Early and late infarct growth rate in ischemic stroke patients after successful endovascular treatment in early time window: correlation of imaging and clinical factors with clinical outcome.

Background: The prospective study assessed infarct growth rate (IGR) in acute ischemic stroke (AIS) with large vessel occlusion (LVO) after recanalization in early time window. Early IGR (EIGR) and late IGR (LIGR) were correlated with imaging and clinical data; we searched for outcome predictors. Methods: We included 71 consecutive patients. Subjects underwent computed tomography perfusion (CTP) for ischemic core volume assessment at 99.0 minutes (median) from stroke onset, recanalization was performed at 78.0 minutes (median) from CTP. Final infarct volume (FIV) was measured on 24±2 hours imaging follow-up. EIGR was calculated as the core volume/time between stroke onset and CTP; LIGR was calculated as FIV/time between CTP and imaging follow-up. Twenty-two subjects were assessed as poor outcome, 49 as good outcome. Group differences were tested by Mann-Whitney test and χ2 test. Bayesian logistic regression models were used to predict clinical outcome, Pearson correlations for the log-transformed predictors. Results: Subjects with poor outcome were older, median age 78.0 [interquartile range (IQR): 71.8, 83.8] versus 68.0 (IQR: 57.0, 73.0) years; 95% confidence interval (CI): 6.00 to 16.00; P<0.001. Their stroke severity scale was higher, median 19.0 (IQR: 16.0, 20.0) versus 15.5 (IQR: 10.8, 18.0); 95% CI: 1.00 to 6.00; P<0.001. They had higher EIGR, median 23.9 (IQR: 6.4, 104.0) versus 6.7 (IQR: 1.7, 13.0) mL/h; 95% CI: 3.26 to 53.68; P=0.002; and larger core, median 52.5 (IQR: 13.1, 148.5) versus 10.0 (IQR: 1.4, 20.0) mL; 95% CI: 11.00 to 81.00; P<0.001. In subjects with poor outcome, infarct growth continued after thrombectomy with LIGR 2.0 (IQR: 1.2, 9.7) versus 0.3 (IQR: 0.0, 0.7) mL/h; 95% CI: 1.10 to 6.10; P<0.001; resulting in larger FIV, median 186.5 (IQR: 49.3, 280.8) versus 18.5 (IQR: 8.0, 34.0) mL; 95% CI: 55.30 to 214.00; P<0.001. Strong correlations among predictors were found e.g., core and EIGR (r=0.942), LIGR and FIV (r=0.779), core and FIV (r=0.761). Clinical outcome was best predicted using data from later measurements as FIV and LIGR. Conclusions: Data from later measurements were more predictive, there was no major benefit to use growth over volume data.

FOXF1 as an Immunohistochemical Marker of Hilar Cholangiocarcinoma or Metastatic Pancreatic Ductal Adenocarcinoma. Single Institution Experience.

Cholangiocarcinoma (CCA) is a liver malignancy associated with a poor prognosis. Its main subtypes are peripheral/intrahepatic and hilar/extrahepatic CCA. Several molecular, morphological and clinical similarities between hilar/extrahepatic CCA and pancreatic ductal adenocarcinoma (PDAC) have been described. FOXF1 is a transcription factor which has been described to have prognostic significance in various tumors and it is involved in the development of bile ducts. The aim of this study is to determine occurrence of nuclear expression of FOXF1 in both subtypes of CCA and metastatic PDAC and assess its potential usefulness as a diagnostic marker. Secondary aims were to investigate the use of C-reactive protein (CRP) immunohistochemistry for diagnosing intrahepatic peripheral CCA and the significance of histological features in CCA subtypes. 32 archive specimens of CCA, combined hepatocellular carcinoma-CCA (HCC-CCA) and liver metastasis of PDAC were stained by FOXF1 and CRP immunohistochemistry and evaluated to determine histological pattern. The CCAs were classified radiologically into peripheral/intrahepatic and hilar subtype. Using Fisher exact test, we identified nuclear FOXF1 as a fairly specific (87%) but insensitive (65%) marker of hilar and extrahepatic CCA and metastatic PDAC (p = 0.005). CRP immunohistochemistry was characterized by a high sensitivity and specificity, of 79% and 88%, respectively (p = 0.001). We did not identify any histomorphological features associated with either types of CCA or metastatic PDAC. As a conclusion of novel finding, FOXF1 immunohistochemistry may be regarded as a specific but insensitive marker of hilar/extrahepatic CCA and metastatic PDAC and it may help distinguish them from peripheral CCA.

Is limited-coverage CT perfusion helpful in treatment decision-making in patients with acute ischemic stroke?

BACKGROUND: The initial core infarct volume predicts treatment outcome in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). According to the literature, CT perfusion (CTP) is able to evaluate cerebral parenchymal viability and assess the initial core in AIS. We prospectively studied whether limited-coverage CTP with automated core calculation correlates with the final infarct volume on follow-up non-enhanced CT (NECT) in patients successfully treated by mechanical thrombectomy. METHODS: We enrolled 31 stroke patients (20 women aged 74.4±12.9 years and 11 men aged 66±15.4 years; median initial NIHSS score 15.5) with occlusion of the medial cerebral artery and/or the internal carotid artery that were treated by successful mechanical thrombectomy. CTP performed in a 38.6 mm slab at the level of basal ganglia was included in the CT stroke protocol, but was not used to determine indication for mechanical thrombectomy. The infarction core volume based on CTP was automatically calculated using dedicated software with a threshold defined as cerebral blood flow <30% of the value in the contralateral healthy hemisphere. The final infarction volume was measured on 24-hour follow-up NECT in the same slab with respect to CTP. Pearson and Spearman correlation coefficients and robust linear regression were used for comparison of both volumes, P values <0.05 were considered as statistically significant. RESULTS: The median time from stroke onset to CT was 77 minutes (range, 31-284 minutes), and the median time from CT to vessel recanalization was 95 minutes (range, 55-215 minutes). The mean CTP-calculated core infarct volume was 24.3±19.2 mL (median 19 mL, range 1-79 mL), while the mean final infarct volume was 21.5±39.5 mL (median 8 mL; range 0-210 mL). Only a weak relationship was found between the CTP-calculated core and final infarct volume [Pr(29) =0.32, P=0.078; rho =0.40, P=0.028]. Regression analysis showed CTP significantly overestimated lower volumes. CONCLUSIONS: In our prospective study, the infarction core calculated using limited-coverage CTP only weakly correlated with the final infarction volume measured on 24-hour follow-up NECT; moreover, CTP significantly overestimated lower volumes. Our results do not support the use of limited-coverage CTP for guiding treatment recommendations in patients with AIS.

Durable Response to Brentuximab Vedotin-Based Chemotherapy in Refractory Hodgkin Lymphoma with Central Nervous System (CNS) Involvement.

BACKGROUND CNS involvement in Hodgkin lymphoma is rare. Despite various treatment options, median overall survival is only 13 months after diagnosis of CNS involvement in relapsed/refractory HL. CASE REPORT A 29-year-old woman with classical HL (mixed cellularity) in clinical stage IIB was treated with multilineage chemotherapy and radiotherapy without achieving a sustained complete remission. Systemic and CNS progression of HL occurred at the age of 32 years and the patient received 2 cycles of brentuximab vedotin with bendamustine alternating with 2 cycles of high-dose methotrexate-based treatment and achieved partial remission. She then underwent autologous stem cell transplantation followed by brentuximab vedotin consolidation. The disease progressed and the patient died 6 months after the last dose of brentuximab vedotin. CONCLUSIONS We demonstrated a durable response to brentuximab vedotin-based chemotherapy in a patient with refractory Hodgkin lymphoma with CNS involvement. Prognosis of these patients is poor and new treatment options are needed.

Hypophysitis and other autoimmune complications related to immune checkpoints inhibitors´ treatment: Spectrum of imaging appearances.

OBJECTIVES: Immune checkpoints inhibitors (ICI) represent a new therapy option for the treatment of several advanced tumors. However, this therapy has been linked to a spectrum of ICI related autoimmune (AI) adverse events. Some may be life threatening and their diagnosis is tricky. The aim of our study was to describe various imaging appearances of ICI related secondary hypophysitis and other coincidental AI diseases. MATERIAL AND METHODS: We included 28 patients (19 females, 9 men, mean aged 58±13 years), who were consecutively treated mostly for advanced stage melanoma by different ICI. All their CT/MRI records and clinical data were reviewed. RESULTS: We found 5 (18%) cases of endocrinology proven secondary hypophysitis; 2 cases of panhypopituitarism and 3 cases of central hypocortisolism. Four cases were MRI positive, 1 case was MRI negative. Three cases were accompanied by other AI diseases: 1 by hemorrhagic colitis and mesenterial lymphadenitis, 1 by AI pancreatitis and 1 by pneumonitis. On MRI pituitary gland was swollen in 3 cases, twice enhanced non-homogenously, once homogenously; infundibular enlargement was present in 2 cases. Those 3 cases reacted to glucocorticoid therapy by hypophyseal shrinkage. In 1 case of MRI positive hypophysitis, the pituitary gland was not enlarged, slightly nonhomogeneous with peripheral contour enhancement; no reaction to glucocorticoids was mentioned. CONCLUSION: Secondary hypophysitis is probably more common ICI related adverse event than reported in the literature. Its MRI appearance is variable. Most of our cases were in coincidence with other AI ICI related events that affected their clinical manifestations.