Endoprosthetic reconstruction for lower extremity soft tissue sarcomas with bone involvement.

BACKGROUND AND OBJECTIVES: Bone resection and endoprosthetic reconstruction (EPR) in the setting of soft tissue sarcoma (STS) management is rare and incurs unique challenges. We aim to report on the surgical and oncological outcomes of this relatively previously undocumented cohort. METHODS: This is a single-center retrospective review of prospectively collected data for patients who required EPRs following resection of STSs of the lower extremity. Following inclusion criteria, we assessed 29 cases of EPR for primary STS of the lower limb. RESULTS: The mean age was 54 years (range 18-84). Of the 29 patients, there were 6 total femur, 11 proximal femur, 4 intercalary, and 8 distal femur EPRs. Fourteen of 29 patients (48%) underwent re-operations for surgical complications, with 9 relating to infection (31%). When a matched cohort analysis was performed comparing our cohort to STSs that did not necessitate EPR, a reduced rate of overall survival and metastasis-free survival was found in those requiring EPR. CONCLUSION: This series identifies a high rate of complication from EPRs performed for STS. Patients should be cautioned about the high rate of infection, surgical complications, and lower overall survival in this setting.

Management of meningeal solitary fibrous tumors/hemangiopericytoma; surgery alone or surgery plus postoperative radiotherapy?

INTRODUCTION: A meningeal solitary fibrous tumor (SFT), also called hemangiopericytoma, is a rare mesenchymal malignancy. Due to anatomic constrains, even after macroscopic complete surgery with curative intent, the local relapse risk is still relatively high, thus increasing the risk of dedifferentiation and metastatic spread. This study aims to better define the role of postoperative radiotherapy (RT) in meningeal SFTs. PATIENTS AND METHODS: A retrospective study was performed across seven sarcoma centers. Clinical information was retrieved from all adult patients with meningeal primary localized SFT treated between 1990 and 2018 with surgery alone (S) compared to those that also received postoperative RT (S + RT). Differences in treatment characteristics between subgroups were tested using independent samples t-test for continuous variables and chi-square tests for proportions. Local control (LC) and overall survival (OS) rates were calculated as time from start of treatment until progression or death from any cause. LC and OS in groups receiving S or S + RT were compared using Kaplan-Meier survival curves. RESULTS: Among a total of 48 patients, 7 (15%) underwent S and 41 (85%) underwent S + RT. Median FU was 65 months. LC was significantly associated with treatment. LC after S at 60 months was 60% versus 90% after S + RT (p = 0.052). Furthermore, R1 resection status was significantly associated with worse LC (HR 4.08, p = 0.038). OS was predominantly associated with the mitotic count (HR 3.10, p = 0.011). CONCLUSION: This retrospective study, investigating postoperative RT in primary localized meningeal SFT patients, suggests that combining RT to surgery in the management of this patient population may reduce the risk for local failures.

Intercalary allograft augmented with intramedullary cement and plate fixation is a reliable solution after resection of a diaphyseal tumour.

AIMS: Intercalary allografts following resection of a primary diaphyseal tumour have high rates of complications and failures. At our institution intercalary allografts are augmented with intramedullary cement and fixed using compression plating. Our aim was to evaluate their long-term outcomes. PATIENTS AND METHODS: A total of 46 patients underwent reconstruction with an intercalary allograft between 1989 and 2014. The patients had a mean age of 32.8 years (14 to 77). The most common diagnoses were osteosarcoma (n = 16) and chondrosarcoma (n = 9). The location of the tumours was in the femur in 21, the tibia in 16 and the humerus in nine. Function was assessed using the Musculoskeletal Tumor Society (MSTS) scoring system and the Toronto Extremity Salvage Score (TESS). The survival of the graft and the overall survival were assessed using the Kaplan-Meier method. RESULTS: The median follow-up was 92 months (4 to 288). The mean MSTS 87 score was 29.1 (19 to 35), the mean MSTS 93 score was 82.2 (50 to 100) and the mean TESS score was 81.2 (43 to 100). Overall survival of the allograft was 84.8%. A total of 15 patients (33%) had a complication. Five allografts were revised for complications and one for local recurrence. CONCLUSION: Intercalary allografts augmented with intramedullary cement and compression plate fixation provide a reliable and durable method of reconstruction after the excision of a primary diaphyseal bone tumour, with high levels of function and satisfaction. Cite this article: Bone Joint J 2017;99-B:973-8.

Epithelioid sarcomas: How important is loco-regional control?

AIMS: To investigate the impact of the method of treatment on the oncological outcomes in patients with epithelioid sarcomas managed at two international speciality sarcoma centres. METHODS: The databases of two centres were used to identify patients treated for epithelioid sarcomas between 1985 and 2012. Patient, tumor, treatment and outcome data was collected. RESULTS: There were 36 males and 18 females with a mean age of 38.3 years (range 9-79). Of 49 patients who were treated surgically, limb salvage surgery was carried out in 38 patients (78%) and limb amputation in 11 (22%). Of 49 total patients who underwent surgery for ES, 48 (98%) with ES had negative margin resection and 24 (49%) received (neo) adjuvant radiotherapy. Regional lymph node metastases developed in 5 (13%) patients. The five-year risk of local recurrence was 14%. The overall survival rate at five and ten years was 70% and 66% respectively. In multivariate analysis of patients with localized disease and negative margins, survival and risk of metastases was worse in those treated by amputation. CONCLUSION: This series has shown that although the rate of local recurrence is not influenced by the type of surgery, the risk of metastases is higher following amputation. This finding is likely due to patients with larger, deeper and more locally advanced tumors requiring amputation. However, we could not prove that immediate amputation was likely to affect overall survival.

Patient, tumour and treatment factors affect complication rates in soft tissue sarcoma flap reconstruction in a synergistic manner.

INTRODUCTION: Flap reconstruction plays an essential role in the management of soft tissue sarcoma, facilitating wide resection while maximizing preservation of function. The addition of reconstruction increases the complexity of the surgery and identification of patients who are at high risk for post-operative complications is an important part of the preoperative assessment. This study examines predictors of complications in these patients. METHODS: 294 patients undergoing flap reconstruction following sarcoma resection were evaluated. Data on patient, tumour and treatment variables as well as post-operative complications were collected. Bivariate and multivariate regression analysis was performed to identify independent predictors of complications. Analysis of synergistic interaction between key patient and tumour risk factors was subsequently performed. RESULTS: A history of cerebrovascular events or cardiac disease were found to be the strongest independent predictors of post-operative complications (OR 14.84, p = 0.003 and OR 5.71, p = 0.001, respectively). Further strong independent tumour and treatment-related predictors were high grade tumours (OR 1.91, p = 0.038) and the need for additional reconstructive procedures (OR 2.78, p = 0.001). Obesity had significant synergistic interaction with tumour resection diameter (RERI 1.1, SI 1.99, p = 0.02) and high tumour grade (RERI 0.86, SI 1.5, p = 0.01). Comorbidities showed significant synergistic interaction with large tumour resections (RERI 0.91, SI 1.83, p = 0.02). CONCLUSION: Patient, tumour and treatment-related variables contribute to complications following flap reconstruction of sarcoma defects. This study highlights the importance of considering the combined effect of multiple risk factors when evaluating and counselling patients as significant synergistic interaction between variables can further increase the risk of complications.

The effect of surgical synovectomy and radiotherapy on the rate of recurrence of pigmented villonodular synovitis of the knee: an individual patient meta-analysis.

Pigmented villonodular synovitis (PVNS) is a rare proliferative process of the synovium which most commonly affects the knee and occurs in either a localised (LPVNS) or a diffuse form (DPVNS). The effect of different methods of surgical synovectomy and adjuvant radiotherapy on the rate of recurrence is unclear. We conducted a systematic review and identified 35 observational studies in English which reported the use of surgical synovectomy to treat PVNS of the knee. A meta-analysis included 630 patients, 137 (21.8%) of whom had a recurrence after synovectomy. For patients with DPVNS, low-quality evidence found that the rate of recurrence was reduced by both open synovectomy (odds ration (OR) = 0.47; 95% CI 0.25 to 0.90; p = 0.024) and combined open and arthroscopic synovectomy (OR = 0.19, 95% CI = 0.06 to 0.58; p = 0.003) compared with arthroscopic surgery. Very low-quality evidence found that the rate of recurrence of DPVNS was reduced by peri-operative radiotherapy (OR = 0.31, 95% CI 0.14 to 0.70; p = 0.01). Very low-quality evidence suggested that the rate of recurrence of LPVNS was not related to the surgical approach. This meta-analysis suggests that open synovectomy or synovectomy combined with peri-operative radiotherapy for DPVNS is associated with a reduced rate of recurrence. Large long-term prospective multicentre observational studies, with a focus on both rate of recurrence and function, are required to confirm these findings.

Fixation of pathological humeral fractures by the cemented plate technique.

Pathological fractures of the humerus are associated with pain, morbidity, loss of function and a diminished quality of life. We report our experience of stabilising these fractures using polymethylmethacrylate and non-locking plates. We undertook a retrospective review over 20 years of patients treated at a tertiary musculoskeletal oncology centre. Those who had undergone surgery for an impending or completed pathological humeral fracture with a diagnosis of metastatic disease or myeloma were identified from our database. There were 63 patients (43 men, 20 women) in the series with a mean age of 63 years (39 to 87). All had undergone intralesional curettage of the tumour followed by fixation with intramedullary polymethylmethacrylate and plating. Complications occurred in 14 patients (22.2%) and seven (11.1%) required re-operation. At the latest follow-up, 47 patients (74.6%) were deceased and 16 (25.4%) were living with a mean follow-up of 75 months (1 to 184). A total of 54 (86%) patients had no or mild pain and 50 (80%) required no or minimal assistance with activities of daily living. Of the 16 living patients none had pain and all could perform activities of daily living without assistance. Intralesional resection of the tumour, filling of the cavity with cement, and plate stabilisation of the pathological fracture gives immediate rigidity and allows an early return of function without the need for bony union. The patient's local disease burden is reduced, which may alleviate tumour-related pain and slow the progression of the disease. The cemented-plate technique provides a reliable option for the treatment of pathological fractures of the humerus.

Clinical features, treatment, and outcome in 102 adult and pediatric patients with localized high-grade synovial sarcoma.

Background. There remains controversy on the routine use of chemotherapy in localized SS. Methods. The records of 87 adult (AP) and 15 pediatric (PP) patients with localized SS diagnosed between 1986 and 2007 at 2 centres in Toronto were reviewed. Results. Median age for AP and PP was 37.6 (range 15-76) and 14 (range 0.4-18) years, respectively. 65 (64%) patients had large tumours (>5 cm). All patients underwent en bloc surgical resection resulting in 94 (92.2%) negative and 8 (7.8%) microscopically positive surgical margins. 72 (82.8%) AP and 8 (53%) PP received radiotherapy. Chemotherapy was administered to 12 (13.8%) AP and 13 (87%) PP. 10 AP and 5 PP were evaluable for response to neoadjuvant chemotherapy, with response rate of 10% and 40%, respectively. 5-year EFS and OS was 69.3 ± 4.8% and 80.3 ± 4.3%, respectively, and was similar for AP and PP, In patients with tumors >5 cm, in whom chemotherapy might be considered most appropriate, relapse occurred in 9/19 (47%) with chemotherapy, compared to 17/46 (37%) In those without. Conclusions. Patients with localized SS have a good chance of cure with surgery and RT. Evidence for a well-defined role of chemotherapy to improve survival In localized SS remains elusive.

Prospective controlled trial of an electrophoretic method of sperm preparation for assisted reproduction: comparison with density gradient centrifugation.

BACKGROUND: A membrane-based electrophoretic filtration system, known as the Cell Sorter-10 (CS-10), that preferentially isolates spermatozoa with very low levels of DNA damage has recently been developed. However, it remains to be proven whether spermatozoa prepared in this way are capable of achieving fertilization in assisted conception. Therefore, this clinical trial was designed to answer this question. METHODS: A split-sample split-cohort study design was employed to control for differences in semen and oocyte quality between 28 couples undergoing either intracytoplasmic sperm injection (ICSI) or IVF in this clinical trial. Each semen sample was split between preparation using the CS-10 and preparation by standard density gradient centrifugation (DGC) and each cohort of oocytes was split for insemination using either CS-10 (n = 197) or DGC (n = 195) prepared spermatozoa. RESULTS: Both methods of sperm preparation yielded comparable rates of sperm recovery, motility and DNA fragmentation. There was no significant difference between the ability of CS-10 and DGC prepared spermatozoa to produce fertilization (62.4% versus 63.6%), cleavage (99.0% versus 88.5%) and high-quality embryos (27.4% versus 26.1%). CONCLUSIONS: This pilot study demonstrates that membrane-based electrophoresis is as effective as DGC in preparing sperm for IVF and ICSI, although it takes only a fraction of the time.

Does the method of treatment affect the outcome in soft-tissue sarcomas of the adductor compartment?

We have investigated the significance of the method of treatment on the oncological and functional outcomes and on the complications in 184 patients with soft-tissue sarcomas of the adductor compartment managed at three international centres. The overall survival at five years was 65% and was related to the grade at diagnosis and the size of the tumour. There was no difference in overall survival between the three centres. There was, however, a significant difference in local control with a rate of 28% in Centre 1 compared with 10% in Centre 2 and 5% in Centre 3. The overall mean functional score using the Toronto Extremity Salvage Score in 70 patients was 77% but was significantly worse in patients with wound complications or high-grade tumours. The scores were not affected by the timing of radiotherapy or the use of muscle flaps. This large series of soft-tissue sarcomas of the adductor compartment has shown that factors influencing survival do not vary across the international boundaries studied, but that methods of treatment affect complications, local recurrence and function.

Multifocality and multifocal postradiation sarcomas.

UNLABELLED: Hypothetically, any site in a radiation portal has potential for late malignant transformation. Secondary malignant neoplasms may occur after almost any index cancer has been treated with radiation and/or chemotherapy. The incidence of secondary malignant neoplasms, histopathology, time delay, radiation dose, cytotoxic agents, age and type of initial malignancy, and outcome all negatively impact cancer survivors. We highlight the new concept of multifocality, defined as greater than two noncontiguous second malignant neoplasms that develop in a prior radiation port. We identified 48 patients with postradiation sarcomas from three prospectively collected databases. Fifteen of these patients (31%) had evidence of multifocal postradiation sarcomas. Five of 10 women had multifocal postradiation sarcomas after breast-conserving surgery for carcinoma. The longer the time interval between the index cancer and post-radiation sarcoma, the greater the likelihood of multifocal malignant transformation occurring. LEVEL OF EVIDENCE: Therapeutic study, level III.

Action of hypoxanthine and meiosis-activating sterol on oocyte maturation in the mouse is strain specific.

Follicular fluid meiosis-activating sterol (FF-MAS) is regarded as an important compound relevant to meiotic resumption in mammalian oocytes. The objective of this study was to investigate the influence of FF-MAS on germinal vesicle breakdown (GVBD) and first polar body (PBI) extrusion with regard to culture conditions, state of the oocyte and mouse strain. Denuded oocytes (DO) and cumulus-enclosed oocytes (CEO) were retrieved from PMSG-primed Quackenbush or C57BL/6J x DBA/2 (C57) mice and cultured for 20 h in alpha-MEM medium under the following conditions: (i) 250 micromol/l dibutyryl cAMP (dbcAMP) +/- EGF, 1 ng/ml or FF-MAS, 20 micromol/l; (ii) 4 mmol/l hypoxanthine (HX) +/- EGF or FF-MAS; (iii) HX + EGF + FF-MAS; and (iv) HX + FF-MAS 5 h priming and subsequent culture with HX + EGF. Oocyte GVBD and PBI emission were recorded and stained with Hoechst 33342. Very limited meiotic inhibition was observed in Quackenbush mice in comparison with C57 mice. FF-MAS promoted maturation in C57 DO and CEO and Quackenbush DO. In Quackenbush DO and CEO and C57 DO a significant increase in atypical PBI extrusion occurred, but not in C57 CEO as well as in EGF-treated Quackenbush CEO primed or co-cultured with FF-MAS. These results support a meiosis resumption function for FF-MAS and suggest that in its presence, the quality of the MII oocytes retrieved appears to be influenced by the strain of the mice, the state of the oocyte and the presence or absence of growth factors in the culture medium.

The influence of anatomic location on functional outcome in lower-extremity soft-tissue sarcoma.

BACKGROUND: The purpose of this study was to explore the relationship between the anatomical location of lower-extremity soft-tissue sarcoma and functional outcome. METHODS: Function was evaluated with the Musculoskeletal Tumor Society (MSTS 1993) score and Toronto Extremity Salvage Score (TESS); 207 patients (median age, 54 years) were eligible. The median maximum tumor diameter was 8.0 cm; 58 tumors were superficial and 149 were deep. Nine locations based on anatomical compartments were defined: 6 tumors were in the groin/femoral triangle; 8, the buttock; 52, the anterior thigh; 22, the medial thigh; 20, the posterior thigh; 10, the popliteal fossa; 13, the posterior calf; 11, the anterolateral leg; and 7, the foot or ankle. RESULTS: Treatment of superficial tumors did not lead to significant changes in MSTS score (mean, 90.6% preoperatively vs. 93.0% postoperatively; P =.566) or TESS (mean, 86.4% preoperatively vs. 90.9% postoperatively; P =.059). Treatment of deep tumors lead to significant reductions in MSTS score and TESS (mean MSTS, 86.9% preoperatively vs. 83.0% postoperatively; P =.001; and mean TESS, 83.0% preoperatively vs. 79.4% postoperatively; P =.015). Anatomical location was not a significant predictor of aggregated MSTS and TESS evaluations. Exploratory analysis showed variation in MSTS pain and gait handicap or limp items and TESS dressing, sitting, bending, and bathing items by anatomical location. CONCLUSIONS: The treatment of superficial tumors does not lead to significant changes in MSTS score or TESS. Anatomical location is not a significant predictor of aggregated MSTS and TESS evaluations. However, there is variation in MSTS and TESS item scores across anatomical locations.

Preoperative radiotherapy is effective in the treatment of fibromatosis.

The use of preoperative radiation is well-established for soft tissue sarcoma, but its use in fibromatosis is not well-characterized. The purpose of this study was to examine the impact of preoperative radiotherapy on the local control of fibromatosis and to assess treatment-related morbidity in this setting. In particular we assessed complication rates in comparison with soft tissue sarcoma treatment. All patients with fibromatosis referred to this unit who received preoperative radiotherapy (50 Gy in 25 fractions) from 1988 to 2000 and who had at least 2 years of followup were included in this study. The rate of recurrence in this group was ascertained. Similarly constructed datasets from all patients with soft tissue sarcomas of the extremities who received preoperative radiation from 1986 to 1997 also were analyzed. The rates of complications in the two groups were compared. Fifty-eight patients were treated with preoperative radiation for fibromatosis and the median followup was 69 months. There were 11 local recurrences (19%). Major wound complications manifested in two patients (3.4%). Wound-related complications arose in 89 of 265 patients with soft tissue sarcomas (33.5%). There was a significant difference in the rate of major wound complications observed in the two groups. The use of radiotherapy before surgery is effective in the combined treatment of fibromatosis.

A rapid population expansion retains genetic diversity within European rabbits in Australia.

The well documented historical translocations of the European rabbit (Oryctolagus cuniculus) offer an excellent framework to test the genetic effects of reductions in effective population size. It has been proposed that rabbits went through an initial bottleneck at the time of their establishment in Australia, as well as multiple founder events during the rabbit's colonization process. To test these hypotheses, genetic variation at seven microsatellite loci was measured in 252 wild rabbits from five populations across Australia. These populations were compared to each other and to data from Europe. No evidence of a genetic bottleneck was observed with the movement of 13 rabbits from Europe to Australia when compared to French data. Within Australia the distribution of genetic diversity did not reflect the suggested pattern of sequential founder effects. In fact, the current pattern of genetic variation in Australia is most likely a result of multiple factors including mutation, genetic drift and geographical differentiation. The absence of reduced genetic diversity is almost certainly a result of the rabbit's rapid population expansion at the time of establishment in Australia. These results highlight the importance of population growth following a demographic bottleneck, which largely determines the severity of genetic loss.

Instability after major tumor resection: prevention and treatment.

Instability is a significant problem after resection of musculoskeletal tumors. In this article, the authors discuss the issue of instability after resections of the pelvis, the femur, and the proximal tibia. The options for reconstruction in each area are discussed along with a review of the literature and a description of the authors' preferred approach.

Pentyl-4-yn-valproic acid enhances both spatial and avoidance learning, and attenuates age-related NCAM-mediated neuroplastic decline within the rat medial temporal lobe.

2-N-Pentyl-4-pentynoic acid [pentyl-4-yn-valproic acid (VPA)] is an analogue of valproic acid that induces neuritogenesis and increases neural cell adhesion molecule (NCAM) prevalence in cultured neural cells. As memory consolidation involves synapse growth, aided by cell adhesion molecule function, we determined whether or not pentyl-4-yn-VPA had cognition-enhancing properties. Pentyl-4-yn-VPA (16-85 mg/kg) significantly improved water maze learning and task retention when given prior to each training session. Acute administration of pentyl-4-yn-VPA also influenced memory consolidation processes as, when given at 3 h post-passive avoidance training, the amnesia induced by scopolamine given 6 h post-training was prevented in a dose-dependent manner. Chronic administration of pentyl-4-yn-VPA (16.8 or 50.4 mg/kg) also significantly reduced escape latencies in the water maze task, 24 h following the last drug administration. This improved spatial learning was accompanied by enhanced neuroplasticity as the expression of NCAM polysialylated neurons in the infragranular zone of the dentate gyrus and in layer II of the perirhinal and piriform cortex was increased significantly following chronic drug treatment. The cognition-enhancing qualities of pentyl-4-yn-VPA, combined with its ability to attenuate the age-related loss of the NCAM polysialylation state, suggest that it may effectively slow the onset of cognitive decline.

Comparison of two methods of reconstruction for primary malignant tumors at the knee: a sequential cohort study.

BACKGROUND AND OBJECTIVES: The purpose of this study was to compare the complications and functional outcome associated with the use of an irradiated allograft-implant composite or a bone-ingrowth modular tumor prosthesis for replacement of the knee joint after resection of a bone sarcoma from the distal femur or proximal tibia. METHODS: Eleven patients initially received an allograft reconstruction, followed by 64 treated with a tumor prosthesis. The primary analysis concerned reconstructive failure, defined by the requirement for removal of the original construct. Functional outcome was assessed by using the 1987 Musculoskeletal Tumor Society rating system. RESULTS: Reconstructive failure occurred in 6 of 11 (55%) allograft constructs compared with 10 of 64 (16%) tumor prostheses (P = 0.009). Failures were due to infection (2 of 11 allografts versus 4 of 64 prostheses; P = 0.2) or mechanical complications (4 of 11 allograft fractures versus 5 of 64 broken prosthetic stems and 1 aseptically loose prosthesis; P = 0.03). The limb salvage rate was 95% (61 of 64) for patients with a tumor prosthesis compared with 64% (7 of 11) for those with an allograft (P = 0.007). Patients with a tumor prosthesis had a better functional outcome with a mean score of 75% compared with 57% for those with an allograft reconstruction (P = 0.006). CONCLUSIONS: This comparative study suggests that limb salvage surgery at the knee has a better and more predictable outcome with a tumor prosthesis than with an allograft-implant reconstruction.

Structure and conformation of a novel genetically engineered polysaccharide P2.

A new exocellular polysaccharide (P2) has been produced by the manipulation of a glycosyl transferase gene (aceP) involved in the biosynthesis of the polysaccharide acetan by the bacterium Acetobacter xylinum strain CKE5. The P2 polysaccharide has been studied by methylation analysis, reductive cleavage, and 1H and 13C NMR spectroscopy. The data are consistent with the structure predicted when the aceP gene is deactivated: [Molecular structure: see text]. The effect of cooling on proton NMR line width indicates a coil-helix transition in P2 at about 70 degrees C.

Classification of positive margins after resection of soft-tissue sarcoma of the limb predicts the risk of local recurrence.

We considered whether a positive margin occurring after resection of a soft-tissue sarcoma of a limb would affect the incidence of local recurrence. Patients with low-grade liposarcomas were expected to be a low-risk group as were those who had positive margins planned before surgery to preserve critical structures. Two groups, however, were expected to be at a higher risk, namely, patients who had undergone unplanned excision elsewhere with a positive margin on re-excision and those with unplanned positive margins occurring during primary resection. Of 566 patients in a prospective database, 87 with positive margins after limb-sparing surgery and adjuvant radiotherapy were grouped according to the clinical scenario by an observer blinded to the outcome. The rate of local recurrence differed significantly between the two low- (4.2% and 3.6%) and the two high-risk groups (31.6% and 37.5%). This classification therefore provides useful information about the incidence of local recurrence after positive-margin resection.