Honey bees are important pollinators in both agriculture and ecosystems, and their health is essential for sustainable human development. Although only two bacteria, Paenibacillus larvae and Melissococcus plutonius, have been identified as bacterial pathogens in honey bee brood for over 100 years, we found three additional Paenibacillus strains (Paenibacillus sp. J27TS7, Paenibacillus azoreducens J34TS1, and Paenibacillus melissococcoides J46TS7) in honey that harmed honey bee brood development. In particular, Paenibacillus sp. J27TS7 was highly virulent in bee larvae (the median lethal dose [LD50] = 12.7 spores/larva) and was comparable to P. larvae (LD50 = 2.3-11.5 spores/larva). Paenibacillus azoreducens J34TS1 showed the second-highest virulence (LD50 = 45.9 spores/larva), and P. melissococcoides J46TS7 was the least virulent (LD50 = 469.0 spores/larva). However, P. melissococcoides was most frequently detected in Japanese honey among the three species, with the highest concentration being 1.8 × 106 spores/mL honey, suggesting its wide distribution in Japanese apiaries. The novel pathogenic Paenibacillus species were categorized into the fast killer (Paenibacillus sp. J27TS7), medium-fast killer (P. melissococcoides), and slow killer (P. azoreducens) like P. larvae strains in terms of the time to kill infected brood; however, histopathological and genome analyses indicated that their pathogenic mechanisms were different from those of P. larvae strains. Moreover, P. melissococcoides showed differences in virulence depending on the lineage of the strain. These findings represent the first discovery of honey bee brood pathogens in more than 100 years and indicate the need to look beyond known pathogens for a comprehensive understanding of honey bee diseases.

Sufficient attention has not been given to machine learning (ML) models using longitudinal data for investigating important predictors of new onset of hypertension. We investigated the predictive ability of several ML models for the development of hypertension.

A total of 15 965 Japanese participants (men/women: 9,466/6,499, mean age: 45 years) who received annual health examinations were randomly divided into a training group (70%, n = 11,175) and a test group (30%, n = 4,790). The predictive abilities of 58 candidates including fatty liver index (FLI), which is calculated by using body mass index, waist circumference and levels of γ-glutamyl transferase and triglycerides, were investigated by statistics analogous to the area under the curve (AUC) in receiver operating characteristic curve analyses using ML models including logistic regression, random forest, naïve Bayes, extreme gradient boosting and artificial neural network.

During a 10-year period (mean period: 6.1 years), 2,132 subjects (19.1%) in the training group and 917 subjects (19.1%) in the test group had new onset of hypertension. Among the 58 parameters, systolic blood pressure, age and FLI were identified as important candidates by random forest feature selection with 10-fold cross-validation. The AUCs of ML models were 0.765-0.825, and discriminatory capacity was significantly improved in the artificial neural network model compared to that in the logistic regression model.

The development of hypertension can be simply and accurately predicted by each ML model using systolic blood pressure, age and FLI as selected features. By building multiple ML models, more practical prediction might be possible.

This study aimed to evaluate the accuracy and reliability of posterior tibial slope (PTS) measurements obtained from radiographs and CT. PTS, particularly its differences in medial and lateral measurements, plays a crucial role in knee alignment, and inconsistencies in measurement techniques across different imaging modalities have raised concerns about accuracy.

This retrospective study included data from 98 Japanese patients legs and 324 Chinese patients legs. PTS was measured on long-leg and short-leg radiographs and CT. Two independent surgeons assessed the measurements, and the inter- and intra-observer reliability were evaluated. The primary outcome was the comparison of medial and lateral PTS measurements, while the secondary aim was to assess the impact of tibial length on measurement accuracy.

The study revealed that lateral PTS was consistently smaller than medial PTS, with an average difference of 1.2°-1.9°. Shorter leg radiographs tend to underestimate PTS compared to full-length tibial measurements. The correlation between measurements from short and long leg radiographs showed that PTS measurements were more prone to errors, which may be due to anatomical factors such as tibial bowing. Inter- and intra-observer reliability were good for medial PTS but poor to moderate for lateral PTS, especially when using radiographs.

For accurate measurement of both medial and lateral PTS, surgeons should consider using additional examination methods such as CT and MRI. If PTS is to be measured on radiographs, the focus should be on the medial PTS, as it tends to provide more reliable results.

The presence of full-thickness cartilage in the lateral compartment on valgus stress radiography is a criterion for medial mobile-bearing unicompartmental knee arthroplasty (UKA). However, the appropriateness of medial UKA is uncertain when preoperative MRI shows extrusion of the lateral meniscus. We therefore assessed how preoperative MRI-detected lateral meniscus extrusion affects mid-term functional outcomes after mobile-bearing UKA.

We retrospectively reviewed the records of our patients that underwent mobile-bearing medial UKA between January 2017 and December 2019. Crema's classification system was used to assess MRI of the lateral meniscus, categorizing patients as either grade 0 or ≥ grade 1. We preoperatively evaluated patient-reported outcomes using the Oxford knee score and Knee Society functional score, and then again at the latest follow-up. We also measured range of motion pre- and postoperatively. We compared preoperative individual data with outcome data obtained for at least three years.

The lateral meniscus extrusion group included 19 knees, and the remainder included 98 knees. Clinical outcomes were similar between these groups (p > 0.05). No progression of lateral arthritis was observed in either group during the follow-up period.

Excluding UKA as an option for cases with lateral meniscus extrusion findings on preoperative MRI may require reconsideration.

Gambling disorder is a behavioral addiction characterized by impulsivity and problem gambling, and it often cooccurs with ADHD. This study investigated the associations between ADHD symptoms and problem gambling, focusing on the roles of various forms of gambling engagement. Based on data from the JASTIS 2024 survey, which included 29,268 valid respondents, this cross-sectional study explored how ADHD symptoms are related to the prevalence of problem gambling and specific forms of gambling engagement. Problem gambling was assessed using the Problem Gambling Severity Index, and ADHD symptoms were measured with the Japanese version of the Adult ADHD Self-Report Scale. The results revealed that 22.2 % of the participants with ADHD symptoms exhibited problem gambling, this proportion was significantly higher than that reported in the general population. Causal mediation analysis revealed that all types of gambling engagement, except for lottery, mediated the relationship between ADHD symptoms and problem gambling. Among them, bicycle racing and online casinos exhibited the strongest effects. Multiple regression analysis revealed that online casino use was the strongest predictor of problem gambling both in the general population and among individuals with ADHD symptoms. These findings suggest that individuals with ADHD characteristics increase the risk of engaging in gambling activities, particularly casino and online gambling, which have a high potential for addiction. Given the association between problem gambling and casino-related experiences, this study underscores the need for stringent regulatory measures and targeted prevention strategies, particularly as Japan considers expanding casino operations.

Assessing lower limb ranges of motion (ROMs) is crucial for diagnosing and treating musculoskeletal and neurological disorders in children. Although prior studies examining decline in flexibility among school-age children suggest potential age-related changes in lower limb ROMs, this hypothesis remains unproven. Therefore, in this study, we aim to examine age-related differences in lower limb ROMs among school-age children.

The passive ROMs in the lower limbs of 572 typically developing children aged 6-15 years were measured by physiotherapists using goniometers. To examine developmental changes in lower limb ROMs, participants were categorized into four groups: 6-7 years (189 participants), 8-9 years (147 participants), 10-11 years (124 participants), and 12-15 years (112 participants).

We observed a consistent trend of decreasing ROMs with age across all measures (hip flexion, popliteal angle, knee flexion, knee extension, ankle dorsiflexion, and ankle plantar flexion), excluding hip extension. Notably, only the popliteal angle exhibited values indicating clinically significant sex differences.

Lower limb ROMs in school-age children generally decrease with age, with notable sex differences observed in the popliteal angle. The lower limb ROM values presented herein can serve as reference values to identify disease- and injury-related changes in lower limb ROMs during this developmental stage.

Prognostic evaluation of canine myxomatous mitral valve disease (MMVD) using circulating biomarkers has been attempted, but comprehensive studies are still limited. The present study aimed to investigate the prognostic value of circulating cardiac and renal biomarkers and imaging data in 37 small-breed dogs with MMVD using retrospective data obtained from 2018 to 2022. The circulating cardiac biomarkers included N-terminal probrain natriuretic peptide (NT-proBNP), atrial natriuretic peptide (ANP), and troponin I. The renal biomarkers included blood urea nitrogen (BUN), creatinine, symmetric dimethylarginine, and cystatin C (Cys-C). The imaging data included vertebral heart score, vertebral left atrial size (VLAS), left-atrial-to-aortic ratio, and left ventricle internal diameter in diastole normalized to bodyweight (LVIDDN) from the medical records. The dogs were categorized into high and low groups based on the cutoff values obtained from the receiver-operating characteristic curves. Kaplan-Meier survival curves were generated, and 1-year MMVD-specific survival rates were compared using the restricted mean survival time (RMST) method. The dogs with high VLAS, LVIDDN, and NT-proBNP, ANP, troponin I, BUN, creatinine, or Cys-C levels had significantly shorter MMVD-specific survival times (p < 0.01). NT-proBNP had the largest RMST difference of 187.0 days (95 % confidence interval [CI]: 104.7-269.3 days), followed by Cys-C with 169.3 days (95 % CI: 98.2-240.5 days). Our study findings highlight the potential of NT-proBNP and Cys-C as key prognostic markers in dogs with MMVD. Incorporating the measurements of blood circulating biomarkers may enhance the accuracy of prognostic prediction in dogs with MMVD.

Acute myeloid leukemia (AML) is characterized by the accumulation of cytogenetic and molecular abnormalities. Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutations occur in 11% to 20% of adults with AML. The outcome of IDH1/2-mutated AML is heterogeneous and affected by co-mutational patterns. We retrospectively analyzed 118 patients with IDH1/2-mutated AML who were retrieved from 1597 patients newly diagnosed with AML and treated with intensive chemotherapy. Univariate analysis revealed the NPM1 mutation was a favorable factor (p = 0.019) for overall survival (OS), whereas the DNMT3A mutation was consistently associated with a poor outcome (3-year OS, 52.0%; 3-year relapse-free survival [RFS], 44.8%; and 3-year cumulative incidence of relapse [CIR], 42.6%). Interestingly, the DNMT3A mutation still identified patients with a poorer prognosis, even when measurable residual disease (MRD) was negative after 2 courses of chemotherapy. In a multivariate regression model, age, DNMT3A mutation and MRD positivity were retained as independent adverse markers for OS, RFS, and CIR. In the absence of the DNMT3A or FLT3-ITD mutations, the NPM1 mutation identified patients with a very favorable OS (3-year OS, 96.3% and 86.3%, respectively). Finally, hematopoietic stem cell transplantation in first complete remission significantly improved RFS (p = 0.015) and there was a trend toward improvement in OS (p = 0.282) for patients with the DNMT3A mutation but it did not benefit 2 subgroups with the IDH1/2+/NPM1+/DNMT3A- and IDH1/2+/NPM1+/FLT3-ITD- genotypes. In summary, this study provides a reference for risk stratification and treatment implications for patients with IDH1/2-mutated AML as well as for comparison with results of IDH inhibitor- or venetoclax-based combination therapy.

Epidermal barrier formation during fetal development, a fundamental biological process in mammals and birds, occurs in the amniotic cavity filled with amniotic fluid (AF). In keratinocytes, indispensable proteins for barrier formation are produced during differentiation, including transglutaminase 1 (TG1) and structural proteins encoded by a gene cluster, epidermal differentiation complex. In general, the chicken fetus rapidly forms a robust epidermal barrier during a relatively short embryonic day (ED); however, little is known about how chicken AF (cAF) contributes to the controls of gene expression of the factors involved in epidermal development. Here, we first demonstrated that the cross-linking activity of TG1 gradually increased, followed by the development of barrier function until ED18 in the chicken fetal epidermis. Then, we revealed that cAF harvested at specific fetal stages had the ability to enhance the expression and activity of TG1, and to facilitate the expression of genes for the other epidermal transglutaminases, structural proteins, and differentiation-related transcription factors in human cultured keratinocytes. Furthermore, the thermal denaturation of cAF components reduced cAF efficacy in promoting the expression of those factors. The fractionated proteinaceous solution of cAF possessed the activity to induce the protein expression of barrier formation-related factors, such as the transcription factor zinc finger protein 750. These results indicated that proteinaceous molecules in cAF have the potential to activate the gene expression networks involved in epidermal barrier formation. This finding will provide novel insights into the physiological role of AF in fetal epidermal development.

Carpal tunnel syndrome (CTS) is a common condition caused by compression of the median nerve, leading to neuropathic pain such as numbness and nocturnal discomfort, thus impacting daily life. Mirogabalin besylate (MGB), a novel gabapentinoid, shows promise for neuropathic pain, but its efficacy in CTS remains unclear.Therefore, this pilot study aimed to evaluate the short-term clinical outcomes of MGB for CTS.

This retrospective observational study examined 21 patients with CTS who received MGB between April 2022 and March 2023. Evaluations included the Carpal Tunnel Syndrome Instrument (CTSI), Quick Disabilities of the Arm, Shoulder and Hand (Quick DASH), and Visual Analog Scale (VAS) before and 12 weeks after treatment. The primary outcome was the change in CTSI-total. Secondary outcomes included CTSI subparts (symptom severity and functional status), Quick DASH, VAS, and adverse drug reactions (ADRs).

MGB led to significant improvement in CTSI-total (p=0.022), with medium standardized response mean (SRM) and effect size (ES). CTSI-symptom severity (p<0.01) and VAS (p<0.001) also improved, showing medium SRM and ES for CTSI and large SRM and ES for VAS. No significant changes were observed in CTSI-functional status (p=0.349) or Quick DASH (p=0.102). ADRs occurred in 42.9 % of patients, mostly mild.

MGB demonstrated significant short-term efficacy in improving CTS symptoms and reducing pain, though mild ADRs were common. Further studies are needed to assess long-term outcomes and compare MGB with other treatments.

Level IV.

Tissue-tracking mitral annular displacement (TMAD) is a simple marker for left ventricular (LV) systolic function. However, its clinical impact in aortic stenosis (AS) remains unclear. We aimed to investigate the significance of TMAD on LV mechanics in comparison with global longitudinal strain (GLS) and its prognostic value in AS.

We retrospectively reviewed 91 patients with moderate or severe AS and preserved LV ejection fraction (≥ 50 %). TMAD was measured from an apical four-chamber view and indexed to the LV long-axis length (%TMAD). The associations between TMAD and LV ejection fraction (LVEF) and GLS, including the regional distribution (apical, mid, and basal) of longitudinal strain (LS), were evaluated. We also assessed the impact of %TMAD on clinical outcomes, including cardiovascular death, heart failure hospitalization, and unplanned aortic valve replacement.

%TMAD showed a moderate correlation with LVEF (r = 0.45, P < 0.001) and a strong correlation with |GLS| (r = 0.81, P < 0.001). In the regional LS analysis, %TMAD correlated strongly with mid and basal LS, but modestly with apical. The cutoff value of %TMAD for predicting impaired GLS (|GLS| < 14.7 %, as previously reviewed) was 9.8 %, which also predicted event-free survival (Log-rank P = 0.001). In a Cox proportional hazards model, lower %TMAD was significantly associated with worse clinical outcomes, independent of AS severity and LVEF.

%TMAD is a marker of LV longitudinal systolic function, particularly reflecting mid-basal longitudinal systolic function, and can be a useful prognosticator in AS patients.

Patients with part-solid adenocarcinomas treated by surgery generally have more favorable outcomes than those with pure-solid adenocarcinomas. We conducted this study to understand the effects of the lepidic components and preoperative characteristics on the postoperative survival of patients with part-solid adenocarcinomas.

The subjects of this retrospective study were 313 patients with stage 1 part-solid adenocarcinomas and 634 patients with pure-solid adenocarcinomas, treated at our institution between 2006 and 2020. Propensity score matching was performed to analyze survival in an unmatched cohort (PSM0, n = 313 vs. 634); a matched cohort based on the consolidation diameter (PSM1, n = 217 each); and a matched cohort based on 11 clinical characteristics (PSM2, n = 103 each). Multivariate analysis was also performed.  RESULTS: The 5-year overall/recurrence-free survival rates for part-solid and pure-solid adenocarcinomas were 90.2%/79.3% and 80.8%/66.0% in the PSM0 cohort (P < 0.0001), 87.4%/79.2% and 76.3%/68.6% in the PSM1 cohort (P < 0.05), and 91.6%/92.1% and 76.6%/79.0% in the PSM2 cohort (P > 0.05), respectively. Multivariate analysis revealed that male sex (P = 0.04) and the carcinoembryonic antigen value (P < 0.0001) were significant factors affecting overall survival, while the carcinoembryonic antigen value (P = 0.0002) and consolidation tumor size (P = 0.002) affected recurrence-free survival. The lepidic component was not related to overall (P = 0.45) or recurrence-free (P = 0.78) survival.

Preoperative factors are strongly associated with "consolidation size", which could be the "representative factor" indicating the malignant potential in adenocarcinomas being consistent with the current eighth edition of the TNM.

Type A acute aortic dissection (TAAAD) is a life-threatening condition often requiring emergency surgery, with approximately 30% of patients needing reoperation. This study aimed to identify predictors of long-term aortic events from early postoperative computed tomography (CT) examinations.

A total of 336 cases underwent TAAAD surgery at two institutions between 2002 and 2018. Of these, 302 patients received CT examinations immediately after initial TAAAD surgery. Predictors of aortic events were evaluated from these early postoperative CT exams. Aortic events were defined as any events involving aortic-related death, open surgery, reoperation, endovascular stenting, or thoracic aorta diameter enlargement to ≥ 55 mm.

Excluding 34 in-hospital deaths (10.1%; 34/336), the 1-, 5-, and 10-year actuarial survival rates after primary TAAAD surgery were 98.2%, 88.6%, and 81.7%, respectively. Over a mean follow-up period of 7.4 ± 5.1 years, 67 aortic events (proximal: 19, distal: 45, both: 3) were observed. Freedom from proximal aortic events was 98.6%, 93.9%, and 85.2% at 1, 5, and 10 years, respectively. Proximal anastomosis new entry was identified as a significant risk factor for aortic events, with a 92% vs. 42% incidence at 10 years (p < 0.001). Freedom from distal aortic events was 99.6%, 84.5%, and 67.2% at 1, 5, and 10 years, respectively. A false/true area ratio greater than 1 and distal anastomosis new entry were significant risk factors for aortic events (low-risk group: 83.3% vs. high-risk group: 42.3% at 10 years, p < 0.001).

Detailed analysis of early postoperative CT scans following primary TAAAD surgery may help identify predictors of subsequent aortic events, potentially improving long-term patient management and outcomes.

Immune-related pneumonitis (irP) is a severe immune-related adverse event that can occur after treatment with immune checkpoint inhibitors (ICIs); accurate monitoring and early diagnosis are crucial. Serum Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) are used to diagnose and monitor the disease activity of various types of interstitial lung disease. This study evaluated the usefulness of KL-6 and SP-D for diagnosing irP in cancer patients receiving ICIs.

This retrospective observational study included cancer patients treated with more than two cycles of ICIs from September 2014 to October 2023. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic utility of KL-6 and SP-D.

Of the 724 cancer patients, 631 were included in the analysis, and 64 developed irP. The ROC analysis showed that KL-6 and SP-D had areas under the curve of 0.803 and 0.845, respectively. Serum KL-6 ≥ 500 U/mL had a sensitivity of 65.6% and a specificity of 83.4% for the diagnosis of irP, while SP-D ≥ 110 ng/mL had a sensitivity of 66.7% and a specificity of 88.6%. Combining both KL-6 ≥ 500 U/mL and SP-D ≥ 110 ng/mL resulted in a specificity of 96.6%, with a sensitivity of 46.7%. Combining either KL-6 ≥ 500 U/mL or SP-D ≥ 110 ng/mL resulted in a sensitivity of 85.0%, with a specificity of 75.5%. SP-D levels were significantly associated with irP severity, while KL-6 levels were not.

Serum KL-6 and SP-D are useful for diagnosing irP in cancer patients receiving ICIs.

Eosinophilic chronic rhinosinusitis (ECRS) is a subgroup of chronic rhinosinusitis with nasal polyps (CRSwNP), which is a disease characterized by eosinophilic infiltration of the sinonasal mucosa. Few studies that reported the effect of dupilumab on CRSwNP focused on a single phenotype of CRSwNP, such as ECRS.

This study aimed to determine the effectiveness of dupilumab in ECRS with postoperative recurrence.

We retrospectively enrolled 107 patients and assessed the effectiveness of dupilumab by various clinical outcomes. We performed multivariable analysis on nasal polyp score (NPS) and computed tomography score and a meta-analysis of the effect of dupilumab on chronic rhinosinusitis regarding improvement in the NPS.

At 12 months of dupilumab treatment, there were 65 patients (60.7%) in the excellent response group and 42 (39.3%) in the moderate response group. Nasal polyps had disappeared in 91 patients (85.9%) at 12 months, and there was improvement in all end points; 104 patients (97.2%) were able to eliminate systemic corticosteroid therapy. In the multivariate analysis, male sex was significantly associated with patients who did not show an improvement to 0 in the NPS and computed tomography score (odds ratios: 7.58 and 2.45; P = .01 and P = .04, respectively). The meta-analysis showed that dupilumab treatment resulted in a trend toward better improvement in the NPS (mean difference = -5.41) than previously reported results.

Dupilumab shows effectiveness in treating ECRS and could serve as an alternative therapeutic option to systemic corticosteroids. This effectiveness may be further enhanced by limiting the target population to recurrent ECRS.

Salvage surgery for primary lung cancer is expected to become increasingly common. This study aimed to clarify the survival impact of pathologic characteristics after salvage surgery.

Consecutive patients who underwent salvage surgery following definitive chemoradiotherapy or systemic therapy for initially unresectable lung cancer from 2010 to 2020 were enrolled in this study. The tumor slides were reviewed to determine the size of the tumor bed and the proportions of viable tumor, necrosis, and stroma.

A total of 23 patients were evaluated, and 18 had clinical stage IIIB-IV disease. Six received chemoradiotherapy and 17 received systemic therapy alone. A major pathologic response (MPR, ≤ 10% of viable tumor) was observed in 6 patients, and 4 patients achieved a pathological complete response. The 3-year overall and recurrence-free survival rates (OS and RFS) were 78.6% and 59.2%, respectively. There was no significant difference in OS between patients with and without MPR, and even non-MPR patients achieved a favorable 3-year OS of 70.2%. Meanwhile, patients with high (≥ 30%) stroma showed significantly better OS than those with low (< 30%) stroma (3-year OS: 100% vs. 23.3%, p < 0.001).

This study showed that the proportion of stroma can be useful for predicting long-term survival after salvage surgery. Further large-scale studies are warranted to confirm the current findings.

It is unknown whether prodromal dizziness (PD) before an attack of vestibular neuritis (VN) has an association with peripheral vestibular lesions. The purpose of this study was to investigate whether the severity of vestibular dysfunction has an association with the presence of PD.

We reviewed the medical records of 88 consecutive unilateral VN patients with unilateral canal paresis in caloric testing. Caloric test, cervical vestibular evoked myogenic potential test to air-conducted sound (ACS cVEMP), ocular vestibular evoked myogenic potential test to bone-conducted vibration (BCV oVEMP) and video head impulse test (vHIT) were used as vestibular function tests. Binomial logistic regression analyses were performed to see whether the subjects' age, sex, disease duration or the presence of PD is associated with the presence of vestibular dysfunction.

Seventeen (19%) experienced an episode of PD. There was no significant association between the presence of PD and abnormality in ACS cVEMPs, BCV oVEMPs, vHIT for the posterior semicircular canal (SCC) or vHIT for the lateral SCC. The presence of PD had a significant positive association with abnormality in vHIT for the anterior SCC (ASCC) (p = 0.0248).

The presence of PD in VN may be associated with the peripheral vestibular lesion.

The distribution of body weight in patients with achalasia and after peroral endoscopic myotomy (POEM) has not been investigated. The role of body weight assessment after treatment remains unclear.

Using the multicenter achalasia cohort, the frequency of underweight (body mass index [BMI] < 18.5 kg/m2) and overweight (BMI ≥ 25.0 kg/m2) and their associated clinical characteristics were analyzed. After POEM, risk factors for insufficient- (underweight persistently) and excessive- (responded to overweight) weight gainers were investigated. The correlation between BMI-increase rate and severity of esophageal symptoms post-POEM was evaluated.

Among 3,410 patients, 23.0% and 15.7% were underweight and overweight, respectively. Factors associated with underweight were higher age, female sex, severe symptoms, high lower esophageal sphincter (LES) pressure, and non-dilated esophagus (all p < 0.01). Longitudinal analyses revealed that weight gain post-POEM was achieved after a long duration (≥ 12 months; p < 0.01). In 528 patients post-POEM, the frequency of underweight reduced to 8.3% (p < 0.01). Risk factors for insufficient-weight gain (36.1% of underweight patients) included low BMI (p < 0.01) and high LES pressure (p = 0.03) and conversely for excessive-weight gain. Machine learning models based on patient characteristics successfully predicted insufficient- and excessive-weight gainers with an area under the curve value of 0.74 and 0.75, respectively. Esophageal symptoms post-POEM did not correlate with BMI increase.

Underweight is not solely a condition of advanced achalasia. After POEM, insufficient- or excessive-weight gainers are not rare and can be predicted preoperatively. Body weight change is an independent nutrition parameter rather than a part of the assessment of residual esophageal symptoms.

The characteristics of bloodstream infections in patients admitted to long-term care wards remain unclear. This study examined differences in nosocomial-onset urinary tract-related bloodstream infections (UTRBSIs) and catheter-related bloodstream infections (CRBSIs) between patients admitted to long-term and acute care wards.

This retrospective cohort study was conducted at a mixed-care hospital with long-term and acute care wards from April 2015 to March 2024. Patient backgrounds, causative pathogens, antibiotic resistance, and treatment patterns were compared between the two groups.

Among the 252 patients, 108 (42.9 %) were diagnosed with UTRBSIs and 87 (34.5 %) with CRBSIs. In UTRBSIs, the long-term care group had significantly longer hospitalization (721 vs. 16 days, P < 0.001), more frequent use of indwelling urinary catheters (76.7 % vs. 28.6 %, P < 0.001), and higher isolation rates of extended-spectrum β-lactamase-producing Enterobacterales (41.1 % vs. 8.6 %, P < 0.001). Piperacillin/tazobactam and meropenem were significantly more frequently used empirically in the long-term care group. In CRBSIs, the isolation rates of main causative pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) (9.5 % vs. 6.7 %, P = 0.707) and methicillin-resistant coagulase-negative Staphylococcus spp. (40.5 % vs. 48.9 %, P = 0.519), showed no significant differences between the two groups despite differences in patient backgrounds. Anti-MRSA agents were rarely used empirically in both groups (19.0 % vs. 15.6 %, P = 0.779).

Patients admitted to long-term care wards may require empirical therapy for UTRBSIs targeting drug-resistant Enterobacterales, while for CRBSIs, empirical use of anti-MRSA agents may be considered, similar to patients admitted to acute care wards.

Chronic respiratory diseases are known to be associated with alterations in mucus rheology, but limited information is available regarding chronic cough. The aim of this study was to determine the sputum rheology in chronic productive cough (CPC) in comparison to bronchial asthma (BA).

The viscoelasticity profiles of spontaneous sputum obtained from 26 patients with CPC (10 sinobronchial syndrome [SBS], 16 non-SBS) and 25 patients with BA (12 mild-persistent, 7 moderate, and 6 severe) were analyzed by rheometry in a single center. The non-SBS group included fungus-associated chronic cough, post-COVID-19 cough, bronchorrhea, and unexplained chronic cough.

Viscoelastic modulus (G∗) and viscous modulus (G″) of the SBS group were similar to those of the total BA group. Although critical strain (γC) and critical stress (σC) tended to be larger in the BA group, and the former was comparable between the non-SBS group and the moderate or severe BA group. In the non-SBS group, G″ was closely correlated with FeNO, and γC was inversely correlated with respiratory function, as in the BA group, but no such correlations were observed in the SBS group.

Quantitative rheological analysis revealed unique viscoelastic characteristics of spontaneous sputum and altered association with clinical biomarkers in the non-SBS group, in which the profile was more similar to BA than SBS in CPC. This new rheometer can identify features of sputum in patients with CPC that cannot be detected by conventional methods. Further investigations of sputum rheology in CPC are warranted to understand its pathogenesis.

Non-robotic transoral surgery (NRTOS) is the mainstream approach for pharyngolaryngeal cancer resection in Japan, whereas the da Vinci surgical system is not widely used. NRTOS employs reusable instruments, resulting in significantly lower costs than those of transoral robotic surgery (TORS). Given the comparable oncological outcomes, this study aimed to investigate the risk factors for complications and mortality following NRTOS as an alternative to TORS.

This retrospective cohort study utilized Japanese claims data from diagnosis procedure combination and receipt databases. Data from patients who underwent NRTOS between April 2020 and December 2022 were collected. The primary outcomes were postoperative bleeding, dysphagia, and laryngopharyngeal edema.

Among the 336 included patients, 88.7% were male, with a median age of 72 years. The incidence rates of bleeding, dysphagia, and laryngopharyngeal edema after NRTOS were 3.3%, 4.2%, and 8.0%, respectively. Univariate logistic regression analysis revealed that history of hypertension [odds ratio (OR): 9.82, 95% confidence interval (CI): 1.24-77.50] was a possible risk factor for postoperative bleeding, while a disease stage ≥ T2 (OR: 5.37, 95% CI: 1.52-19.00), a body mass index < 18.5 kg/m2 (OR: 5.51, 95% CI: 1.46-20.80), and concurrent neck dissection with NRTOS (OR: 10.20, 95% CI: 3.26-32.10) were risk factors for postoperative dysphagia. No variables were identified as risk factors for laryngopharyngeal edema. Only one patient (0.3%) died during this study.

NRTOS demonstrated relatively low complication and mortality rates, establishing it as a safe technique for pharyngolaryngeal cancer resection.

Fludarabine and myeloablative busulfan (FluBu4) in allogeneic hematopoietic stem cell transplantation (HSCT) for older people have not been adequately examined. This retrospective study analyzed data from a large-scale, nationwide database in Japan. Adult patients (> 15 years old, y/o) who received their first HSCT with FluBu4 for hematological malignancies were included. They were categorized into the younger (< 60 y/o, N = 1295) and the older group (≥ 60 y/o, N = 993). The 3-year overall survival (OS) rate after HSCT was significantly worse in the older group than in the other (p < 0.01, 39.9% vs. 48.5%). The 3-year non-relapse mortality (NRM) was significantly higher in the older group than in the other (p < 0.01, 30.9% vs. 23.0%), and the 3-year cumulative incidence of relapse was comparable between them. According to the multivariate analysis, age ≥ 60 years was significantly associated with poor OS and high NRM. In a subgroup analysis of the older group, the use of additional chemotherapeutic drugs to FluBu4 was significantly associated with poor OS and high NRM. Total body irradiation was significantly associated with high NRM and 1-year incidence of sinusoidal obstruction syndrome but not with OS. Thus, FluBu4 should be used with caution in older people.

Catechol-O-methyltransferase (COMT) inhibitors are used to alleviate motor fluctuations, such as wearing-off, in people with Parkinson's disease (PwPD). Opicapone, a COMT inhibitor has long-lasting efficacy when administered once daily, but there is limited real-world clinical data in Japanese participants. This study aimed to evaluate the one-year continuation rate of opicapone in Japanese PwPD in real-world clinical practice and to identify factors influencing this continuation rate.

This retrospective study analyzed data from 58 Japanese PwPD treated with opicapone at the Department of Neurology, Fukuoka University Hospital. We compared patients who continued opicapone for one year with those who discontinued it and examined factors influencing the continuation rate.

Among the 58 PwPD, 26 (44.8%) continued opicapone for one year. Binomial logistic regression analysis identified male sex (odds ratio: 0.223, 95 % confidence interval: 0.056-0.878) and switching from entacapone (odds ratio: 0.215, 95 % confidence interval: 0.056-0.825) as significant factors influencing the one-year continuation rate.

Switching to opicapone in patients with suboptimal responses to entacapone may enhance the continuation rate.

DNA flow cytometry using LC-1000 is utilized for analyzing cellular and nuclear lengths and DNA content in individual cells with samples in cell preservation solutions to acquire the cell proliferation index (CPIx). This study aimed to evaluate the performance of body cavity fluid cytology using LC-1000. As cell preservation solutions, liquid-based cytology (LBC) by Cellprep (CP) was compared with CelVerse (CeV), specifically designed for the LC-1000.

Overall, we evaluated 43 samples (20 malignant and 23 benign) of body cavity fluids suspended in CeV and 59 samples (28 malignant and 31 benign) suspended in CP. The CPIx was compared between malignant and benign cases of CeV and CP. Further, the subject groups were divided according to the SubG1% in a sample.

The CPIx in CeV was 0.14-10.22 (median 0.62) in malignant cases and 0.09-4.64 (median 0.19) in benign cases (p < 0.001); additionally, CP displayed 0.14-9.87 (median 0.84) in malignant cases and 0.11-3.02 (median 0.22) in benign cases (p < 0.001). The area under the curve (AUC) was 0.811 for CeV and 0.776 for CP. The difference in SubG1% between the CeV and CP groups was statistically significant (p < 0.0001) and influenced the AUC in CP.

The CPIx in CeV or CP samples using the LC-1000 may be applicable as an objective indicator in body cavity fluid cytology. Samples preserved in CeV provided more consistent results, unaffected by SubG1%, when compared to those stored in CP.

High-grade appendiceal mucinous neoplasm (HAMN) is used to describe a rare epithelial neoplasm of the appendix characterized by pushing-type invasion and high-grade cytologic atypia. Its implications regarding lymph node spread and the necessity of right colectomy are currently debate. The objective of the present study was to assess the clinicopathologic characteristics, the risk of lymph node and peritoneal metastasis, and long-term outcomes of patients diagnosed as HAMN in comparison to low-grade appendiceal mucinous neoplasm (LAMN) and appendiceal adenocarcinoma, treated by right hemicolectomy. A total of 443 patients diagnosed with LAMN (n=246), HAMN (n=34), or appendiceal adenocarcinoma (n=163) and who underwent right colectomy with lymph node dissection in all cases within 32 institutions of the French Network for Rare Peritoneal Malignancies (RENAPE) were included. The median age was 56.5 years (range: 21 to 91), and the majority were female (n=250, 56.4%) without difference between groups ( P =0.604). Lymph node metastases were identified in 17.8% of appendiceal adenocarcinoma cases (29/163); none were found among LAMN or HAMN cases. A higher number of lymph nodes were analyzed in those treated for appendiceal adenocarcinoma than LAMN ( P <0.001) and HAMN ( P =0.035). Regarding peritoneal metastasis, a higher proportion of cases were classified as high-grade with/without signet cells in patients treated for HAMN ( P <0.001) and appendiceal adenocarcinoma ( P <0.001) than those treated for LAMN. Among patients with perforation of the appendix, those treated for LAMN had longer overall survival (OS; P <0.001) and progression-free survival (PFS; P <0.0001) than those treated for appendiceal adenocarcinoma or those treated for HAMN; among patients without perforation, those treated for LAMN and HAMN had longer OS ( P =0.042) and PFS ( P =0.012) than those treated for appendiceal adenocarcinoma. No lymph node metastases were observed in patients treated for HAMN, and those without appendix perforation had a similar prognosis to LAMN. This study supports staging HAMN using the same system as LAMN and treating it with appendectomy alone in the absence of appendix perforation.

Osteoporosis is a major risk factor for fractures among the older population. Despite osteoporosis being a significant concern in super-aged societies such as Japan, the heritability of bone mineral density within the Japanese populace remains unexplored. Therefore, we conducted a twin study among Japanese women to determine the extent of genetic and environmental influences on bone mineral density.

The bone area ratio of 298 healthy, female Japanese twins (comprising 149 pairs, 136 monozygotic and 13 dizygotic twin pairs) registered in the Osaka University Twin Registry was measured using quantitative ultrasound. Classical twin analysis was employed to ascertain the heritability of bone mineral density.

The heritability of bone mineral density for the entire cohort was 0.51 (95 % confidence interval 0.38-0.63). For the women younger than 50 years, the effects of menopause were adjusted, and the best-fit model was also found to be the additive genetics and unique environment (AE) model, with a heritability estimate of 0.53 (95 % confidence interval 0.34-0.72).

Compared with women from other countries, Japanese women appear to have a lower heritability of bone mineral density. Consequently, environmental factors may exert a larger influence on osteoporosis among Japanese women than among women of other races and ethnicities.

The strength of evidence supporting use of PET in the evaluation of suspected histological transformation (HT) of follicular lymphoma (FL) is unknown. We conducted a systematic review of studies reporting the diagnostic performance of ≥1 PET parameters for the detection of HT in patients with known FL. We searched PubMed for any study reporting ≥1 diagnostic performance metrics. Risk of bias was evaluated with the QUADAS2 tool. We included 7 studies encompassing 152 patients with a biopsy showing FL (or indolent non-Hodgkin lymphoma) and 111 with a biopsy confirming HT. Study designs and study populations differed substantially. PET methods were poorly reported and 18F-FDG dose was highly variable. Most studies were judged to be at high risk of bias in the patient and index test domains of QUADAS2. The diagnostic performance of 5 PET parameters were reported in at least one study but only SUVmax (n = 7) was reported in >2. Median SUVmax ranged from 9.2 to 10.9 in FL/iNHL and from 13.7 to 24.4 in HT. While SUVmax was consistently higher in the HT group, there was considerable overlap between the two groups and significant variability between studies. Area under the ROC curve for SUVmax to distinguish between FL/iNHL and HT ranged from 0.68 to 0.97. Sensitivity and specificity of the proposed cutoffs also varied widely (sensitivity ∼0.6 to 1, specificity ∼0.4 to 1). In conclusion, few studies - mostly small and potentially biased - have addressed this question. Although SUVmax is generally higher in HT than in FL, the diagnostic performance and optimal cutoffs remain unclear. Proposed SUVmax cutoffs should not be used to determine whether a patient has HT or to decide whether a biopsy should be obtained. For now, we encourage physicians to evaluate results of their own practice to devise a prudent workup of suspected.

Although the hematopoietic cell transplantation (HCT)-comorbidity index (HCT-CI) score is associated with an increased risk of mortality after allogeneic HCT, it remains unclear how pre-HCT liver dysfunction affects clinical outcomes. We retrospectively compared clinical HCT outcomes among four groups stratified according to the presence of HCT-CI liver and other organ scores, using a Japan transplant registry database between 2010 and 2020. Of the 14235 recipients, 1527 tested positive for an HCT-CI liver score including HBV or HCV hepatitis (n = 503). The 5-year overall survival (OS) was significantly lower in the HCT-CI liver(+) other(+) and HCT-CI liver(-) other(+) groups compared to the HCT-CI liver(+) other(-) and HCT-CI liver(-) other(-) groups [49.9% vs. 59% vs. 66.5% vs. 68.3%, p < 0.001]. A multivariate analysis showed that both the HCT-CI liver(+) other(+) [HR 1.62, p < 0.001] and HCT-CI liver(-) other(+) groups [HR 1.21, p < 0.001] were significantly associated with inferior OS. Similarly, both the HCT-CI liver(+) other(+) [HR 1.89, p < 0.001] and liver(-) other(+) groups [HR 1.26, p < 0.001] were significantly associated with an increased risk of NRM. On the other hand, the HCT-CI liver(+) other(-) group was not associated with either OS or NRM. Separately analyzing the subcohorts with or without HCT-CI other scores, the presence of an HCT-CI liver score alone did not affect survival, while the co-presence of pretransplant liver dysfunction seemed to synergistically increase the adverse impact on OS and NRM among recipients with other organ comorbidities. Further studies will be needed to identify optimal strategies for recipients with pretransplant liver dysfunction.

To evaluate the treatment strategies for closure of patent ductus arteriosus (PDA) and clinical outcomes among very preterm infants based upon the availability of cardiac surgeons in neonatal intensive care units (NICUs).

This study retrospectively assessed infants born at 23-29 weeks of gestation who participated in a prior prospective cohort study in Japan. The primary outcome was PDA surgery. The secondary outcomes included mortality and various morbidities, such as intraventricular hemorrhage and chronic lung disease (CLD). Outcomes were compared between with-surgeon and no-surgeon NICUs using generalized linear mixed effect models, adjusted for gestational age, antenatal corticosteroid, small-for-gestational age, and unit patient volume.

This study included 613 infants from 27 NICUs, including 245 from 9 no-surgeon NICUs and 368 from 18 with-surgeon NICUs. Infants received significantly more prophylactic indomethacin in the no-surgeon NICUs than those in the with-surgeon NICUs. The frequency of PDA surgery showed no significant difference between the groups (9.0% vs 12%, adjusted odds ratio [aOR]: 0.56 [95% confidence interval: 0.21-1.51]). CLD was significantly more frequent in no-surgeon NICUs than in with-surgeon NICUs (55% vs 40%, aOR: 3.24 [95% CI 1.45-7.29]).

The frequency of PDA surgery did not differ significantly according to the availability of surgeons. The incidence of CLD was higher in no-surgeon NICUs; however, the risk of unmeasured confounding cannot be excluded due to the observational study design.

The study aimed to investigate the therapeutic effect of various initial treatments incorporating glucocorticoid (GC) in TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly). Cases of TAFRO syndrome up to November 2023 were retrospectively collected. Overall survival (OS) and resistance to GC therapy were assessed, with resistance analyzed based on the time to the next treatment or death (TTNTD). The study included 95 patients, including 5 diagnosed at our hospital. OS did not differ significantly between patients who received GC monotherapy and those who had a second-line therapy added within 2 weeks (100-day OS rate: 86.6% vs. 77.7%; p = 0.338). Moreover, 100-day OS did not differ between patients who received GC pulse therapy within 2 weeks and those who did not (77.5% vs. 93.1%, p = 0.129). In multivariate analyses, pretreatment severity score ≥ 8 (hazard ratio [HR], 2.99; 95% confidence interval [CI] 1.05-8.50) and platelets ≥ 6.9 × 10^4/µL (HR, 2.26; 95% CI 1.01-5.02) were significantly associated with shorter TTNTD. Additional second-line or GC pulse therapy provided no advantage in the hyperacute phase. Higher severity scores and platelet values may predict resistance to GC therapy.

Identifying which biomarkers and comorbidities of type 2 (T2) inflammation to focus on when selecting biologics has remained challenging. We retrospectively examined which biomarkers and comorbidities could influence asthma control among T2-high severe asthma patients receiving biologics. Patients without any maintenance oral corticosteroids and exacerbations requiring systemic corticosteroids indicated super-responder (SR). Clinical remission (CR) was defined as fulfilling the following criteria in addition to achieving SR: asthma symptom improvement (asthma control test score ≥23) and pulmonary function improvement (%forced expiratory volume in 1 s ≥ 80%). We initiated and switched biologics to achieve SR and CR. In total, 111 patients were evaluated, among whom 85.6% and 27.0%-50.5% demonstrated SR and CR, respectively. CR was more frequently observed among patients with severe eosinophilic chronic rhinosinusitis (ECRS) than among those without it. Attention must be paid to the existence of severe ECRS to achieve CR in patients with uncontrolled T2-high severe asthma.

Muscle mass and fatty infiltration can be assessed on computed tomography (CT) images using the cross-sectional area (CSA) and computed tomography attenuation value (CTV). Femoral head collapse in osteonecrosis of the femoral head (ONFH) may affect both values. We investigated factors influencing the CSA and CTV of the periarticular muscles in patients with ONFH.

Overall, 101 patients with ONFH with unilateral hip pain (stage 2, 24 patients; stage 3 A, 49 patients; and stage 3B, 28 patients) were included. The CSA and mean CTV of the bilateral gluteus maximus (Gmax), gluteus medius (Gmed), gluteus minimus (Gmin), and iliopsoas (IP) muscles were measured using CT cross-sections. Bilateral comparisons and associations with Japanese Investigation Committee (JIC) stage were analysed. Multiple regression analysis was used to evaluate factors associated with the CSA and CTV.

On the symptomatic side, the CSA was significantly lower for the Gmax, Gmed, and IP, whereas the CTV was significantly lower for all tested muscles (all p < 0.01). The CTV, but not the CSA, of the Gmax, Gmed, and Gmin was significantly associated with the JIC stage severity bilaterally (all p < 0.01). Multiple regression analysis showed significant associations of the CTV with age, sex, and JIC stage (all p < 0.01).

Symptomatic ONFH leads to decreased muscle mass and increased fatty infiltration. Femoral head collapse progression is associated with a decrease in the CTV. Periarticular muscle assessment, including on the contralateral side, is important in patients with ONFH, particularly in older women.

Patients with rare diseases worldwide face substantial unmet therapeutic needs. In Japan, drug lag-delays in drug approval compared to other countries-has resurfaced as a pressing public health issue. This study analyzes orphan drugs (ODs) approved in the United States (US) from 2005 to 2021, examining OD lag trends, and research and development (R&D) models to streamline OD development in Japan. Despite increased OD approval in the United States since 2018, the number of unapproved ODs in Japan has substantially increased. Although OD lag decreased, it has resurged since 2017. This is largely due to changes in the R&D strategies of pharmaceutical companies, which are driven by the growing presence of US- and Europe-based small- to mid-sized enterprises (SMEs) and the evolving industry landscape. Large foreign pharmaceutical companies have shifted toward a global development strategy for Japan, aiming for more efficient development and competitive advantage. This has been propelled by a move toward in-licensing earlier-stage drug candidates with global exclusivity from SMEs. Japanese pharmaceutical companies have focused on in-licensing late-stage drug candidates for the Japanese market from SMEs without a business presence in Japan, which have not been developed locally, thereby employing a bridging strategy for Japan. With the increase in ODs developed in the United States by these SMEs, this practice has substantially exacerbated the OD lag. As these SMEs are unlikely to enter the Japanese market, it is crucial for Japanese pharmaceutical companies to proactively pursue earlier, more proactive global partnerships with SMEs.

The importance of tumor markers is well established; yet little is known about their prognostic value for patients with obstructive colorectal cancer (OCRC). We investigated the clinical significance of carcinoembryonic antigen (CEA) and CA 19-9 levels in patients with non-metastatic OCRC, who underwent insertion of a self-expandable metallic stent and curative surgery.

Clinical data on 91 patients with OCRC were analyzed retrospectively to evaluate the associations of preoperative serum values of tumor makers with short- and long-term outcomes.

The 91 patients comprised 53 men and 38 women, with a median age of 71 years. Twelve patients had an elevated preoperative CA 19-9 level. Multivariate analyses revealed that an elevated CA 19-9 level was independently associated with poor disease-free survival (DFS) [hazard ratio (HR) = 4.57, 95% confidence interval (CI) 2.06-10.14, P < 0.001] and overall survival (HR = 4.06, 95% CI 1.46-11.24, P = 0.007). A CEA level > 5 ng/ml had no prognostic value, whereas a CEA level > 10.8 ng/ml was significantly associated with worse DFS (P = 0.032).

Measuring the CA 19-9 level concomitantly with the CEA level for patients with advanced CRC, including OCRC, may provide a valuable means to improve prognostication.

One of the most serious adverse events associated with trastuzumab treatment is cardiac dysfunction, including congestive heart failure. Therefore, regular cardiac screening with echocardiography is commonly performed during trastuzumab treatment, although it is unclear for how long the patient will continue to be evaluated. We investigated the time to the occurrence of trastuzumab-induced cardiac dysfunction using the Japanese Adverse Drug Event Report (JADER) database. We examined the optimal duration of cardiac function evaluation in patients treated with trastuzumab.

This study used data registered between April 2004 and September 2023 in the JADER database. We investigated the time to onset of cardiotoxicity in patients treated with trastuzumab, trastuzumab emtansine, or trastuzumab deruxtecan. We considered the time to exclude outliers detected using the Smirnov-Grubbs test as the optimal follow-up duration for cardiac function tests.

Of 868,478 patients who reported adverse drug events, 977 experienced cardiac dysfunctions among those treated with trastuzumab. A total of 375 patients were included in the analysis after excluding patients for whom the time to onset of cardiotoxicity was unknown or those who experienced cardiac dysfunction after receiving trastuzumab followed by anthracycline. The median time to cardiotoxicity was 4.5 months (range 0-100 months). However, ≥ 19 months after the start of trastuzumab administration was detected as an outlier in the target population (P = 0.036).

The duration of regular follow-up of cardiac function using echocardiography during anti-HER2 therapy can be 18 months from the start of treatment.

Gastric-type adenocarcinoma (GAS) is the most common subtype of human papillomavirus (HPV)-independent cervical adenocarcinomas and is associated with a poor prognosis. We used a gross morphologic classification system and imaging analysis to compare the clinicopathological features of GAS and HPV-associated adenocarcinoma (HPVA) and identify factors contributing to the poor prognosis of GAS. This retrospective 2-center study analyzed 33 patients with GAS and 70 with HPVA (stages IB-IVB) who underwent surgery between 1997 and 2023. GAS had a higher rate of positive surgical margins (21.2% vs. 0%, respectively, P <0.001) and unclear tumor boundaries on gross morphologic findings (47.8% vs. 8.8%, respectively, P <0.001). Discrepancies between clinical and pathologic T classifications were more common in GAS, leading to frequent upstaging (51.5% vs. 28.6%, respectively, P =0.029). Imaging analysis revealed that GAS was associated with a smaller median tumor cell area (19.8% vs. 55.7%, respectively, P <0.001), which was significantly correlated with unclear tumor boundaries. Perineural invasion (PNI) was significantly more frequent in GAS (69.7% vs. 10.0%, respectively, P <0.001). A Kaplan-Meier analysis showed that patients with PNI had significantly poorer overall survival ( P <0.001). A Cox multivariate analysis identified an advanced pathologic stage, positive peritoneal cytology, and positive surgical margins as independent risk factors. The present results indicate that GAS has a unique "stealth" invasion pattern, possibly caused by low tumor density, leading to undetectable tumor boundaries and positive surgical margins. This suggests a greater risk of incomplete resection than HPVA, leading to a poorer prognosis.