Initial validation of the clinical significance of the NETest in Japanese gastroenteropancreatic neuroendocrine tumor patients.

As novel biomarkers for gastroenteropancreatic neuroendocrine tumors (GEPNET) are in demand, we aimed to validate the clinical value of the NETest in Japanese patients. Between 2021 and 2023, blood and clinical data were collected from patients with GEPNET. Among 35 patients (median age: 59 [49-66] years), 27 cases originated from the pancreas and eight from the gastrointestinal tract. Of 69 samples sent to the laboratory, 56 (81.2%) underwent NETest. The diagnostic sensitivity was 97.1%. Among three patients who underwent R0 resection and four treated with peptide receptor radionuclide therapy, the changes in NETest scores closely correlated with disease progression. The NETest demonstrated high diagnostic efficacy and accurate therapeutic monitoring capabilities in a Japanese population.

Maximum standardized uptake value in 11C-methionine positron emission tomography may predict the prognosis of patients with oral squamous cell carcinoma.

The present study aimed to elucidate the correlation between the uptake of 11C-methionine (MET) by a primary tumor and the survival of patients with oral squamous cell carcinoma (OSCC). This study enrolled 31 patients who underwent radical surgery for OSCC. The patients underwent pretreatment MET-positron emission tomography (PET) scanning. We analyzed correlations between the maximum standardized uptake value (SUVmax) of MET-PET in a primary tumor and the clinicopathological features. Further, we compared overall survival (OS), disease-specific survival (DSS), and loco-regional recurrence (LRR) rates between the two groups according to SUVmax of MET-PET. SUVmax of MET-PET in a primary tumor was higher in patients with advanced T-classification and advanced clinical stage, with significant differences (P = 0.001 and P = 0.016, respectively). The patients with SUVmax of MET-PET ≥ 4.4 showed significantly lower DSS rates and higher LRR rates than those with SUVmax of < 4.4 (P = 0.015 and P = 0.016, respectively). SUVmax of MET-PET and OS rates showed no significant correlation (P = 0.073). The present study revealed that SUVmax of MET-PET may predict clinical outcomes and prognosis in patients with OSCC who underwent radical surgery.

Safety and efficacy of multiple-dose versus single-dose MIBG therapy in patients with refractory pheochromocytoma and paraganglioma: a single-center retrospective analysis.

OBJECTIVE: To investigate the incidence of adverse events (AEs) following single and multiple administrations of I-131 metaiodobenzylguanidine (MIBG) therapy for inoperable pheochromocytomas and paragangliomas (PPGLs). METHODS: A single-center retrospective study was conducted on patients with inoperable PPGLs who underwent I-131 MIBG therapy between January 2000 and December 2020. A total of 28 patients with available electronic medical records were included. The treatment consisted of a single intravenous administration of 150 mCi (5.55 GBq) of I-131 MIBG. We evaluated the first MIBG treatment and repeated MIBG treatments performed within 200 days of the previous treatment. AEs for each treatment were evaluated using CTCAE version 4.0, and the statistical analysis was conducted at a significance level of p < 0.05. Objective response based on RECIST 1.1 criteria and biochemical response based on urinary catecholamines were assessed. RESULTS: The study included a total of 63 administrations, consisting of 28 single administrations (SAs), including the first administration for all 28 cases, and 35 multiple administrations (MAs), which included the second or later administrations. Hematological AEs were evaluable for 23 SAs and 29 MAs. Grade 3 or higher leukopenia occurred in 9.8% of all administrations, and Grade 3 or higher lymphopenia in 23.5%; both were manageable through observation. There were no significant differences in clinical AE Grades 1-2 (p = 0.32), hematological AE Grades 1-2 (p = 0.22), or hematological AE Grades 3-4 (p = 0.12) between MAs and SAs. Statistical analysis for each type of AE revealed significant increases in leukopenia (p < 0.01) and lymphopenia (p = 0.04). No significant difference in anemia, thrombocytopenia, or neutropenia was observed between MAs and SAs. There was no significant increase in the incidence rate of Grade 3 or higher hematological AEs for any of the parameters. The objective response rate was 0% for SAs and 36% for MAs. Biochemical response rates were 18% for SAs and 67% for MAs. CONCLUSION: In I-131 MIBG therapy for PPGLs, multiple administrations significantly increased only Grade 1 or 2 lymphopenia and leukopenia compared to single administration.

Intracerebral transplantation of MRI-trackable autologous bone marrow stromal cells for patients with subacute ischemic stroke.

BACKGROUND: Ischemic stroke is one of the leading causes of death and neurological disability worldwide, and stem cell therapy is highly expected to reverse the sequelae. This phase 1/2, first-in-human study evaluated the safety, feasibility, and monitoring of an intracerebral-transplanted magnetic resonance imaging (MRI)-trackable autologous bone marrow stromal cell (HUNS001-01) for patients with subacute ischemic stroke. METHODS: The study included adults with severe disability due to ischemic stroke. HUNS001-01 cultured with human platelet lysates and labeled with superparamagnetic iron oxide was stereotactically transplanted into the peri-infarct area 47-64 days after ischemic stroke onset (dose: 2 or 5 × 107 cells). Neurological and radiographic evaluations were performed throughout 1 year after cell transplantation. The trial was registered at UMIN Clinical Trial Registry (number UMIN000026130). FINDINGS: All seven patients who met the inclusion criteria successfully achieved cell expansion, underwent intracerebral transplantation, and completed 1 year of follow-up. No product-related adverse events were observed. The median National Institutes of Health Stroke Scale and modified Rankin scale scores before transplantation were 13 and 4, which showed improvements of 1-8 and 0-2, respectively. Cell tracking proved that the engrafted cells migrated toward the infarction border area 1-6 months after transplantation, and the quantitative susceptibility mapping revealed that cell signals at the migrated area constantly increased throughout the follow-up period up to 34% of that of the initial transplanted site. CONCLUSIONS: Intracerebral transplantation of HUNS001-01 was safe and well tolerated. Cell tracking shed light on the therapeutic mechanisms of intracerebral transplantation. FUNDING: This work was supported by the Japan Agency for Medical Research and Development (AMED; JP17bk0104045 and JP20bk0104011).

Identifying G6PC3 as a Potential Key Molecule in Hypoxic Glucose Metabolism of Glioblastoma Derived from the Depiction of 18F-Fluoromisonidazole and 18F-Fluorodeoxyglucose Positron Emission Tomography.

Purpose: Glioblastoma is the most aggressive primary brain tumor, characterized by its distinctive intratumoral hypoxia. Sequential preoperative examinations using fluorine-18-fluoromisonidazole (18F-FMISO) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) could depict the degree of glucose metabolism with hypoxic condition. However, molecular mechanism of glucose metabolism under hypoxia in glioblastoma has been unclear. The aim of this study was to identify the key molecules of hypoxic glucose metabolism. Methods: Using surgically obtained specimens, gene expressions associated with glucose metabolism were analyzed in patients with glioblastoma (n = 33) who underwent preoperative 18F-FMISO and 18F-FDG PET to identify affected molecules according to hypoxic condition. Tumor in vivo metabolic activities were semiquantitatively evaluated by lesion-normal tissue ratio (LNR). Protein expression was confirmed by immunofluorescence staining. To evaluate prognostic value, relationship between gene expression and overall survival was explored in another independent nonoverlapping clinical cohort (n = 17) and validated by The Cancer Genome Atlas (TCGA) database (n = 167). Results: Among the genes involving glucose metabolic pathway, mRNA expression of glucose-6-phosphatase 3 (G6PC3) correlated with 18F-FDG LNR (P = 0.03). In addition, G6PC3 mRNA expression in 18F-FMISO high-accumulated glioblastomas was significantly higher than that in 18F-FMISO low-accumulated glioblastomas (P < 0.01). Protein expression of G6PC3 was consistent with mRNA expression, which was confirmed by immunofluorescence analysis. These findings indicated that the G6PC3 expression might be facilitated by hypoxic condition in glioblastomas. Next, we investigated the clinical relevance of G6PC3 in terms of prognosis. Among the glioblastoma patients who received gross total resection, mRNA expressions of G6PC3 in the patients with poor prognosis (less than 1-year survival) were significantly higher than that in the patients who survive more than 3 years. Moreover, high mRNA expression of G6PC3 was associated with poor overall survival in glioblastoma, as validated by TCGA database. Conclusion: G6PC3 was affluently expressed in glioblastoma tissues with coincidentally high 18F-FDG and 18F-FMISO accumulation. Further, it might work as a prognostic biomarker of glioblastoma. Therefore, G6PC3 is a potential key molecule of glucose metabolism under hypoxia in glioblastoma.

A Review of Hypoxia Imaging Using 18F-Fluoromisonidazole Positron Emission Tomography.

Tumor hypoxia is an essential factor related to malignancy, prognosis, and resistance to treatment. Positron emission tomography (PET) is a modality that visualizes the distribution of radiopharmaceuticals administered into the body. PET imaging with [18F]fluoromisonidazole ([18F]FMISO) identifies hypoxic tissues. Unlike [18F]fluorodeoxyglucose ([18F]FDG)-PET, fasting is not necessary for [18F]FMISO-PET, but the waiting time from injection to image acquisition needs to be relatively long (e.g., 2-4 h). [18F]FMISO-PET images can be displayed on an ordinary commercial viewer on a personal computer (PC). While visual assessment is fundamental, various quantitative indices such as tumor-to-muscle ratio have also been proposed. Several novel hypoxia tracers have been invented to compensate for the limitations of [18F]FMISO.

Nuclear medicine practice in Japan: a report of the ninth nationwide survey in 2022.

Subcommittee on Survey of Nuclear Medicine Practice in Japan has performed a nationwide survey of nuclear medicine practice every 5 years since 1982 to survey contemporary nuclear medicine practice and its changes over the years. The subcommittee sent questionnaires, including the number and category of examinations as well as the kind of the radiopharmaceuticals during the 30 days of June 2022 to all nuclear medicine institutes in Japan. The total numbers of them for the year 2022 were estimated depends on the 1-month data. A total of 1095 institutes responded to the survey, including 364 positron emission tomography (PET) centers. The recovery rate was 90.6%. The number of gamma cameras installed was 1299 in total, with 2.5% decrease in 5 years. Dual-head cameras and hybrid SPECT/CT scanners accounted for 83.8% and 35.5%, respectively. The number of single-photon tracer studies in 2022 was 1.11 million which means increase in 2.7% in 5 years. Bone scintigraphy was a leading examination (31.0%), followed by myocardial scintigraphy (27.1%) and cerebral perfusion study (23.8%) in order. The percentage of SPECT studies showed an increase from 63.5% in previous survey to 66.8% in this survey. PET centers have also increased from 389 to 412, as compared with the previous one. One hundred and twenty-two PET centers have installed one or two in-house cyclotrons. Increasing trends of the PET studies were observed from 1992 to 2017, the trend changed and PET studies showed 1.5% decrease in 5 years. 18F-FDG accounted for 98.6% (610,497 examinations). PET examinations using 11C-methionine, 13N-NH3 and 11C-PIB have decreased, with 1624, 2146 and 525 examinations, respectively in 2022. The total number of nuclear medicine examination was eventually increased by 1.0%. Therapies for pheochromocytoma or paraganglioma (PPGL) with 131I-MIBG and for neuroendocrine tumor with 177Lu-DOTA-TATE were newly started, however, a total number of targeted radionuclide therapy was decreased by 17.7% because 131I-radioiodine and 223Ra targeted therapies were decreased and supply of some radioisotopes was discontinued. 131I-radioiodine targeted therapy showed a decrease in 5 years (- 15.9%), including 4099 patients for thyroid cancer. The number of out-patient thyroid bed ablation therapy with 1110 MBq of 131I was also decreased to 1015 per year. The number of admission rooms specialized for radionuclide targeted therapy increased from 157 to 160. The number of 223Ra targeted therapies for castration-resistant metastatic prostate cancer (mCRPC) was 1041 patients. This survey was performed during COVID-19 pandemic, however, total number of nuclear medicine examinations was almost same as previous survey (+ 1.0%). Radionuclide therapies with 131I-MIBG and 177Lu-DOTA-TATE were newly started, and new radionuclide therapy will be available in future, therefore, the development of radionuclide therapy will be continued. We are convinced that this survey report is useful in understanding the current status of the nuclear medicine practice in Japan, and in devising the new strategy to strengthen a role of nuclear medicine.

Diagnosis of skull-base invasion by nasopharyngeal tumors on CT with a deep-learning approach.

PURPOSE: To develop a convolutional neural network (CNN) model to diagnose skull-base invasion by nasopharyngeal malignancies in CT images and evaluate the model's diagnostic performance. MATERIALS AND METHODS: We divided 100 malignant nasopharyngeal tumor lesions into a training (n = 70) and a test (n = 30) dataset. Two head/neck radiologists reviewed CT and MRI images and determined the positive/negative skull-base invasion status of each case (training dataset: 29 invasion-positive and 41 invasion-negative; test dataset: 13 invasion-positive and 17 invasion-negative). Preprocessing involved extracting continuous slices of the nasopharynx and clivus. The preprocessed training dataset was used for transfer learning with Residual Neural Networks 50 to create a diagnostic CNN model, which was then tested on the preprocessed test dataset to determine the invasion status and model performance. Original CT images from the test dataset were reviewed by a radiologist with extensive head/neck imaging experience (senior reader: SR) and another less-experienced radiologist (junior reader: JR). Gradient-weighted class activation maps (Grad-CAMs) were created to visualize the explainability of the invasion status classification. RESULTS: The CNN model's diagnostic accuracy was 0.973, significantly higher than those of the two radiologists (SR: 0.838; JR: 0.595). Receiver operating characteristic curve analysis gave an area under the curve of 0.953 for the CNN model (versus 0.832 and 0.617 for SR and JR; both p < 0.05). The Grad-CAMs suggested that the invasion-negative cases were present predominantly in bone marrow, while the invasion-positive cases exhibited osteosclerosis and nasopharyngeal masses. CONCLUSIONS: This CNN technique would be useful for CT-based diagnosis of skull-base invasion by nasopharyngeal malignancies.

Convolutional neural network-based program to predict lymph node metastasis of non-small cell lung cancer using 18F-FDG PET.

PURPOSE: To develop a convolutional neural network (CNN)-based program to analyze maximum intensity projection (MIP) images of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) positron emission tomography (PET) scans, aimed at predicting lymph node metastasis of non-small cell lung cancer (NSCLC), and to evaluate its effectiveness in providing diagnostic assistance to radiologists. METHODS: We obtained PET images of NSCLC from public datasets, including those of 435 patients with available N-stage information, which were divided into a training set (n = 304) and a test set (n = 131). We generated 36 maximum intensity projection (MIP) images for each patient. A residual network (ResNet-50)-based CNN was trained using the MIP images of the training set to predict lymph node metastasis. Lymph node metastasis in the test set was predicted by the trained CNN as well as by seven radiologists twice: first without and second with CNN assistance. Diagnostic performance metrics, including accuracy and prediction error (the difference between the truth and the predictions), were calculated, and reading times were recorded. RESULTS: In the test set, 67 (51%) patients exhibited lymph node metastases and the CNN yielded 0.748 predictive accuracy. With the assistance of the CNN, the prediction error was significantly reduced for six of the seven radiologists although the accuracy did not change significantly. The prediction time was significantly reduced for five of the seven radiologists with the median reduction ratio 38.0%. CONCLUSION: The CNN-based program could potentially assist radiologists in predicting lymph node metastasis by increasing diagnostic confidence and reducing reading time without affecting diagnostic accuracy, at least in the limited situations using MIP images.

Revolutionizing radiation therapy: the role of AI in clinical practice.

This review provides an overview of the application of artificial intelligence (AI) in radiation therapy (RT) from a radiation oncologist's perspective. Over the years, advances in diagnostic imaging have significantly improved the efficiency and effectiveness of radiotherapy. The introduction of AI has further optimized the segmentation of tumors and organs at risk, thereby saving considerable time for radiation oncologists. AI has also been utilized in treatment planning and optimization, reducing the planning time from several days to minutes or even seconds. Knowledge-based treatment planning and deep learning techniques have been employed to produce treatment plans comparable to those generated by humans. Additionally, AI has potential applications in quality control and assurance of treatment plans, optimization of image-guided RT and monitoring of mobile tumors during treatment. Prognostic evaluation and prediction using AI have been increasingly explored, with radiomics being a prominent area of research. The future of AI in radiation oncology offers the potential to establish treatment standardization by minimizing inter-observer differences in segmentation and improving dose adequacy evaluation. RT standardization through AI may have global implications, providing world-standard treatment even in resource-limited settings. However, there are challenges in accumulating big data, including patient background information and correlating treatment plans with disease outcomes. Although challenges remain, ongoing research and the integration of AI technology hold promise for further advancements in radiation oncology.

Comparative study of physiological FDG uptake in small structures between silicon photomultiplier-based PET and conventional PET.

OBJECTIVE: Silicon photomultiplier-based positron emission tomography/computed tomography (SiPM-PET/CT) has the superior spatial resolution to conventional PET/CT (cPET/CT). This head-to-head comparison study compared the images of physiological 18F-fluorodeoxyglucose (FDG) accumulation in small-volume structures between SiPM-PET/CT and cPET/CT in patients scanned with both modalities, and we investigated whether the thresholds that are reported to be useful for differentiating physiological accumulations from malignant lesions can also be applied to SiPM-PET/CT. METHODS: We enrolled 21 consecutive patients with head and neck malignancies who underwent whole-body FDG-PET/CT for initial staging or a follow-up evaluation (October 2020 to March 2022). After being injected with FDG, all patients underwent PET acquisition on both Vereos PET-CT and Gemini TF64 PET-CT systems (both Philips Healthcare) in random order. For each patient, the maximum standardized uptake value (SUVmax) was measured in the pituitary gland, esophagogastric junction (EGJ), adrenal glands, lumbar enlargement of the spinal cord, and epididymis. We measured the liver SUVmean and the blood pool SUVmean to calculate the target-to-liver ratio (TLR) and the target-to-blood ratio (TBR), respectively. Between-groups differences in each variable were examined by a paired t-test. We also investigated whether there were cases of target uptake greater than the reported threshold for distinguishing pathological from physiological accumulations. RESULTS: Data were available for 19 patients. Ten patients were in Group 1, i.e., the patients who underwent SiPM-PET first, and the remaining nine patients who underwent cPET first were in Group 2. In the SiPM-PET results, the SUVmax of all targets was significantly higher than that obtained by cPET in all patients, and this tendency was also observed when the patients were divided into Groups 1/2. The TLRs of all targets were significantly higher in SiPM-PET than in cPET in all patients, and SiPM-PET also showed significantly higher TBRs for all targets except the EGJ (p = 0.052). CONCLUSIONS: The physiological uptake in the small structures studied herein showed high accumulation on SiPM-PET. Our results also suggest that the thresholds reported for cPET to distinguish pathological accumulations likely lead to false-positive findings in SIPM-PET evaluations.

Bone Echinococcosis Mimicking Malignancy on FDG PET.

ABSTRACT: MRI revealed a thoracic vertebrae lesion in a 40-year-old woman with back pain. She was referred to our institution; MRI demonstrated a mass from the second to the fifth thoracic vertebra and compression fractures. CT revealed a splenic mass, multiple pulmonary nodules, and low-density masses in the liver. 18 F-FDG PET/CT showed increased uptake (SUV max , 10.6) in the peripheral rim of the thoracic vertebra mass, with central parts showing lower uptake than the peripheral rim. The splenic mass exhibited increased accumulation (SUV max , 4.8). The thoracic spine lesion was fixed; a biopsy was performed. Alveolar echinococcosis was confirmed immunologically. Alveolar echinococcosis can present with bone lesions. It must be differentiated from malignancy.

From FDG and beyond: the evolving potential of nuclear medicine.

The radiopharmaceutical 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) has been dominantly used in positron emission tomography (PET) scans for over 20 years, and due to its vast utility its applications have expanded and are continuing to expand into oncology, neurology, cardiology, and infectious/inflammatory diseases. More recently, the addition of artificial intelligence (AI) has enhanced nuclear medicine diagnosis and imaging with FDG-PET, and new radiopharmaceuticals such as prostate-specific membrane antigen (PSMA) and fibroblast activation protein inhibitor (FAPI) have emerged. Nuclear medicine therapy using agents such as [177Lu]-dotatate surpasses conventional treatments in terms of efficacy and side effects. This article reviews recently established evidence of FDG and non-FDG drugs and anticipates the future trajectory of nuclear medicine.

Predictive factors of early FDG-PET response to [131I] MIBG treatment for unresectable or metastatic pheochromocytomas and paragangliomas (PPGLs).

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours that produce catecholamines. [131I] MIBG-avid unresectable or metastatic PPGLs are treated with [131I] MIBG therapy. A high metabolic tumour volume (MTV) and total lesion glycolysis (TLG) can be poor prognostic factors. Therefore, we evaluated the metabolic responses to [131I] MIBG therapy with respect to other clinical factors.A retrospective study was performed on a series of 20 patients who underwent FDG-PET before and after [131I] MIBG therapy. We administered a single dose comprising 5.5 GBq of [131I] MIBG. Semi-quantitative parameters (SUVmax, MTV, and TLG) were calculated using the liver SUV (mean + 3SD) as a threshold on Metavol software. The semi-quantitative FDG-PET parameters for determining response were complete response , partial remission, stable disease, and progressive disease (PD). We divided our study participants into the PD and non-PD groups and compared the overall survival between the two groups. Subsequently, we evaluated the relationships between metabolic response and age, sex, tumour type, metastatic site, chemotherapy or external radiation history, and 24-hour urine catecholamine levels by univariate logistic regression analyses. Both MTV-based and TLG-based criteria for PD vs. non-PD were significant prognostic factors (p = 0.014). However, treatment response as evaluated based on the SUVmax was not a significant predictor. Higher urinary dopamine levels were associated with poor metabolic response as assessed by MTV and TLG. The other clinical parameters were non-significant. Poor metabolic response (measured with MTV and TLG) to [131I] MIBG therapy in unresectable or metastatic PPGLs was related to shorter OS. The poor metabolic response can be predicted using the urinary dopamine level.

Early prediction of treatment outcome for lenvatinib using 18F-FDG PET/CT in patients with unresectable or advanced thyroid carcinoma refractory to radioiodine treatment: a prospective, multicentre, non-randomised study.

BACKGROUND: Lenvatinib is widely used to treat unresectable and advanced thyroid carcinomas. We aimed to determine whether 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) performed 1 week after lenvatinib treatment initiation could predict treatment outcomes. RESULTS: This was a prospective, nonrandomised, multicentre study. Patients with pathologically confirmed differentiated thyroid carcinoma (DTC) and lesions refractory to radioiodine treatment were eligible for inclusion. Patients were treated with 24 mg lenvatinib as the initial dose and underwent PET/CT examination 1 week after treatment initiation. Contrast-enhanced CT was scheduled at least 4 weeks later as the gold standard for evaluation. The primary endpoint was to evaluate the discrimination power of maximum standardised uptake value (SUVmax) obtained by PET/CT compared to that obtained by contrast-enhanced CT. Evaluation was performed using the area under the receiver operating characteristic (ROC-AUC) curve. Twenty-one patients were included in this analysis. Receiver operating characteristic (ROC) curve analysis yielded an AUC of 0.714 for SUVmax after 1 week of lenvatinib treatment. The best cut-off value for the treatment response for SUVmax was 15.211. The sensitivity and specificity of this cut-off value were 0.583 and 0.857, respectively. The median progression-free survival was 26.3 months in patients with an under-cut-off value and 19.7 months in patients with an over-cut-off value (P = 0.078). CONCLUSIONS: The therapeutic effects of lenvatinib were detected earlier than those of CT because of decreased FDG uptake on PET/CT. PET/CT examination 1 week after the initiation of lenvatinib treatment may predict treatment outcomes in patients with DTC. TRIAL REGISTRATION: This trial was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (number UMIN000022592) on 6 June, 2016.

Comparison of simultaneous versus staged bilateral total hip arthroplasty via the direct anterior approach: A propensity score matched analysis.

PURPOSE: It remains unclear whether simultaneous bilateral total hip arthroplasty (SimBTHA) or staged bilateral total hip arthroplasty (StaBTHA) is clinically superior. No study has compared these two procedures matching surgical approach and patient background. This study aimed to clarify the differences between SimBTHA using direct anterior approach (SimBTHA-DAA) and StaBTHA using the direct anterior approach (StaBTHA-DAA). METHODS: Patients who underwent THA between 2012 and 2020 were enrolled, resulting in a total of 1658 hips of 1388 patients. After propensity score matching for patient background, 204 hips of 102 patients (51 patients in each group) were examined. Clinical and radiographic outcomes, complications, intraoperative blood loss and blood transfusions (BT) were evaluated. In complications, we evaluated periprosthetic fractures, pulmonary embolism, deep venous thrombosis, surgical site infection and dislocation. RESULTS: At the final follow-up, clinical and radiographic outcomes and complications were not significantly different between the groups. Intraoperative blood loss was equivalent for SimBTHA and the sum in the first- and second-stage StaBTHA. The total-BT rate was significantly higher for SimBTHA-DAA than for StaBTHA-DAA (p < .0001). The allogeneic BT rate was significantly higher in SimBTHA-DAA in the supine position (32.3%) than in StaBTHA-DAA (8.3%) (p = .007). However, no patient who received autologous BT required allogeneic BT. CONCLUSIONS: Clinical and radiographic outcomes were equivalent between SimBTHA-DAA and StaBTHA-DAA. The allogeneic BT rate was significantly higher in SimBTHA-DAA than in StaBTHA-DAA. Autologous BT reduced the use of allogeneic BT in SimBTHA-DAA. Auto-BT may be useful for avoiding allo-BT in SimBTHA.

In vivo imaging of acute physiological responses after treatment of cancer with near-infrared photoimmunotherapy.

PURPOSE: Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer phototherapy using an antibody-photosensitizer conjugate (Ab-IR700). By NIR light irradiation, Ab-IR700 forms a water-insoluble aggregation on the plasma membrane of cancer cells, leading to lethal membrane damage of cancer cells with high selectivity. However, IR700 produces singlet oxygen, which induces non-selective inflammatory responses such as edema in normal tissues around the tumor. Understanding such treatment-emergent responses is important to minimize side effects and improve clinical outcomes. Thus, in this study, we evaluated physiological responses during NIR-PIT by magnetic resonance imaging (MRI) and positron emission tomography (PET). PROCEDURES: Ab-IR700 was intravenously injected into tumor-bearing mice with two tumors on the right and left sides of the dorsum. At 24 h after injection, a tumor was irradiated with NIR light. Edema formation was examined by T1/T2/diffusion-weighted MRI and inflammation was investigated by PET with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). Because inflammation can increase vascular permeability via inflammatory mediators, we evaluated changes in oxygen levels in tumors using a hypoxia imaging probe, [18F]fluoromisonidazole ([18F]FMISO). RESULTS: The uptake of [18F]FDG in the irradiated tumor was significantly decreased compared to the control tumor, indicating the impairment of glucose metabolism induced by NIR-PIT. MRI and [18F]FDG-PET images showed that inflammatory edema with [18F]FDG accumulation was present in the surrounding normal tissues of the irradiated tumor. Furthermore, [18F]FMISO accumulation in the center of the irradiated tumor was relatively low, indicating the enhancement of oxygen supply due to increased vascular permeability. In contrast, high [18F]FMISO accumulation was observed in the peripheral region, indicating enhancement of hypoxia in the region. This could be because inflammatory edema was formed in the surrounding normal tissues, which blocked blood flow to the tumor. CONCLUSIONS: We successfully monitored inflammatory edema and changes in oxygen levels during NIR-PIT. Our findings on the acute physiological responses after light irradiation will help to develop effective measures to minimize the side effects in NIR-PIT.

Clinical applications of artificial intelligence in liver imaging.

This review outlines the current status and challenges of the clinical applications of artificial intelligence in liver imaging using computed tomography or magnetic resonance imaging based on a topic analysis of PubMed search results using latent Dirichlet allocation. LDA revealed that "segmentation," "hepatocellular carcinoma and radiomics," "metastasis," "fibrosis," and "reconstruction" were current main topic keywords. Automatic liver segmentation technology using deep learning is beginning to assume new clinical significance as part of whole-body composition analysis. It has also been applied to the screening of large populations and the acquisition of training data for machine learning models and has resulted in the development of imaging biomarkers that have a significant impact on important clinical issues, such as the estimation of liver fibrosis, recurrence, and prognosis of malignant tumors. Deep learning reconstruction is expanding as a new technological clinical application of artificial intelligence and has shown results in reducing contrast and radiation doses. However, there is much missing evidence, such as external validation of machine learning models and the evaluation of the diagnostic performance of specific diseases using deep learning reconstruction, suggesting that the clinical application of these technologies is still in development.

Safety and efficacy of tisagenlecleucel in patients with relapsed or refractory B-cell lymphoma: the first real-world evidence in Japan.

BACKGROUND: Tisagenlecleucel, an autologous CD19-directed T-cell immunotherapy, can induce a durable response in adult patients with relapsed/refractory (r/r) B-cell lymphoma. METHODS: To elucidate the outcome of chimeric antigen receptor (CAR) T-cell therapy in Japanese, we retrospectively analyzed the outcomes of 89 patients who received tisagenlecleucel for r/r diffuse large B-cell lymphoma (n = 71) or transformed follicular lymphoma (n = 18). RESULTS: With a median follow-up of 6.6-months, 65 (73.0%) patients achieved a clinical response. The overall survival (OS) and event-free survival (EFS) rates at 12 months were 67.0% and 46.3%, respectively. Overall, 80 patients (89.9%) had cytokine release syndrome (CRS), and 6 patients (6.7%) had a grade ≥ 3 event. ICANS occurred in 5 patients (5.6%); only 1 patient had grade 4 ICANS. Representative infectious events of any grade were cytomegalovirus viremia, bacteremia and sepsis. The most common other adverse events were ALT elevation, AST elevation, diarrhea, edema, and creatinine elevation. No treatment-related mortality was observed. A Sub-analysis showed that a high metabolic tumor volume (MTV; ≥ 80 ml) and stable disease /progressive disease before tisagenlecleucel infusion were both significantly associated with a poor EFS and OS in a multivariate analysis (P < 0.05). Notably, the combination of these 2 factors efficiently stratified the prognosis of these patients (HR 6.87 [95% CI 2.4-19.65; P < 0.05] into a high-risk group). CONCLUSION: We report the first real-world data on tisagenlecleucel for r/r B-cell lymphoma in Japan. Tisagenlecleucel is feasible and effective, even in late line treatment. In addition, our results support a new algorithm for predicting the outcomes of tisagenlecleucel.