Calculating the Tumor Nuclei Content for Comprehensive Cancer Panel Testing.

Comprehensive genetic panel testing generally requires that the analyzed tissues have a percent tumor nuclei (%TN) content of 20% or more to achieve assay performance comparable to the validated specifications. Pathologists play a crucial role in ensuring that the optimal results are achieved by accurately assigning %TN content of the available specimens and selecting the best material to submit for sequencing. This study addresses the issues in evaluating %TN, such as intraobserver variability, and examines whether focused training and feedback can improve pathologist performance. Nine referring institution pathologists (all board-certified and working at the core institute and the alignment hospitals under the National Cancer Genome scheme) evaluated 18 tumors that had been subjected to comprehensive genetic panel testing with the FoundationOne CDx assay. The %TN estimates provided by referring institution pathologists were compared with two standards: %TN assigned by the tumor sequencing institution's pathologist (a board-certified pathologist at Foundation Medicine, Inc.) and the computational %TN estimated from the mutant allele frequencies after sequencing was completed. The pathologists generally overestimated %TN in the first pretraining round of the evaluation, and the differences in the averaged %TN from the tumor sequencing institution and computational standards were statistically significant. However, the posttraining second-round results became significantly concordant with the standards. This study suggests that %TN content is empirically overestimated but the evaluation skill can be improved by providing a training and feedback program.

[Three Patients with Acute Myocardial Infarction Associated with Targeted Therapy of Sorafenib for Metastatic Renal Cell Carcinoma : Case Report].

Sorafenib is a tyrosine kinase inhibitor (TKI) of the vascular endothelial growth factor receptor (VEGFR) used for advanced renal cell carcinoma. Treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal cell carcinoma. However, in spite of its therapeutic efficacy, sorafenib causes a wide range of adverse events. Cardiovascular adverse events have been observed when sorafenib was used with targeted agents. Although these adverse events like hypertension, reduced left ventricular ejection fraction, cardiac ischemia or infarction were manageable with standard medical therapies in most cases, some had a poor clinical outcome. We report three cases of acute myocardial infarction associated with sorafenib in patients with metastatic renal cell carcinoma.

Subdural spinal granuloma resulting from Candida albicans without immunosufficiency: case report.

STUDY DESIGN: This was a case of spinal subdural granuloma of Candida albicans. A high cerebrospinal fluid protein level without pleocytosis (albuminocytologic dissociation) was observed. This case proved difficult to diagnose and treat. OBJECTIVES: To clarify the important issues in regard to the diagnosis and treatment of possible spinal subdural granuloma resulting from C. albicans. SUMMARY OF BACKGROUND DATA: Reports on subdural infection of C. albicans are very rare. Moreover, there are no reports of cases in which patients have survived this type of infection. METHODS: A 66-year-old man developed paralysis in the lower limbs, as well as vesicorectal disorder (anuresis). There were no obvious causes. Signs of meningeal irritation later appeared. A high cerebrospinal fluid protein level without pleocytosis was observed through a laboratory test. The cause of these disorders was unclear, and a final diagnosis could not be made on the basis of the test results and angiograph. Possible diagnoses included tumor, infection, and others such as Guillain-Barré syndrome. The authors therefore carried out surgery to reduce the pressure on the spinal cord and ultimately make a definitive diagnosis. RESULTS: The final diagnosis was spinal subdural granuloma of C. albicans. Granuloma was widespread (T3-T10). Surgery, various drug treatments, and hyperbaric oxygen therapy all contributed to saving the patient's life. CONCLUSION: This was a very rare case of spinal subdural granuloma resulting from C. albicans, and the authors had difficulty diagnosing and treating the patient. A distinctive gadolinium-enhanced MRI was obtained. The effect of treatment by drugs alone was limited. An intraoperative ultrasonography proved useful. The authors concluded that a combination of early surgery and hyperbaric oxygen therapy was effective.