A precision medicine approach in sarcoma: identification of patients who may benefit from early use of pazopanib.

Soft tissue sarcomas (STS) are a heterogeneous group of over 100 histologically and genetically distinct mesenchymal tumors. Standard of care for metastatic STS has historically relied on anthracycline-based chemotherapy regimens. Although effective for some patients, conventional chemotherapeutic agents used in STS are associated with substantial toxicity and also are not equally effective in all histologic subtypes of sarcoma. Pazopanib is an orally active antiangiogenic drug that is approved for non-adipogenic sarcomas after failure of at least one line of previous chemotherapy, and has a relatively favorable toxicity profile. Earlier use of pazopanib may be a better choice for patients with subtypes of sarcoma that do not respond well to conventional chemotherapy or those who are unlikely to tolerate chemotherapy. Here we review the evidence for the activity and toxicity profile of pazopanib and consider potential histologic, clinical, and genetic predictive factors that can help to guide treatment choices. Further prospective studies validating these observations may lead to refinement of a precision medicine approach to match ideal sarcoma patients to earlier treatment with pazopanib over traditional chemotherapy.

The potential role of complements in cocaine-induced thrombotic microangiopathy.

Thrombotic microangiopathy (TMA) is a rare disorder characterized by microvascular injury and occlusion resulting in tissue ischemia and dysfunction. TMA occurs in a variety of settings including cocaine use. Although cocaine is widely used in the United States, cocaine-associated TMA is only rarely reported. Therefore, other factors may predispose cocaine users to the development of TMA. Emerging evidence indicates that cocaine activates complements. Therefore, complement activation may contribute to the development of cocaine-induced TMA. Here, we report a cocaine user who presented with renal failure. Renal biopsy demonstrated TMA. Laboratory tests revealed reduced serum complement C3 and normal complement C4 levels indicative of alternative complement activation. We postulate that complement activation is involved in the pathogenesis of cocaine-induced TMA.

The Diagnostic Accuracy of Frozen Section Compared to Permanent Section: A Single Center Study in Iran.

BACKGROUND: The diagnostic accuracy of frozen section as an important source of information in surgical pathology is important not only in the management of surgical patients but also as a measure of quality control in surgical pathology. In this study, we evaluated the diagnostic accuracy of frozen sections over a 6-year period in a teaching hospital in Iran. METHODS: We retrospectively reviewed frozen sections performed in the Pathology Department of Taleghani Hospital (Shahid Beheshti University of Medical Sciences), Tehran, Iran from 2007 to 2013. The results were compared to the permanent sections to evaluate diagnostic accuracy, sensitivity and specificity, of frozen section test. Discordant cases were reassessed to find the reasons for discrepancy. RESULTS: A total of 306 frozen section specimens from 176 surgical cases were evaluated. In eleven specimens (3.59%) the diagnoses were deferred. Of the remaining 295 specimens, 6 (2.03%) were discordant and 289 (97.96%) were concordant to permanent diagnoses. Specimens were primarily from the head & neck, thyroid, ovary, parathyroid and lymph nodes. The overall sensitivity, specificity, positive predictive value and negative predictive value of the frozen section compared to permanent section (as gold standard) were 92.95%, 99.55%, 98.50% and 97.80% respectively. Of the 6 discordant diagnoses, two (33.3%) were due to sampling error and four (66.6%) were due to interpretative errors. CONCLUSION: Frozen section is an accurate and valuable test and can be relied on in surgical managements. The results of this study also confirm that the accuracy of frozen section diagnosis in our institution compares well with internationally published rates.