nonisoprene Degradation and Naturally Occurring Network during Maturation on the Properties of Natural Rubber.

It well-known that the superior performance of natural rubber (NR) compared to its synthetic counterpart mainly derives from nonisoprene components and naturally occurring network, which varies during the progress of the maturation and thereby results in technically graded rubber with different properties. However, identifying the roles of these two factors in the forming of excellent performance of NR is still a challenge as they change simultaneously during the maturation process. Here, influences of naturally occurring networking and nonisoprene degradation on the components, structures and properties of NR were systematically investigated by tailored treatments of maturation. It was found that the maturation-induced formation of natural network structure contributes to the increase in initial plastic value, Mooney viscosity and gel content for un-crosslinked NR, while the decomposition of nonisoprene components plays a dominant role in improving the mechanical properties of vulcanized NR. Stress-strain curve and Mooney-Rivlin analysis demonstrate that the biodegradation of the nonisoprene components significantly boost the vulcanization process, which significantly increases the number of chemical cross-link networks and effective cross-link density of the material, greatly improving the mechanical properties of NR vulcanizates. This resulted in the tensile strength of TSR 10CV being able to reach 22.6 MPa, which is significantly improved compared to 15.8 MPa of TSR 3CV. Evidenced by tubular model fitting, the increase in chemical cross-linking points effectively reduces the movable radius of the molecular chain under dynamic loading, making the molecular chain more difficult to move, which suppresses the entropy change under dynamic loading and consequently endows NR excellent dynamic mechanical properties. This resulted in a significant decrease in the temperature rising of TSR 10CV to 3.3 °C, while the temperature rising of TSR 3CV was still as high as 14.5 °C. As a minor factor, the naturally occurring network improves the mechanical properties of vulcanizates in the form of sacrificial bonds.

Lateral Malleolus Reconstruction After Tumor Resection in Children: A Case Report and Literature Review.

BACKGROUND: Pediatric reconstruction of lateral malleolus was necessary and challengeable. Up to now, vascularized fibular was the optimal graft to reconstruct epiphyseal defection. However, the sophisticated microvascular operation has limited the wide application of this technique. CASE PRESENTATION: We present the case of a 9-year-old boy with Ewing sarcoma in left distal fibula. In order to restore the growth capacity, we used reverse-flow vascularized fibular epiphyseal graft with tibialis anterior artery to reconstruct the bone defect after tumor resection with no microvascular anastomosis. More than 4 years after the operation and adjuvant chemotherapy, the patient was free of pain and recurrence, and the function and stability of ankle joint was perfect. Radiology examination revealed satisfied bony union of fibula and normal growth of the fibular head transplant. CONCLUSIONS: The advantage of reverse-flow vascularized fibular epiphyseal graft is requiring no microvascular anastomosis which could not only shorten operating time, but also reduce factitious damage of vessels. This report presented that this technique might be an available option for reconstruction of lateral malleolus in children.

Establishment of a rabbit's model for modified Capanna technique.

BACKGROUND: Massive bone allograft with an intramedullary vascularized fibula (Capanna technique) represents one of the most widely used methods for the reconstruction of massive bone defect. However, the mechanisms, healing process, and underlying influential factors were poorly understood due to the lack of suitable experimental animal models. METHODS: Critical-sized defects (CSD) in bone were constructed in the proximal tibia of 24 rabbits and randomly divided into two groups. Allogeneic bone segments of the same size as CSDs were obtained from another 12 rabbits and then inactivated. In group Ⅰ, an ipsilateral pedicled vascularized fibula was dissociated and transferred into the intramedullary cavity of allograft to assemble a composite for CSD reconstruction (Capanna technique), while group Ⅱ received a reconstruction with allogeneic bone alone. Radiographic evaluation was performed every week after the operation to assess union status. All animals were sacrificed at 16th week, and the specimens were histologically analyzed. RESULTS: All animals survived without severe intraoperative complications. There was one rabbit (8.33%) in group Ⅰ developed a postoperative infection and died, while three rabbits (25%) had postoperative complications in group Ⅱ (two died of infection and one died of internal fixation fracture). Radiographically, the mean time to union at the allograft-host junction in group Ⅰ was 12.8 ± 1.80 weeks, significantly shorter than in group II (>15.18±1.12 weeks; p<0.001). The grade of graft union of group Ⅰ was significantly higher than that of group Ⅱ both at 8th and 16th week (8th week: p = 0.035; 16th week: p = 0.033). Fully bone union at the junctions was histologically confirmed in all specimens in group Ⅰ and 66.67% (8/12) in group Ⅱ. CONCLUSION: Combined allograft and intramedullary vascularized fibula transfer in rabbit's tibia represent an ideal model that accurately simulates the Capanna technique for CSD reconstruction.

Is the Capanna Technique a Reliable Method for Revision Surgery after Failure of Previous Limb-Salvage Surgery?

BACKGROUND: Reconstruction of a massive bone defect caused by previous failed limb-salvage surgery in patients with bone sarcoma is challenging. Many procedures have been used, but they all have their inherent disadvantages. The Capanna technique has demonstrated good functional outcomes and a low incidence of complications in primary reconstructive surgery of massive bone defect. However, few studies have focused on its usage in revision surgery after failed primary limb-salvage surgery. METHODS: Between June 2011 and January 2017, 13 patients underwent revision surgery with the Capanna technique for reconstruction of a secondary segmental bone defect caused by a previous failed surgical procedure. The demographics, operating procedures, graft union, functional outcomes, oncologic outcomes, and postoperative complications of each patient were recorded. RESULTS: The current study investigated 13 patients. The rate of limb salvage was 100 %. Bone union was achieved for all patients during a mean time of 8.54 ± 2.15 months (range 4-11 months) at the fibula-host bone junction and 14.92 ± 2.33 months (range 12-21 months) at the allograft-host bone junction. The postoperative complications included wound healing issues and internal fixation loosening. Allograft fracture, nonunion, and infection were not observed. All the patients achieved good functional outcomes, with a Musculoskeletal Tumor Society (MSTS) score of 0.86 ± 0.03 at the latest follow-up visit. CONCLUSIONS: The Capanna technique is a reliable alternative method for revision reconstruction of a segmental bone defect caused by a previous failed surgical procedure. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Cryoablation-aided joint retention surgery for epiphysis involvement in osteosarcoma compared with endoprosthetic replacement.

AIMS: We have previously reported cryoablation-assisted joint-sparing surgery for osteosarcoma with epiphyseal involvement. However, it is not clear whether this is a comparable alternative to conventional joint arthroplasty in terms of oncological and functional outcomes. METHODS: A total of 22 patients who had localized osteosarcoma with epiphyseal involvement around the knee and underwent limb salvage surgery were allocated to joint preservation (JP) group and joint arthroplasty (JA) group. Subjects were followed with radiographs, Musculoskeletal Tumor Society (MSTS) score, and clinical evaluations at one, three, and five years postoperatively. RESULTS: Patients in both groups (ten in JP and 12 in JA) did not differ in local recurrence (p ≥ 0.999) and occurrence of metastases (p ≥ 0.999). Overall survival was similar in both groups (p = 0.858). Patients in the JP group had less range of motion (ROM) of the knee (p < 0.001) and lower MSTS scores (p = 0.010) compared with those of the JA group only at one year postoperatively. There was no difference between groups either at three years for ROM (p = 0.185) and MSTS score (p = 0.678) or at five years for ROM (p = 0.687) and MSTS score (p = 0.536), postoperatively. Patients in the JA group tended to have more complications (p = 0.074). Survival of primary reconstruction in the JP group was better than that of the JA group (p = 0.030). CONCLUSION: Cryoablation-aided joint-sparing surgery offers native joint preservation with comparable functional recovery and more durable reconstruction without jeopardizing oncological outcomes compared with conventional limb salvage surgery. Cite this article: Bone Joint J 2021;103-B(8):1421-1427.

Use of Vascularized Fibular Epiphyseal Transfer with Massive Bone Allograft for Proximal Humeral Reconstruction in Children with Bone Sarcoma.

BACKGROUND: The vascularized fibula epiphyseal transfer provides a reconstructive option for longitudinal growth after oncologic resection of the proximal humerus in pediatric patients. However, postoperative fractures and poor shoulder function are common. The purpose of this review was to introduce a composite approach in oncologic reconstruction of the proximal humerus and assess its clinical outcomes. METHODS: We retrospectively investigated five children (3 osteosarcoma and 2 Ewing's sarcoma) who underwent biological reconstruction with combination of vascularized fibula epiphyseal transfer and massive bone allograft after oncologic resection of the proximal humerus. The mean follow-up was 46.8 months. RESULTS: All patients were alive at the last follow-up. There was no graft fracture, hardware failure, or infection. The mean time of osseous union was 2.9 months at fibula-humerus junction and 6.2 months at allograft-humerus junction. Hypertrophy and axial growth were evident in all, except one patient who has avascular necrosis of the fibula head. The mean hypertrophy index was 51.5%, and the mean growth was 4.4 mm per annum. The mean arm discrepancy was 4.6 cm. All reconstruction was in situ with the average abduction of 113° and forward flexion of 69°. The mean Musculoskeletal Tumor Society (MSTS) score was 85.4% at the final follow-up. All patients experienced dropped foot and resolved spontaneously. CONCLUSIONS: The combination of vascularized fibula epiphyseal transfer with massive allograft bone provides a reliable oncologic reconstruction of proximal humerus in children. It not only offers the ability of longitudinal growth, hypertrophy, and osseous union but also diminishes reconstructive complications and improves shoulder function. LEVEL OF EVIDENCE: Therapeutic Level IV.

Effective treatment of anlotinib in giant delayed pulmonary metastasis of osteosarcoma: a case report and literature review.

Tumor relapse and pulmonary metastasis, especially unresectable lesions, are the major cause of poor prognosis of patients with osteosarcoma. Anlotinib, a novel small-molecule tyrosine kinase inhibitor (TKI), has been proved to have desirable anti-tumor effects via blocking VEGFR2 and PDGFRß phosphorylation in several tumors, including non-small cell lung cancer and soft tissue sarcoma. In this study, we presented a case of giant delayed pulmonary metastasis of osteosarcoma which was effectively treated by anlotinib. CT scan of this patient showed a giant neoplasm with the size of 1,366 cm3 in the left lung, clinically diagnosed as pulmonary metastasis of osteosarcoma. Due to refusing to chemotherapy and not eligible for surgery of the giant neoplasm, anlotinib was recommended. As a result, the tumor volume decreased more than 82% during 24-week anlotinib administration, from 1,366 to 247 cm3. Unfortunately, disease progression was observed at 27-week. Although argon-helium cryoablation (AHC) was performed followed by apatinib administration, the patient was dead in 16 weeks after disease progression. The progression-free survival (PFS) and overall survival since anlotinib administration of this patient was 27 weeks and 43 weeks, respectively. The toxicity included hypertension, fatigue and hand-foot skin syndrome in grade 1-2, which were controllable and well tolerated. Meanwhile, immunohistochemical staining showed that the expression of VEGFR2 and PDGFRß was decreased significantly and the whole exon sequencing revealed that c-MYC was duplicated, which was potentially associated with anlotinib resistance. Anlotinib had promising anti-tumor efficiency in the treatment of delayed pulmonary metastatic osteosarcoma. However, the potential mechanism of anlotinib resistance and the subsequent therapy after resistance were still challengeable and needed further investigation.

Is frozen tumour-bearing autograft with concurrent vascularized fibula an alternative to the Capanna technique for the intercalary reconstruction after resection of osteosarcoma in the lower limb?

AIMS: The use of frozen tumour-bearing autograft combined with a vascularized fibular graft (VFG) represents a new technique for biological reconstruction of massive bone defect. We have compared the clinical outcomes between this technique and Capanna reconstruction. METHODS: From June 2011 to January 2016 a retrospective study was carried out of patients with primary osteosarcoma of lower limbs who underwent combined biological intercalary reconstruction. Patients were categorized into two groups based on the reconstructive technique: frozen tumour-bearing autograft combined with concurrent VFG (Group 1) and the Capanna method (Group 2). Demographics, operating procedures, oncological outcomes, graft union, limb function, and postoperative complications were compared. RESULTS: A total of 23 patients were identified for analysis: eight in Group 1 and 15 in Group 2. There was no difference in the demographics (age, sex, and affected site) and operating procedures (resection length, duration of surgery, and blood loss) between the two groups. No significant difference was found in local recurrence in Group 1 versus Group 2 (p = 0.585). Mean union time for the frozen autograft-host junction was 8.4 months (7.0 to 11.0), significantly earlier than for the allograft-host junction in Group 2 (mean 14.1 months (10.0 to 28.0); p < 0.001). Mean Musculoskeletal Tumor Society scores in groups 1 and 2 were 90.3% (SD 7.4%) and 88.0% (SD 9.0%), respectively, with no significant statistical difference (p = 0.535). In terms of complications, infection (n = 1, 6.7%) and delayed union (n = 2, 13.3%) occurred in Group 2, but no such complications were observed in Group 1. CONCLUSION: Frozen tumour-bearing autograft in combination with VFG can be used as an alternative to the Capanna reconstruction in properly selected patients with osteosarcoma. Cite this article: Bone Joint J 2020;102-B(5):646-652.

Factors Influencing Osseous Union Following Surgical Treatment of Bone Tumors with Use of the Capanna Technique.

BACKGROUND: The Capanna technique involves the use of a vascularized fibular graft inlaid in a massive bone graft in intercalary reconstruction for diaphyseal long-bone defects caused by tumor resection. Allograft-host union time varies in different reports, and few studies have focused on the underlying factors affecting union time. The purpose of the present study was to analyze factors relevant to union time and to report complications of the Capanna technique. METHODS: We identified 60 patients who underwent segmental reconstruction with use of the Capanna technique following tumor resection (in the humerus in 10 patients, the femur in 33 patients, and the tibia in 17 patients). Multivariable linear multiple regression model analysis was performed with allograft-host osseous union time as the dependent variable. Union time was evaluated on radiographs. Independent variables included age, tumor site, adjuvant treatment, a previous surgical procedure, defect length, fixation method, and fibular viability. A retrieved specimen of the composite was histologically assessed. RESULTS: The mean defect length was 16 cm. All allografts and host bone united, with the mean time to union of 13 months (range, 6 to 27 months). Prolonged union time was associated with devitalization of the fibular graft (p < 0.001), use of chemotherapy (p = 0.031), and a previous surgical procedure (p = 0.048). Patient age (p = 0.742), amount of resection (p = 0.907), operative site (p = 0.508), and fixation method (p = 0.105) were not associated with union time. On histological analysis, we found that the allograft-host cortical junction was united by callus from both periosteum of the host bone and the fibula. CONCLUSIONS: The Capanna technique appears to be a reliable method for intercalary reconstruction with a low rate of complications. Devitalization of the transplanted fibula, chemotherapy, and a previous surgical procedure are adverse factors leading to prolonged union time. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Kinematic parameter analysis and pilot clinical trial of dual-mobility semi-Knee prosthesis.

BACKGROUND: To address large tumor-related defects and lower limb-length discrepancies during limb-salvage surgery in children with malignant tumors in the distal femur, a new custom-made dual-mobility semi-knee prosthesis (DMK) was made. This study aimed to provide a theory and references for further clinical applications of this prosthesis. METHODS: Based on computed tomography data from adult knee joint samples, we used Mimics/Geomagic/Pro-E software and computer numerical control milling technology to design and manufacture the DMK. An in vitro study was carried out to examine the related kinematic parameters in the normal knee, total knee arthroplasty and DMK groups of cadaveric specimens. Then, a pilot clinical trial was performed. RESULTS: The in vitro study revealed that the kinematics of the novel custom-made DMK are more similar to those of the normal knee than the total knee prosthesis. The pilot clinical trial showed that patients recovered well, and postoperative serial X-ray films did not demonstrate any disfigurations, loosening, dislocations or breaks in the prosthesis after a follow-up period ranging from 11 months to 5 years. CONCLUSION: The DMK is a novel concept and method for the treatment of malignant tumors in the distal femur in children, and the device used for ligament reattachment provides a solution for knee ligament reconstruction. However, DMK might be replaced by a total knee prosthesis after epiphyseal closure, because of incompatibility of tibial plateau with the prosthesis.