Research Spotlight

Draoua, M., N. Titze, A. Gupta, H. T. Fernandez, M. Ramsay, G. Saracino, G. McKenna, G. Testa, G. B. Klintmalm and P. T. W. Kim (2017). “Significance of measured intraoperative portal vein flows after thrombendvenectomy in deceased donor liver transplantations with portal vein thrombosis.” Liver Transpl 23(8): 1032-1039.

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Adequate portal vein (PV) flow in liver transplantation is essential for a good outcome, and it may be compromised in patients with portal vein thrombosis (PVT). This study evaluated the impact of intraoperatively measured PV flow after PV thrombendvenectomy on outcomes after deceased donor liver transplantation (DDLT). The study included 77 patients over a 16-year period who underwent PV thrombendvenectomy with complete flow data. Patients were classified into 2 groups: high PV flow (>1300 mL/minute; n = 55) and low PV flow (60 years (hazard ratio [HR], 3.04, 95% confidence interval [CI], 1.36-6.82; P = 0.007) and low portal flow (HR, 2.31; 95% CI, 1.15-4.65; P = 0.02) were associated with worse survival. In conclusion, PV flow <1300 mL/minute after PV thrombendvenectomy for PVT during DDLT was associated with higher rates of biliary strictures and worse graft survival. Consideration should be given to identifying reasons for low flow and performing maneuvers to increase PV flow when intraoperative PV flows are <1300 mL/minute.

Osborne, C., J. D. Challagalla, C. F. Eisenbeis, F. A. Holmes, M. A. Neubauer, N. W. Koutrelakos, C. A. Taboada, S. J. Vukelja, S. T. Wilks, M. A. Allison, P. Reddy, S. Sedlacek, Y. Wang, L. Asmar and J. O’Shaughnessy (2017). “Ixabepilone and carboplatin for hormone receptor positive/her2-neu negative and triple negative metastatic breast cancer.” Clin Breast Cancer: 2017 Jul [Epub ahead of print].

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BACKGROUND: Hormonal therapies and single-agent sequential chemotherapeutic regimens are the standards of care for HER2- metastatic breast cancer (MBC). However, treating patients with hormone-refractory and triple negative (TN) MBC remains challenging. We report the results of combined ixabepilone and carboplatin in a single-arm phase II trial. PATIENTS AND METHODS: In the present prospective analysis of hormone receptor-positive (HR+)/HER2- and TN MBC cohorts, patients could have received 0 to 2 chemotherapy regimens for MBC before enrollment. All patients received ixabepilone 20 mg/m2 and carboplatin (area under the curve, 2.5) on days 1 and 8 every 21 days. The primary endpoint was the objective response rate (ORR). The secondary objectives included progression-free survival (PFS), clinical benefit rate (CBR), overall survival (OS), and toxicity. RESULTS: We enrolled 54 HR+ and 49 TN patients (median, 1 previous chemotherapy regimen for metastatic disease; most in addition to adjuvant chemotherapy). The ORR was 34% and 30.4% for the HR+ and TN patients, respectively, with a corresponding CBR of 56.6% and 41.3%. The ORRs were similar in taxane-pretreated patients (ORR, 31.4% and 28.6% for HR+ and TN patients, respectively). The median OS was 17.9 months for HR+ patients and 12.5 months for TN patients. The median PFS was similar for both groups at 7.6 months. Grade 3/4 nonhematologic toxicities included neuropathy (9%) and fatigue (8%). Nine patients developed grade 3/4 neuropathy, 7 of whom had received previous taxane treatment. CONCLUSION: Ixabepilone plus carboplatin is active even in later-line HR+ and TN disease. Toxicities were manageable without cumulative myelosuppression. This combination is a reasonable option for those patients with MBC who require combination chemotherapy.

Sikka, S., A. Vrooman, L. Callender, D. Salisbury, M. Bennett, R. Hamilton and S. Driver (2017). “Inconsistencies with screening for traumatic brain injury in spinal cord injury across the continuum of care.” J Spinal Cord Med: 1-10.

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OBJECTIVE: Explore how traumatic brain injury (TBI) is screened among spinal cord injury (SCI) patients across the continuum of care. DESIGN: Retrospective chart review Setting: Emergency department, trauma, inpatient rehabilitation Participants: 325 patients with SCI from inpatient rehabilitation facility (IRF) between March 1, 2011 and December 31, 2014 were screened. 49 eligible subjects had traumatic SCI and received care in adjoining acute care (AC) hospital. OUTCOME MEASURES: Demographic characteristics and variables that capture diagnosis of TBI/SCI included documentation from ambulance, emergency department, AC, and IRF including ICD-9 codes, altered mental status, loss of consciousness (LOC), Glasgow Coma Score, Post Traumatic Amnesia (PTA), neuroimaging, and cognitive assessments. RESULTS: Participants were male (81%), white (55%), privately insured (49%), and aged 39.3+/-18.0 years with 51% paraplegic and 49% tetraplegic. Mechanisms of injury were gunshot wound (31%), fall (29%), and motor vehicle accident (20%). TBI occurred in 65% of SCI individuals, however documentation of identification of TBI, LOC, and CT imaging results varied in H&P, discharge notes, and ICD-9 codes across the continuum. Cognitive assessments were performed on 16% of subjects. CONCLUSIONS: Documentation showed variability between AC and IRF and among disciplines. Imaging and GCS were more consistently documented than LOC and PTA. It is necessary to standardize screening processes between AC and IRF to identify dual diagnosis.

Rosenthal, R. L. (2017). “Revisiting the historical origins of clinically meaningful coronary artery obstruction.” Mayo Clin Proc 92(8): 1312.

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As part of a recent informative editorial on the significance of nonobstructive coronary artery disease, Rumberger1 reviewed the historical origins of the 50% coronary stenosis standard for the definition of myocardial ischemia and the relationship of percentage stenosis to coronary flow reserve and fractional flow reserve. I believe some corrections are warranted.

Richmond, A. M., E. A. Blake, K. Torkko, E. E. Smith, M. A. Spillman and M. D. Post (2017). “Fascin is associated with aggressive behavior and poor outcome in uterine carcinosarcoma.” Int J Gynecol Cancer: 2017 Jul [Epub ahead of print].

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OBJECTIVE: The mechanisms underlying the histogenesis and aggressiveness of uterine carcinosarcoma (UCS) are poorly understood; however, previous studies implicate epithelial-mesenchymal transition (EMT). Fascin is a proinvasive, actin-bundling protein and an important component of EMT. It is associated with poor outcomes in human carcinoma, especially in estrogen receptor (ER)-negative tumors arising in organs normally expressing ER. We sought to evaluate fascin expression in UCS and its relationship to ER status, clinicopathologic indicators of tumor aggressiveness, and survival outcomes. METHOD: Forty-four surgically staged cases of UCS were immunohistochemically evaluated for fascin and estrogen receptor-alpha expression and correlated with clinicopathologic parameters derived from electronic medical records and pathology reports. RESULTS: Fascin was only expressed in malignant epithelium and mesenchyma and was uniformly absent in background benign counterparts. Increased expression was associated with extrapelvic disease (P = 0.028), higher stage (P = 0.021), larger tumor size (P = 0.032), shorter progression-free interval (P = 0.035), and reduced estrogen receptor-alpha expression (P = 0.04). CONCLUSION: Fascin is aberrantly expressed in both elements of UCS and is associated with aggressive behavior and worse outcome. As a component of EMT and mediator of invasion, fascin may serve as a target in future therapies.