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A 72-year-old man was referred to our hospital for the examination of a pancreatic head mass. Abdominal computed tomography revealed a contrasted 8-cm-diameter tumor extending from the dorsal pancreatic head to the porta hepatis. The preoperative diagnosis was challenging due to the absence of specific imaging findings and the inability to perform a biopsy. Positron emission tomography/computed tomography and diffusion-weighted imaging suggested a malignant tumor originating from the organs surrounding the pancreatic head. Subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection was performed, as dissection from the pancreatic head proved unfeasible. Pathological examination identified the tumor as an enlarged lymph node consisting of pleomorphic large cells forming clusters, positive for follicular dendritic cell markers cluster of differentiation (CD) 21 and CD23. No evidence of tumor capsule infiltration, other organ infiltration, or metastasis to other lymph nodes was observed. The final diagnosis was nodal follicular dendritic cell sarcoma (FDCS) originating from the pancreatic head lymph nodes. No recurrence occurred at 3 years postoperatively with no postoperative treatment. Intraperitoneal nodal FDCS is extremely rare, and occasionally, it can lead to postoperative recurrence and progression. It is crucial to differentiate neoplastic lymph node enlargement around the pancreatic head from nodal FDCS. [ABSTRACT FROM AUTHOR]

Nicotinamide adenine dinucleotide (NAD +) plays a pivotal role in numerous cellular functions. Reduced NAD + levels are postulated to be associated with cancer. As interest in understanding NAD + dynamics in cancer patients with therapeutic applications in mind grows, there remains a shortage of comprehensive data. This study delves into NAD + dynamics in patients undergoing surgery for different digestive system cancers. This prospective study enrolled 99 patients with eight different cancers. Fasting blood samples were obtained during the perioperative period. The concentrations of NAD + , nicotinamide mononucleotide (NMN), and nicotinamide riboside were analyzed using tandem mass spectrometry. After erythrocyte volume adjustment, NAD + remained relatively stable after surgery. Meanwhile, NMN decreased the day after surgery and displayed a recovery trend. Interestingly, liver and pancreatic cancer patients exhibited poor postoperative NMN recovery, suggesting a potential cancer type-specific influence on NAD + metabolism. This study illuminated the behavior of NAD + in surgically treated cancer patients. We identified which cancer types have particularly low levels and at what point depletion occurs during the perioperative period. These insights suggest the need for personalized NAD + supplementation strategies, calibrated to individual patient needs and treatment timelines. Clinical trial registration jRCT1020210066. [ABSTRACT FROM AUTHOR]

Background: Combination therapy with docetaxel (DTX) and ramucirumab (RAM) has been used as a second-line treatment for advanced or recurrent lung cancer. However, there is insufficient evidence regarding the safety of angiogenesis inhibitors in older patients. Objective: This multicenter retrospective study aimed to investigate the efficacy and safety of second-line treatment regimens in older patients with advanced or recurrent non-small cell lung cancer (NSCLC). Patients and Methods: We retrospectively analyzed 145 patients aged ≥ 70 years with advanced or recurrent NSCLC treated with second-line chemotherapy after platinum-based therapy between April 1, 2016, and March 31, 2021. Patients were subdivided into the DTX + RAM (n = 38) and single-agent (n = 107) groups. Results: The median time to treatment failure was 6.3 months (95% confidence interval [CI] 3.6–9.6) in the DTX + RAM group and 2.3 months (95% CI 1.7–3.0) in the single-agent group (p < 0.01). The median overall survival was 15.9 months (95% CI 12.3–Not Achieved) in the DTX + RAM group and 9.4 months (95% CI 6.9–15.1) in the single-agent group (p = 0.01). Grade ≥ 3 adverse events frequency was not significantly different between the two groups, except for edema. Patients in the DTX + RAM group who did not discontinue treatment owing to adverse events exhibited the most favorable prognosis. Conclusions: These findings suggest that the DTX + RAM combination is an effective second-line therapy for older patients with advanced or recurrent NSCLC, offering favorable efficacy without treatment discontinuation owing to adverse events. [ABSTRACT FROM AUTHOR]

Recently, an astatine-labeled prostate-specific membrane antigen (PSMA) ligand ([211At]PSMA-5) has been developed for the targeted alpha therapy of patients with prostate cancer. This manual delineates its physicochemical characteristics to assist healthcare professionals in understanding the α-ray-emitting drug of [211At]PSMA-5 when administered to patients. The safety considerations regarding the handling and use of this drug in clinical trials are outlined, based on the proper usage manual of previous studies. The dose limits, as defined by the guidelines of the International Commission on Radiological Protection (ICRP) and the International Atomic Energy Agency (IAEA), are assessed for patients' caregivers and the general public. According to the calculations provided in this manual, clinical trials involving [211At]PSMA-5 can be safely conducted for these populations even if patients are released after its administration. Moreover, this manual provides comprehensive guidance on the handling of [211At]PSMA-5 for healthcare facilities, and compiles a list of precautionary measures to be distributed among patients and their caregivers. While this manual was created by a research team supported by Ministry of Health, Labour, and Welfare in Japan and approved by Japanese Society of Nuclear Medicine, its applicability extends to healthcare providers in other countries. This manual aims to facilitate conducting clinical trials using [211At]PSMA-5 in patients with prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: Predicting progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD) or dementia with Lewy bodies (DLB) is important. We evaluated morphological and functional differences between MCI with Lewy bodies (MCI-LB) and MCI due to AD (MCI-AD), and a method for differentiating between these conditions using brain MRI and brain perfusion SPECT. Methods: A continuous series of 101 subjects, who had visited our memory clinic and met the definition of MCI, were enrolled retrospectively. They were consisted of 60 MCI-LB and 41 MCI-AD subjects. Relative cerebral blood flow (rCBF) on SPECT images and relative brain atrophy on MRI images were evaluated. We performed voxel-based analysis and visually inspected brain perfusion SPECT images for regional brain atrophy, occipital hypoperfusion and the cingulate island sign (CIS), for differential diagnosis of MCI-LB and MCI-AD. Results: MRI showed no significant differences in regional atrophy between the MCI-LB and MCI-AD groups. In MCI-LB subjects, occipital rCBF was significantly decreased compared with MCI-AD subjects (p < 0.01, family wise error [FWE]-corrected). Visual inspection of occipital hypoperfusion had sensitivity, specificity, and accuracy values of 100%, 73.2% and 89.1%, respectively, for differentiating MCI-LB and MCI-AD. Occipital hypoperfusion was offered higher diagnostic utility than the CIS. Conclusions: The occipital lobe was the region with significantly decreased rCBF in MCI-LB compared with MCI-AD subjects. Occipital hypoperfusion on brain perfusion SPECT may be a more useful imaging biomarker than the CIS for visually differentiating MCI-LB and MCI-AD. [ABSTRACT FROM AUTHOR]

Deep learning (DL) has recently attracted attention for data processing in positron emission tomography (PET). Attenuation correction (AC) without computed tomography (CT) data is one of the interests. Here, we present, to our knowledge, the first attempt to generate an attenuation map of the human head via Sim2Real DL-based tissue composition estimation from model training using only the simulated PET dataset. The DL model accepts a two-dimensional non-attenuation-corrected PET image as input and outputs a four-channel tissue-composition map of soft tissue, bone, cavity, and background. Then, an attenuation map is generated by a linear combination of the tissue composition maps and, finally, used as input for scatter+random estimation and as an initial estimate for attenuation map reconstruction by the maximum likelihood attenuation correction factor (MLACF), i.e., the DL estimate is refined by the MLACF. Preliminary results using clinical brain PET data showed that the proposed DL model tended to estimate anatomical details inaccurately, especially in the neck-side slices. However, it succeeded in estimating overall anatomical structures, and the PET quantitative accuracy with DL-based AC was comparable to that with CT-based AC. Thus, the proposed DL-based approach combined with the MLACF is also a promising CT-less AC approach. [ABSTRACT FROM AUTHOR]

We report a case of intraductal papillary neoplasms of the bile duct (IPNB) that metachronously developed twice in the downstream bile duct after radical resection. The first lesion was located in the left intrahepatic bile duct, the second lesion in the perihilar bile duct, and the third lesion in the distal bile duct. All lesions were IPNBs with associated invasive carcinoma (pancreatobiliary type). The depth of invasion was to the Glisson's capsule in the first lesion, to the subserosa in the second lesion, and to the fibromuscular layer in the third lesion, without lympho-vascular/perineural invasion and lymph-node metastasis. These were resected radically and had no biliary intraepithelial neoplasia and hyperplasia in the surrounding mucosa. In immunohistochemical examination, each lesion showed a different pattern. Although the downstream occurrence suggests intrabiliary dissemination, the mechanism of these metachronous developments may be multicentric. A literature review revealed that most metachronous cholangiocarcinomas have a grossly papillary appearance and tend to arise downstream. Our findings suggest that IPNB may develop metachronously in the residual bile duct after radical surgery, which may assist in early detection. [ABSTRACT FROM AUTHOR]

In this article, a pseudo-stress for local residual and an algebraically derived consistent tangent are applied to elastic–plastic boundary value problems of shells. The authors define a coupled problem of the weak form of the equilibrium equation for the overall structure and the constrained equations for stress state, which include the yield condition and the plane stress condition, at every material point. Since the pseudo-stress for the residuals of yield criterion and plane stress state is incorporated into the linearized weak form of the equilibrium equation, the proposed scheme does not have any local iterative calculations and enables us to decrease the residuals in the coupled boundary value problems simultaneously. Some numerical examples using shell elements demonstrate the validity and effectiveness of the procedures in complex situation with material and geometrical nonlinearities. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to estimate the impact of respiratory and electrocardiogram (ECG)-gated FDG positron emission tomography (PET)/computed tomography (CT) on the diagnosis of cardiac sarcoidosis (CS). Methods and Results: Imaging from thirty-one patients was acquired on a PET/CT scanner equipped with a respiratory- and ECG-gating system. Non-gated PET images and three kinds of gated PET/CT images were created from identical list-mode clinical PET data: respiratory-gated PET during expiration (EX), ECG-gated PET at end diastole (ED), and ECG-gated PET at end systole (ES). The maximum standardized uptake value (SUVmax) and cardiac metabolic volume (CMV) were measured, and the locations of FDG accumulation were analyzed using a polar map. The mean SUVmax of the subjects was significantly higher after application of either respiratory-gated or ECG-gated reconstruction. Conversely, the mean CMV was significantly lower following the application of respiratory-gated or ECG-gated reconstruction. The segment showing maximum accumulation was shifted to the adjacent segment in 25.8%, 38.7%, and 41.9% of cases in EX, ED, and ES images, respectively. Conclusion: In FDG PET/CT scanning for the diagnosis of CS, gated scanning is likely to increase quantitative accuracy, but the effect depends on the location and synchronization method. [ABSTRACT FROM AUTHOR]

Germline mutations in RUNX1 result in rare autosomal-dominant familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). As genetic analysis is becoming increasingly prevalent, the diagnosis rate of FPD/AML is expected to increase. In this report, we present two pedigrees, one diagnosed molecularly and another highly suspected to be FPD/AML, whose members both received allogeneic hematopoietic stem cell transplantation (HSCT). Both pedigrees had a family history of thrombocytopenia, platelet dysfunction, and hematological malignancies. One family inherited a frameshift mutation (p.P240fs) of RUNX1, a known pathogenic variant. Another family inherited a point mutation (p.G168R) in the runt-homology domain, the clinical significance of which is uncertain at this point. As this mutation was completely absent from all population databases and had a relatively high REVEL score of 0.947, we thought that it would be dangerous to ignore its possible pathogenicity. Consequently, we avoided choosing HSCT donors from relatives of both families and performed HSCT from unrelated donors. In conclusion, our experience with two families of FPD/AML highlights the importance of searching for gene mutations associated with germline predisposition and indicates the necessity of developing a donor coordination system for FPD/AML patients, as well as a support system for families. [ABSTRACT FROM AUTHOR]

Crispin Wright in his 1982 paper argues for strict finitism, a constructive standpoint that is more restrictive than intuitionism. In its appendix, he proposes models of strict finitistic arithmetic. They are tree-like structures, formed in his strict finitistic metatheory, of equations between numerals on which concrete arithmetical sentences are evaluated. As a first step towards classical formalisation of strict finitism, we propose their counterparts in the classical metatheory with one additional assumption, and then extract the propositional part of 'strict finitistic logic' from it and investigate. We will provide a sound and complete pair of a Kripke-style semantics and a sequent calculus, and compare with other logics. The logic lacks the law of excluded middle and Modus Ponens and is weaker than classical logic, but stronger than any proper intermediate logics in terms of theoremhood. In fact, all the other well-known classical theorems are found to be theorems. Finally, we will make an observation that models of this semantics can be seen as nodes of an intuitionistic model. [ABSTRACT FROM AUTHOR]

In the reverse transition in pipe flow, turbulent flow changes to less disturbed laminar flow. The entropy of the flow appears to decrease. This study examined the reverse transition experimentally and theoretically using entropy change and momentum balance models, not in terms of disturbance in the flow. The reverse transition was accomplished by decreasing the Reynolds number. The transitions approximately correlated with local Reynolds numbers. The initial Reynolds number of the transition became larger, and the pressure at low Reynolds numbers was greater than in ordinary pipe flow. These behaviours were caused by turbulent flow in the pipe undergoing a reverse transition. We showed that the entropy did not decrease in the reverse transition by including the entropy due to friction in the development region. [ABSTRACT FROM AUTHOR]

In this article, an introduction of pseudo-stress for local residual and an algebraic derivation of consistent tangent are presented. The authors define a coupled problem of the equilibrium equation for the overall structure and the constrained equations for stress state at every material point, and the pseudo-stress and the derived consistent tangent can be implemented easily to finite element analysis. In the proposed block Newton method, the internal variables are also updated algebraically without any local iterative calculations. In addition, the authors demonstrate the performance of the proposed approach for both J 2 plasticity and J 2 plasticity under plane stress state. [ABSTRACT FROM AUTHOR]

In genetic counseling, information must be provided in ways that the client and general public can understand to ensure that decisions are made autonomously. To realize this, we must assess the extent of knowledge held by the general public regarding genetics. To identify the client's original knowledge before genetic counseling, we explored the fundamental knowledge related to genetic counseling that is taught in Japanese compulsory education. A qualitative study was conducted. We selected 50 textbooks for compulsory education (Japanese, social studies, science, health and physical education, technology and home economics, morality, and life) that had been used in more than half of the districts in Japan. The text data were analyzed using qualitative content analysis, and quantitative data were analyzed for methodological triangulation. Codes, subcategories, and categories were generated from the contexts that met the following criteria: the contents included in the official textbook for clinical geneticists, contents derived from such descriptions that were related to genetic counseling, and contents clearly related to genetics. Among the 50 textbooks, 33 textbooks contained fundamental knowledge regarding genetic counseling. A qualitative content analysis identified four major categories: (1) basics of genetics, (2) understanding and control of diseases, (3) efforts and barriers to the realization of a harmonious society, and (4) technology and humans. We found that fundamental knowledge related to genetic counseling is directly or indirectly taught in compulsory education. Our results are an important resource for understanding the client's knowledge baseline and will be helpful for effective genetic counseling. [ABSTRACT FROM AUTHOR]

Background: Programmed death-ligand 1 (PD-L1) inhibitor plus platinum–etoposide chemotherapy is used as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC), regardless of age. Objective: We examined the role of the Geriatric 8 (G8) screening tool for evaluating treatment outcomes in patients with ES-SCLC treated with PD-L1 inhibitor plus platinum–etoposide chemotherapy as first-line therapy. Patients and Methods: Between September 2019 and October 2021, we prospectively evaluated patients with ES-SCLC treated with immunochemotherapy at ten institutions in Japan. The G8 score was assessed before treatment initiation. Results: We evaluated 44 patients with ES-SCLC. Patients with G8 score > 11 had longer overall survival (OS) than those with G8 score ≤ 11 (not reached versus 8.3 months; log-rank test, p = 0.005). In univariate and multivariate analyses, G8 score > 11 [hazard ratio (HR) 0.34; 95% confidence interval (CI) 0.15–0.75; p = 0.008 and HR 0.34; 95% CI 0.14–0.82; p = 0.02, respectively) and performance status (PS) of 2 (HR 5.42; 95% CI 2.08–14.2; p < 0.001 and HR 6.94; 95% CI 2.25–21.4; p < 0.001, respectively) were independent prognostic factors for OS. Among patients with good PS (0 or 1), the OS in patients with G8 score > 11 was significantly longer than that in patients with G8 score ≤ 11 (not reached versus 12.3 months; log-rank test, p = 0.02). Conclusions: G8 score evaluation before treatment initiation was useful as a prognostic factor for ES-SCLC patients who received PD-L1 inhibitors and platinum–etoposide chemotherapy, even with good PS. [ABSTRACT FROM AUTHOR]

Next-generation sequencing (NGS)-based gene profiling can identify patients with pancreatic cancer with homologous recombinant repair gene pathogenic variants (HRRv). Several retrospective studies have reported a positive association between HRRv and the efficacy of platinum-based chemotherapy. However, this association remains to be validated in a prospective study. This multicenter, prospective, observational study included patients with histologically confirmed unresectable or recurrent pancreatic cancer who required systemic chemotherapy. Patients who were oxaliplatin-naïve patients were eligible. The HRRv status was measured using a College of American Pathologists-accredited NGS panel. One-year overall survival rate (1yr-OS%) was calculated after initiation of oxaliplatin-based chemotherapy and was set as the primary endpoint. Forty patients were enrolled between August 2018 and March 2020. The NGS success rate was 95% (38/40). HRRv was detected in 11 patients (27.5%). Oxaliplatin-based chemotherapy was administered to 9 of 11 patients with HRRv (81.8%) and 15 of 29 patients with non-HRRv (51.7%). The 1yr-OS% after initiation of oxaliplatin-based chemotherapy was 44.4% [95% confidence interval (CI) 13.7–71.9] and 57.1% (95% CI 28.4–78.0) in HRRv-positive and -negative cohorts, respectively. These data suggested that HRRv status alone could not be a potential predictive marker of oxaliplatin-based chemotherapy in patients with advanced pancreatic cancer. These results were in line with the results of a recent phase II study reporting the limited efficacy of poly(adenosine diphosphate–ribose) polymerase inhibitor in patients with pancreatic cancer who harbored HRRv other than BRCA. Future studies investigating patients with biallelic HRRv in the first-line setting are warranted. Trial registration UMIN000033655. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the physical performance of a positron emission tomography (PET) system dedicated to the head and breast according to the National Electrical Manufacturers Association (NEMA) NU2-2012 standard. Methods: The spatial resolution, sensitivity, scatter fraction, count rate characteristics, corrections for count losses and randoms, and image quality of the system were determined. All measurements were performed according to the NEMA NU2-2012 acquisition protocols, but image quality was assessed using a brain-sized phantom. Furthermore, scans of the three-dimensional (3D) Hoffmann brain phantom and mini-Derenzo phantom were acquired to allow visual evaluation of the imaging performance for small structures. Results: The tangential, radial, and axial full width at half maximum (FWHM) at a 10-mm offset in half the axial field of view were measured as 2.3, 2.5, and 2.9 mm, respectively. The average system sensitivity at the center of the field of view and at a 10-cm radial offset was 7.18 and 8.65 cps/kBq, respectively. The peak noise-equivalent counting rate was 35.2 kcps at 4.8 kBq/ml. The corresponding scatter fraction at the peak noise-equivalent counting rate was 46.8%. The peak true rate and scatter fraction at 8.6 kBq/ml were 127.8 kcps and 54.3%, respectively. The percent contrast value for a 10-mm sphere was approximately 50%. On the 3D Hoffman brain phantom image, the structures of the thin layers composing the phantom were visualized on the sagittal and coronal images. On the mini-Derenzo phantom, each of the 1.6-mm rods was clearly visualized. Conclusion: Taken together, these results indicate that the head- and breast-dedicated PET system has high resolution and is well suited for clinical PET imaging. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluates the phantom attenuation correction (PAC) method as an alternative to maximum-likelihood attenuation correction factor (ML-ACF) correction in time-of-flight (TOF) brain positron emission tomography (PET) studies. Methods: In the PAC algorithm, a template emission image λ Ref and a template attenuation coefficient image μ Ref are prepared as a data set based on phantom geometry. Position-aligned attenuation coefficient image μ Acq is derived by aligning μ Ref using parameters that match the template emission image λ Ref to measured emission image λ Acq . Then, attenuation coefficient image μ Acq combined with a headrest image is used for scatter and attenuation correction in the image reconstruction. To evaluate the PAC algorithm as an alternative to ML-ACF, Hoffman 3D brain and cylindrical phantoms were measured to obtain the image quality indexes of contrast and uniformity. These phantoms were also wrapped with a radioactive sheet to obtain attenuation coefficient images using ML-ACF. Emission images were reconstructed with attenuation correction by PAC and ML-ACF, and the results were compared using contrast and uniformity as well as visual assessment. CT attenuation correction (CT-AC) was also applied as a reference. Results: The contrast obtained by ML-ACF was slightly overestimated due to its unique experimental condition for applying ML-ACF in Hoffman 3D brain phantom but the uniformity was almost equivalent among ML-ACF, CT-AC, and PAC. PAC showed reasonable result without overestimation compared to ML-ACF and CT-AC. Conclusions: PAC is an attenuation correction method that can ensure the performance in phantom test, and is considered to be a reasonable alternative to clinically used ML-ACF-based attenuation correction. [ABSTRACT FROM AUTHOR]

Purpose: The primary objective of this study was to identify the potential predictors to assess the impact of maintenance therapy after induction immunochemotherapy in the real-world setting of patients with advanced non-small cell lung cancer (NSCLC). Methods: We retrospectively identified 152 patients with advanced NSCLC who received immunochemotherapy at 8 hospitals in Japan between January 2019 and December 2019. Patients who received at least four cycles of induction immunochemotherapy and one cycle of maintenance therapy with immune checkpoint inhibitors were included. We investigated the biomarkers for progression-free survival (PFS) for maintenance therapy after induction immunochemotherapy. Results: Out of the 92 patients with advanced NSCLC included in the study, 42 received maintenance therapy with cytotoxic agents, whereas 50 received maintenance therapy without cytotoxic agents. Among those who received maintenance therapy without cytotoxic agents, responders to prior immunochemotherapy had significantly longer PFS than non-responders (p = 0.004), except those with maintenance therapy with cytotoxic agents. In non-responders to prior immunochemotherapy, patients with maintenance therapy with cytotoxic agents had significantly longer PFS than those with maintenance therapy without cytotoxic agents (log-rank p = 0.007), whereas, among responders to prior immunochemotherapy, there was no significant difference in PFS for different maintenance regimens (log-rank p = 0.31). Conclusions: This retrospective study showed that response to prior immunochemotherapy was associated with clinical outcomes among patients with advanced NSCLC who received maintenance therapy. [ABSTRACT FROM AUTHOR]

Background: Somatic and germline variants are not distinguishable by circulating tumor DNA (ctDNA) testing without analyzing non-tumor samples. Although confirmatory germline testing is clinically relevant, the criteria for selecting presumed germline variants have not been established in ctDNA testing. In the present study, we aimed to evaluate the prevalence of pathogenic germline variants in clinical ctDNA testing through their variant allele fractions (VAFs). Methods: A total of consecutive 106 patients with advanced solid tumors who underwent ctDNA testing (Guardant360®) between January 2018 and March 2020 were eligible for this study. To verify the origin of pathogenic variants reported in ctDNA testing, germline sequencing was performed using peripheral blood DNA samples archived in the Clinical Bioresource Center in Kyoto University Hospital (Kyoto, Japan) under clinical research settings. Results: Among 223 pathogenic variants reported in ctDNA testing, the median VAF was 0.9% (0.02–81.8%), and 88 variants with ≥ 1% VAFs were analyzed in germline sequencing. Among 25 variants with ≥ 30% VAFs, seven were found in peripheral blood DNA (BRCA2: n = 6, JAK2: n = 1). In contrast, among the 63 variants with VAFs ranging from 1 to < 30%, only one variant was found in peripheral blood DNA (TP53: n = 1). Eventually, this variant with 15.6% VAF was defined to be an acquired variant, because its allelic distribution did not completely link to those of neighboring germline polymorphisms. Conclusion: Our current study demonstrated that VAFs values are helpful for selecting presumed germline variants in clinical ctDNA testing. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to investigate whether induction chemotherapy with less than four courses is as effective as induction chemotherapy with more than four courses in non-small cell lung cancer (NSCLC) patients receiving chemoimmunotherapy. Methods: We retrospectively enrolled 249 patients with NSCLC who received chemoimmunotherapy at 12 centers in Japan between January and December 2019. The patient group that completed less than four courses owing to adverse events (AEs), and received subsequent maintenance therapy was compared to the group that received at least four courses of induction chemotherapy followed by maintenance therapy. Results: On univariate and multivariate analyses, the patient group that transitioned to maintenance therapy after completing less than four courses of induction chemotherapy had significantly shorter progression-free survival (PFS) than those who completed at least four courses (hazard ratio [HR] 2.15, 95% confidence interval: 1.38–3.37, p < 0.001 and HR 2.32, 95% confidence interval: 1.40–3.84, p = 0.001, respectively). There was no obvious difference in PFS between the group in which induction chemotherapy ended in two or three courses leading to partial or complete response, and the group that continued at least four courses of induction chemotherapy (log-rank test p = 0.53). Conclusion: Treatment efficacy may be maintained if induction chemotherapy is completed in less than four courses owing to development of AEs, and is administered for more than two courses with partial or complete response; efficacy is maintained even on transitioning to maintenance therapy. [ABSTRACT FROM AUTHOR]

In this manuscript, we present the guideline for use of meta-[211At] astatobenzylguanidine ([211At] MABG), a newly introduced alpha emitting radiopharmaceutical to the up-coming World's first clinical trial for targeted alpha therapy (TAT) at Fukushima Medical University in Japan, focusing on radiation safety issues in Japan. This guideline was prepared based on a study supported by the Ministry of Health, Labour, and Welfare, and approved by the Japanese Society of Nuclear Medicine on Oct. 5th, 2021. The study showed that patients receiving [211At] MABG do not need to be admitted to a radiotherapy room and that TAT using [211At] MABG is possible on an outpatient basis. The radiation exposure from the patient is within the safety standards of the ICRP and IAEA recommendations for the general public and caregivers or patient's family members. In this guideline, the following contents are also included: precautions for patients and their families, safety management associated with the use of [211At] MABG, education and training, and disposal of medical radioactive contaminants. TAT using [211At] MABG in Japan should be carried out according to this guideline. Although this guideline is based on the medical environment and laws and regulations in Japan, the issues for radiation protection and evaluation methodology presented in this guideline are useful and internationally acceptable as well. [ABSTRACT FROM AUTHOR]

Background: The European Society for Medical Oncology Precision Medicine Working Group (ESMO-PMWG) published recommendations regarding confirmatory germline testing for presumed germline pathogenic variants (PGPVs) in tumor-only comprehensive genomic profiling (CGP). However, the clinical validity of these recommendations has not been investigated in a real-world practice. Methods: Medical records of 180 consecutive patients who obtained the results of a tumor-only CGP (FoundationOne® CDx, Foundation Medicine, Inc, Cambridge, MA, USA) between October 2018 and March 2020, were retrospectively reviewed. After excluding patients with no reported variants in 45 actionable genes (n = 6), or no archived germline DNA samples (n = 31), 143 patients were investigated. The PGPVs were selected from the CGP report and germline sequencing were performed using DNA samples archived in Clinical Bioresource Center in Kyoto University Hospital (Kyoto, Japan). Results: A total of 195 variants were classified as PGPV based on the conventional criteria. Germline sequencing disclosed that 12 variants (6.2%) were of germline origin. In contrast, after filtering these 195 variants through the ESMO-PMWG recommendation criteria for confirmatory germline testing, following seven PGPVs, BRCA2 (n = 2), BRIP1 (n = 1), BAP1 (n = 1), PMS2 (n = 1), MSH2 (n = 1), and SDHB (n = 1) remained and six variants (85.7%) were confirmed to be of germline origin. Conclusion: Our current data suggested that the application of ESMO-PMWG criteria is helpful in selecting PGPVs with a high likelihood of germline origin in a tumor-only CGP in daily clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the diagnostic performance of MRI-based radiomics model for differentiating phyllodes tumors of the breast from fibroadenomas. Methods: This retrospective study included 88 patients (32 with phyllodes tumors and 56 with fibroadenomas) who underwent MRI. Radiomic features were extracted from T2-weighted image, pre-contrast T1-weighted image, and the first-phase and late-phase dynamic contrast-enhanced MRIs. To create stable machine learning models and balanced classes, data augmentation was performed. A least absolute shrinkage and selection operator (LASSO) regression was performed to select features and build the radiomics model. A radiological model was constructed from conventional MRI features evaluated by radiologists. A combined model was constructed using both radiomics features and radiological features. Machine learning classifications were done using support vector machine, extreme gradient boosting, and random forest. The area under the receiver operating characteristic (ROC) curve (AUC) was computed to assess the performance of each model. Results: Among 1070 features, the LASSO logistic regression selected 35 features. Among three machine learning classifiers, support vector machine had the best performance. Compared to the radiological model (AUC: 0.77 ± 0.11), the radiomics model (AUC: 0.96 ± 0.04) and combined model (0.97 ± 0.03) had significantly improved AUC values (both p < 0.01) in the validation set. The combined model had a relatively higher AUC than that of the radiomics model in the validation set, but this was not significantly different (p = 0.391). Conclusions: Radiomics analysis based on MRI showed promise for discriminating phyllodes tumors from fibroadenomas. Key Points: • The radiomics model and the combined model were superior to the radiological model for differentiating phyllodes tumors from fibroadenomas. • The SVM classifier performed best in the current study. • MRI-based radiomics model could help accurately differentiate phyllodes tumors from fibroadenomas. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate an image reconstruction algorithm, including a new maximum-likelihood attenuation correction factor (ML-ACF) for time of flight (TOF) brain positron emission tomography (PET). Methods: The implemented algorithm combines an ML-ACF method that simultaneously estimates both the emission image and attenuation sinogram from TOF emission data, and a scaling method based on anatomical features. To evaluate the algorithm's quantitative accuracy, three-dimensional brain phantom images were acquired and soft-tissue attenuation coefficients and emission values were analyzed. Results: The heterogeneous distributions of attenuation coefficients in soft tissue, skull, and nasal cavity were sufficiently visualized. The attenuation coefficient of soft tissue remained within 5% of theoretical value. Attenuation-corrected emission showed no lateral differences, and significant differences among soft tissue were within the error range. Conclusion: The ML-ACF-based attenuation correction implemented for TOF brain PET worked well and obtained practical levels of accuracy. [ABSTRACT FROM AUTHOR]

Objective: This study aimed at investigating the correlation between recurrent visual hallucinations (VHs) and regional cerebral blood flow (rCBF) in patients with dementia with Lewy bodies (DLB). Methods: In 147 DLB patients, the correlation between noise pareidolia scores and rCBF in brain perfusion single photon emission computed tomography (SPECT) was evaluated. The 147 subjects comprised 52 probable and 95 possible DLB patients, of whom 107 did not have visual hallucinations and 40 had visual hallucinations. Brain perfusion SPECT was then performed, and memory impairment was assessed using the Mini-Mental State Examination (MMSE), while the optical illusion "pareidolia" (the tendency to see a specific image in a random visual pattern) was evaluated using noise pareidolia test. The correlations between rCBF and MMSE or noise pareidolia scores were then analyzed. Results: The rCBF and MMSE scores were positively correlated, and rCBF was correlated with MMSE scores in a region that was consistent with a previously reported memory-related site. There was no correlation between noise pareidolia scores and occipital CBF, but there were weak correlations between noise pareidolia scores and rCBF in the bilateral frontal lobes (Brodmann area [BA]8 and BA9), left cingulate cortex (BA31), and left angular and supramarginal gyri (BA39 and BA40) in DLB patients. Conclusion: Weak correlation was found between noise pareidolia scores and rCBF in several sites (BA8, BA9, BA31, BA39 and BA40) other than in occipital lobe. These findings suggest that DLB hallucinations may be manifested by more complex brain network disorders, rather than by primary visual cortex disorders alone. [ABSTRACT FROM AUTHOR]

Pv11 is an insect cell line established from the midge Polypedilum vanderplanki, whose larval form exhibits an extreme desiccation tolerance known as anhydrobiosis. Pv11 itself is also capable of anhydrobiosis, which is induced by trehalose treatment. Here we report the successful construction of a genome editing system for Pv11 cells and its application to the identification of signaling pathways involved in anhydrobiosis. Using the Cas9-mediated gene knock-in system, we established Pv11 cells that stably expressed GCaMP3 to monitor intracellular Ca2+ mobilization. Intriguingly, trehalose treatment evoked a transient increase in cytosolic Ca2+ concentration, and further experiments revealed that the calmodulin–calcineurin–NFAT pathway contributes to tolerance of trehalose treatment as well as desiccation tolerance, while the calmodulin–calmodulin kinase–CREB pathway conferred only desiccation tolerance on Pv11 cells. Thus, our results show a critical contribution of the trehalose-induced Ca2+ surge to anhydrobiosis and demonstrate temporally different roles for each signaling pathway. [ABSTRACT FROM AUTHOR]

Purpose: To determine the association between occipital amyloid-PET uptake and neurocognitive performance in Alzheimer's disease (AD). Materials and methods: Fifty-eight participants with normal aged, mild cognitive impairment (MCI) due to AD and AD subjects who underwent F-18 florbetapir brain PET/CT scans were divided into four groups (A, normal; B, MCI; C, mild AD; and D, moderate/severe AD). Semiquantitative analyses of SUVR images were performed. The differences between groups and the correlations between florbetapir uptake and Thai Mental State Examination (TMSE) scores were determined. Significant differences were defined using a P < 0.001, uncorrected, or a P < 0.05, FWE for the voxel-based analyses with Statistical Parametric Mapping (SPM). Results: There was a slightly higher florbetapir uptake in the precuneus, parietal, and occipital association cortices in Group B > A. The occipital florbetapir uptake in Groups C and D was significantly higher than in Group A, in addition to the precuneus, anterior cingulate, posterior cingulate, temporoparietal, and frontal cortices. There was a strong negative correlation between TMSE scores and florbetapir uptake in the occipital lobe. Conclusions: Occipital amyloid uptake is associated with clinically advanced AD, and is inversely correlated with neurocognitive performance and may be useful for evaluating AD severity. [ABSTRACT FROM AUTHOR]

The use of breast density as a biomarker for breast cancer treatment has not been well established owing to the difficulty in measuring time-series changes in breast density. In this study, we developed a surmising model for breast density using prior mammograms through a multiple regression analysis, enabling a time series analysis of breast density. We acquired 1320 mediolateral oblique view mammograms to construct the surmising model using multiple regression analysis. The dependent variable was the breast density of the mammary gland region segmented by certified radiological technologists, and independent variables included the compressed breast thickness (CBT), exposure current times exposure second (mAs), tube voltage (kV), and patients’ age. The coefficient of determination of the surmising model was 0.868. After applying the model, the correlation coefficients of the three groups based on the CBT (thin group, 18–36 mm; standard group, 38–46 mm; and thick group, 48–78 mm) were 0.913, 0.945, and 0.867, respectively, suggesting that the thick breast group had a significantly low correlation coefficient (p = 0.00231). In conclusion, breast density can be accurately surmised using the CBT, mAs, tube voltage, and patients’ age, even in the absence of a mammogram image.Graphical Abstract: The use of breast density as a biomarker for breast cancer treatment has not been well established owing to the difficulty in measuring time-series changes in breast density. In this study, we developed a surmising model for breast density using prior mammograms through a multiple regression analysis, enabling a time series analysis of breast density. We acquired 1320 mediolateral oblique view mammograms to construct the surmising model using multiple regression analysis. The dependent variable was the breast density of the mammary gland region segmented by certified radiological technologists, and independent variables included the compressed breast thickness (CBT), exposure current times exposure second (mAs), tube voltage (kV), and patients’ age. The coefficient of determination of the surmising model was 0.868. After applying the model, the correlation coefficients of the three groups based on the CBT (thin group, 18–36 mm; standard group, 38–46 mm; and thick group, 48–78 mm) were 0.913, 0.945, and 0.867, respectively, suggesting that the thick breast group had a significantly low correlation coefficient (p = 0.00231). In conclusion, breast density can be accurately surmised using the CBT, mAs, tube voltage, and patients’ age, even in the absence of a mammogram image. [ABSTRACT FROM AUTHOR]

Symmetrical lesions in the temporal poles and external capsules on brain MRI are known as radiological markers of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); however, similar imaging findings have also been reported in neuromyelitis optica spectrum disorder (NMOSD), and this study investigated the frequency of such findings. The study included 55 NMOSD patients who met the 2015 international NMO diagnosis panel (IPND) criteria and were positive for aquaporin-4 antibodies (AQP4-Ab). Images were evaluated based on the consensus of two neuroradiologists, and brain lesions were detected in 33 patients, of whom 2 (6%) had symmetrical lesions in both the temporal poles and external capsules, and 1 (3%) had symmetrical lesions confined to the external capsules. Therefore, when symmetrical lesions in the temporal poles and external capsules are observed on MRI, NMOSD should be considered in the differential diagnosis. [ABSTRACT FROM AUTHOR]

Background: Lynch syndrome (LS) is a hereditary cancer syndrome caused by pathogenic germline variants in mismatch repair (MMR) genes, which predisposes to various types of cancers showing deficient MMR (dMMR). Identification of LS probands is crucial to reduce cancer-related deaths in affected families. Although universal screening is recommended for colorectal and endometrial cancers, and age-restricted screening is proposed as an alternative, LS screening covering a broader spectrum of cancer types is needed. In the current study, we elucidated the rate of dMMR tumors and evaluated the outcome of LS screening in young-onset extra-colorectal LS-associated cancers.Immunohistochemistry for MMR proteins were retrospectively performed in a total of 309 tissue samples of endometrial, non-mucinous ovarian, gastric, urothelial, pancreatic, biliary tract, and adrenal cancers in patients < 50 years of age. Clinicopathological information and the results of genetic testing were obtained from medical charts.There were 24 dMMR tumors (7.8%) including 18 endometrial, three ovarian, two urothelial, and one gastric cancer. Co-occurrence of colorectal cancer and family history of LS-associated cancers was significantly enriched in patients with dMMR tumors. Among the 16 patients with dMMR tumors who were informed of the immunohistochemistry results, five with endometrial and one with urothelial cancer were diagnosed as LS with positive pathogenic variants in MMR genes.We report the outcome of immunohistochemistry for MMR proteins performed in multiple types of young-onset extra-colorectal LS-associated cancers. Our study demonstrates the feasibility of a comprehensive LS screening program incorporating young-onset patients with various types of extra-colorectal LS-associated cancers.Methods: Lynch syndrome (LS) is a hereditary cancer syndrome caused by pathogenic germline variants in mismatch repair (MMR) genes, which predisposes to various types of cancers showing deficient MMR (dMMR). Identification of LS probands is crucial to reduce cancer-related deaths in affected families. Although universal screening is recommended for colorectal and endometrial cancers, and age-restricted screening is proposed as an alternative, LS screening covering a broader spectrum of cancer types is needed. In the current study, we elucidated the rate of dMMR tumors and evaluated the outcome of LS screening in young-onset extra-colorectal LS-associated cancers.Immunohistochemistry for MMR proteins were retrospectively performed in a total of 309 tissue samples of endometrial, non-mucinous ovarian, gastric, urothelial, pancreatic, biliary tract, and adrenal cancers in patients < 50 years of age. Clinicopathological information and the results of genetic testing were obtained from medical charts.There were 24 dMMR tumors (7.8%) including 18 endometrial, three ovarian, two urothelial, and one gastric cancer. Co-occurrence of colorectal cancer and family history of LS-associated cancers was significantly enriched in patients with dMMR tumors. Among the 16 patients with dMMR tumors who were informed of the immunohistochemistry results, five with endometrial and one with urothelial cancer were diagnosed as LS with positive pathogenic variants in MMR genes.We report the outcome of immunohistochemistry for MMR proteins performed in multiple types of young-onset extra-colorectal LS-associated cancers. Our study demonstrates the feasibility of a comprehensive LS screening program incorporating young-onset patients with various types of extra-colorectal LS-associated cancers.Results: Lynch syndrome (LS) is a hereditary cancer syndrome caused by pathogenic germline variants in mismatch repair (MMR) genes, which predisposes to various types of cancers showing deficient MMR (dMMR). Identification of LS probands is crucial to reduce cancer-related deaths in affected families. Although universal screening is recommended for colorectal and endometrial cancers, and age-restricted screening is proposed as an alternative, LS screening covering a broader spectrum of cancer types is needed. In the current study, we elucidated the rate of dMMR tumors and evaluated the outcome of LS screening in young-onset extra-colorectal LS-associated cancers.Immunohistochemistry for MMR proteins were retrospectively performed in a total of 309 tissue samples of endometrial, non-mucinous ovarian, gastric, urothelial, pancreatic, biliary tract, and adrenal cancers in patients < 50 years of age. Clinicopathological information and the results of genetic testing were obtained from medical charts.There were 24 dMMR tumors (7.8%) including 18 endometrial, three ovarian, two urothelial, and one gastric cancer. Co-occurrence of colorectal cancer and family history of LS-associated cancers was significantly enriched in patients with dMMR tumors. Among the 16 patients with dMMR tumors who were informed of the immunohistochemistry results, five with endometrial and one with urothelial cancer were diagnosed as LS with positive pathogenic variants in MMR genes.We report the outcome of immunohistochemistry for MMR proteins performed in multiple types of young-onset extra-colorectal LS-associated cancers. Our study demonstrates the feasibility of a comprehensive LS screening program incorporating young-onset patients with various types of extra-colorectal LS-associated cancers.Conclusions: Lynch syndrome (LS) is a hereditary cancer syndrome caused by pathogenic germline variants in mismatch repair (MMR) genes, which predisposes to various types of cancers showing deficient MMR (dMMR). Identification of LS probands is crucial to reduce cancer-related deaths in affected families. Although universal screening is recommended for colorectal and endometrial cancers, and age-restricted screening is proposed as an alternative, LS screening covering a broader spectrum of cancer types is needed. In the current study, we elucidated the rate of dMMR tumors and evaluated the outcome of LS screening in young-onset extra-colorectal LS-associated cancers.Immunohistochemistry for MMR proteins were retrospectively performed in a total of 309 tissue samples of endometrial, non-mucinous ovarian, gastric, urothelial, pancreatic, biliary tract, and adrenal cancers in patients < 50 years of age. Clinicopathological information and the results of genetic testing were obtained from medical charts.There were 24 dMMR tumors (7.8%) including 18 endometrial, three ovarian, two urothelial, and one gastric cancer. Co-occurrence of colorectal cancer and family history of LS-associated cancers was significantly enriched in patients with dMMR tumors. Among the 16 patients with dMMR tumors who were informed of the immunohistochemistry results, five with endometrial and one with urothelial cancer were diagnosed as LS with positive pathogenic variants in MMR genes.We report the outcome of immunohistochemistry for MMR proteins performed in multiple types of young-onset extra-colorectal LS-associated cancers. Our study demonstrates the feasibility of a comprehensive LS screening program incorporating young-onset patients with various types of extra-colorectal LS-associated cancers. [ABSTRACT FROM AUTHOR]