Vision transformer to differentiate between benign and malignant slices in 18F-FDG PET/CT.

Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) is widely used for the detection, diagnosis, and clinical decision-making in oncological diseases. However, in daily medical practice, it is often difficult to make clinical decisions because of physiological FDG uptake or cancers with poor FDG uptake. False negative clinical diagnoses of malignant lesions are critical issues that require attention. In this study, Vision Transformer (ViT) was used to automatically classify 18F-FDG PET/CT slices as benign or malignant. This retrospective study included 18F-FDG PET/CT data of 207 (143 malignant and 64 benign) patients from a medical institute to train and test our models. The ViT model achieved an area under the receiver operating characteristic curve (AUC) of 0.90 [95% CI 0.89, 0.91], which was superior to the baseline Convolutional Neural Network (CNN) models (EfficientNet, 0.87 [95% CI 0.86, 0.88], P < 0.001; DenseNet, 0.87 [95% CI 0.86, 0.88], P < 0.001). Even when FDG uptake was low, ViT produced an AUC of 0.81 [95% CI 0.77, 0.85], which was higher than that of the CNN (DenseNet, 0.65 [95% CI 0.59, 0.70], P < 0.001). We demonstrated the clinical value of ViT by showing its sensitive analysis of easy-to-miss cases of oncological diseases.

Semiquantitative analysis using whole-body dynamic F-18 fluoro-2-deoxy-glucose-positron emission tomography to differentiate between benign and malignant lesions.

OBJECTIVES: To investigate whether whole-body dynamic positron emission tomography (PET) is useful for differentiating benign and malignant lesions. METHODS: In this retrospective study, data from a cohort of 146 lesions from 187 patients who consecutively underwent whole-body dynamic PET scans at our hospital for suspected lesions in the lung, lymph nodes, liver, bone, esophagus, and colon were analyzed. Patients with malignant lymphomas, accumulations > 5 cm in length along the long axis of the esophagus, or lesions in the colon in which the site of accumulation moved during the imaging period were excluded. Patients were administered 3.7 MBq/kg of fluorine-18-fluorodeoxyglucose (F-18 FDG), and dynamic imaging was initiated 60 min after administration. We defined the 60-65, 65-70, 70-75, and 75-80 min time mark as the first, second, third, and fourth pass, respectively. The static image is the summed average of all the four pass images. We measured the accumulation in the mean image of the whole-body dynamic PET scan, which was arithmetically similar to the maximum standardized uptake value (SUVmax) throughout the whole-body static images obtained during 20 min of imaging (S-SUVmax). The ratio of SUVmax in the dynamic first pass(60-65 min after FDG administration) and fourth pass(75-80 min after FDG administration) was calculated as R-SUVmax. RESULTS: The S-SUVmax in the lung, lymph nodes, and bone did not differ significantly between the benign and malignant groups. However, there was a significant difference in R-SUVmax, which was > 1 in most malignant lesions indicating an increase in accumulation during routine scan time. Significant differences were observed between benign and malignant lesions of the liver in both S-SUVmax and R-SUVmax values, with the latter being > 1 in most malignant lesions. CONCLUSIONS: Whole-body dynamic PET for 20 min starting 1 h after FDG administration improved the accuracy of malignant lesion detection in the liver, lymph nodes, lung, and bone. The incremental improvement was small, and the FDG dynamics in the distribution of values between benign and malignant overlapped. Additional information from whole-body dynamic imaging can help detect malignant lesions in these sites without increasing patient burden or prolonging imaging time.

A Case of Gorlin-Goltz Syndrome Without the Characteristic Physical Features That Was Diagnosed After the Development of a Fifth Cancer.

We present a case of Gorlin-Goltz syndrome (GGS) in a patient who developed medulloblastoma, osteosarcoma, myelodysplastic syndrome, basal cell carcinoma, and odontogenic keratocyst by the age of 19 years. He had no known family history and no characteristic physical features of GGS. A frameshift mutation in the PTCH1 gene was found in the oral mucosa as a low-frequency mosaicism, basal cell carcinoma, and normal skin by whole exome sequencing of cancer susceptibility genes. Setting a therapeutic strategy with regard to second cancer development is important for pediatric cancer patients who have a background of cancer predisposition. Advances in comprehensive multigenetic analysis are anticipated to aid in developing such a strategy.

Development of multi-class computer-aided diagnostic systems using the NICE/JNET classifications for colorectal lesions.

BACKGROUND AND AIM: Diagnostic support using artificial intelligence may contribute to the equalization of endoscopic diagnosis of colorectal lesions. We developed computer-aided diagnosis (CADx) support system for diagnosing colorectal lesions using the NBI International Colorectal Endoscopic (NICE) classification and the Japan NBI Expert Team (JNET) classification. METHODS: Using Residual Network as the classifier and NBI images as training images, we developed a CADx based on the NICE classification (CADx-N) and a CADx based on the JNET classification (CADx-J). For validation, 480 non-magnifying and magnifying NBI images were used for the CADx-N and 320 magnifying NBI images were used for the CADx-J. The diagnostic performance of the CADx-N was evaluated using the magnification rate. RESULTS: The accuracy of the CADx-N for Types 1, 2, and 3 was 97.5%, 91.2%, and 93.8%, respectively. The diagnostic performance for each magnification level was good (no statistically significant difference). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the CADx-J were 100%, 96.3%, 82.8%, 100%, and 96.9% for Type 1; 80.3%, 93.7%, 94.1%, 79.2%, and 86.3% for Type 2A; 80.4%, 84.7%, 46.8%, 96.3%, and 84.1% for Type 2B; and 62.5%, 99.6%, 96.8%, 93.8%, and 94.1% for Type 3, respectively. CONCLUSIONS: The multi-class CADx systems had good diagnostic performance with both the NICE and JNET classifications and may aid in educating non-expert endoscopists and assist in diagnosing colorectal lesions.

Advantages of FBPA PET in evaluating early response of anti-PD-1 immunotherapy in B16F10 melanoma-bearing mice: Comparison to FDG PET.

Purpose: PET with L-4-borono-2-[18F] fluoro-phenylalanine (FBPA) was reported to be useful to differentiate malignant tumors and inflammation. Although immunotherapy with immune checkpoint inhibitors (ICIs) has been applied to cancer treatment recently, FDG PET may not be suitable to determine the effect of ICIs because of false-positive findings caused by treatment-related inflammation. In this study, we aimed to demonstrate that FBPA PET allowed detection of the early response of anti-PD-1 immunotherapy in tumor-bearing mice, comparing the results with those of FDG PET. Materials and methods: Mice with B16F10 melanoma tumor xenografts were prepared. Anti-mouse PD-1 antibody or PBS was administered twice intraperitoneally to the tumor-bearing mice on Day 0 (3 days after inoculation) and Day 5 (treatment or control group ). PET/CT imaging was performed twice for each mouse on Day 0 before the anti-PD-1 antibody/PBS administration and on Day 7 using a micro-PET/CT scanner. FBPA and FDG PET/CT studies were conducted separately. SUVmax and the tumor to liver ratio (T/L ratio) were used as parameters exhibiting tumor activity. Tumor uptake volume (TUV) and metabolic tumor volume (MTV) were also calculated for FBPA and FDG, respectively. Changes between pre- and posttreatment SUVmax or T/L ratio were observed using the formula as follows: [(posttreatment parameter values/pretreatment values - 1) × 100] (%). Results: Tumors in TrG were smaller than those in CoG on Day 7. SUVmax and T/L ratio represented no differences between TrG and CoG in FBPA and FDG PET before treatment. FBPA PET on Day 7 demonstrated that SUVmax, T/L ratio, and TUV in TrG were statistically smaller than those in CoG. %T/L ratio and %SUVmax exhibited the same trend in FBPA PET. However, FDG PET on Day 7 revealed no differences in all parameters between TrG and CoG. T/L ratio and %SUVmax in TrG represented larger values than those in CoG without statistical significances. Conclusion: This study demonstrated that FBPA PET allowed detection of the early response of anti-PD-1 immunotherapy in B16F10 melanoma-bearing mice. FDG PET did not detect the response. Further studies are required to determine whether FBPA PET is useful in evaluating the treatment effect of ICIs in humans.

Effects of New Bayesian Penalized Likelihood Reconstruction Algorithm on Visualization and Quantification of Upper Abdominal Malignant Tumors in Clinical FDG PET/CT Examinations.

PURPOSE: This study evaluated the effects of new Bayesian penalized likelihood (BPL) reconstruction algorithm on visualization and quantification of upper abdominal malignant tumors in clinical FDG PET/CT examinations, comparing the results to those obtained by an ordered subset expectation maximization (OSEM) reconstruction algorithm. Metabolic tumor volume (MTV) and texture features (TFs), as well as SUV-related metrics, were evaluated to clarify the BPL effects on quantification. MATERIALS AND METHODS: A total of 153 upper abdominal lesions (82 liver metastatic and 71 pancreatic cancers) were included in this study. FDG PET/CT images were acquired with a GE Discovery 710 scanner equipped with a time-of-flight system. Images were reconstructed using OSEM and BPL (beta 700) algorithms. In 58 lesions <1.5 cm in greatest diameter (small-lesion group), visual image quality of each lesion was evaluated using a four-point scale. SUVmax was obtained for quantitative metrics. Visual scores and SUVmax were compared between OSEM and BPL images. In 95 lesions >2.0 cm in greatest diameter (larger-lesion group), SUVmax, SUVpeak, MTV, and six TFs were compared between OSEM and BPL images. In addition to the size-based analyses, an increase of SUVmax with BPL was evaluated according to the original SUVmax in OSEM images. RESULTS: In the small-lesion group, both visual score and SUVmax were significantly higher in the BPL than OSEM images. The increase in visual score was observed in 20 (34%) of all 58 lesions. In the larger-lesion group, no statistical difference was observed in SUVmax, SUVpeak, or MTV between OSEM and BPL images. BPL increased high gray-level zone emphasis and decreased low gray-level zone emphasis among six TFs compared to OSEM with statistical significance. No statistical differences were observed in other TFs. SUVmax-based analysis demonstrated that BPL increased and decreased SUVmax in lesions with low (<5) and high (>10) SUVmax in original OSEM images, respectively. CONCLUSION: This study demonstrated that BPL improved conspicuity of small or low-count upper abdominal malignant lesions in clinical FDG PET/CT examinations. Only two TFs represented significant differences between OSEM and BPL images of all quantitative metrics in larger lesions.

Intratumoral administration of astatine-211-labeled gold nanoparticle for alpha therapy.

BACKGROUND: 211At is a high-energy α-ray emitter with a relatively short half-life and a high cytotoxicity for cancer cells. Its dispersion can be imaged using clinical scanners, and it can be produced in cyclotrons without the use of nuclear fuel material. This study investigated the biodistribution and the antitumor effect of 211At-labeled gold nanoparticles (211At-AuNP) administered intratumorally. RESULTS: AuNP with a diameter of 5, 13, 30, or 120 nm that had been modified with poly (ethylene glycol) methyl ether (mPEG) thiol and labeled with 211At (211At-AuNP-S-mPEG) were incubated with tumor cells, or intratumorally administered to C6 glioma or PANC-1 pancreatic cancers subcutaneously transplanted into rodent models. Systemic and intratumoral distributions of the particles in the rodents were then evaluated using scintigraphy and autoradiography, and the changes in tumor volumes were followed for about 40 days. 211At-AuNP-S-mPEG was cytotoxic when it was internalized by the tumor cells. After intratumoral administration, 211At-AuNP-S-mPEG became localized in the tumor and did not spread to systemic organs during a time period equivalent to 6 half-lives of 211At. Tumor growth was strongly suppressed for both C6 and PANC-1 by 211At-AuNP-S-mPEG. In the C6 glioma model, the strongest antitumor effect was observed in the group treated with 211At-AuNP-S-mPEG with a diameter of 5 nm. CONCLUSIONS: The intratumoral single administration of a simple nanoparticle, 211At-AuNP-S-mPEG, was shown to suppress the growth of tumor tissue strongly in a particle size-dependent manner without radiation exposure to other organs caused by systemic spread of the radionuclide.

Greater reductions in blood flow after anti-angiogenic treatment in non-small cell lung cancer patients are associated with shorter progression-free survival.

To evaluate tumor blood flow using 15O-water positron emission tomography (PET) in patients with non-small cell lung cancer (NSCLC) before and after chemotherapy with bevacizumab, and to investigate the effects of bevacizumab on tumor blood flow changes and progression-free survival (PFS). Twelve patients with NSCLC were enrolled. Six patients underwent chemotherapy with bevacizumab and the other six without bevacizumab. 15O-water dynamic PET scans were performed within 1 week before the start of chemotherapy and within 1 week after the first day of chemotherapy. Tumor blood flow was analyzed quantitatively using a single one-tissue compartment model with the correction of pulmonary circulation blood volume and arterial blood volume via an image-derived input function. In the bevacizumab group, mean tumor blood flow was statistically significantly reduced post-chemotherapy (pre-chemotherapy 0.27 ± 0.14 mL/cm3/min, post-chemotherapy 0.18 ± 0.12 mL/cm3/min). In the no bevacizumab group, there was no significant difference between mean tumor perfusion pre-chemotherapy (0.42 ± 0.42 mL/cm3/min) and post-chemotherapy (0.40 ± 0.27 mL/cm3/min). In the bevacizumab group, there was a positive correlation between the blood flow ratio (tumor blood flow post-chemotherapy/tumor blood flow pre-chemotherapy) and PFS (correlation coefficient 0.94). Mean tumor blood flow decreases after bevacizumab administration and was positively correlated with longer PFS.

SGLT2 inhibition alleviated hyperglycemia, glucose intolerance, and dumping syndrome-like symptoms in a patient with glycogen storage disease type Ia: a case report.

BACKGROUND: Glycogen storage disease (GSD) type Ia is a glycogenesis disorder with long-term complications such as hepatomegaly and renal dysfunction and is caused by congenital loss of glucose-6-phosphatase (G6Pase) expression. G6Pase is essential for the final step of gluconeogenesis and glycogenolysis, and its deficiency causes clinical hypoglycemia in the fasting state during infancy. Contrastingly, patients also show blood glucose trends and glucose intolerance similar to those in type II diabetes. Owing to the contrasting presentation of hypoglycemia with glucose intolerance, glucose control in patients remains a challenge, requiring management of both fasting hypoglycemia and post-prandial hyperglycemia. CASE PRESENTATION: The patient was a 45-year old Asian (Japanese) woman who showed disease onset at 3 years of age, when hypoglycemia and hepatomegaly were observed, and GDS type Ia was diagnosed by the lack of G6Pase activity. Over the past 45 years, she presented hyperglycemia and dumping syndrome like symptoms (a feeling of fullness, even after eating just a small amount, abdominal cramping, nausea, sweating, flushing, or light-headedness and rapid heartbeat) at 2 hours after food intake. Her liver and kidney dysfunction also worsened over time. Treatment with exercise combined with a sodium-glucose co-transporter 2 inhibitor and an alpha glucosidase inhibitor alleviated her glucose intolerance and dumping syndrome-like symptoms, without increasing hypoglycemic events. CONCLUSION: This case suggests SGLT2 inhibitor as a promising candidate for treating glucose intolerance in GSD type Ia without worsening of hypoglycemia.

Pharmacokinetics, Efficacy and Safety of Bosutinib in a Pediatric Patient With Chronic Myeloid Leukemia.

Bosutinib is a second-generation tyrosine kinase inhibitor indicated for treatment of chronic myeloid leukemia (CML) in adult patients. The safety and efficacy of bosutinib in patients younger than 18 years of age have not been established. We here report the case of a 4-year-old male with CML who was treated with bosutinib during coordination of human leukocyte antigen-matched unrelated bone-marrow transplantation because of insufficient responses to imatinib and dasatinib. The patient achieved a complete cytogenetic response immediately after starting bosutinib at 180 mg/day (290 mg/m2/day). Because toxicity was tolerable, the dose was increased to 200 mg/day (330 mg/m2/day). A complete cytogenetic response was maintained, but a major molecular response was not achieved 6 months after initiation of treatment with bosutinib. At steady state, maximum plasma concentration, minimum plasma concentration, and area under the plasma concentration-time curve were 89.2 ng/mL, 16.7 ng/mL, and 1017.4 ng·hr/mL, respectively, at 290 mg/m2/day; and 141.1 ng/mL, 18.9 ng/mL, and 1278.5 ng·hr/mL, respectively, at 330 mg/m2/day. To the best of our knowledge, this is the first case report to show the pharmacokinetics of bosutinib with efficacy and safety in a pediatric patient with CML. This rare case in a very young child with CML can also be valuable reference for clinical practice.

Pulmonary tumor thrombotic microangiopathy caused by prostate carcinoma.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal malignancy-related condition that involves rapidly progressing hypoxia and pulmonary hypertension. We report a case of PTTM caused by prostate carcinoma, which was diagnosed before autopsy in an 81-year-old man. Computed tomography showed diffuse ground-glass opacities, consolidation, and small nodules in the peripheral regions of the lung. Autopsy showed adenocarcinoma cells embolizing small pulmonary arteries with fibrocellular intimal proliferation, which was consistent with PTTM caused by prostate carcinoma.

Ion-Free and Ion-Pairing Assemblies of Anion-Responsive π-Electronic Systems Possessing Directly Linked Alkyl Chains.

Alkyl-substituted pyrrole-based anion-responsive π-electronic systems formed supramolecular gels and liquid crystals through effective π-π stacking and van der Waals interactions. The addition of chloride as a planar cation salt afforded ion-pairing assemblies as soft materials comprising planar receptor-Cl(-) complexes and the cation.

[Successful anesthetic management of a patient with thyroid storm using landiolol].

We report successful anesthetic management of a 38-year-old man with thyroid storm using an ultra-short acting beta blocker, landiolol. The patient was admitted to the hospital for severe abdominal pain. An emergency laparotomy was scheduled for perforated gastric ulcer under a condition of uncontrolled thyrotoxicosis. On arriving the operating room, he showed tachycardia of 140 beats x min(-1) and blood pressure of 140/75 mmHg and high fever of 39 degrees C with tremor, sweating and diarrhea. He was anesthetized with oxygen, nitrous oxide, sevoflurane and fentanyl. Heart rate was around 130 beats x min(-1), and the landiolol was given continuously at a rate of 0.02-0.04 microg x kg(-1) x min(-1). Heart rate was controlled bellow 120 beats x min(-1) without hypotension during anesthesia. Thiamazole and inorganic iodine were given through an enterostomy tube postoperatively, and heart rate decreased gradually. He was extubated on the third postoperative day without any sequelae.

[Perioperative management of abdominal operation in three patients with pulmonary emphysema associated with pulmonary hypertension].

Anesthesia for abdominal operation in patients with emphysema is accompanied with a high risk of respiratory insufficiency requiring postoperative artificial ventilation. Furthermore, in patients whose pulmonary emphysema progresses and leads to pulmonary hypertension, there is the risk of developing right heart failure with postoperative respiratory insufficiency. Because perioperative circulatory drifting is massive in abdominal operation, they develop right heart failure easily during the postoperative refilling phase. Therefore, it is important to avoid right heart failure during the postoperative period in these patients. We estimate pulmonary artery pressure using echocardiography at bedside and give dopamine for diuresis during the postoperative period. We succeeded in perioperative management of abdominal operation in three patients with pulmonary emphysema associated with pulmonary hypertension.

Effect of beta-casein (1-28) on proliferative responses and secretory functions of human immunocompetent cell lines.

The effect of bovine beta-casein (1-28) purified from commercial casein phosphopeptide preparations on human T, B, and monocyte cell lines was evaluated. Beta-casein (1-28) enhanced the proliferation of the following: T cell lines HUT-78, Jurkat Clone E6-1, and MOLT-4; B cell lines BALL, KHM-1B, and U266B1; and monocyte cell lines U937 and HL-60. Moreover, beta-casein (1-28) stimulated IgA production by KHM-1B over 96 h of culture. Semiquantitative reverse transcriptional-polymerase chain reaction analysis indicated that beta-casein (1-28) enhanced mRNA expression of interleukin (IL)-6 in U266B1 and KHM-1B. These results suggest that beta-casein (1-28) exerts a mitogenic effect on human T, B, and monocyte cells, and an IgA-enhancing effect on B cells.

[Epidural blood patch as a successful treatment of Barrè-Lièou syndrome: report of two cases].

Barrè-Lièou syndrome accompanies neurological symptoms after neck sprain, and is often difficult to treat. We describe two young men with various neurological symptoms after traffic accident, who were diagnosed with Barrè-Lièou syndrome. Both case 1 (41-year-old man) and case 2 (34-year-old man) showed no abnormal findings in head and cervical X-ray, CT-scan and MRI. Only radionuclide cisternography (RNC) showed cerebrospinal fluid (CSF) leak into epidural space at thoracolumbar level. Three months (case 1) and four years (case 2) had passed after each accident. Two patients underwent epidural blood patch (EBP) for total of three times. The average volumes of the blood used for EBP were 30 ml (case 1) and 24 ml (case 2). The procedure improved various symptoms except for neck stiffness and dizziness. EBP had led to low back pain, which disappeared within three days. CSF leak vanished in RNC after EBP. Severe complication, for example epidural infection or neurological disorders due to hematoma, was not noticed. While neural blockade did not relieve pain before EBP, we could get good effect from neural blockade for remaining symptoms after EBP. We consider that Barrè-Lièou syndrome is due to CSF leak and EBP may be one of the useful treatments.