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Bone is one of the most common sites of metastasis in breast cancer patients. Although bone scintigraphy is widely used to detect metastatic breast cancer, the usefulness of18FDG-PET for detecting bone metastasis has not been clearly evaluated. The purpose of this study was to compare the diagnostic accuracy of18FDG-PET with bone scintigraphy in detecting bone metastasis in breast cancer patients. Forty-four women aged 35 to 81 years (mean, 56 years) with breast cancer were examined in this study. Both18FDG-PET and bone scintigraphy were performed for each patient with 0-69 day intervals (mean, 11.5 days). The results of each image interpretation were compared retrospectively. Whole-body bones were classified into 9 anatomical regions. Metastases were confirmed at 45/187 regions in 14 patients by bone biopsy or clinical follow-up including other imaging techniques for a period of at least 6 months afterwards. On a region basis, the sensitivity, specificity, and accuracy of18FDG-PET were 84%, 99% and 95%, respectively. Although these results were comparable to those of bone scintigraphy, the combination of18FDG-PET and bone scintigraphy improved the sensitivity (98%) and accuracy (97%) of detection. False negative lesions of bone scintigraphy were mostly bone marrow metastases and those of18FDG-PET were mostly osteoblastic metastases.18FDG-PET was superior to bone scintigraphy in the detection of osteolytic lesions (92% vs. 73%), but inferior in the detection of osteoblastic lesions (74% vs. 95%). This study shows that18FDG-PET tends to be superior to bone scintigraphy in the detection of osteolytic lesions, but inferior in the detection of osteoblastic lesions.18FDG-PET should play a complementary role in detecting bone metastasis with bone scintigraphy. [ABSTRACT FROM AUTHOR]

1. In the [13C]-octanoic acid breath test, the time versus pulmonary [13CO2] excretion rate curve is analysed using mathematical curve-fitting techniques to calculate gastric emptying parameters. Thus, the goodness-of-fit highly influences the accuracy of the breath test. However, a double-peaked [13CO2] excretion curve, which occasionally develops owing to the presence of an interval of quiescent gastric emptying (the plateau phase), is likely to be fitted poorly. 2. In pharmacokinetics, the Wagner-Nelson method has been used to describe precisely the absorption kinetics of orally administered drugs and its reliability is independent of the nature of gastric emptying. A recent study has shown the potential of the Wagner-Nelson method to generate a realistic gastric emptying flow curve from [13CO2] excretion data. In the present report, we have demonstrated that the Wagner-Nelson method can visualize the plateau emptying phase responsible for the cases of double peaks. 3. Wagner-Nelson analysis applied to the breath test described precisely the characteristic emptying pattern of the two emptying phases being interrupted by the plateau phase. Conventional analysis for the breath test failed to detect the plateau phase. 4. The Wagner-Nelson method is a useful tool for analysing atypical double-peaking [13CO2] excretion curves. [ABSTRACT FROM AUTHOR]

Background. Cigarette smoking is associated with an increased risk of peptic ulcer and gastroesophageal reflux disease. Gastric emptying disorders may play a role in the development of these upper gastrointestinal diseases. Thus, studies examining a link between smoking and gastric emptying disorders have clinical relevance. This study was conducted to investigate the effect of smoking on gastric emptying of solids in Japanese smokers. Methods. The 13C-octanoic acid breath test was performed in eight male habitual smokers on two randomized occasions (either sham smoking or actively smoking). The time vs 13CO2 excretion rate curve was mathematically fitted to a conventional formula of y (t) = m*k*β*e-k*t*(1 - e-k*t)β-1, and the parameters of k and were determined: under the crossover protocol, a larger (smaller) β indicates slower (faster) emptying in the early phase, and a larger (smaller) k indicates faster (slower) emptying in the later phase. The half 13CO2 excretion time (t1/2b = -[1n(1 - 2-1/β)]/k) and the time of maximal 13CO2 excretion rate (tmax = [1nβ]/k) were also calculated. Between the two occasions, k, βt1/2b, and tmax were compared by the Wilcoxon signed-rank test. Results. After smoking, k was significantly increased. No significant differences were found in β, t1/2, and tmax between the two occasions. Conclusions. The increase in k suggests the acceleration of gastric emptying in the later phase. For the first time, this study has revealed that acute smoking speeds the gastric emptying of solids in Japanese habitual smokers. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to clarify the period of extraosseous accumulation of (99m)Tc-hydroxymethylenediphosphonate (HMDP) to radiation nephropathy mimicking recurrent or remnant neuroblastoma in the pararenal region.Methods: We reviewed five neuroblastoma and one ganglioneuroblastoma patients (2 boys and 4 girls aged 1-9 years) who underwent (99m)Tc-HMDP bone scintigraphies periodically before and after radiation therapy.Results: Increased renal uptake coincident with the radiation port appeared in 5 of 6 patients from 0 to 3 months (mean 1.7 months), and persisted up to 7 months after the completion of radiotherapy. Renal uptake of (99m)Tc-HMDP was gradually decreased, and eventually became accumulation defects in 5 of 6 patients from 6 to 17 months (mean 8.9 months) after radiotherapy.Conclusion: When extraosseous accumulation is found after radiation therapy in neuroblastoma patients, radiation nephropathy would be a candidate in the differential diagnosis besides recurrent or remnant tumor. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to clarify the period of extraosseous accumulation of99mTc-hydroxymethylenediphosphonate (HMDP) to radiation nephropathy mimicking recurrent or remnant neuroblastoma in the pararenal region. Methods: We reviewed five neuroblastoma and one ganglioneuroblastoma patients (2 boys and 4 girls aged 1–9 years) who underwent99mTc-HMDP bone scintigraphies periodically before and after radiation therapy. Results: Increased renal uptake coincident with the radiation port appeared in 5 of 6 patients from 0 to 3 months (mean 1.7 months), and persisted up to 7 months after the completion of radiotherapy. Renal uptake of99mTc-HMDP was gradually decreased, and eventually became accumulation defects in 5 of 6 patients from 6 to 17 months (mean 8.9 months) after radiotherapy. Conclusion: When extraosseous accumulation is found after radiation therapy in neuroblastoma patients, radiation nephropathy would be a candidate in the differential diagnosis besides recurrent or remnant tumor. [ABSTRACT FROM AUTHOR]

The effect of local injections with streptococcal preparation OK432 on the antitumor effect induced by adoptive immunotherapy (AIT) was investigated. Draining lymph node cells on day 14 after B7-P815 inoculation were used for AIT after in vitro stimulation. AIT on days 7 and 10 showed no effect on the growth of s.c. established P815 mastocytoma, but local injections with OK432 into the tumor sites on days 3, 6 and 9 resulted in a moderate antitumor effect. On the other hand, the combination therapy significantly suppressed tumor growth, and the tumor-bearing mice survived longer than those receiving only one of the treatment modalities. The significant infiltration of CD4+ or CD8+ T cells and multiple necrosis in the tumor sites were observed only when the tumor-bearing mice were treated with the combination therapy. In addition, a transfer experiment using labeled effector cells revealed these infiltrated CD8+ T cells and CD4+ T cells to be derived from the donor and the host respectively. More importantly, the combination therapy clearly led to higher expression of the mRNA for Th1-type cytokines and CXC3 chemokines in the tumor sites than resulted from each of the treatment modalities alone. Collectively, these results indicate that local injections with OK432 can help the infiltration of adoptively transferred CD8+ T cells into the tumor sites and synergistically induce the local production of the Th1-type cytokines and CXC3 chemokines. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions In recent years, the majority of patients eligible for endoscopic retrograde cholangiopancreatography (ERCP) have been aged ≥75 years. We investigated ERCP safety in very elderly patients (aged ≥90 years).We included patients aged ≥75 years who underwent ERCP between January 2015 and December 2020. We compared background factors, comorbidities, ERCP indications, complications, and outcomes and identified risk factors for complications using binary logistic regression and inverse probability of treatment weighting with propensity scores.The study included 1344 patients aged ≥75 years (137 and 1207 very elderly and elderly patients, respectively). The very elderly group had more women, less frequent diabetes, fewer antithrombotic medications, more frequent parapapillary diverticulum, less frequent post‐cholecystectomy, and worse performance status. No significant differences were observed in the ERCP indications. Experienced endoscopists were likely to perform the procedure, and the procedure time was shorter for the very elderly. Complications occurred in 21 (15%) very elderly patients and 120 (10%) elderly patients, with no significant differences. The very elderly did not have an increased risk of complications but were less likely to be discharged home and had a significantly worse performance status at discharge.ERCP could be safely performed in the very elderly, and age did not increase the risk of complications. Geriatr Gerontol Int 2024; ••: ••–••. [ABSTRACT FROM AUTHOR]

In order to enhance the antitumor vaccination effect of dendritic cells (DC) pulsed with class I tumor peptide, we tried to utilize the local cytokine help of CD4+ T cells reactive to a streptococcal preparation OK432. DC were prepared from murine bone marrow cells by culture with both granulocyte/macrophage-colony-stimulating factor and interleukin(IL)-4. The peritumoral injections of OK432 induced OK432-reactive CD4+ T cells in the draining lymph nodes, and their in vitro production of interferon γ was thus significantly enhanced by restimulation with OK432-pulsed DC. In addition, anti-P815 mastocytoma cytotoxic T lymphocytes were generated from the in vivo OK432-treated P815-draining lymph node cells only when the lymph node cells were restimulated in vitro with the DC pulsed with both P1A peptide and OK432. Moreover, the peritumoral injections of OK432 and the subsequent vaccination of the DC, pulsed with both OK432 and P1A peptide, significantly suppressed the growth of s.c. inoculated P815. Interestingly, a significant level of IL-12 was detected in the coculture supernatant of both OK432-pulsed DC and OK432-reactive CD4+ T cells. Collectively, our results suggest that the antitumor vaccination effect of DC pulsed with class I tumor peptide could thus be effectively augmented by locally utilizing the Th1-type cytokines from OK432-reactive CD4+ T cells. [ABSTRACT FROM AUTHOR]

Background and Aim: The risk for erosive esophagitis (EE) with low-dose aspirin (ASA) remains unknown, especially among Japanese patients. We conducted the present study to compare the risk of EE with that of gastroduodenal mucosal injury among Japanese patients taking ASA. Methods: From 5555 patients undergoing upper gastrointestinal endoscopy from January 2005 to December 2006 at Teikyo University Hospital, Tokyo, Japan, 159 patients (76 males and 83 females, mean age: 69.3 ± 11 years) fulfilling the following conditions were selected: (i) taking ASA (less than 100 mg/day) continuously; (ii) not taking acid suppressants; and (iii) no history of gastrointestinal tract surgery, malignancies, severe cardiac failure, or liver cirrhosis. Age- and sex-matched patients not taking aspirin were randomly chosen as controls ( n = 159). Two well-experienced endoscopic examiners evaluated endoscopic records to determine the presence or absence of esophageal hiatal hernia, EE, and gastroduodenal ulcers. Results: The prevalence of EE in patients taking aspirin (9.4%) was not different from that of the controls (6.3%, odds ratio [OR]: 1.5, 95% confidence interval [CI]: 0.7–3.2), whereas peptic ulcers were found more frequently in the aspirin group (14%) than in the control group (4%, OR: 3.6, 95% CI: 1.5–8.8). Conclusion: In Japanese patients taking ASA, EE was not as common as peptic ulcers. [ABSTRACT FROM AUTHOR]

Background: Pembrolizumab plus cisplatin and 5-fluorouracil administered as first-line therapy for advanced esophageal cancer patients has shown a better objective response and survival than conventional chemotherapy with less severe hematological adverse events. The safety and efficacy of this regimen were evaluated in patients with T4b esophageal squamous cell carcinoma (ESCC). Methods: Eight consecutive patients with T4b ESCC received this regimen according to KEYNOTE-590 as induction, and they were evaluated after 1–3 courses. The programmed death-ligand 1 (PD-L1) combined positive score (CPS) was also evaluated before chemotherapy. Efficacy for the primary lesion was evaluated by our original formula for the tumor reduction rate. Results: The numbers of patients with partial response (PR), stable disease, and progressive disease (PD) were 5, 1, and 2, respectively. The tumor reduction rate ranged from 69 to 87% in PR patients, and all PR patients had relief from T4b. Two patients underwent conversion surgery with R0 resection. PD-L1 CPS was over 90 in 2 PR patients, but under 10 in 2 other PR patients. PD-L1 CPS was under 10 in PD patients. One patient had hyperprogression, resulting in an esophago-pulmonary fistula. Greater than grade 3 adverse events were bleeding gastric ulcer in one patient (12.5%), neutropenia without G-CSF in 3 patients (37.5%), and hypopotassemia in 1 patient (12.5%). No patient had febrile neutropenia. Conclusions: Marked tumor reduction was confirmed in 62.5% of patients with pembrolizumab plus cisplatin and 5-fluorouracil with less adverse events. This regimen could be administered as induction chemotherapy for patients with T4b ESCC. [ABSTRACT FROM AUTHOR]

Background: Diagnosis and evaluation of cardiac sarcoidosis (CS) are mainly based on the combined use of cardiac magnetic resonance imaging (CMR) and 18F fludeoxyglucose positron emission tomography (FDG). Though these modalities can detect the pathological feature of the disease, combined assessment has not been fully examined. Multimodality image fusion is known to be useful for further comprehension, while most image interpretation is performed with a side by side comparison in clinical routine. We investigated the similarity and discrepancy of active inflammation, regional fibrosis, and wall function by image fusion of CMR and FDG. Methods: Patients with CS who underwent both CMR and FDG were retrospectively enrolled. The extent of myocardial late gadolinium enhancement (LGE) in left ventricle (LGE volume), cardiac function, and volume (left ventricular ejection fraction, LVEF; end-diastolic volume, EDV) was measured from CMR. The FDG uptake in whole myocardium (whole SUVmax), cardiac metabolic volume (CMV), and cardiac metabolic activity (CMA) was calculated from FDG. CMR and FDG were fused and divided into AHA 17 model for segmental analysis. Wall motion, the magnitude of LGE in myocardial wall (LGE%wall), and corresponding FDG uptake (segmental SUVmax) were analyzed. Results: Forty-one patients were retrospectively enrolled. In patients with FDG uptake, LVEF inversely correlated to LGE volume and positively correlated to SUVmax (r = − 0.56, p < 0.0001, and r = 0.08, p = 0.048, respectively). Discrepancy between LGE volume and CMV showed a significant positive correlation to whole SUVmax and CMA (r = 0.49, p < 0.0001, and r = 0.96, p < 0.0001, respectively). In image fusion analysis, segmental SUVmax showed a significant inverse correlation to LGE%wall (Spearman's rank correlation coefficient; r = − 0.15, p = 0.008). LGE%wall also showed significant inverse correlation to wall motion (r = − 0.13, p = 0.0011). Conclusion: Combined and fusion analysis with CMR and FDG demonstrated the discrepancy of myocardial inflammation and extensive fibrosis. Active inflammation was present in the earlier stage of myocardial fibrosis and was found to be less in the wall with advanced fibrosis and remodeling. Combined analysis of CMR and FDG can incrementally reclassify the pathological stage of CS. [ABSTRACT FROM AUTHOR]

Endoscopic submucosal dissection (ESD) is almost always performed with a sedative because of the longer procedure times involved. The risk of post-ESD deep vein thrombosis (DVT) has been reported as relatively high, and D-dimer levels are sometimes elevated after ESD. This retrospective study evaluated factors affecting changes in D-dimer levels from before to after ESD to identify causes of elevated D-dimer levels after ESD. This retrospective analysis included 117 patients with gastrointestinal tumors resected using ESD. After excluding eight patients with pre-ESD levels of D-dimer >1.5 μg/mL, factors correlating with changes in D-dimer from before to after ESD were analyzed using logistic regression analysis in 109 patients. Sedation was accomplished primarily using midazolam, but, because the sedative effect of midazolam shows marked inter-individual variability, a "corrected midazolam dose" was determined by dividing the total midazolam dose by the initial dose to correct for inter-individual differences in the sedative effect of midazolam. This value was used as one potential explanatory variable in the subgroup analysis of the 103 patients who received midazolam. In the subgroup analysis using the corrected midazolam dose as an explanatory variable, only the corrected midazolam dose correlated with a change in D-dimer ≥1.0 μg/mL in multivariate analysis (odds ratio (OR) = 1.5, 95% confidence interval (CI) 0.43–0.95; p = 0.030). The corrected midazolam dose correlated with increases in post-ESD D-dimer levels. This potential relationship indicates that patients undergoing ESD and requiring extended sedation may be at increased risk of DVT. [ABSTRACT FROM AUTHOR]

A letter to the editor on selective serotonin reuptake inhibitors (SSRI) is presented.

Factors associated with serious colonic diverticular bleeding (CDB) are unclear, although the incidence of CDB has increased. We carried out this study to clarify factors associated with serious CDB and rebleeding. Subjects included 329 consecutive patients hospitalized for confirmed or suspected CDB between 2004 and 2021. Patients were surveyed regarding backgrounds, treatment, and clinical course. Of 152 with confirmed CDB, 112 showed bleeding from the right colon, and 40 did from the left colon. Patients received red blood cell transfusions in 157 (47.7%), interventional radiology in 13 (4.0%), and surgery in 6 (1.8%) cases. Early rebleeding within one month occurred in 75 (22.8%) patients, and late rebleeding within one year occurred in 62 (18.8%). Factors associated with red blood cell transfusion included confirmed CDB, anticoagulants, and high shock index. The only factor related to interventional radiology or surgery was confirmed CDB, which was also associated with early rebleeding. Late rebleeding was associated with hypertension, chronic kidney disease and past CDB. Right CDB showed higher rates of transfusion and invasive treatment than left CDB. Confirmed CDB had high frequencies of transfusion, invasive treatment, and early rebleeding. Right CDB seemed to be a risk for serious disease. Factors related to late rebleeding were different from those related to early rebleeding of CDB. [ABSTRACT FROM AUTHOR]

Purpose: Gastric cancer patients with para-aortic lymph node metastases may achieve long-term survival with radical gastrectomy and para-aortic lymph nodal dissection (PAND) following neoadjuvant therapy. We introduced the Cattell-Braasch maneuver to facilitate safe and complete PAND for advanced gastric cancer with extensive lymph node metastases. Methods: Between January 2014 and March 2020, 7 patients with highly advanced gastric cancer received preoperative chemotherapy followed by radical gastrectomy and PAND using the Cattell-Braasch maneuver. This maneuver consists of mobilization of the right hemi-colon and the total small intestine. Results: Five patients received preoperative chemotherapy for para-aortic lymph node metastases and 2 for bulky lymph node metastases around the supra-pancreatic area. All patients received S-1 + cisplatin therapy, and one was additionally treated with paclitaxel chemotherapy followed by nivolumab. After chemotherapy, 2 patients with para-aortic lymph node metastases achieved down-staging on imaging tests. Total gastrectomy with PAND by the Cattell-Braasch maneuver was performed on all patients and was accompanied by splenectomy (n = 5) and distal pancreatectomy (n = 1). Pathological assessments revealed that 3 patients had para-aortic lymph node metastases, and the median number of retrieved para-aortic lymph nodes was 16. Three patients without para-aortic lymph node metastasis survived for more than 5 years without recurrence. Conclusion: The Cattell-Braasch maneuver provides a good surgical field and is useful for complete PAND for gastric cancer. [ABSTRACT FROM AUTHOR]

Foxc1 and Foxc2 play key roles in mouse development. Foxc1 mutant mice develop duplex kidneys with double ureters, and lack calvarial and sternal bones. Foxc2 null mice have been reported to have glomerular abnormalities in the kidney and axial skeletal anomalies. Expression patterns of Foxc1 and Foxc2 overlap extensively and are believed to have interactive roles. However, cooperative roles of these factors in glomerular and skeletal development are unknown. Therefore, we examined the kidneys and skeleton of mice that were double heterozygous for Foxc1 and Foxc2. Double heterozygotes were generated by mating single heterozygotes for Foxc1 and Foxc2. Newborn double heterozygous mice showed many anomalies in the kidney and urinary tract resembling Foxc1 phenotypes, including duplex kidneys, double ureters, hydronephrosis and mega-ureter. Some mice had hydronephrosis alone. In addition to these macroscopic anomalies, some mice had abnormal glomeruli and disorganized glomerular capillaries observed in Foxc2 phenotypes. Interestingly, these mice also showed glomerular cysts not observed in the single-gene knockout of either Foxc1 or Foxc2 but observed in conditional knockout of Foxc2 in the kidney. Serial section analysis revealed that all cystic glomeruli were connected to proximal tubules, precluding the possibility of atubular glomeruli resulting in cyst formation. Dorsally opened vertebral arches and malformations of sternal bones in the double heterozygotes were phenotypes similar to Foxc1 null mice. Absent or split vertebral bodies in the double heterozygotes were phenotypes similar to Foxc2 null mice, whilst hydrocephalus noted in the Foxc1 phenotype was not observed. Thus, Foxc1 and Foxc2 have a role in kidney and axial skeleton development. These transcription factors might interact in the regulation of the embryogenesis of these organs. [ABSTRACT FROM AUTHOR]

Phospholipase Cy isozymes (PLCγ1 and PLCγ2) have a crucial role in the regulation of a variety of cellular functions. Both enzymes have also been implicated in signaling events underlying aberrant cellular responses. Using N-ethyl-N-nitrosourea (ENU) mutagenesis, we have recently identified single point mutations in murine PLCγ2 that lead to spontaneous inflammation and autoimmunity. Here we describe further, mechanistic characterization of two gain-of-function mutations, D993G and Y495C, designated as ALIS and ALI14. The residue Asp-993, mutated in ALI5, is a conserved residue in the catalytic domain of PLC enzymes. Analysis of PLCγ1 and PLCγ2 with point mutations of this residue showed that removal of the negative charge enhanced PLC activity in response to EGF stimulation or activation by Rac. Measurements of PLC activity in vitro and analysis of membrane binding have suggested that ALI5-type mutations facilitate membrane interactions without compromising substrate binding and hydrolysis. The residue mutated in ALI14 (Tyr-495) is within the spPH domain. Replacement of this residue had no effect on folding of the domain and enhanced Rac activation of PLCγ2 without increasing Rac binding. Importantly, the activation of the ALI14-PLCγ2 and corresponding PLCγ1 variants was enhanced in response to EGF stimulation and bypassed the requirement for phosphorylation of critical tyrosine residues. ALI5and ALI14-type mutations affected basal activity only slightly; however, their combination resulted in a constitutively active PLC. Based on these data, we suggest that each mutation could compromise auto-inhibition in the inactive PLC, facilitating the activation process; in addition, ALI5-type mutations could enhance membrane interaction in the activated state. [ABSTRACT FROM AUTHOR]

Background: Demonstrating mortality reduction in new colorectal cancer (CRC) screening programs through randomized clinical trials (RCTs) is challenging. We systematically reviewed single-round program performance outcomes using a stepwise approach proposed by the World Endoscopy Organization CRC Screening Committee framework., Methods: The MEDLINE, EMBASE, Central, and Ichushi Web databases were searched until October 28, 2024, to find RCTs comparing guaiac-based and immunochemical fecal occult blood testing (gFOBT and FIT), flexible sigmoidoscopy (FS), computed tomographic colonography (CTC), and total colonoscopy (TCS). Paired reviewers screened studies, extracted data, and assessed bias risk. A Bayesian random-effects network meta-analysis was conducted, and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. The primary outcome was advanced neoplasia (AN) detection, and the secondary outcomes were participation and colorectal cancer (CRC) detection, all during the first screening round., Results: Eighteen RCTs (437,072 invitees) were included. The risk of bias was low or raised some concerns for screening participation, but it was high for detection outcomes. In the network meta-analysis of 15 RCTs not allowing crossover, the FIT-based program had a higher AN detection rate than the gFOBT-based program (relative risk [RR] 2.48; 95% credible interval [CrI] 1.52-4.21; moderate certainty). AN detection rates were not different in the CTC- (RR 1.01; CrI 0.43-2.23; very low certainty) and TCS-based (RR 1.03; CrI 0.54-1.78; low certainty) programs compared with the FS-based program. All the visualization modality programs had higher AN detection rates than the FIT-based program (FS: RR 2.13 [CrI 1.38-3.77]; CTC 2.16 [1.11-4.51]; and TCS 2.19 [1.43-3.48]; all with low certainty). Low event rates precluded definitive conclusions regarding CRC detection (very low to low certainty). The TCS-based program had the worst participation rate (very low to low certainty). Comparative data allowing crossover were limited., Conclusions: This is the first network meta-analysis that evaluates program-level initial performance indicators. FIT-based programs likely detect more AN cases than gFOBT-based programs, while FS-, CTC-, and TCS-based programs may outperform FIT. Due to limitations in first-round results, long-term outcomes should be assessed after 10-15 years., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval is not applicable as this is a secondary analysis of publicly available data. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction : Direct oral anticoagulants (DOACs) are frequently used to prevent embolism in atrial fibrillation. Gastrointestinal bleeding is frequent, but its drug-specific characteristics remain unclear. This study examined the frequency and characteristics of gastrointestinal bleeding in patients with nonvalvular atrial fibrillation for different DOACs. Methods : The present study included 978 patients receiving treatment with DOACs for nonvalvular atrial fibrillation between 2011 and 2018 and examined the frequencies of clinically significant events including major cardiovascular and cerebrovascular events, hemorrhagic events, or death during the first 5 years of prescription. Gastrointestinal bleeding was evaluated for the frequency, source and severity of gastrointestinal bleeding by DOAC type. Results : The median age of subjects was 73 years (interquartile range, 65-80 years), and 622 (64%) were male. The overall observation period was 2499 person-years. During this period, 102 (4.1/100 person-years) major cardiovascular events and 107 (4.3/100 person-years) clinically significant bleeding were reported, including 60 cases (2.4/100 person-years) of gastrointestinal bleeding and 37 cases (1.5/100 person-years) of all-cause mortality. Gastrointestinal bleeding accounted for more than half of all bleeding events among DOAC users, and bleeding from the lower gastrointestinal tract was more common than that from the upper gastrointestinal tract, particularly with dabigatran. No significant difference was seen in the rate of gastrointestinal bleeding by drug type. Peptic ulcer accounted for half of the events of upper gastrointestinal bleeding, all of which were severe. Conclusions : Gastrointestinal bleeding is frequent among patients taking DOACs, especially from the lower alimentary tract. The tendency was more pronounced with dabigatran. In the upper gastrointestinal tract, severe peptic ulcer bleeding is common and requires caution.

Objectives: A relationship between endoscopic submucosal dissection (ESD) and deep vein thrombosis has been recognized. We previously reported that a high corrected midazolam dose (total midazolam dose/initial dose of midazolam used to induce sedation) is related to elevated D-dimer levels after ESD. In this study, the effect of compression stockings (CSs) in preventing thrombosis following ESD under sedation was evaluated by measuring D-dimer levels before and after ESD., Methods: The participants were patients who underwent ESD for upper gastrointestinal tumors during the period between April 2018 and October 2022. Patients with pre-ESD D-dimer levels ≥1.6 µg/m and patients with corrected midazolam doses ≤3.0 were excluded. A retrospective investigation of the relationship between CS use and high post-ESD D-dimer levels (difference in D-dimer levels ≥1.0 µg/mL between before and after ESD) was conducted., Results: There were 27 patients in the non-CS group (NCS) and 33 patients in the CS group. The number of patients with high post-ESD D-dimer levels was 13 (48.2%) in the non-CS group and six (18.2%) in the CS group; the number in the CS group was significantly lower ( p = 0.024). On logistic regression analysis, a relationship was seen between the wearing of CSs and a lower number of patients with high post-ESD D-dimer levels (odds ratio 0.24, 95% confidence interval 0.08-0.79, p = 0.019)., Conclusion: Wearing CSs was related to a lower risk of high post-ESD D-dimer levels. This result suggests that thrombus formation is a cause of elevated D-dimer levels after ESD., Competing Interests: None., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Research on the relationship between neuron-specific enolase (NSE) levels and normal organs, particularly the central nervous system, in small cell lung cancer is limited. Therefore, this study aimed to investigate the relationship between positron emission tomography-computed tomography (PET-CT) accumulation at hypothalamic/pituitary regions, tumor activity, and NSE level in limited-stage small cell lung cancer. We retrospectively analyzed patients who were diagnosed with limited-stage small cell lung cancer at Tokyo Medical University Hospital between July 1, 2019, and May 31, 2023, and were treated with chemoradiotherapy or radiotherapy. Leukocytes, erythrocytes, hemoglobin, platelets, total protein, albumin, NSE, and carcinoembryonic antigen were measured in blood samples obtained before treatment initiation. The maximum standardized uptake value (SUVmax), volume, and total lesion glycolysis (TLG) of each hypothalamic /pituitary region, primary tumor, and lymph node metastases were extracted from PET-CT images. The total tumor volume (primary tumor volume plus lymph node metastases volume) and total TLG (primary tumor TLG plus lymph node metastases TLG) were calculated., Results: This study included 19 patients (mean age, 70.1 ± 8.8 years; 13 men and 6 women); the pathology in all patients was small cell lung cancer. Patients were classified into two groups according to the NSE reference value (16.3 ng/mL): six patients having NSE level below the reference value and 13 having NSE level above the reference value. The SUVmax in the hypothalamic/pituitary region was 2.95 in the NSE < 16.3 ng/mL group and 4.10 in the NSE > 16.3 ng/mL group, with a statistically significant difference (p = 0.03). The total tumor volume was 17.8 mL in the NSE < 16.3 ng/mL group and 98.9 mL in the NSE > 16.3 ng/mL group, with a statistically significant difference (p < 0.01). A correlation coefficient of r = 0.458 (p = 0.0486) was observed between SUVmax in the hypothalamus/pituitary and NSE level. A correlation coefficient of r = 0.647 (p < 0.01) was also observed between total tumor volume and NSE level. Finally, a correlation coefficient of r = 0.53 (p = 0.01) was observed between hypothalamic/pituitary TLG and primary tumor TLG., Conclusions: The findings demonstrated a correlation between hypothalamic/pituitary activity and tumor activity, suggesting the prognostic significance of NSE., (© 2024. The Author(s).)

Objective: To investigate the positron emission tomography/computed tomography (PET/CT) findings of T1/T2N0M0 glottic cancer (hereafter referred to as T1/T2) and dose distribution in radiotherapy., Subjects and Methods: We retrospectively collected data from patients diagnosed with T1/T2N0M0 glottic cancer who received radiotherapy. The extent of fluorine-18-fluorodeoxyglucose ( 18 F-FDG) accumulation in primary tumors, maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), tumor volume of primary tumors on PET/CT were compared. Furthermore, the tumor identified on PET/CT was incorporated into the radiotherapy plans. A dummy plan (radiation field 6x6cm, prescription point facing the vertebral body, maximum dose ≤107%, T1/T2 66Gy/33 fractions) was developed for three-dimensional conformal radiotherapy, and the dose distribution of primary tumors was calculated., Results: Twenty-nine patients (27 men and two women) were included; their mean age was 67.2±15.0 years. Increased 18 F-FDG accumulation in primary tumors was observed on PET/CT in 22/29 (78.5%; T1: 14/21 [67%], T2: 8/8 [100%]) patients. The median SUVmax, TLG, and primary tumor volume were significantly different between T1 and T2 (SUVmax, T1: 4.56 vs. T2: 8.43, P=0.035; TLG, T1: 1.01 vs. T2: 3.71 SUVxmL, P<0.01; primary tumor volume, T1: 0.38mL vs. T2: 0.80mL, P=0.01). At a TLG cut-off value of 3.470, the area under the curve was 0.875, sensitivity was 0.875, and specificity was 0.929 for T1-T2 differentiation. In 20 patients with 18 F-FDG accumulation, the minimum radiation dose was significantly different between T1 and T2 (66Gy vs. 64Gy, P<0.01) at the same 66Gy prescription. The minimum radiation dose and primary tumor volume show the correlation value (r=-0.516, P=0.02)., Conclusion: In glottic cancer, T1 and T2 can be differentiated by the extent of 18 F-FDG accumulation in primary tumors on PET/CT. The minimum radiation dose rate decreases as volume increases.

Background: As hepatic myelolipoma is rarely encountered, its radiological diagnosis using ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) is challenging. Hepatic myelolipoma is similar to fat-contained hepatic lesions seen in hepatocellular carcinoma and angiomyolipoma. Therefore, further development of techniques to diagnose hepatic myelolipoma is warranted., Case Summary: A 44-year-old obese man was found to have a hepatic lesion during his medical checkup. The lesion was 50 mm × 57 mm in size and was detected in segment 8 (S8) of the liver by US. The patient was diagnosed with hepatic lesion 20 years ago, but it was left unresolved. The patient had no symptoms, liver dysfunction, hepatitis virus antibody, or tumor marker elevation. Plain CT showed a well-defined lesion in S8 of the liver. The central and peripheral areas of the lesion primarily exhibited fat density and hypodensity, respectively. MRI revealed a capsule-like structure. Biopsy was performed to address the probability of hepatocellular carcinoma. The lesion was pathologically confirmed as a myelolipoma. Bone marrow scintigraphy performed using 111 InCl 3 revealed accumulation of the radiopharmaceutical in the soft tissue component, except in the fat-dominant part of the tumor, as well as in the surrounding liver parenchyma due to the presence of reticuloendothelial cells in the liver., Conclusion: This is the first report on the diagnosis of hepatic myelolipoma using 111 InCl 3 scintigraphy. The effectiveness of bone marrow scintigraphy for diagnosing hepatic myelolipoma might be limited. As radiopharmaceuticals accumulate in both hematopoietic and reticuloendothelial cells, the accumulation of radiopharmaceuticals in the lesion is obscure., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Balloon-occluded retrograde transvenous obliteration (BRTO) was developed as an effective treatment for gastric varices in patients with cirrhosis. Because liver fibrosis in these patients is assumed to be advanced, their prognosis is expected to be poor. In this study, we investigated the prognosis and characteristics of the patients., Methods: We enrolled 55 consecutive patients with liver cirrhosis treated with BRTO between 2009 and 2021 at our department. To evaluate factors related to variceal recurrence and long-term prognosis, survival analysis was performed on 45 patients, excluding those who died within 1 month, had an unknown prognosis, or whose treatments were converted to other treatments., Results: During a mean follow-up period of 2.3 years, esophageal varices recurred in 10 patients and could be treated endoscopically. Non-alcoholic steatohepatitis (NASH) was related to the variceal recurrence (hazard ratio [HR] = 4.27, 95% CI: 1.17-15.5, p = 0.028). The survival rate after the procedure at 1, 3, and 5 years was 94.2%, 74.0%, and 63.5%, respectively, and 10 patients died of hepatocellular carcinoma (n = 6), liver failure (n = 1), sepsis (n = 1), and unknown reasons (n = 2). The estimated glomerular filtration rate (eGFR) level was proved to be a significant poor prognostic factor (HR = 0.96, 95% CI: 0.93-0.99, p = 0.023). The comorbid hypertension (HTN) was the main cause of low eGFR, and HTN was also significantly related to survival (HR = 6.18, 95% CI: 1.57-24.3, p = 0.009). Most of the patients with HTN were treated with calcium channel blocker and/or angiotensin receptor blocker., Conclusion: The clinical course of patients with cirrhosis treated with BRTO was dependent on the metabolic factors including renal function, comorbid HTN, and NASH., (© 2023 S. Karger AG, Basel.)

Although concomitant medications have been raised as a factor affecting hemorrhage during direct oral anticoagulant (DOAC) therapy, details remain unelucidated. This study was conducted to clarify the relationship between concomitant medications with possible pharmacokinetic interactions and number of concomitant medications, and bleeding and embolism in patients with nonvalvular atrial fibrillation on DOACs. The subjects were 1010 patients prescribed DOACs from a single-center at the Teikyo University Hospital between April 2011 and June 2018. This study was an exploratory analysis and investigated their course between the first prescription and December 2018, including the presence or absence of clinically relevant bleeding, gastrointestinal bleeding, and major cardiovascular and cerebrovascular events. Impacts of medications were evaluated by the general linear model with inverse probability-weighted propensity score. The observation period was 2272 patient-years. The rate of bleeding was 4.7%/year, gastrointestinal bleeding was 2.8%/year, and major cardiovascular and cerebrovascular events were 2.0%/year. Taking 10 or more oral medications concurrently was a significant risk for gastrointestinal bleeding (hazard ratio, 2.046 [95%CI, 1.188-3.526]; P = .010). Nonsteroidal anti-inflammatory drugs were the only significant risk for gastrointestinal bleeding. Clinicians should be aware of gastrointestinal bleeding when using DOACs with patients taking more than 10 medications and/or nonsteroidal anti-inflammatory drugs., (© 2022, The American College of Clinical Pharmacology.)

Patients with adrenal Cushing's syndrome have a poor prognosis due to the autonomous hypersecretion of endogenous cortisol from the adrenal gland. Although several clinical examinations have been developed to manifest the autonomous hypersecretion of endogenous cortisol in this syndrome, it is unknown which parameter of cortisol overproduction is best associated with the adrenal cortisol content and bone and vascular complications of this syndrome. Therefore, the present study was undertaken to evaluate the parameter(s) associated with the adrenal cortisol content in patients with adrenal Cushing's syndrome, as well as to assess the associations between these parameters and the vascular and bone complications of this syndrome. Cardiovascular factors such as blood pressure and pulse rate, glucose metabolism, lipid metabolism, renal function, and indices of arteriosclerosis, except for diastolic blood pressure, failed to show an association with the adrenal cortisol content. Twenty-four-hour urinary free cortisol excretion (ρ = 0.893, P = 0.007) and plasma cortisol levels after the 1-mg (ρ = 0.857, P = 0.014) or 8-mg (ρ = 0.900, P = 0.037) overnight dexamethasone suppression test, but not plasma cortisol levels in the morning or late at night or indices of 131 I-adosterol single-photon emission computed tomography-computed tomography, were significantly and positively associated with the adrenal cortisol content. Twenty-four-hour urinary free cortisol excretion, and not plasma cortisol levels after the 1- or 8-mg overnight dexamethasone suppression test, was significantly and negatively associated with lumbar spine bone density (lumbar spine bone mineral density, ρ = -0.786, P = 0.036; lumbar spine T score, ρ = -0.883, P = 0.009; and lumbar spine Z score, ρ = -0.883, P = 0.009). These results indicate that 24-h urinary free cortisol excretion is best associated with a decrease in bone density via increased adrenal cortisol overproduction and suggest that it could be used as a marker for osteoporosis in these patients., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)