Using CT to evaluate mediastinal great vein invasion by thymic epithelial tumors: measurement of the interface between the tumor and neighboring structures.

OBJECTIVES: For thymic epithelial tumors, simple contact with adjacent structures does not necessarily mean invasion. The purpose of our study was to develop a simple noninvasive technique for evaluating organ invasion using routine pretreatment computed tomography (CT). METHODS: This retrospective study analyzed the pathological reports on 95 mediastinal resections performed between January 2003 and June 2020. Using CT images, the length of the interface between the primary tumor and neighboring structures (arch distance; Adist) and maximum tumor diameter (Dmax) was measured, after which Adist/Dmax (A/D) ratios were calculated. Receiver operating characteristic (ROC) curves were used to analyze the Adist and A/D ratios. RESULTS: An Adist cut-off of 37.5 mm best distinguished between invaded and non-invaded mediastinal great veins based on ROC curves. When Adist > 37.5 mm was used for diagnosis of invasion of the brachiocephalic vein (BCV) or superior vena cava (SVC), the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the ROC curve for diagnosis of invasion were 61.9%, 92.5%, 81.25%, 82.2%, 81.97%, and 0.76429, respectively. Moreover, there were significant differences between BCV/SVC Adist > 37.5 mm and ≤ 37.5 mm for 10-year relapse-free survival and 10-year overall survival (p < 0.01). CONCLUSIONS: When diagnosing invasion of the mediastinal great veins based on Adist > 37.5 mm, we achieved a higher performance level than the conventional criteria such as irregular interface with an absence of the fat layer. Measurement of Adist is a simple noninvasive technique for evaluating invasion using CT. Key Points • Simple contact between the primary tumor and adjacent structures on CT does not indicate direct invasion. • Using CT images, the length of the interface between the primary tumor and neighboring structures (arch distance; Adist) is a simple noninvasive technique for evaluating invasion. • Adist > 37.5 mm can be a supportive tool to identify invaded mediastinal great veins and surgical indications for T3 and T4 invasion by thymic epithelial tumors.

Usability of detecting delivery errors during treatment of prostate VMAT with a gantry-mounted transmission detector.

Volumetric-modulated arc therapy (VMAT) requires highly accurate control of multileaf collimator (MLC) movement, rotation speed of linear accelerator gantry, and monitor units during irradiation. Pretreatment validation and monitoring of these factors during irradiation are necessary for appropriate VMAT treatment. Recently, a gantry mounted transmission detector "Delta4 Discover® (D4D)" was developed to detect errors in delivering doses and dose distribution immediately after treatment. In this study, the performance of D4D was evaluated. Simulation plans, in which the MLC position was displaced by 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 mm from the clinically used original plans, were created for ten patients who received VMAT treatment for prostate cancer. Dose deviation (DD), distance-to-agreement (DTA), and gamma index analysis (GA) for each plan were evaluated by D4D. These results were compared to the results (DD, DTA and GA) measured by Delta4 Phantom + (D4P). We compared the deviations between the planned and measured values of the MLC stop positions A-side and B-side in five clinical cases of prostate VMAT during treatment and measured the GA values. For D4D, when the acceptable errors for DD, DTA, and GA were determined to be ≤3%, ≤2 mm, and ≤3%/2 mm, respectively, the minimum detectable errors in the MLC position were 2.0, 1.5, and 1.5 mm based on DD, DTA, and GA respectively. The corresponding minimum detectable MLC position errors were 2.0, 1.0, and 1.5 mm, respectively, for D4P. The deviation between the planned and measured position of MLC stopping point of prostate VMAT during treatment was stable at an average of -0.09 ± 0.05 mm, and all GA values were above 99.86%. In terms of delivering doses and dose distribution of VMAT, error detectability of D4D was comparable to that of D4P. The transmission-type detector "D4D" is thus suitable for detecting delivery errors during irradiation.

New PET/CT criterion for predicting lymph node metastasis in resectable advanced (stage IB-III) lung cancer: The standard uptake values ratio of ipsilateral/contralateral hilar nodes.

BACKGROUND: The aim of the present study was to use surgical and histological results to develop a simple noninvasive technique to improve nodal staging using preoperative PET/CT in patients with resectable lung cancer. METHODS: Preoperative PET/CT findings (pStage IB-III 182 patients) and pathological diagnoses after surgical resection were evaluated. Using PET/CT images to determine the standardized uptake value (SUV) ratio, the SUVmax of a contralateral hilar lymph node (on the side of the chest opposite to the primary tumor) was measured simultaneously. The I/C-SUV ratio was calculated as ipsilateral hilar node SUV/contralateral hilar node SUV. Receiver operating characteristic (ROC) curves were then used to analyze those data. RESULTS: Based on ROC analyses, the cutoff I/C-SUV ratio for diagnosis of lymph node metastasis was 1.34. With a tumor ipsilateral lymph node SUVmax ≥2.5, an IC-SUV ratio ≥1.34 had the highest accuracy for predicting N1/N2 metastasis; the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of nodal staging were 60.66, 85.11, 84.09, 62.5 and 71.29%, respectively. CONCLUSIONS: When diagnosing nodal stage, a lymph node I/C-SUV ratio ≥1.34 can be an effective criterion for determining surgical indications in advanced lung cancer.

Harmonization across programmed death ligand 1 (PD-L1) assays for lung cancer by immunohistochemistry using noncontact alternating current electric field mixing.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a promising advance in the treatment of patients with lung cancer. However, each ICI has been tested with an independently designed companion diagnostic assay that is based on a unique antibody. Consequently, the different trial-validated programmed death ligand 1 (PD-L1) immunohistochemistry (IHC) assays should not be considered interchangeable. Our aim was to compare the performance of each available PD-L1 antibody for its ability to accurately measure PD-L1 expression and to investigate the possibility of harmonization across antibodies through the use of a new rapid IHC system, which uses noncontact alternating current (AC) mixing to achieve more stable staining. METHODS: First, 58 resected non-small cell lung cancer (NSCLC) specimens were stained using three PD-L1 IHC assays (28-8, SP142, and SP263) to assess the harmonization achieved with AC mixing IHC. Second, specimens from 27 patients receiving ICIs for postoperative recurrent NSCLC were stained using the same IHC method to compare the clinical performance of ICIs to PD-L1 scores. All patients received a tumor proportion score (TPS) with the 22C3 companion diagnostic test. RESULTS: Better staining was achieved with the new AC mixing IHC method than the conventional IHC in PD-L1-positive cases, and the interchangeability of some combinations of assays was increased in PD-L1-positive. In addition, AC mixing IHC provided more appropriate overall response rates for ICIs in all assays. CONCLUSIONS: Stable PD-L1 IHC driven by AC mixing helped to improve TPS scoring and patient selection for ICIs through interchangeable assays.

Intraoperative diagnosis of lymph node metastasis during segmentectomy for non-small cell lung cancer by rapid immunohistochemistry using noncontact alternating current electric field mixing.

BACKGROUND: Although lobectomy is considered the standard surgery for any non-small cell lung cancer (NSCLC), recent evidence indicates that for early NSCLCs segmentectomy may be equally effective. For segmentectomy to be oncologically safe, however, adequate intraoperative lymph node staging is essential. The aim of this study was to compare the results of a new rapid-IHC system to the HE analysis for intraoperative nodal diagnosis in lung cancer patients considered for segmentectomy. METHODS: This retrospective study analyzed the pathological reports from NSCLC resections over a six-year period between 2014 and 2020. Using a new device for rapid-IHC, we applied a high-voltage, low-frequency alternating current (AC) field, which mixes the antipancytokeratin antibody as the voltage is switched on/off. Rapid-IHC can provide a nodal diagnosis within 20 minutes. RESULTS: Frozen sections from 106 resected lymph nodes from 70 patients were intraoperatively evaluated for metastasis. Of those, five nodes were deemed positive based on both HE staining and rapid-IHC. In addition, rapid-IHC alone detected isolated tumor cells in one hilar lymph node. Three cStage IA patients with nodal metastasis detected with HE staining and rapid-IHC received complete lobectomies. Five-year relapse-free survival and overall survival among patients receiving segmentectomy with rapid-IHC were 88.77% and 88.79%, respectively. CONCLUSIONS: Rapid-IHC driven by AC mixing is simple, highly accurate, and preserves nodal tissue for subsequent tests. This system can be used effectively for intraoperative nodal diagnosis. Rapid immunohistochemistry based on alternating-current field mixing (completed within 20 minutes) is simple and highly accurate. This system will assist clinicians when making intraoperative diagnoses of lymph node metastasis and deciding upon the appropriate surgical procedure in segmentectomy for lung cancer. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Rapid immunohistochemistry driven by alternating-current field mixing (completed within 20 minutes intraoperatively) is simple, highly accurate, and preserves lymph node tissue for subsequent pathological examination, including molecular assessments. WHAT THIS STUDY ADDS: Segmentectomy for lung cancer is oncologically safe, but only when there is adequate intraoperative node staging. Rapid immunohistochemistry will assist clinicians when making intraoperative nodal diagnoses.

Implantable image sensor based on intra-brain image transmission.

We developed and fabricated a micro-imager based on wireless intra-brain communication using conductive property of living tissues. An pixel array, analog-to-digital converter and transmitter are integrated on a single chip. The dimensions of the chip are 1 mm × 1mm × 0.15 mm. We demonstrate wireless image transmission through phosphate buffer saline as a brain phantom.

Effects of vitamin K2, vitamin D, and calcium on the bone metabolism of rats in the growth phase.

Using 168 female Sprague-Dawley rats, we determined whether the peak bone mass could be increased, and which drugs would be effective in suppressing the rate of decrease in bone mass by continuous administration from childhood. At the age of 3 months, these 168 rats were divided into five groups depending on the type of diet that they were fed (control, regular; group A, vitamin K2; group B, vitamin D; group C, high calcium; group D, vitamins D and K2 and high calcium) and kept to the age of 16 months. Dual-energy X-ray absorptiometry (DXA) was used to measure the bone mineral density of the femoral epiphysis and microcomputed tomography (CT) to analyze its fine structure. The average bone mass increased rapidly with age and reached a peak at the age of 8 months. Peak bone mass for the four drug administration groups was higher than that for the control group. Among these four groups, the peak bone mass was the highest in group C and the rate of decrease the smallest in group D. The results of the present animal study suggest that the peak bone mass of humans can be raised by consuming sufficient amounts of vitamins K2 and D and calcium continuously from childhood, and that this diet will suppress the rate of decrease in bone mass, thus ultimately preventing bone fractures caused by osteoporosis.

Mechanical properties of the femur after injection of calcium phosphate cement containing arbekacin sulfate and polylactic acid in a rat model of experimental osteoporosis.

We developed a calcium phosphate cement containing arbekacin sulfate and polylactic acid (CPC95AP) and examined its effects on bone strength by injecting the CPC95AP into the femoral medullary cavity in model rats with osteoporosis. Favorable cortical bone strength was maintained for more than 6 months when CPC95AP was injected into the femoral cavities. This phenomenon was more significant in the weakened femur of osteoporotic rats. The reasons for the increased bone strength are thought to be that the CPC95AP filling increased the geometric moment of inertia and that the binding of CPC95AP with the bones increased Young's modulus. The most important factor is believed to be the increased Young's modulus. The binding of CPC95AP with the bones after filling the femur cavities compensates for the weak extensional strength of CPC95AP, and provides an opportunity to utilize the compressive strength, which is the advantage of CPC95. CPC95AP has antibiotic properties and biocompatibility, and it increases the mechanical strength of the weakened bone; therefore, it is considered useful in bone filling and stiffening.

Bilateral plica synovialis mediopatellaris syndrome: a case report.

The plica synovialis mediopatellaris, a so-called shelf, is found in 20%-50% of normal knees. A shelf syndrome with pain or functional injury is uncommon, however, and cases that occur during the adolescent growth phase are rare. We report a rare case of a bilateral shelf syndrome that developed simultaneously in both knees. The patient was a 13-year-old girl who presented with bilateral knee pain and severely decreased range of motion. The symptoms were not alleviated after internal therapy, so arthroscopy was performed. It showed a white hypertrophied synovialis mediopatellaris, a shelf from the suprapatellar pouch, in both knees. The shelf had an opening between the free margin and the insertion point, giving rise to a synovialis mediopatellaris with a detached structure (type D according to the Sakakibara classification). The cause of the pain was thought to be impingement of the synovialis mediopatellaris. The shelf was ablated by arthroscopy using a holmium-YAG laser. Since the patient was a 13-year-old girl in the growth phase, it is possible that the growth resulted in tension on the shelf remnant bilaterally, intruding into the medial aspect of the patellofemoral joint and increasing the tension, resulting in the symptoms reported.

Experimental study on thermal welding for the knee meniscal white zone.

It is difficult to repair tears of the meniscus at the white zone by suturing. We considered that there might be an optimal tissue welding temperature when thermally welding the meniscal white zone, so we conducted a thermal welding experiment using bovine and human menisci. The samples prepared after thermal welding were investigated by measuring the tensile strength, analyzing the histological findings of the welded portion and the meniscal parenchyma, and conducting biochemical analyses. In the experiment using human menisci, histological findings were investigated using transmission electron microscopy (TEM). As the findings on the welded tissue in the white zone of the bovine meniscus indicated positive results at 63 degrees C and 69 degrees C, the experiments using human meniscal white zone were conducted at these two temperatures. The highest tensile strength after thermal welding of the human meniscal white zone was 101.4 +/- 2.6 g/cm(2) at 63 degrees C. Although there were no significant differences in the amount of pyridinoline per unit collagen weight [Pyr/Hpr (%)] in the human meniscus after thermal welding between the control group and various temperature groups (55 degrees C, 63 degrees C, 69 degrees C, 75 degrees C), the amount of pyridinoline per unit of collagen weight tended to decline as the welding temperature increased. According to the TEM findings, the internal structure of the nuclei of the cells was preserved in the 63 degrees C group, whereas cells were denatured inside the nuclei in the 69 degrees C group. They exhibited necrosis, making cell regeneration difficult. Therefore, it seems feasible that thermal welding at 63 degrees C can repair tears in the human meniscal white zone.

Effects of drug treatment on bone strength and structural changes with aging: an experimental study in rats.

The purpose of the present study was to evaluate the profiles of the bone strength of rats treated from infancy with various drugs. Young female Sprague-Dawley rats were classified into five groups according to the composition of their diets. They underwent resection of their femurs for a three-point flexion test and an impaction test at 6, 8, 12, and 16 months of age. A microcomputed tomography unit was used to evaluate the microstructure of their femoral condyles at 16 months of age. The diet given to the rats in the control group contained 0.5% Ca. The rats in groups A, B, C, and D were placed on the following regimens, respectively: vitamin K mixed diet, vitamin D oral administration, 1.8% Ca-fortified diet, and 1.8% Ca-fortified diet plus vitamin K and vitamin D. In the impaction tests conducted on the rats at each age, the results from groups A and B were nearly the same as those from the control group. At 16 months of age, the rats in groups C and D had significantly higher test results than those in the control group. In the three-point flexion tests at 16 months of age, the results from groups A, B, and C were nearly the same as those from the control group. The results from group D, however, showed a significant increase. Examination of the microstructure of the femoral condyles at 16 months of age revealed controlled destruction of the trabecular structure in groups C and D. These findings suggest that supplementing the diet from infancy with Ca, vitamin K, and vitamin D might prevent bone fractures due to osteoporosis.