Resolving spatial response heterogeneity in glioblastoma.

PURPOSE: Spatial intratumoral heterogeneity poses a significant challenge for accurate response assessment in glioblastoma. Multimodal imaging coupled with advanced image analysis has the potential to unravel this response heterogeneity. METHODS: Based on automated tumor segmentation and longitudinal registration with follow-up imaging, we categorized contrast-enhancing voxels of 61 patients with suspected recurrence of glioblastoma into either true tumor progression (TP) or pseudoprogression (PsP). To allow the unbiased analysis of semantically related image regions, adjacent voxels with similar values of cerebral blood volume (CBV), FET-PET, and contrast-enhanced T1w were automatically grouped into supervoxels. We then extracted first-order statistics as well as texture features from each supervoxel. With these features, a Random Forest classifier was trained and validated employing a 10-fold cross-validation scheme. For model evaluation, the area under the receiver operating curve, as well as classification performance metrics were calculated. RESULTS: Our image analysis pipeline enabled reliable spatial assessment of tumor response. The predictive model reached an accuracy of 80.0% and a macro-weighted AUC of 0.875, which takes class imbalance into account, in the hold-out samples from cross-validation on supervoxel level. Analysis of feature importances confirmed the significant role of FET-PET-derived features. Accordingly, TP- and PsP-labeled supervoxels differed significantly in their 10th and 90th percentile, as well as the median of tumor-to-background normalized FET-PET. However, CBV- and T1c-related features also relevantly contributed to the model's performance. CONCLUSION: Disentangling the intratumoral heterogeneity in glioblastoma holds immense promise for advancing precise local response evaluation and thereby also informing more personalized and localized treatment strategies in the future.

Appearance of COVID-19 pneumonia on 1.5 T TrueFISP MRI / Aspectos da pneumonia por COVID-19 na ressonância magnética 1.5 T TrueFISP

Abstract Objective: To evaluate the performance of 1.5 T true fast imaging with steady state precession (TrueFISP) magnetic resonance imaging (MRI) sequences for the detection and characterization of pulmonary abnormalities caused by coronavirus disease 2019 (COVID-19). Materials and Methods: In this retrospective single-center study, computed tomography (CT) and MRI scans of 20 patients with COVID-19 pneumonia were evaluated with regard to the distribution, opacity, and appearance of pulmonary lesions, as well as bronchial changes, pleural effusion, and thoracic lymphadenopathy. McNemar's test was used in order to compare the COVID-19-associated alterations seen on CT with those seen on MRI. Results: Ground-glass opacities were better visualized on CT than on MRI (p = 0.031). We found no statistically significant differences between CT and MRI regarding the visualization/characterization of the following: consolidations; interlobular/intralobular septal thickening; the distribution or appearance of pulmonary abnormalities; bronchial pathologies; pleural effusion; and thoracic lymphadenopathy. Conclusion: Pulmonary abnormalities caused by COVID-19 pneumonia can be detected on TrueFISP MRI sequences and correspond to the patterns known from CT. Especially during the current pandemic, the portions of the lungs imaged on cardiac or abdominal MRI should be carefully evaluated to promote the identification and isolation of unexpected cases of COVID-19, thereby curbing further spread of the disease.

Resumo Objetivo: Avaliar o desempenho da ressonância magnética (RM) de 1,5 T true fast imaging with steady state precession (TrueFISP) para detecção e caracterização de anormalidades pulmonares causadas por doença do coronavírus 2019 (COVID-19). Materiais e Métodos: Neste estudo retrospectivo unicêntrico, imagens de tomografia computadorizada (TC) e RM de 20 pacientes com pneumonia COVID-19 foram avaliadas em relação a distribuição, opacidade e forma das lesões pulmonares, anormalidades brônquicas, derrame pleural e linfadenopatia torácica. O teste de McNemar foi usado para comparar os achados associados à COVID-19 na TC e na RM. Resultados: As opacidades em vidro fosco foram mais bem visualizadas na TC do que na RM (p = 0,031). Não foram encontradas diferenças estatisticamente significantes entre TC e RM em relação aos outros aspectos, ou seja, visualização de consolidações e espessamento septal interlobular/intralobular, distribuição ou forma de anormalidades pulmonares, doenças brônquicas, derrame pleural ou linfadenopatia torácica. Conclusão: As anomalias pulmonares causadas pela pneumonia por COVID-19 podem ser detectadas nas sequências TrueFISP e correspondem aos padrões conhecidos da TC. Especialmente em face da pandemia atual, as porções de imagem dos pulmões na RM cardíaca ou abdominal devem ser cuidadosamente avaliadas para apoiar a identificação e o isolamento de casos inesperados de COVID-19 e, assim, conter a disseminação.

Bone volume change following vascularized free bone flap reconstruction of the mandible.

BACKGROUND: Bone volume changes following vascularized bone flaps and possible confounding factors over time are described in the literature with some controversy. The purpose of this study was to evaluate the bone volume behavior of two frequently used free flaps. MATERIALS AND METHODS: Computed tomography (CT) scans were examined with regard to bone volume using the software program ITK-SNAP for all patients who required mandibular reconstruction with a free fibula flap (FFF, conventionally vs assisted by computer-aided design/computer-aided manufacturing (CAD/CAM)) or iliac crest flap (DCIA) following mandibular resection because of benign or malign processes, between August 2010 and August 2015. Clinical data, complication rates, and CT scans were analyzed retrospectively. Additionally, complication rates (microvascular revision, flap loss, postoperative fistula or dehiscence, and postoperative bone exposure) were compared within early (≤30 days), late (31st-100th day), and overall (≤100th day) postoperative time intervals. RESULTS: 113 cases, comprizing 89 FFF and 24 DCIA cases, were included. FFF showed superior bone volume behavior over the DCIA flap. Multivariable regression models assessed the relationships between the following and bone volume behavior: interval between operation and CT scan (p < 0.683), age (p = 0.004), gender (p = 0.006), BMI (p = 0.400), adjuvant radiation therapy (p = 0.334), reconstruction with DCIA flap (p < 0.0001), number of segments (p = 0.02), and incidence of dental implant insertion (p = 0.45). CONCLUSIONS: The bone volume of FFFs remains stable. DCIA flaps show a higher bone volume reduction, but the postoperative course might be associated with fewer complications. Time interval between operation and CT scan, age, gender, reconstruction with DCIA flap, and number of fibula segments contributed significantly to bone volume behavior.

Monitoring treatment effects in lung cancer-bearing mice: clinical CT and clinical MRI compared to micro-CT.

BACKGROUND: Compared to histology-based methods, imaging can reduce animal usage in preclinical studies. However, availability of dedicated scanners is limited. We evaluated clinical computed tomography (CT) and magnetic resonance imaging (MRI) in comparison to dedicated CT (micro-CT) for assessing therapy effects in lung cancer-bearing mice. METHODS: Animals received cisplatin (n = 10), sham (n = 12), or no treatment (n = 9). All were examined via micro-CT, CT, and MRI before and after treatment. Semiautomated tumour burden (TB) calculation was performed. The Bland-Altman, receiver operating characteristic (ROC), and Spearman statistics were used. RESULTS: All modalities always allowed localising and measuring TB. At all modalities, mice treated with cisplatin showed a TB reduction (p ≤ 0.012) while sham-treated and untreated individuals presented tumour growth (p < 0.001). Mean relative difference (limits of agreement) between TB on micro-CT and clinical scanners was 24.7% (21.7-27.7%) for CT and 2.9% (-4.0-9.8%) for MRI. Relative TB changes before/after treatment were not different between micro-CT and CT (p = 0.074) or MRI (p = 0.241). Mice with cisplatin treatment were discriminated from those with sham or no treatment at all modalities (p ≤ 0.001). Using micro-CT as reference standard, ROC areas under the curves were 0.988-1.000 for CT and 0.946-0.957 for MRI. TB changes were highly correlated across modalities (r ≥ 0.900, p < 0.001). CONCLUSIONS: Clinical CT and MRI are suitable for treatment response evaluation in lung cancer-bearing mice. When dedicated scanners are unavailable, they should be preferred to improve animal welfare.

Regional variation in paraspinal muscle composition using chemical shift encoding-based water-fat MRI.

BACKGROUND: Paraspinal musculature forms one of the largest muscle compartments of the human body, but evidence for regional variation of its composition and dependency on gender or body mass index (BMI) is scarce. METHODS: This study applied six-echo chemical shift encoding-based water-fat magnetic resonance imaging (MRI) at 3 Tesla in 76 subjects (24 males and 52 females, age: 40.0±13.7 years, BMI: 25.4±5.6 kg/m2) to evaluate the proton density fat fraction (PDFF) of psoas muscles and erector spinae muscles, with the latter being divided into three segments in relation to levels of spine anatomy (L3-L5, T12-L2, and T9-T11). RESULTS: For the psoas muscles and the erector spinae muscles (L3-L5), gender differences in PDFF values were observed (PDFF psoas muscles: males: 5.1%±3.4% vs. females: 6.0%±2.2%, P=0.006; PDFF erector spinae muscles L3-L5: males: 10.7%±7.6% vs. females: 18.2%±6.8%, P<0.001). Furthermore, the PDFF of the erector spinae muscles (L3-L5) showed higher PDFF values when compared to the other segments (PDFF erector spinae muscles L3-L5 vs. T12-L2: P<0.001; PDFF erector spinae muscles L3-L5 vs. T9-T11: P<0.001) and showed to be independent of BMI, which was not the case for the other segments (T12-L2 or T9-T11) or the psoas muscles. When considering age and BMI as control variables, correlations of PDFF between segments of the erector spinae muscles remained significant for both genders. CONCLUSIONS: This study explored regional variation of paraspinal muscle composition and dependency on gender and BMI, thus offering new insights into muscle physiology. The PDFF of the erector spinae muscles (L3-L5) was independent of BMI, suggesting that this level may be suited for representative paraspinal muscle segmentation and PDFF extraction as a biomarker for muscle alterations in the future.

Diagnostic imaging in the management of patients with possible cerebral venous thrombosis: a cost-effectiveness analysis.

PURPOSE: Imaging is crucial for management of patients with possible cerebral venous thrombosis (CVT). To evaluate the cost-effectiveness of different noninvasive imaging strategies in patients with possible CVT. METHODS: A decision model based on Markov simulations estimated lifetime costs and quality-adjusted life years (QALY) associated with the following imaging strategies: non-contrast CT (NCCT), NCCT plus CT venography (CTV), routine MRI without vascular imaging (R-MRI), and MRI with venography (MRV). The analysis was performed from a US healthcare perspective. Model input was based on best available and most recent evidence, including outcome data from the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Starting age was 37 years; both high and low pre-test probabilities of CVT were evaluated. Probabilistic sensitivity analyses (PSA) estimated model uncertainty. RESULTS: In the base-case analysis, NCCT and CTV were dominant over R-MRI and MRV. CTV led to incremental lifetime QALYs compared with NCCT (23.385 QALYs vs. 23.374 QALYs) at slightly higher lifetime costs ($5210 vs. $5057). In PSA, CTV was the strategy with the highest percentage of cost-effective iterations if willingness-to-pay (WTP) thresholds were higher than $13,750/QALY. Complying with contemporary WTP thresholds, CTV was thus identified as the most cost-effective strategy. When the pre-test probability was set to 50%, CTV was also preferred. CONCLUSION: In patients at the peak age of CVT incidence yet low clinical pre-test probability, diagnostic imaging with CTV is the most cost-effective strategy.

Consistency of normalized cerebral blood volume values in glioblastoma using different leakage correction algorithms on dynamic susceptibility contrast magnetic resonance imaging data without and with preload.

BACKGROUND AND PURPOSE: Several leakage correction algorithms for dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI)-based cerebral blood volume (CBV) measurement have been proposed, and combination with a preload of contrast agent is generally recommended. A single bolus application scheme would largely simplify and facilitate standardized clinical applications, while reducing contrast agent (CA) dose. The aim of this study was, therefore, to investigate whether appropriate leakage correction redundantizes prebolus application by comparing normalized DSC-based CBV (nCBV) measures of two consecutive CA boli. MATERIALS AND METHODS: Twenty-seven patients with suspected glioblastoma (WHO-grade-IV) underwent DSC-MRI during two consecutive boli of Gd-based CA. Four variants of two post-processing leakage correction techniques were compared with respect to nCBV in contrast enhancing tumor tissue. First, a reference curve approach with first pass and full integration of corrected ΔR2*(t), and second, a deconvolution-based approach using singular value decomposition (SVD) with a standard noise-dependent cutoff or Tikhonov regularization. RESULTS: Compared to respective uncorrected values, all leakage correction techniques increased nCBV for data acquired without prebolus, while there was no consistent trend for data acquired with prebolus. The best agreement between corrected nCBV values in contrast enhancing tumor, obtained in the same patients without and with prebolus, respectively, was obtained for the reference curve-based correction approach with either first pass or full integration. CONCLUSION: The reference curve-based leakage correction approach with integration-based nCBV calculation yielded a high accordance between nCBV values without and with prebolus, respectively. Thus, it appears possible to obtain valid nCBV in glioblastoma with a single CA injection.

Endovascular Stroke Treatment on Single-Plane vs. Bi-Plane Angiography Suites : Technical Considerations and Evaluation of Treatment Success.

INTRODUCTION: Endovascular stroke therapy is mostly available in comprehensive stroke centers with state of the art bi-plane angiography suites. The aim of the present study was to analyze if it is justifiable to treat patients with alternative x­ray machines in the case of capacity constraints, or if it is mandatory to refer patients in such cases. Secondly, we wanted to draw conclusions for the feasibility of different logistic approaches in stroke treatment, such as a "helistroke" concept. METHODS: This was a retrospective dual center analysis of all patients treated on a single-plane angiography suite between 2009 and 2017. A propensity scored matching analysis at a 1:3 ratio was performed with patients treated on a bi-plane angiography suite to receive homogeneous groups. RESULTS: A total of 42 patients were treated on a single-plane angiography suite and were compared to 126 patients treated on a bi-plane angiography suite. No significant differences in technical parameters, procedure times, recanalization success and complications could be detected. Also, there was no difference in the clinical outcome between the two groups. The only significant difference was the higher amount of radiation dose used on the bi-plane angiography machines to achieve the final results (205,660 mGy × cm2 vs. 114,565 mGy × cm2; p < 0.001). DISCUSSION: In an era of an ever-changing stroke infrastructure and an increasing demand in thrombectomy procedures, it is feasible and safe for experienced neurointerventionalists to perform endovascular stroke procedures on single-plane angiography units.

Stress Distribution Patterns within Viscero- and Neurocranium during Nasoalveolar Molding: a Finite Element Analysis.

BACKGROUND: The purpose of this study was to evaluate the stress distribution patterns within the viscero- and neurocranium of neonates during nasoalveolar molding. METHODS: Finite element models of 3 different healthy neonates at different times of life (date of birth, 4 weeks, and 3.5 months) were generated on the basis of computed tomography scans. A validated workflow, including segmentation, meshing, setting of boundary conditions, and implementation of a bone density-dependent material model, was carried out for each model. A small and a large unilateral alveolar and hard palatal cleft were virtually cut in each model. The stress distribution pattern in each model was then analyzed by using Ansys APDL. RESULTS: Convergence analysis validated the results. The virtual experiments at the date of birth showed a stress pattern above a previously defined threshold value of 30,000 Pa in the ipsilateral naso-orbital-complex, frontal sinus, and the anterior fossa of the base of the skull, with von Mises values > 35,000 Pa. Stress patterns at the age of 4 weeks and 3.5 months showed reduced von Mises values at < 15,000 Pa. CONCLUSIONS: Nasoalveolar molding therapy is a safe presurgical treatment modality without significant influence on the viscero- and neurocranium of neonates. Treatment, considering the stress distribution at the naso-orbital-complex and anterior fossa of the base of the skull, should begin in the second week of life, and treatment initiation of preterm infants should be adapted respectively.

Establishment of a finite element model of a neonate's skull to evaluate the stress pattern distribution resulting during nasoalveolar molding therapy of cleft lip and palate patients.

Nasoalveolar Molding (NAM) is associated with ambivalent acceptance regarding effectiveness and unknown long-term results. Our purpose was to analyze the stress distribution patterns within the viscero- and neurocranium of neonates during the first phase of NAM therapy. A finite element (FE) model of a healthy four-week-old neonate was generated, derived from a computed tomography scan allowing the implementation of a bone-density-dependent material model. The influence of dental germs with variable material properties, the cleft width and area of expected force application were analyzed in a worst-case scenario. The resulting stress distribution patterns for each situation were analyzed using the software Ansys APDL. The established FE model was verified with a convergence analysis. Overall, stress patterns at the age of four weeks showed von Mises stress values below 60.000 Pa in the viscero- and neurocranium. The influences of the allocation of material properties for the dental germs, the area of force application, and the cleft width were negligible. A workflow to simulate the stress distribution and deformation in neonates attributable to various areas of force application has been established. Further analyses of the skulls of younger and older neonates are needed to describe the stress distribution patterns during NAM therapy.

PROTECT: PRoximal balloon Occlusion TogEther with direCt Thrombus aspiration during stent retriever thrombectomy - evaluation of a double embolic protection approach in endovascular stroke treatment.

PURPOSE: Stent retriever-based mechanical thrombectomy (MT) for emergent large vessel occlusions (ELVO) is often complicated by thrombus fragmentation causing distal embolization and embolization to new vascular territories. Well-established embolic protection approaches include proximal flow arrest and distal aspiration techniques during stent retriever maneuvers. Aiming at the reduction of thrombus fragmentation during MT we evaluated a technical approach combining proximal balloon occlusion together with direct thrombus aspiration during MT: the PROTECT technique. METHODS: We performed a case-control study comparing the PROTECT technique with sole distal aspiration during MT regarding technical and procedural parameters, n=200 patients with ELVO of either the terminus of the internal carotid artery or the proximal middle artery were included. RESULTS: PROTECT resulted in a shorter procedure time (29 vs 40 min; P=0.002), in a higher rate of successful recanalizations (100% vs 78%; P=0.001) and a higher rate of complete reperfusions (70% vs 39%; P<0.001) compared with sole distal aspiration during MT. CONCLUSION: The PROTECT technique is a promising new approach to significantly reduce thrombus fragmentation and, hence distal embolization during MT. This safe and efficient technique needs to be validated in larger trials to confirm our results.

Impact of time to endovascular reperfusion on outcome differs according to the involvement of the proximal MCA territory.

BACKGROUND: The time interval between symptom onset and reperfusion is a major determinant of the benefit of endovascular therapy (ET) and patients' outcome. The impact of time may be attenuated in patients with robust collaterals. However, not all regions in the middle cerebral artery (MCA) territory have access to collaterals. PURPOSE: To evaluate if the involvement of the poorly collateralized proximal MCA territory has an impact on the degree of time dependency of patients' outcome. METHODS: Patients with MCA occlusions treated with ET and involvement/sparing of the proximal striatocapsular MCA territory (SC+/SC-, each n=97) were matched according to their symptom onset to reperfusion times (SORTs). Correlation and impact of time on outcome was evaluated with strata of SC+/SC- using multivariate logistic regression models (LRMs), including interaction terms. Discharge National Institute of Health Stroke Scale (NIHSS-DIS) score <5 and discharge modified Rankin Scale (mRS-DIS) score ≤2 were prespecified outcome measures. RESULTS: A stronger correlation between all outcome measures (NIHSS-DIS/ΔNIHSS/mRS-DIS) and SORTs was found for SC+ patients than for SC-patients. SORTs were significant variables in LRMs for mRS-DIS score ≤2 and NIHSS-DIS score <5 in SC+ but not in SC- patients. Interaction of SC+ and SORTs was significant in LRMs for both endpoints. CONCLUSION: Time dependency of outcome after ET is more pronounced if parts of the proximal MCA territory are affected. This may reflect the lack of collateralization in the striatocapsular region and a more stringent cell death with time. If confirmed, this finding may affect the selection of patients based on different time windows according to the territory at risk.

Effects of Bariatric Surgery on Non-alcoholic Fatty Liver Disease: Magnetic Resonance Imaging Is an Effective, Non-invasive Method to Evaluate Changes in the Liver Fat Fraction.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disease worldwide and is highly associated with obesity. The prevalences of both conditions have markedly increased in the Western civilization. Bariatric surgery is the most effective treatment for morbid obesity and its comorbidities such as NAFLD. OBJECTIVES: Measure postoperative liver fat fraction (LFF) in bariatric patients by using in-opposed-phase MRI, a widely available clinical tool validated for the quantification of liver fat METHODS: Retrospective analyses of participants, who underwent laparoscopic Roux-Y-gastric-bypass (17) or laparoscopic sleeve gastrectomy (2) were performed using magnetic resonance imaging (MRI), bioelectrical impedance analysis (BIA), and anthropometric measurements 1 day before surgery, as well as 6, 12, and 24 weeks after surgery, LFF was calculated from fat-only and water-only MR images. RESULTS: Six months after surgery, a significant decrease of LFF and liver volume has been observed along with weight loss, decreased waist circumference, and parameters obtained by body fat measured by BIA. LFF significantly correlated with liver volume in the postoperative course. CONCLUSIONS: MRI including in-opposed-phase imaging of the liver can detect the quantitative decrease of fatty infiltration within the liver after bariatric surgery and thus could be a valuable tool to monitor NAFLD/NASH postoperatively.

Biventricular myocardial strain analysis in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) using cardiovascular magnetic resonance feature tracking.

BACKGROUND: Fibrofatty degeneration of myocardium in ARVC is associated with wall motion abnormalities. The aim of this study was to examine whether Cardiovascular Magnetic Resonance (CMR) based strain analysis using feature tracking (FT) can serve as a quantifiable measure to confirm global and regional ventricular dysfunction in ARVC patients and support the early detection of ARVC. METHODS: We enrolled 20 patients with ARVC, 30 with borderline ARVC and 22 subjects with a positive family history but no clinical signs of a manifest ARVC. 10 healthy volunteers (HV) served as controls. 15 ARVC patients received genotyping for Plakophilin-2 mutation (PKP-2), of which 7 were found to be positive. Cine MR datasets of all subjects were assessed for myocardial strain using FT (TomTec Diogenes Software). Global strain and strain rate in radial, circumferential and longitudinal mode were assessed for the right and left ventricle. In addition strain analysis at a segmental level was performed for the right ventricular free wall. RESULTS: RV global longitudinal strain rates in ARVC (-0.68 ± 0.36 sec⁻¹) and borderline ARVC (-0.85 ± 0.36 sec⁻¹) were significantly reduced in comparison with HV (-1.38 ± 0.52 sec⁻¹, p ≤ 0.05). Furthermore, in ARVC patients RV global circumferential strain and strain rates at the basal level were significantly reduced compared with HV (strain: -5.1 ± 2.7 vs. -9.2 ± 3.6%; strain rate: -0.31 ± 0.13 sec(-1) vs. -0.61 ± 0.21 sec⁻¹). Even for patients with ARVC or borderline ARVC and normal RV ejection fraction (n=30) global longitudinal strain rate proved to be significantly reduced compared with HV (-0.9 ± 0.3 vs. -1.4 ± 0.5 sec(-1); p < 0.005). In ARVC patients with PKP-2 mutation there was a clear trend towards a more pronounced impairment in RV global longitudinal strain rate. On ROC analysis RV global longitudinal strain rate and circumferential strain rate at the basal level proved to be the best discriminators between ARVC patients and HV (AUC: 0.9 and 0.92, respectively). CONCLUSION: CMR based strain analysis using FT is an objective and useful measure for quantification of wall motion abnormalities in ARVC. It allows differentiation between manifest or borderline ARVC and HV, even if ejection fraction is still normal.

Autoimmune pancreatitis complicated by carcinoma of the pancreatobiliary system: a case report and review of the literature.

We present the case of a 67-year-old woman who developed a metastatic adenocarcinoma of the pancreatobiliary system shortly after the histologically confirmed diagnosis of autoimmune pancreatitis (AIP). This case highlights the need for increased alertness not only in differentiating AIP from pancreatic cancer at the time of diagnosis, but also to exclude concomitant malignancies of the pancreatobiliary system in the management of histologically confirmed AIP.

B7-h3 and its role in antitumor immunity.

B7-H3 is one of the most recently identified members of the B7/CD28 superfamily of costimulatory molecules serving as an accessory modulator of T-cell response. Recently, B7-H3 expression has been reported in several human cancers indicating an additional function of B7-H3 as a regulator of antitumor immunity. However, its precise physiologic role is still elusive, because both stimulatory and inhibitory capacities have been demonstrated. This paper summarizes the available data on B7-H3 in the regulation of T-cell response focusing on its potential role in antitumor immunity.

Expression of the costimulatory molecule B7-H3 is associated with prolonged survival in human pancreatic cancer.

BACKGROUND: Costimulatory signaling has been implicated as a potential regulator of antitumor immunity in various human cancers. In contrast to the negative prognostic value of aberrant B7-H1 expression by pancreatic cancer cells, the role of B7-H3 is still unknown. Therefore, we investigated the expression pattern and clinical significance of B7-H3 expression in human pancreatic cancer. METHODS: B7-H3 expression was evaluated by immunohistochemistry in 68 patients with pancreatic cancer who underwent surgical tumor resection. Expression data was correlated with clinicopathologic features and with the number of tumor-infiltrating T cells. RESULTS: B7-H3 expression was significantly upregulated in pancreatic cancer compared to normal pancreas (p < 0.05). In 60 of 68 examined tumors B7-H3 protein was detectable in pancreatic cancer cells. Patients with high tumor B7-H3 levels had a significantly better postoperative prognosis than patients with low tumor B7-H3 levels (p = 0.0067). Furthermore, tumor B7-H3 expression significantly correlated with the number of tumor-infiltrating CD8+ T cells (p = 0.018). CONCLUSION: We demonstrate for the first time that B7-H3 is abundantly expressed in pancreatic cancer and that tumor-associated B7-H3 expression significantly correlates with prolonged postoperative survival. Our findings suggest that B7-H3 might play an important role as a potential stimulator of antitumor immune response in pancreatic cancer.