ObjectivesThe clinical utility of routine cross sectional imaging of the
abdomen and pelvis in the screening and surveillance of patients
with primary soft-tissue sarcoma of the extremities for metastatic
disease is controversial, based on its questionable yield paired
with concerns regarding the risks of radiation exposure, cost, and
morbidity resulting from false positive findings.MethodsThrough retrospective review of 140 patients of all ages (mean
53 years; 2 to 88) diagnosed with soft-tissue sarcoma of the extremity
with a mean follow-up of 33 months (0 to 291), we sought to determine
the overall incidence of isolated abdominopelvic metastases, their
temporal relationship to chest involvement, the rate of false positives, and
to identify disparate rates of metastases based on sarcoma subtype.ResultsA total of four patients (2.9%) exhibited isolated abdominopelvic
metastatic disease during the surveillance period. In all cases
of concomitant chest and abdominopelvic disease, chest involvement
preceded abominopelvic involvement. There was a significant false
positive rate requiring invasive workup.ConclusionsIn the setting of a relative paucity of evidence concerning a
rare disease process and in difference to recently published investigations,
we add a clinical cohort not supportive of routine cross sectional
imaging of the abdomen and pelvis.Cite this article: Bone Joint Res 2015;4:45–9.
Synovial sarcoma (SS) is frequently diagnosed in teenagers and young adults and continues to be treated with polychemotherapy with variable success. The SS18-SSX gene fusion is pathognomonic for the disease, and high expression of the anti-apoptotic BCL-2 pathologically supports the diagnosis. As the oncogenic SS18-SSX fusion gene itself is not druggable, BCL-2 inhibitor-based therapies are an appealing therapeutic opportunity. Venetoclax, an FDA-approved BCL-2 inhibitor that is revolutionizing care in some BCL-2-expressing hematological cancers, affords an intriguing therapeutic possibility to treat SS. In addition, there are now dozens of venetoclax-based combination therapies in clinical trials in hematological cancers, attributing to the limited toxicity of venetoclax. However, preclinical studies of venetoclax in SS have demonstrated an unexpected ineffectiveness. In this study, we analyzed the response of SS to venetoclax and the underlying BCL-2 family biology in an effort to understand venetoclax treatment failure and find a therapeutic strategy to sensitize SS to venetoclax. We found remarkably depressed levels of the endogenous MCL-1 inhibitor, NOXA, in SS compared to other sarcomas. Expressing NOXA led to sensitization to venetoclax, as did the addition of the MCL-1 BH3 mimetic, S63845. Importantly, the venetoclax/S63845 combination induced tumor regressions in SS patient-derived xenograft (PDX) models. As a very close analog of S63845 (S64315) is now in clinical trials with venetoclax in AML (NCT03672695), the combination of MCL-1 BH3 mimetics and venetoclax should be considered for SS patients as a new therapy.
Patellar osteonecrosis is a rare condition, although knee osteonecrosis has been described in the arthroplasty literature. This is the first case describing knee arthroscopy as the cause of osteonecrosis. A 50-year-old woman who was experiencing knee pain during her marathon training and singles tennis underwent knee arthroscopy for a torn medial meniscus. The result of her partial medial meniscectomy led to patellar osteonecrosis 3 months following the index procedure. Osteonecrosis of the knee has been reported in the arthroplasty and sports medicine literature following surgical intervention, usually in total knee replacement or more complex surgical operations. However, patellar osteonecrosis following knee arthroscopy has not been reported previously. Taking care of the anterior fat pad is essential to avoid disruption of important blood supply to the patella. [
Orthopedics
. 2019; 42(6):e552–e554.]
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