Raimondo Piana

Rugby players' awareness of concussion.

PurposeConcussion is a common issue in most contact sports, such as rugby, being one of the most troublesome injuries facing the sports medicine physician. The aim of this article was to survey the knowledge and beliefs concerning concussion in a sample of young rugby athletes in the northwest of Italy. MethodsThe athletes of 4 amateur rugby teams completed a questionnaire about their knowledge about the signs and symptoms of concussion and of return-to-play strategies and protocols. ResultsTwenty-five athletes reported that they had not been informed by anyone about symptoms of concussion and its consequences. Among these, 7 players thought they could return to play immediately after a concussion during the very same match. ConclusionsThe surveyed group in this study presented a general lack of knowledge of concussion. Rugby athletes and coaches must be made aware about signs and symptoms of concussion to suspect this injury. It would be desirable that rugby players are educated regarding the potential risks of playing while symptomatic.

The management of soft tissue sarcomas

BACKGROUND Soft tissue sarcomas are a rare and heterogenous group of malignancies that are derived from the mesenchymal cell lines. In the last few decades, the management of these lesions has been improved by the introduction of dedicated Multi Disciplinary Teams (MDTs) where most bone and soft tissue tumours are now treated.(1) Following the recent changes to management outlined by the NICE/IOGs, we believe it is pertinent to review the current thinking on soft tissue tumour management.(2) We also discuss the principles of diagnosis and treatment and the role of adjuvant therapy. METHODS This is a retrospective review. In the preparation of this paper, we have referred to recent NICE guidelines in this field and have performed a Medline search of the existing literature. RESULTS The key to the success is early and appropriate patient referral. Whilst the responsibility for performing surgery has shifted away from the generalist and towards the super specialist, improvements in survivability can be achieved by promoting basic knowledge within the medical profession as a whole. CONCLUSIONS Both excision and biopsy of a soft tissue sarcoma by a non-specialist surgeon have been shown to increase the risk of tumour recurrence and all invasive procedures should now be performed within the MDT setting.

Accuracy of core-needle biopsy after contrast-enhanced ultrasound in soft-tissue tumours

ObjectivePercutaneous biopsies are gaining acceptance in the diagnosis of soft-tissue tumours. Sampling in the most representative area is not easy in sarcomas of huge dimension. We hypothesised that ultrasound (US) contrast medium could identify the representative area for focus core-needle biopsy (CNB)MethodsThis is a retrospective cohort series of 115 soft-tissue masses treated from January 2007 to November 2008. Accuracy of US-guided CNB after contrast-enhanced US (CEUS) was determined by comparing the histology of the biopsy with the definitive diagnosis in 105 surgically excised samples (42 benign, 63 malignant) and with the expected outcome in the remaining ten malignant cases not surgically treated. A myxoid component was present in 21 sarcomas (34.4%).ResultsOf samples, 94.8% were adequate for diagnosis with 97.1% sensitivity and 92.5% specificity. Sensitivity and specificity in specific histopathological subgroupings were 100%, and in grading definition they were 100% and 96.8%.DiscussionUS-guided CNB is safe and effective. US contrast medium depicts tumour vascular supply and identifies the representative area(s) for sampling. Sensitivity and specificity are also high in subgrouping and grading, including myxoid types. Discussion about biopsy is part of the essential multidisciplinary strategy for these tumours.

Perfusion pattern and time of vascularisation with CEUS increase accuracy in differentiating between benign and malignant tumours in 216 musculoskeletal soft tissue masses

INTRODUCTION Musculoskeletal Soft Tissue Tumours (STT) are frequent heterogeneous lesions. Guidelines consider a mass larger than 5 cm and deep with respect to the deep fascia potentially malignant. Contrast Enhanced Ultrasound (CEUS) can detect both vascularity and tumour neoangiogenesis. We hypothesised that perfusion patterns and vascularisation time could improve the accuracy of CEUS in discriminating malignant tumours from benign lesions. MATERIALS AND METHODS 216 STT were studied: 40% benign lesions, 60% malignant tumours, 56% in the lower limbs. Seven CEUS perfusion patterns and three types of vascularisation (arterial-venous uptake, absence of uptake) were applied. Accuracy was evaluated by comparing imaging with the histological diagnosis. Univariate and multivariate analysis, Chi-square test and t-test for independent variables were applied; significance was set at p<0.05 level, 95% computed CI. RESULTS CEUS pattern 6 (inhomogeneous perfusion), arterial uptake and location in the lower limb were associated with high risk of malignancy. CEUS pattern has PPV 77%, rapidity of vascularisation PPV 69%; location in the limbs is the most sensitive indicator, but NPV 52%, PPV 65%. The combination of CEUS-pattern and vascularisation has 74% PPV, 60% NPV, 70% sensitivity. No correlation with size and location in relation to the deep fascia was found. CONCLUSION US with CEUS qualitative analysis could be an accurate technique to identify potentially malignant STT, for which second line imaging and biopsy are indicated in Referral Centers. Intense inhomogeneous enhancement with avascular areas and rapid vascularisation time could be useful in discriminating benign from malignant SST, overall when the lower limbs are involved.

Adipose Derived-Mesenchymal Stem Cells Viability and Differentiating Features for Orthopaedic Reparative Applications: Banking of Adipose Tissue

Osteoarthritis is characterized by loss of articular cartilage also due to reduced chondrogenic activity of mesenchymal stem cells (MSCs) from patients. Adipose tissue is an attractive source of MSCs (ATD-MSCs), representing an effective tool for reparative medicine, particularly for treatment of osteoarthritis, due to their chondrogenic and osteogenic differentiation capability. The treatment of symptomatic knee arthritis with ATD-MSCs proved effective with a single infusion, but multiple infusions could be also more efficacious. Here we studied some crucial aspects of adipose tissue banking procedures, evaluating ATD-MSCs viability, and differentiation capability after cryopreservation, to guarantee the quality of the tissue for multiple infusions. We reported that the presence of local anesthetic during lipoaspiration negatively affects cell viability of cryopreserved adipose tissue and cell growth of ATD-MSCs in culture. We observed that DMSO guarantees a faster growth of ATD-MSCs in culture than trehalose. At last, ATD-MSCs derived from fresh and cryopreserved samples at −80°C and −196°C showed viability and differentiation ability comparable to fresh samples. These data indicate that cryopreservation of adipose tissue at −80°C and −196°C is equivalent and preserves the content of ATD-MSCs in Stromal Vascular Fraction (SVF), guaranteeing the differentiation ability of ATD-MSCs.

Eight- to ten-year results of a variable geometry stem.

This prospective study was conducted on 108 consecutive implantations straight, cementless, taper-designed stem with variable lateral flare (Pegasus; DePuy, Warsaw, Indiana) at an 8- to 10-year follow-up; DEXA scanning was performed at 3 and 12 months on a second cohort of 40 patients. The mean Harris hip score was 94.2, and no revision was performed. Measurable subsidence of the stem was found in three (2.8%) patients; the subsidence was always measured within the first year of follow-up, and did not progress at the subsequent controls. Bone mineral density decreased at 1 year, 15.1% in zone 1 and 3.4% in zone 7. Uncemented stems with a taper design, which provide a high metaphyseal fit and a low diaphyseal fit, lead to comparable and reproducible long-term results independently from other design characteristics.

Management of the first episode of traumatic shoulder dislocation

Shoulder joint dislocation is the most common joint dislocation seen in the emergency department. Traumatic dislocation may cause damage to the soft-tissues surrounding the shoulder joint and sometimes to the bone. The treatment, which aims at restoration of a fully functioning, pain-free and stable shoulder, includes either conservative or surgical management preceded by closed reduction of the acute dislocation. Conservative management usually requires a period of rest, generally involving immobilisation of the arm in a sling, even though it is still debated whether to immobilise the shoulder in internal or external rotation. Operative management, with no significant differences in term of re-dislocation rates between open and arthroscopic repair, incorporates soft-tissue reconstructions and/or bony procedures and is recommended in young male adults engaged in highly demanding physical activities. At our institution, non-operative management is favoured particularly for patients with multi-directional instability or soft-tissue laxity. Conservative measures are often preferred in older patients or younger patients that are not actively engaged in overhead activities. Immediate surgery on all first-time dislocations may subject many patients to surgery who would not have had any future subluxation. For these reasons, initially we will always try physical therapy and activity modification for the vast majority of our patients. Cite this article: EFORT Open Rev 2017;2:35-40.DOI: 10.1302/2058-5241.2.160018.

Trabectedin and olaparib in patients with advanced and non-resectable bone and soft-tissue sarcomas (TOMAS): an open-label, phase 1b study from the Italian Sarcoma Group

BACKGROUND Trabectedin is an alkylating drug with a unique mechanism of action causing single-strand and double-strand DNA breaks that activate DNA damage-response pathways. Based on our preclinical data, we hypothesised that poly(ADP-ribose) polymerase 1 (PARP1) inhibitors might be an ideal partner of trabectedin and aimed to assess the safety, identify the recommended phase 2 dose, and explore preliminary signs of activity of trabectedin and olaparib combination treatment in patients with bone and soft-tissue sarcoma. METHODS We did an open-label, multicentre, phase 1b study, recruiting patients from the national Italian sarcoma network aged 18 years and older with histologically confirmed bone and soft-tissue sarcoma progressing after standard treatments with Eastern Cooperative Oncology Group performance status of 1 or less. In a classic 3 + 3 design, patients received a 24 h infusion of trabectedin on day 1 and olaparib orally twice a day in 21-day cycles across six dose levels (trabectedin 0·675-1·3 mg/m2 every 3 weeks; olaparib 100-300 mg twice a day from day 1 to 21). Intermediate dose levels were permitted to improve safety and tolerability. The primary endpoint was determination of the recommended phase 2 dose (the maximum tolerated dose). Safety and antitumour activity were assessed in all patients who received at least one dose of the study drugs. We report the results of the dose-escalation and dose-expansion cohorts. The trial is still active but closed to enrolment, and follow-up for patients who completed treatment is ongoing. This trial is registered with ClinicalTrials.gov, number NCT02398058. FINDINGS Between Nov 17, 2014, and Jan 30, 2017, of 54 patients assessed for eligibility, we enrolled 50 patients: 28 patients in the dose-escalation cohort and 22 patients in the dose-expansion cohort. Patients received a median of four cycles of treatment (IQR 2-6; range 1-17 [the patients who received the highest number of cycles are still on treatment]) with a median follow-up of 10 months (IQR 5-23). Considering all dose levels, the most common grade 3-4 adverse events were lymphopenia (32 [64%] of 50 patients), neutropenia (31 [62%]), thrombocytopenia (14 [28%]), anaemia (13 [26%]), hypophosphataemia (20 [40%]), and alanine aminotransferase concentration increase (9 [18%]). No treatment-related life-threatening adverse events or deaths occurred. One (2%) patient interrupted treatment without progression without reporting any specific toxicity. Observed dose-limiting toxicities were thrombocytopenia, neutropenia for more than 7 days, and febrile neutropenia. We selected intermediate dose level 4b (trabectedin 1·1 mg/m2 every 3 weeks plus olaparib 150 mg twice a day) as the recommended phase 2 dose. Seven (14%; 95% CI 6-27) of 50 patients achieved a partial response according to Response Evaluation Criteria In Solid Tumors 1.1. INTERPRETATION Trabectedin and olaparib in combination showed manageable toxicities at active dose levels for both drugs. Preliminary data on antitumour activity are encouraging. Two dedicated phase 2 studies are planned to assess activity of this combination in both ovarian cancer (EudraCT2018-000230-35) and soft-tissue sarcomas. FUNDING Italian Association for Cancer Research, Italian Sarcoma Group, Foundation for Research on Musculoskeletal and Rare Tumors, and Italian Ministry of Health.

Midfoot reconstruction with serratus anterior–rib osteomuscular free flap following oncological resection of synovial sarcoma

During recent decades, the concept of surgical treatment of malignant bone and soft tissue sarcomas has evolved, with the aim of preserving limb function. In this paper we report a case of metatarsal reconstruction by means of serratus and rib free flap after excision of a synovial sarcoma located in the dorsal aspect of the midfoot. Five years after the operation, the patient was free from recurrence and recovered full foot function. Amputation has been widely used in the past and this procedure still remains a valuable option when limb salvage is not possible. Nevertheless, in selected cases, reconstruction by means of composite free flaps may be successfully used for limb preservation in the treatment of malignant foot tumors after surgical excision.

Lower Limb Core Scale: A New Application to Evaluate and Compare the Outcomes of Bone and Soft-Tissue Tumours Resection and Reconstruction

Several methods are used to evaluate the functional outcome of tumour resections and reconstructions in the lower limb. However, one of their most common limitations is that they are specifically developed to evaluate only oncological patients. We introduced the Lower Limb Core Scale (LLCS) to overcome this limitation. The aim of this study was to evaluate the functional and subjective results in the lower limb and to evaluate the use of the LLCS. We conducted a retrospective cohort study using various tools to investigate the outcomes. The results of the LLCS were correlated with the results of other functional tests. A total of 44 patients were included in the study. None of the demographic variables correlated with the functional or health-related quality of life (QoL) scores except for gender, whereby male patients had an increased functional score. The correlation between LLCS and other scores was positive (r 2 = 0.77). The satisfactory QoL scores, and functional outcomes scores indicated the LLCS to be a reliable option for general and specific evaluation of lower limb reconstructions. We suggest using the LLCS for comparisons of oncological reconstructions with lower limb reconstructions in different disciplines.