Extra-abdominal desmoid tumors are rare, locally aggressive neoplasms without metastatic potential. There is no clear consensus regarding their optimal management. The disappointing results of ...current treatments and the ability of extra-abdominal desmoid tumors to spontaneously stabilize have increasingly drawn interest toward conservative management. The objective of this study was to evaluate a wait-and-see policy as a first-line management for extra-abdominal desmoid tumors.
This two-center retrospective study involved fifty-five patients with a histologically proven extra-abdominal desmoid tumor. The primary outcome was the cumulative probability of dropping out from the wait-and-see policy. The wait-and-see policy included aggressive management of symptoms. We conducted a review of the relevant published series in which a watchful-waiting strategy was used.
The cumulative probability of dropping out from the wait-and-see policy was 9.6% at the time of the last follow-up. Spontaneous arrest of tumor growth was noted for forty-seven patients (85%) over the course of the study. Half of the tumors were stabilized at one year, and a potential to increase beyond three years was a sporadic event (one case). Regrowth was found in two patients (4%).
A wait-and-see policy is an effective front-line management for patients with primary or recurrent extra-abdominal desmoid tumor. These tumors tend to stabilize spontaneously, on average after one year of evolution, and the cumulative probability of the failure of a wait-and-see policy is approximately 10%.
Purpose
Chronic ankle instability is the main complication of ankle sprains and requires surgery if non-operative treatment fails. The goal of this study was to validate a tool to quantify ...psychological readiness to return to sport after ankle ligament reconstruction.
Methods
The form was designed like the anterior cruciate ligament-return to sport after injury scale and “Knee” was replaced by the term “ankle”. The ankle ligament reconstruction-return to sport after injury (ALR-RSI) scale was filled by patients who underwent ankle ligament reconstruction and were active in sports. The scale was then validated according to the international COSMIN methodology. The AOFAS and Karlsson scores were used as reference questionnaires.
Results
Fifty-seven patients (59 ankles) were included, 27 women. The ALR-RSI scale was strongly correlated with the Karlsson score (
r
= 0.79 0.66–0.87) and the AOFAS score (
r
= 0.8 0.66–0.87). A highly significant difference was found in the ALR-RSI between the subgroup of 50 patients who returned to playing sport and the seven who did not: 68.8 (56.5–86.5) vs 45.0 (31.3–55.8), respectively,
p
= 0.02. The internal consistency of the scale was high (
α
= 0.96). Reproducibility of the test–retest was excellent (
ρ
= 0.92; 95% CI 0.86–0.96).
Conclusion
The ALR-RSI is a valid, reproducible scale that identifies patients who are ready to return to the same sport after ankle ligament reconstruction. This scale may help to identify athletes who will find sport resumption difficult.
Level of evidence
III.
Extra-articular resection (EAR) of the hip joint is prone to significant complications and morbidity. Thus, this study evaluates the cumulative incidences and main reasons of reoperation following ...EAR of primary malignant bone tumors (PMBT) of the hip to determine whether the outcomes are different between EAR of the pelvis and that of the proximal femur.
Thirty-three patients presented with a PMBT of the proximal femur or pelvis were included in this study. Among all PMBTs, 58% originated from the pelvis and 42% were from the proximal femur. Twenty patients had chondrosarcomas (61%), 10 had osteosarcomas (30%), and 3 had sarcomas of another histological subtype (9%).
The mean follow-up was of 76 months (range: 24-220 months). The cumulative probabilities of revision for any reason were 52% (95% confidence interval CI 30-70%) 5 years after surgery. The 5-year cumulative probabilities of revision were 13% (95% CI 4-27%), 24% (95% CI 10-42%), and 34% (95% CI 14-56%) for mechanical, infectious, and tumoral reasons, respectively. The 5-year cumulative probabilities of revision for any reason were 78% (95% CI 37-94%) and 14% (95% CI 2-38%) for the pelvis and proximal femur, respectively (p = 0.004). Posterior column preservation was significantly associated with more mechanical complications even after adjusting for the resection site (p = 0.043).
Half of patients undergoing EAR of the hip joint for PMBT of the proximal femur or acetabulum will require another operation. EAR of the pelvis is associated with significantly worse outcome than EAR of the proximal femur.
Chondrosarcomas are primary cancers of cartilaginous tissue with highly contrasting prognoses. These tumors are defined by recurrent mutations in the IDH genes and other genetic alterations including ...inactivation of CDKN2A and COL2A1; however, these have no clinical value. Here we use multi-omics molecular profiles from a series of cartilage tumors and find an mRNA classification that identifies two subtypes of chondrosarcomas defined by a balance in tumor differentiation and cell cycle activation. The microRNA classification reveals the importance of the loss of expression of the 14q32 locus in defining the level of malignancy. Finally, DNA methylation is associated with IDH mutations. We can use the multi-omics classifications to predict outcome. We propose an mRNA-only classifier to reproduce the integrated multi-omics classification, and its application to relapsed tumor samples shows the progressive nature of the classification. Thus, it may be possible to use mRNA-based signatures to detect patients with high-risk chondrosarcomas.
This review provides an overview of histopathology, clinical presentation, molecular pathways, and potential new systemic treatments of high-grade chondrosarcomas (CS), including grade 2−3 ...conventional, dedifferentiated, and mesenchymal CS. The diagnosis of CS combines radiological and histological data in conjunction with patient clinical presentations. Conventional CS is the most frequent subtype of CS (85%) and represents about 25% of primary bone tumors in adults; they can be categorized according to their bone location into central, peripheral, and periosteal chondrosarcomas. Central and peripheral CS differ at the molecular level with either IDH1/2 mutations or EXT1/2 mutations, respectively. CDKN2A/B deletions are also frequent in conventional CS, as well as COL2A1 mutations. Dedifferentiated CS develops when low-grade conventional CS transforms into a high-grade sarcoma and most frequently exhibits features of osteosarcoma, fibrosarcoma, or undifferentiated pleomorphic sarcoma. Their molecular characteristics are similar to conventional CS. Mesenchymal CS is a totally different pathological entity exhibiting recurrent translocations. Their clinical presentation and management are different too. The standard treatment of CSs is wide en-bloc resection. CS are relatively radiotherapy resistant; therefore, doses >60 Gy are needed in an attempt to achieve local control in unresectable tumors. Chemotherapy is possibly effective in mesenchymal chondrosarcoma and is of uncertain value in dedifferentiated chondrosarcoma. Due to resistance to standard anticancer agents, the prognosis is poor in patients with metastatic or unresectable chondrosarcomas. Recently, the refined characterization of the molecular profile, as well as the development of new treatments, allow new therapeutic options for these rare tumors. The efficiency of IDH1 inhibitors in other malignancies suggests that these inhibitors will be part of IDH1/2 mutated conventional CS management soon. Other treatment approaches, such as PIK3-AKT-mTOR inhibitors, cell cycle inhibitors, and epigenetic or immune modulators based on improving our understanding of CS molecular biology, are emerging.
Osteoclasts and osteoblasts express IL‐27 under specific stimulation in vitro; IL‐27‐producing bone cells are detected in situ in human bone tissues in various inflammatory settings.
IL‐27 regulates ...immune responses as well as hematopoiesis and bone remodeling, but its cellular sources in the bone remain unknown. In this study, we investigated whether osteoclasts and osteoblasts—the 2 cell types orchestrating bone homeostasis—could be a source of IL‐27 and identified stimuli that induce its expression in vitro. We observed that human monocyte‐derived osteoclasts expressed a broader range of TLRs than did human primary osteoblasts and that both cell types exhibited a differential induction of IL‐27 expression in response to TLR or cytokine stimulation. Whereas several TLR agonists, notably TLR4 and TLR7/8 agonists, induced substantial expression of IL‐27 by osteoclasts, stimulation of osteoblasts with agonists of TLR3 and/or TLR4—the 2 TLRs selectively expressed by these cells—resulted in no or low IL‐27 expression. In addition, IL‐27 increased TLR3 expression in osteoclasts and enhanced poly(I:C)‐mediated induction of IL‐27 in these cells. IFN‐γ, when combined with either IL‐1β plus TNF‐α, IL‐11, or CNTF, induced significant levels of IL‐27 in osteoclasts but not in osteoblasts. In the latter cells, the addition of type I IFN, together with proinflammatory cytokines, was necessary to induce substantial levels of IL‐27. Immunohistochemical studies of inflamed and remodeling bone tissue, including cases of infectious osteomyelitis and bone metastases, provided evidence that osteoclasts, osteoblasts, and occasionally osteocytes or chondrocytes, could express IL‐27 in situ. This autocrine production of IL‐27 by TLR‐ or cytokine‐activated bone cells might constitute a negative‐feedback mechanism to limit bone erosion and to dampen T cell–mediated immune pathology during bone inflammation.
Context: Adrenocortical carcinomas (ACC) are rare tumors with a poor prognosis. Few reports concerning large and homogeneous series are available.
Objective: We aimed to determine the clinical ...characteristics and outcome of ACC and to identify prognostic factors.
Design and Setting: This study is a descriptive and multivariate analysis of a cohort from a single endocrinology center.
Patients: A total of 202 consecutive patients with ACC were studied.
Results: The sex ratio (female to male) was 2.7. Mean age at diagnosis was 44 ± 16 yr (range, 11–88 yr). We found that 154 patients (76%) had hypersecreting tumors mostly cortisol and androgens (47%), cortisol alone (27%), or androgens alone (6%) and 43 patients (21%) had metastases at diagnosis. At initial staging or during follow-up, 85 patients (42%) had liver metastases, 79 patients (39%) had lung metastases, and 20 patients had bone metastases (10%). The survival rate was 37% at 5 yr. Multivariate analysis identified the following independent prognostic factors associated with shorter survival: older age at diagnosis hazard ratio (HR), 1.03; P < 0.0001, initial MacFarlane extension stages 3 (HR, 4.42; P = 0.005) and 4 (HR, 7.93; P < 0.0001), and cortisol hypersecretion (HR, 3.90; P < 0.0001). Treatment with 1,1-dichlorodiphenildichloroethane (o,p’DDD) in the 3 months after surgery increased the survival rate of patients with cortisol-secreting tumors (HR, 0.40; P = 0.04).
Conclusion: This study highlights the better prognosis of ACC diagnosed at a noninvasive local stage, the particularly poor prognosis of patients with cortisol-secreting tumors, and the beneficial effect of o,p’DDD therapy in this subgroup of patients.
Metastatic disease, myeloma, and lymphoma are the most common malignant spinal tumors. Hemangioma is the most common benign tumor of the spine. Other primary osseous lesions of the spine are more ...unusual but may exhibit characteristic imaging features that can help the radiologist develop a differential diagnosis. Radiologic evaluation of a patient who presents with osseous vertebral lesions often includes radiography, computed tomography (CT), and magnetic resonance (MR) imaging. Because of the complex anatomy of the vertebrae, CT is more useful than conventional radiography for evaluating lesion location and analyzing bone destruction and condensation. The diagnosis of spinal tumors is based on patient age, topographic features of the tumor, and lesion pattern as seen at CT and MR imaging. A systematic approach is useful for recognizing tumors of the spine with characteristic features such as bone island, osteoid osteoma, osteochondroma, chondrosarcoma, vertebral angioma, and aneurysmal bone cyst. In the remaining cases, the differential diagnosis may include other primary spinal tumors, vertebral metastases and major nontumoral lesions simulating a vertebral tumor, Paget disease, spondylitis, echinococcal infection, and aseptic osteitis. In many cases, vertebral biopsy is warranted to guide treatment.
Up to 25% of patients undergoing knee arthroplasty report chronic pain postoperatively. Early identification of high-risk individuals can enhance pain management strategies. This retrospective ...analysis investigates the incidence of severe postoperative pain and its associated risk factors among 740 patients who underwent total knee arthroplasty. Utilizing a digital application, patients provided comprehensive data encompassing pre- and postoperative pain levels, analgesic usage, and completed a chronic pain risk assessment. Participants were categorized into two distinct groups based on their pain status at three months post-op: Group D+ (14%), characterized by pain scores exceeding 40/100 and/or the utilization of level 2 or 3 analgesics, and Group D- (86%), who did not meet these criteria. An analysis of pain trajectories within these groups revealed a non-linear progression, with specific patterns emerging amongst those predisposed to chronic pain. Notably, patients with a trajectory towards chronic pain exhibited a plateau in pain intensity approximately three weeks post-surgery. Significant preoperative risk factors were identified, including elevated initial pain levels, the presence of comorbidities, pain in other body areas, heightened joint sensitivity and stiffness. This study highlights the utility of digital platforms in enhancing patient care, particularly through the continuous monitoring of pain. Such an approach facilitates the early identification of potential complications and enables timely interventions.
In the OS2006 study, patients younger than 18 years were treated with a methotrexate‐based regimen (MTX), patients older than 25 years with a doxorubicin–cisplatin–ifosfamide‐based regimen (API–AI), ...whereas patients aged 18–25 years received either API–AI or MTX. We herein report the prespecified subgroup analysis of the outcome of 106 patients treated with API–AI. Preoperative chemotherapy combined three doxorubicin–ifosfamide–cisplatin (API) and two doxorubicin–ifosfamide (AI) courses. Postoperative chemotherapy was assigned by risk group: localised patients with a good histological response (<10% viable cells) received two AI and two cisplatin–ifosfamide (PI) courses; patients with synchronous metastases, poor histological response or unresectable primary received five cycles of etoposide–ifosfamide (EI). Of the 106 patients, 61 were randomised to receive or not zoledronate. Median age was 30 years (range 18–67), 66 (62%) patients were >25 years. The primary tumours were axial in 28 patients (26%), and 28 (26%) presented with metastases. Ninety‐six patients (91%) had surgery, conservative in 82 (85%); 36 patients (38%, 95% CI 28–48%) were good responders. Toxicity was manageable, with no significant difference in severe acute toxicity between patients aged >25 years and those younger. With a median follow‐up of 4.8 years, the 5‐year event‐free survival and overall survival rates were 46% (95% CI 36–56) and 57% (95% CI 47–67), respectively. The primary tumour size and initial metastases correlated with a higher risk of event. In these 106 osteosarcoma adult patients, API–AI proved feasible with no excess of toxicity, and favourable activity despite poor‐prognosis factors.
What's new?
Osteosarcoma paediatric patients are commonly treated with high‐dose methotrexate combined to other active agents. Methotrexate pharmacokinetics varies considerably with age, however, with few prospective studies dedicated to adult patients and currently no consensus concerning the optimal chemotherapy regimen in these patients. This paper describes the population of 106 adult osteosarcoma patients enrolled in the OS 2006 phase III study, their treatment and their outcomes using a chemotherapy backbone without methotrexate that combines doxorubicin, cisplatin, and ifosfamide. This study confirms prior findings that the API‐AI regimen has acceptable toxicity and yields favourable activity in adult osteosarcoma patients with poor prognosis factors.
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