Rib fracture after stereotactic radiotherapy on follow-up thin-section computed tomography in 177 primary lung cancer patients

<p>Abstract</p> <p>Background</p> <p>Chest wall injury after stereotactic radiotherapy (SRT) for primary lung cancer has recently been reported. However, its detailed imaging findings are not clarified. So this study aimed to fully characterize the findings on computed tomography (CT), appearance time and frequency of chest wall injury after stereotactic radiotherapy (SRT) for primary lung cancer</p> <p>Materials and methods</p> <p>A total of 177 patients who had undergone SRT were prospectively evaluated for periodical follow-up thin-section CT with special attention to chest wall injury. The time at which CT findings of chest wall injury appeared was assessed. Related clinical symptoms were also evaluated.</p> <p>Results</p> <p>Rib fracture was identified on follow-up CT in 41 patients (23.2%). Rib fractures appeared at a mean of 21.2 months after the completion of SRT (range, 4 -58 months). Chest wall edema, thinning of the cortex and osteosclerosis were findings frequently associated with, and tending to precede rib fractures. No patients with rib fracture showed tumors > 16 mm from the adjacent chest wall. Chest wall pain was seen in 18 of 177 patients (10.2%), of whom 14 patients developed rib fracture. No patients complained of Grade 3 or more symptoms.</p> <p>Conclusion</p> <p>Rib fracture is frequently seen after SRT for lung cancer on CT, and is often associated with chest wall edema, thinning of the cortex and osteosclerosis. However, related chest wall pain is less frequent and is generally mild if present.</p

Immune Responses following Stereotactic Body Radiotherapy for Stage I Primary Lung Cancer

Purpose. Immune responses following stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC) were examined from the point of view of lymphocyte subset counts and natural killer cell activity (NKA). Patients and Methods. Peripheral blood samples were collected from 62 patients at 4 time points between pretreatment and 4 weeks post-treatment for analysis of the change of total lymphocyte counts (TLC) and lymphocyte subset counts of CD3 + , CD4 + , CD8 + , CD19 + , CD56 + , and NKA. In addition, the changes of lymphocyte subset counts were compared between patients with or without relapse. Further, the correlations between SBRT-related parameters and immune response were analyzed for the purpose of revealing the mechanisms of the immune response. Results. All lymphocyte subset counts and NKA at post-treatment and 1 week post-treatment were significantly lower than pre-treatment ( &lt; 0.01). No significant differences in the changes of lymphocyte subset counts were observed among patients with or without relapse. The volume of the vertebral body receiving radiation doses of 3 Gy or more (VV 3 ) significantly correlated with the changes of nearly all lymphocyte subset counts. Conclusions. SBRT for stage I NSCLC induced significant immune suppression, and the decrease of lymphocyte subset counts may be associated with exposure of the vertebral bone marrow

Quantification of image quality of intra-fractional cone-beam computed tomography for arc irradiation with various imaging condition

BACKGROUND: 3-dimensional intra-cone beam computed tomography (intra-CBCT) could be a potentially powerful tool for use with arc irradiation such as volumetric modulated arc therapy. The aim of the study was to evaluate the image quality of intra-cone beam computed tomography (intra-CBCT) for arc irradiation with various imaging condition. MATERIALS AND METHODS: Two types of intra-CBCT imaging techniques were evaluated — intra-fractional CBCT with flattening filtered (FF) beam (intra-FF CBCT) and that with flattening filter free (FFF) beam (intra-FFF CBCT). For the intra-MV beams, four different field sizes (2 cm x 2 cm, 5 cm x 5 cm, 10 cm x 10 cm, and 20 cm x 20 cm) were used with dose rates of 500 MU/min and 1600 MU/min, for 6 MV FF and 6 MV FFF, respectively. For all image acquisitions, two rotation angles (full-arc and half-arc) were investigated. Thereafter, the linearity, contrast-to-noise ratio (CNR), and uniformity index (UI) of intra-CBCT image were compared with those of conventional CBCT image. RESULTS: All acquisition conditions had good linearity of the CT value (R2 &gt; 0.99). For CNR, the change rates from conventional CBCT ranged from 0.6–33.7% for a 2 cm x 2 cm beam, whereas that for a 20 cm x 20 cm beam ranged from 62.7–82.3%. Similarly, the UI increased from 1.5% to 7.0% as the field size increased. CONCLUSION: Quality of intra-CBCT image was affected by the field size and acquisition angle. Image quality of intra-CBCT was worse than that of conventional CBCT, but it was better under a smaller field and wider correction angle and would be acceptable for clinical use.

Angiotensin II induces tumor progression and fibrosis in intrahepatic cholangiocarcinoma through an interaction with hepatic stellate cells

富山県立中央病院金沢大学医薬保健研究域医学系金沢大学附属病院胃腸外科Intrahepatic cholangiocarcinoma (ICC) is characterized as a highly fatal tumor with poor prognosis because of its strong progression, early invasion, widespread metastasis and rich cancerous stroma. Although it is widely accepted that fibroblasts facilitate stromal fibrosis and tumor progression, the mechanisms of the interaction between cancer cells and activated fibroblasts have not been fully elucidated thus far. In this study, we demonstrate the presence of angiotensin II (AngII) in ICC tissues and explore the interaction between hepatic stellate cells (HSCs) and ICC cells as one of the sources of stromal fibrosis and tumor progression through the interaction of the AngII/AngII type 1 receptor (AT-1) axis. The concentrations of AngII in ICC tissues were significantly higher than those of HCC and normal liver. Two human ICC cell lines (HuCCT-1, CCKS-1) and a human HSC cell line (LI-90) expressed AT-1 mRNA and protein. The proliferative activity of ICC cells and HSCs to which AngII was added dose-dependently increased and AT-1 antagonist inhibited the proliferative effects. HSCs to which AngII was added showed a higher expression of α-smooth muscle actin (α-SMA, a marker of activated HSCs and myofibroblasts), glial fibrillary acidic protein (GFAP, a specific marker of HSCs) and collagen type I than control cells. AT-1 antagonist also inhibited the activation and transformation of HSCs stimulated by AngII. These findings suggested that locally formed AngII in ICC tissues plays a role in the proliferation and activation of ICC cells and HSCs expressing AT-1 as a growth factor in autocrine and paracrine fashions. Our mechanistic findings provide the first insight into an autocrine and paracrine AngII-initiated signaling pathway that regulates ICC proliferation and fibrosis

Tumor-derived trypsin enhances proliferation of intrahepatic cholangiocarcinoma cells by activating protease-activated receptor-2

金沢大学医薬保健研究域医学系In primary malignant liver tumors, trypsinogen-immunoreactivity was present in 70% of intrahepatic cholangiocarcinoma (ICC) specimens, but absent in hepato-cellular carcinoma (HCC) specimens. We suggest the secretion of trypsinogen to be a key difference in biological behavior between ICC and HCC cells. The purpose of this study was to investigate the secretion of tumor-derived trypsin and the expression of its specific receptor, protease-activated receptor-2 (PAR-2), in ICC using cell lines and surgical specimens. The expression of trypsinogen-1 mRNA was observed in three of four ICC cell lines, but none of three HCC cell lines. Western blot analysis detected trypsinogen-1 in serum-free conditioned medium from one of the ICC cell lines positive for the mRNA. Gelatin zymography revealed a gelatinolytic activity for trypsin, the activated form of trypsinogen, in the same conditioned medium. PAR-2 mRNA and protein were observed in ICC cell lines. The proliferative activity of ICC cells was increased by concentrations of trypsin as low as 10 nM, and peaked at 100 nM. The effect of trypsin was suppressed by a serine protease inhibitor, gabexate mesilate. PAR-2 expression was detected in 64% of ICC surgical specimens immunohistochemically. In addition, stroma fibroblasts expressed PAR-2 in 52% of ICC specimens. These results suggest that trypsinogen-1 contributes to the growth of ICC cells and also tumor-associated fibroblasts.Embargo Period 6 month

Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors

IntroductionProgrammed cell death ligand 1 (PD-L1) expression in tumor tissues is measured as a predictor of the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in many cancer types. PD-L1 expression is evaluated by immunohistochemical staining using 3,3´-diaminobenzidine (DAB) chronogenesis (IHC-DAB); however, quantitative and reproducibility issues remain. We focused on a highly sensitive quantitative immunohistochemical method using phosphor-integrated dots (PIDs), which are fluorescent nanoparticles, and evaluated PD-L1 expression between the PID method and conventional DAB method.MethodsIn total, 155 patients with metastatic or recurrent cancer treated with ICIs were enrolled from four university hospitals. Tumor tissue specimens collected before treatment were subjected to immunohistochemical staining with both the PID and conventional DAB methods to evaluate PD-L1 protein expression.ResultsPD-L1 expression assessed using the PID and DAB methods was positively correlated. We quantified PD-L1 expression using the PID method and calculated PD-L1 PID scores. The PID score was significantly higher in the responder group than in the non-responder group. Survival analysis demonstrated that PD-L1 expression evaluated using the IHC-DAB method was not associated with progression-free survival (PFS) or overall survival (OS). Yet, PFS and OS were strikingly prolonged in the high PD-L1 PID score group.ConclusionQuantification of PD-L1 expression as a PID score was more effective in predicting the treatment efficacy and prognosis of patients with cancer treated with ICIs. The quantitative evaluation of PD-L1 expression using the PID method is a novel strategy for protein detection. It is highly significant that the PID method was able to identify a group of patients with a favorable prognosis who could not be identified by the conventional DAB method

Effect of paired-pulse electrical stimulation on the activity of cortical circuits

Objective: We investigated the transient effect of short-duration paired-pulse electrical stimulation (ppES) on corticospinal excitability and the after-effect of long-duration ppES on excitability, short-latency afferent inhibition (SAI), and afferent facilitation (AF). Methods: A total of 28 healthy subjects participated in two different experiments. In Experiment 1, motor-evoked potentials (MEPs) were measured in the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles before and immediately after short-duration ppES (5 s) at various inter-pulse intervals (2, 3, 4, 5, 6, 7, 10, 15, 20, and 30 ms). In Experiment 2, MEPs, SAI, and AF were measured before, immediately, and 20 and 40 min after long-duration ppES (20 min, inter-pulse interval of 5 and 15 ms) and peripheral electrical stimulation (20 min, 10 and 20 Hz). Results: Short-duration ppES with inter-pulse intervals of 5 and 20 ms significantly increased MEP measured in APB but not in ADM. Long-duration ppES with an inter-pulse interval of 5 ms significantly decreased SAI but not MEPs in APB. In contrast, long-duration ppES did not affect ADM. Conclusion: The afferent inputs induced by ppES-5 ms were effective for transiently increasing MEP and sustaining SAI reduction