Internal carotid artery-persistent primitive anterior choroidal artery aneurysms: report of two cases and literature review.

PURPOSE: Persistent primitive anterior choroidal artery (PPAChA) is a rare vascular anomaly. The clinical course of internal carotid artery (ICA)-PPAChA aneurysms has not been well described. CASE REPORTS: We report two patients with an ICA-PPChA aneurysm and summarize previously reported cases. RESULTS: Including our two, a total of 10 patients with an ICA-PPAChA aneurysm have been reported. Data were not described for one. Among the remaining nine, five patients (56%) experienced aneurysmal rupture. Five patients underwent surgical clipping and four underwent endovascular coiling. The procedure was completed in all but one patient who had a tiny branch artery adherent to the aneurysm; this patient was converted from clipping to aneurysm coating with a cotton sheet. Among the other eight patients, one who underwent coiling experienced an internal capsule infarction. The remaining seven had a satisfactory postoperative course; however, an asymptomatic occlusion of the PPAChA at its origin was noted on postoperative angiography in one. CONCLUSION: PPChA is associated with a high incidence of aneurysm formation and rupture. During treatment of ICA-PPAChA aneurysms, obstruction of the PPAChA and any surrounding perforating arteries should be avoided to prevent ischemic stroke.

Transcriptional Up-Regulation of FBXW7 by KCa1.1 K+ Channel Inhibition through the Nrf2 Signaling Pathway in Human Prostate Cancer LNCaP Cell Spheroid Model.

The tumor suppressor gene F-box and WD repeat domain-containing (FBXW) 7 reduces cancer stemness properties by promoting the protein degradation of pluripotent stem cell markers. We recently demonstrated the transcriptional repression of FBXW7 by the three-dimensional (3D) spheroid formation of several cancer cells. In the present study, we found that the transcriptional activity of FBXW7 was promoted by the inhibition of the Ca2+-activated K+ channel, KCa1.1, in a 3D spheroid model of human prostate cancer LNCaP cells through the Akt-Nrf2 signaling pathway. The transcriptional activity of FBXW7 was reduced by the siRNA-mediated inhibition of the CCAAT-enhancer-binding protein C/EBP δ (CEBPD) after the transfection of miR223 mimics in the LNCaP spheroid model, suggesting the transcriptional regulation of FBXW7 through the Akt-Nrf2-CEBPD-miR223 transcriptional axis in the LNCaP spheroid model. Furthermore, the KCa1.1 inhibition-induced activation of FBXW7 reduced (1) KCa1.1 activity and protein levels in the plasma membrane and (2) the protein level of the cancer stem cell (CSC) markers, c-Myc, which is a molecule degraded by FBXW7, in the LNCaP spheroid model, indicating that KCa1.1 inhibition-induced FBXW7 activation suppressed CSC conversion in KCa1.1-positive cancer cells.

The Anti-Inflammatory Effects and Clinical Potential of Dexmedetomidine in Pulmonary Arterial Hypertension.

A pathogenic aspect of pulmonary arterial hypertension (PAH) is the aberrant pulmonary arterial smooth muscle cell (PASMC) proliferation. PASMC proliferation is significantly affected by inflammation. A selective α-2 adrenergic receptor agonist called dexmedetomidine (DEX) modulates specific inflammatory reactions. We investigated the hypothesis that anti-inflammatory characteristics of DEX could lessen PAH that monocrotaline (MCT) causes in rats. In vivo, male Sprague-Dawley rats aged 6 weeks were subcutaneously injected with MCT at a dose of 60 mg/kg. Continuous infusions of DEX (2 µg/kg per hour) were started via osmotic pumps in one group (MCT plus DEX group) at day 14 following MCT injection but not in another group (MCT group). Right ventricular systolic pressure (RVSP), right ventricular end-diastolic pressure (RVEDP), and survival rate significantly improved in the MCT plus DEX group compared with the MCT group [RVSP, 34 mmHg ± 4 mmHg versus 70 mmHg ± 10 mmHg; RVEDP, 2.6 mmHg ± 0.1 mmHg versus 4.3 mmHg ± 0.6 mmHg; survival rate, 42% versus 0% at day 29 (P < 0.01)]. In the histologic study, the MCT plus DEX group showed fewer phosphorylated p65-positive PASMCs and less medial hypertrophy of the pulmonary arterioles. In vitro, DEX dose-dependently inhibited human PASMC proliferation. Furthermore, DEX decreased the expression of interleukin-6 mRNA in human PASMCs treated with fibroblast growth factor 2 (FGF2). These consequences suggest that DEX improves PAH by inhibiting PASMC proliferation through its anti-inflammatory properties. Additionally, DEX may exert anti-inflammatory effects via blocking FGF2-induced nuclear factor κ B activation. SIGNIFICANCE STATEMENT: Dexmedetomidine, a selective α-2 adrenergic receptor agonist utilized as a sedative in the clinical setting, improves pulmonary arterial hypertension (PAH) by inhibiting pulmonary arterial smooth muscle cell proliferation through its anti-inflammatory effect. Dexmedetomidine may be a new PAH therapeutic agent with vascular reverse remodeling effect.

High hydrostatic pressure induces slow contraction in mouse cardiomyocytes.

Cardiomyocytes are contractile cells that regulate heart contraction. Ca2+ flux via Ca2+ channels activates actomyosin interactions, leading to cardiomyocyte contraction, which is modulated by physical factors (e.g., stretch, shear stress, and hydrostatic pressure). We evaluated the mechanism triggering slow contractions using a high-pressure microscope to characterize changes in cell morphology and intracellular Ca2+ concentration ([Ca2+]i) in mouse cardiomyocytes exposed to high hydrostatic pressures. We found that cardiomyocytes contracted slowly without an acute transient increase in [Ca2+]i, while a myosin ATPase inhibitor interrupted pressure-induced slow contractions. Furthermore, transmission electron microscopy showed that, although the sarcomere length was shortened upon the application of 20 MPa, this pressure did not collapse cellular structures such as the sarcolemma and sarcomeres. Our results suggest that pressure-induced slow contractions in cardiomyocytes are driven by the activation of actomyosin interactions without an acute transient increase in [Ca2+]i.

Infliximab treatment for refractory COVID-19-associated multisystem inflammatory syndrome in a Japanese child.

Patients with multisystem inflammatory syndrome in children (MIS-C) can develop clinical features resembling Kawasaki disease (KD). A full picture of MIS-C in East Asia which has higher incidence of KD than other regions remains unclear. We report on a 15-year-old Japanese boy with refractory MIS-C who was successfully treated with infliximab. A Japanese boy who was diagnosed with coronavirus disease 2019 (COVID-19) before a month developed MIS-C with fulfilling six principal symptoms of KD. Laboratory data showed extreme hyperferritinemia (11,404 ng/mL), besides lymphopenia and thrombocytopenia. The patient was refractory to initial therapy with intravenous immunoglobulin (IVIG; 2 g/kg), aspirin, and prednisolone. He was therefore administered a second IVIG (2 g/kg) and infliximab (5 mg/kg) on days 7 and 8 from the onset of fever, respectively, which resulted in an improvement of clinical symptoms. Only four Japanese cases with MIS-C were reported and all of them were responsive to IVIG. The hyperferritinemia in this case was distinctive from previously reported MIS-C cases in Japan and other cohorts and may be associated with refractoriness to IVIG therapy. Marked elevation of circulating ferritin levels is known to be induced by tumor necrosis factor-α, which plays a key role in the pathogenesis of both KD and MIS-C. Thus, for MIS-C patients with hyperferritinemia, early intervention with adjunctive infliximab may induce a more rapid resolution of inflammation and improve outcome. Because MIS-C may be heterogeneous with respect to immunopathology, genetic background, clinical phenotypes and response to therapies, optimized treatment strategies according to immunopathogenesis are required.

Oral challenge with Streptococcus sanguinis induces aortic inflammation and accelerates atherosclerosis in spontaneously hyperlipidemic mice.

Atherosclerosis is exacerbated by periodontal pathogens, which induce vascular inflammation after entering the bloodstream. Among oral indigenous bacteria, Streptococcus sanguinis and S. anginosus are related to systemic disorders, such as infective endocarditis and abscess, and are sometimes detected in human atherosclerotic plaques or blood. Thus, these oral streptococci may contribute to the progression of atherosclerosis. To test this hypothesis, apolipoprotein E-deficient spontaneously hyperlipidemic mice were intraorally challenged with S. sanguinis or S. anginosus. Atherosclerotic plaque formation increased significantly in the S. sanguinis-challenged group compared with the carboxymethylcellulose-treated control group. Expression levels of mRNAs of proinflammatory cytokines in the aorta and levels of atherosclerosis-related mediators in blood increased upon S. sanguinis challenge. Adaptor molecule TNF receptor-associated factor 6 was also enhanced in the aorta when mice were challenged with S. sanguinis. Furthermore, challenge with S. anginosus induced systemic inflammation, but inflammation-related mRNA expression levels in the aorta only increased slightly and were accompanied by minimal expansion of the lesion area. By contrast, with the exception of IL-1α, the expression levels of inflammation-related genes did not change in gingival tissues of both bacteria- and sham-challenged groups. These results reveal that S. sanguinis causes aortic inflammation that leads to accelerated progression of atherosclerosis.

Nasal Cavity of Green Sea Turtles Contains 3 Independent Sensory Epithelia.

The morphological and histological features of the nasal cavity are diverse among animal species, and the nasal cavities of terrestrial and semiaquatic turtles possess 2 regions lined with each different type of sensory epithelium. Sea turtles can inhale both of volatile and water-soluble odorants with high sensitivity, but details of the architectural features and the distribution of the sensory epithelia within the sea turtle nasal cavity remain uncertain. The present study analyzed the nasal cavity of green sea turtles using morphological, computed tomographic, and histological methods. We found that the middle region of the sea turtle nasal cavity is divided into anterodorsal, anteroventral, and posterodorsal diverticula and a posteroventral excavation by connective tissue containing cartilages. The posterodorsal diverticulum was lined with a thin sensory epithelium, and the anterodorsal and anteroventral diverticula were occupied by a single thick sensory epithelium. In addition, a relatively small area on the posteroventral excavation was covered by independent sensory epithelium that differed from other 2 types of epithelia, and a single thin bundle derived from the posteroventral excavation comprised the most medial nerve that joins the anterior end of the olfactory nerve tract. These findings suggested that the posteroventral excavation identified herein transfers stimuli through an independent circuit and plays different roles when odorants arise from other nasal regions.

Feasibility and Reproducibility of Fetal Left Ventricular Twist Using Two-Dimensional Speckle-Tracking Analysis in a Japanese Population.

In fetal echocardiography, conventional parameters for assessing cardiac function are limited because of limited echocardiographic windows or the fetus' position. We aimed to evaluate the feasibility and reproducibility of fetal left ventricular (LV) twist by two-dimensional, speckle-tracking echocardiography (2DSTE) in a Japanese population.We included 55 normal fetuses at gestational ages between 21 and 36 weeks. Subjects with adverse maternal health issues were excluded. LV twist was calculated as the net difference between LV basal and apical rotation at end-systole estimated with 2DSTE.We were able to analyze the 2DSTE images in 44 cases (80%). The mean (±SE) apical rotation, basal rotation, and LV twist were 7.88 ± 0.77, -3.68 ± 0.50, and 11.1 ± 0.75 degrees, respectively. We could not analyze 11 cases (20%) because of poor image quality due to fetal position in five cases (45.5%), failure to track the endocardium because of blurred images in five cases (45.5%), and failure to obtain images of the heart due to the presence of the placenta in front of the fetus in one case (9.1%). There were no significant differences in the demographic data between pregnant women in whom LV twist analysis was feasible and not feasible. The intra- and interobserver intraclass correlation coefficients were 0.67 and 0.64, respectively.LV twist analysis by 2DSTE in the fetus was feasible in a substantial population and may provide new insight into cardiac function during the prenatal period. On the other hand, its reproducibility was moderate and needs to be improved.

[Successful treatment of pre-engraftment disseminated fusariosis with high-dose liposomal amphotericin B in a cord blood transplant recipient].

A 47-year-old man with acute myeloid leukemia and myelodysplastic-related changes relapsed after an allogenic bone marrow transplant and received a cord blood transplant as salvage therapy. The patient developed febrile neutropenia that was resistant to broad-spectrum antibiotics and multiple, painful, nodular skin lesions on his trunk and extremities before engraftment. A skin biopsy and blood culture found mold, and the subsequent microscopic examination, mass spectrometry, and DNA sequencing of the fungal colonies identified Fusarium solani. The patient's fever and skin lesions began to improve with the administration of liposomal amphotericin B at 5 mg/kg/day. Neutrophilic engraftment occurred on day 19. Stage 3 acute skin graft-versus-host disease was cured by the application of topical steroid. Unexpectedly, a change from liposomal amphotericin B to voriconazole on day 38 exacerbated the Fusarium infection. The Fusarium infection was finally cured by the administration of liposomal amphotericin B for a total of 19 weeks. Neutrophilic engraftment, an immediate definitive diagnosis, the sufficient and long-term administration of appropriate antifungal medication, and avoidance of the systemic administration of steroids might have contributed to the successful outcome of this patient.

Regulation of the NLRP3 inflammasome in Porphyromonas gingivalis-accelerated periodontal disease.

OBJECTIVE: Porphyromonas gingivalis is involved in the pathogenesis of chronic inflammatory periodontal disease. Recent studies have suggested that the NLRP3 inflammasome plays an important role in the development of chronic inflammation. We investigated a possible association between the inflammasome in gingival inflammation and bone loss induced by P. gingivalis infection using NLRP3-deficient mice. METHODS: Wild-type and NLRP3-deficient mice were injected orally with P. gingivalis. We assessed alveolar bone loss, expression of pro-interleukin (IL)-1ß, pro-IL-18, receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) in gingival tissue, as well as IL-1ß, IL-18, and IL-6 production and caspase-1 activity in peritoneal macrophages. RESULTS: Porphyromonas gingivalis challenge significantly increased alveolar bone loss; gingival gene expression of pro-IL-1ß, pro-IL-18, and RANKL; production of IL-1ß, IL-18, and IL-6; and caspase-1 activity in peritoneal macrophages of wild-type mice, but did not affect NLRP3-deficient mice. Meanwhile, OPG mRNA expression in gingival tissue and peritoneal IL-6 production were significantly higher in NLRP3-knockout mice. CONCLUSIONS: Porphyromonas gingivalis activated innate immune cells via the NLRP3 inflammasome. These results suggest that the NLRP3 inflammasome, followed by a response from the IL-1 family, is critical in periodontal disease induced by wild-type P. gingivalis challenge via sustained inflammation.

A Novel Diagnostic and Prognostic Biomarker Panel for Endothelial Cell Damage-Related Complications in Allogeneic Transplantation.

Noninfectious transplantation-related complications (TRCs), such as graft-versus-host disease or TRC with endothelial cell damage (TRC-EC), remain as the major obstacle for successful allogeneic hematopoietic cell transplantation (allo-HCT). However, the diagnosis and prognosis for the emergence of these complications are difficult to define during the early post allo-HCT period. Here, we tried to generate a novel diagnostic system for TRC-EC by analyzing 188 adult patients who received allo-HCT. Our study found that the peripheral blood levels of angiopoietin 2 (ANG2), C-reactive protein (CRP), D-dimer, and thrombomodulin (TM) at the onset of TRCs were significantly associated with the development of TRC-EC. We next developed a composite biomarker panel incorporating the risk values of ANG2, CRP, D-dimer, and TM at the onset of TRCs, which classified these patients into 3 risk groups: low, intermediate, and high risk. As a result, the panel was useful not only for the diagnosis of TRC-EC with high specificity and sensitivity, but also for the prediction of the patients' long-term outcome. The 5-year overall survival (OS) rates of patients in the low-, intermediate-, and high-risk groups since the occurrence from TRCs were 76.2%, 54.9%, and 26.9%, respectively, and the high-risk score was significantly associated with both poor OS (hazard ratio [HR], 5.60; 95% confidence interval [CI], 2.81 to 11.20; P < .01) and frequent nonrelapse mortality (HR, 19.75; 95% CI, 5.59 to 69.77; P < .01). Thus, the composite panel proposed in this study provides a powerful tool for the diagnosis of TRC-EC and for the prediction of survival for patients with TRC-EC after allo-HCT.

Evaluation of the MGL method to detect Paragonimus eggs and its improvement.

Dog feces containing 500 Paragonimus westermani eggs per gram were examined by the Medical General Laboratory (MGL), the simple sedimentation (SS), and the Army Medical School III (AMS III) methods. The number of eggs per gram of feces (EPG) obtained by the MGL method was 17.2 and was significantly lower than those obtained by the SS method (324.0) and the AMS III method (505.6). When isolated P. westermani eggs were processed by the MGL method and four layers (ether, ether-fecal, formalin layers, and sediment) of the final centrifugation product were separately examined, almost 100% of eggs were found at the ether-fecal layer. Similarly, when fecal samples containing P. westermani, Paragonimus skrjabini miyazakii, Paragonimus ohirai, or Paragonimus harinasutai eggs were processed by the MGL method, more than 95% of the eggs were found in the supernatant layers. The formalin-ethyl acetate (FEA) method showed a similar tendency as the MGL method and over 90% of eggs remained in the supernatant layers. Contrary to Paragonimus eggs, 63 and 96% of Clonorchis and Metagonimus eggs were found in the sediment in the MGL method, respectively. When surfactant (Tween 80) was added to fecal solution, most of Paragonimus eggs spun down in the sediment in the MGL and FEA methods, suggesting that Paragonimus eggs have hydrophobic components on their surface. It is suggested that surfactant addition to the fecal solution should be considered when the MGL method is used for detection of Paragonimus eggs.

Effect of Laser Irradiation Modes and Photosensitizer Types on Antimicrobial Photodynamic Therapy (aPDT) for Streptococcus sobrinus in the Crown Dentin of Bovine Teeth: An Experimental In Vitro Study.

This study aimed to assess the impact of different laser irradiation modes and photosensitizer types on the bactericidal efficacy of antimicrobial photodynamic therapy (aPDT). Dentin plates were prepared by sectioning the crown dentin of bovine teeth infected with Streptococcus sobrinus (n = 11). Nine aPDTs involving the combination of three 1% solutions of photosensitizers (brilliant blue, BB; acid red, AR; and methylene blue, MB) and three irradiation modes of semiconductor lasers (50 mW for 120 s, 100 mW for 60 s, and 200 mW for 30 s) were performed for each infected dentin plate, and the control consisted of the specimens not applied with aPDT. The bactericidal effects in 10 groups were evaluated using both assays of the colony count (colony-forming-unit: CFU) and adenosine triphosphate (ATP) (relative-light-unit: RLU). The data obtained were analyzed using the Kruskal-Wallis test (α = 0.05). The most aPDT groups exhibited significantly lower RLU and CFU values compared with the control (p < 0.05). The effect of irradiation modes on RLU and CFU values was significant in the aPDT group using BB (p < 0.05) but not in the aPDT group using AR or MB. The aPDT performed with AR or MB exerted a remarkable bactericidal effect.

Endovascular treatment of acute atherothrombotic internal carotid artery occlusion associated with persistent primitive hypoglossal artery.

Persistent primitive hypoglossal artery is a relatively rare anatomical variation and a type of persistent carotid-basilar anastomosis. Acute internal carotid artery occlusion associated with persistent primitive hypoglossal artery is rare, and atherothrombotic occlusion is extremely rare. We present a case of acute atherothrombotic internal carotid artery occlusion associated with persistent primitive hypoglossal artery that was successfully treated by endovascular treatment. A 70-year-old male with a history of left internal carotid artery stenosis was transferred to our hospital by ambulance because of abnormal behaviors and aphasia. He was diagnosed with cerebral infarction and left internal carotid artery occlusion. Left carotid angiography revealed the persistent primitive hypoglossal artery arising from the cervical internal carotid artery and complete internal carotid artery occlusion distal to the origin of the persistent primitive hypoglossal artery. Therefore, we performed endovascular treatment. Mechanical thrombectomy was performed under minimal flow arrest with consideration of brain ischemia causing coma. After additional balloon angioplasty, recanalization was achieved, and the patient's symptoms improved. During the 1.5-year follow-up period, no recurrence or restenosis was observed. This report provides evidence that atherosclerotic internal carotid artery stenosis associated with persistent primitive hypoglossal artery can occur even distal to the origin of the persistent primitive hypoglossal artery and that the lesion may become acutely occluded, leading to acute stroke. Endovascular treatment considering brain ischemia was effective in this case.

Long insular artery damage might be a key sign for predicting functional prognosis of putaminal hemorrhage.

OBJECTIVE: Although the putamen is the most common area of spontaneous intracerebral hemorrhage, previous reports about the effects of surgery are limited. We sometimes experience a poor prognosis in patients in whom there is no damage to the internal capsule, but with injury in the long insular artery (LIA) region. The purpose of this study was to confirm the relationship between LIA damage and patient prognosis following surgery for putaminal hemorrhage. METHODS: We retrospectively collected data of 287 surgical cases who presented with putaminal hemorrhage between January 2004 and March 2022. Among them, we chose patients without initial damage to the posterior limb of the internal capsule, and divided these patients into two groups, those without (Group A) and with (Group B) final damage in the LIA region. We compared positivity rates of final manual muscle test (MMT) scores≥3 and related factors. RESULTS: Sixty-three of the 287 patients were included in this study. Of them, 11 cases in Group A were positive for MMT scores≥3 (68.8%) and 9 cases (19.1%) in Group B had MMT scores≥3 seven days after surgery. Group A thus had a significantly higher rate of MMT scores≥3 than group B (p=0.00). CONCLUSION: In patients without initial damage to the internal capsule, LIA injury might be a key sign for predicting the functional prognosis of putaminal hemorrhage.

Effect of transcranial direct current stimulation on the functionality of 40 Hz auditory steady state response brain network: graph theory approach.

Introduction: Measuring whole-brain networks of the 40 Hz auditory steady state response (ASSR) is a promising approach to describe the after-effects of transcranial direct current stimulation (tDCS). The main objective of this study was to evaluate the effect of tDCS on the brain network of 40 Hz ASSR in healthy adult males using graph theory. The second objective was to identify a population in which tDCS effectively modulates the brain network of 40 Hz ASSR. Methods: This study used a randomized, sham-controlled, double-blinded crossover approach. Twenty-five adult males (20-24 years old) completed two sessions at least 1 month apart. The participants underwent cathodal or sham tDCS of the dorsolateral prefrontal cortex, after which 40 Hz ASSR was measured using magnetoencephalography. After the signal sources were mapped onto the Desikan-Killiany brain atlas, the statistical relationships between localized activities were evaluated in terms of the debiased weighted phase lag index (dbWPLI). Weighted and undirected graphs were constructed for the tDCS and sham conditions based on the dbWPLI. Weighted characteristic path lengths and clustering coefficients were then measured and compared between the tDCS and sham conditions using mixed linear models. Results: The characteristic path length was significantly lower post-tDCS simulation (p = 0.04) than after sham stimulation. This indicates that after tDCS simulation, the whole-brain networks of 40 Hz ASSR show a significant functional integration. Simple linear regression showed a higher characteristic path length at baseline, which was associated with a larger reduction in characteristic path length after tDCS. Hence, a pronounced effect of tDCS is expected for those who have a less functionally integrated network of 40 Hz ASSR. Discussion: Given that the healthy brain is functionally integrated, we conclude that tDCS could effectively normalize less functionally integrated brain networks rather than enhance functional integration.

Tumor-infiltrating lymphocytes in breast FNA biopsy cytology: A predictor of tumor-infiltrating lymphocytes in histologic evaluation.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are associated with various clinicopathological features. Using cytologic specimens for assessing TILs remains to be established. This retrospective study aimed to establish a practical method to assess TILs in cytologic samples. METHODS: The authors found 1101 breast fine-needle aspiration biopsy (FNAB) cytology samples in their hospital, and 214 of them met the inclusion criteria. The TILs score was evaluated using histologic slides, and breast cancers were divided into 2 groups: low- (<60%) and high-TILs (≥60%). Training and validation tests composed of 50 breast cancer samples each were constructed. A cytologic TILs (cTILs) score was introduced to evaluate lymphocytes in FNAB cytology and it was compared with histologically evaluated TILs. The cTILs score was calculated by subtracting the number of neutrophils from the number of lymphocytes surrounding the tumor cells. RESULTS: In the training test, a 2-tier system with low- and high-TILs groups showed a large area under the curve (AUC) (0.943; 95% confidence interval [CI], 0.84-0.99). A cTILs score cutoff value of >8 had 87.5% sensitivity and 90.5% specificity. In the validation test, the AUC was 0.79 (95% CI, 0.6-0.93) whereas sensitivity and specificity were 57% and 89.5%, respectively. When small tumors <0.5 cm were excluded, the AUC improved to 0.93 (95% CI, 0.83-1.0), and sensitivity and specificity were 80% and 88.5%, respectively. CONCLUSIONS: The cTILs scoring system had acceptable reproducibility and concordance with TILs on histologic samples for tumors ≥0.5 cm. Cytologic evaluation can potentially substitute for histologic evaluation of TILs.

Accidental duodenal foreign body of toothbrush removed laparoscopically: a case report.

BACKGROUND: Foreign body ingestion is a common case in daily medical care, and it usually passes through the entire gastrointestinal tract naturally and is excreted in the feces. However, long and sharp foreign bodies may be difficult to pass naturally due to their shape. Here, we present a rare case of a duodenal foreign body, a toothbrush, that required laparoscopic surgical removal after a failed endoscopic attempt. CASE PRESENTATION: A 51-year-old male with intellectual disability presented to our hospital due to fever. Initially, he was diagnosed with aspiration pneumonia by chest X-ray and blood examination. However, abdominal X-ray examination suggested a foreign body, and a computed tomography scan revealed a toothbrush in the duodenum. Therefore, upper gastrointestinal endoscopy was immediately attempted to remove it, but it could not be safely removed because the handle part of the toothbrush seemed deeply embedded in the duodenal mucosa. Therefore, this case was diagnosed as duodenal incarceration of the toothbrush, and it was removed by laparoscopic surgery. The operation was performed safely, and the patient's postoperative course was good without any complications. The extracted toothbrush was 15 cm in length. CONCLUSION: We experienced a rare case of a duodenal foreign body, which was a toothbrush. The duodenal foreign body was safely removed by laparoscopic surgery for the first time.

A rare case of intracytoplasmic mucin-rich nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated tumor with a high incidence in Asian countries. NPC is a type of squamous cell carcinoma originating from the nasopharyngeal mucosa. Although rare, NPCs show some uncommon histologic variants; these variations remain to be understood. We described the cytologic characteristics of a rare NPC variant with abundant intracytoplasmic mucin. A 37-year-old Japanese man presented to our hospital with bilateral ear discomfort and palpable lymph nodes. Nasopharyngeal biopsy showed tumor cells with abundant intracytoplasmic, Alcian blue-PAS-positive mucin. Immunohistochemical analysis demonstrated that the tumor cells were positive for p40 and p53. Epstein-Barr encoding region (EBER) in situ hybridization (ISH) showed EBV infection of the tumor cells. Fluorescence in situ hybridization (FISH) using MAML2 break-apart probes did not show split signals. Fine needle aspiration biopsy (FNAB) cytology of the metastatic lymph nodes was also performed. Smear samples had a necrotic and inflammatory background with both lymphocyte and neutrophil infiltration. Highly cellular tumor clusters and dispersed cells with naked nuclei were observed. The tumor cells showed a clear cytoplasm with distinct cell borders. Intracytoplasmic mucin pushing the nucleus to the periphery was observed in the scattered tumor cells in a liquid-based cytology sample. Given these findings, the final diagnosis was advanced nasopharyngeal carcinoma; cisplatin-based chemoradiation therapy was performed as the first-line treatment. The tumor recurred 8 months after completing the treatment. The recurrent nasopharyngeal tumor was a typical non-keratinizing NPC and lacked intracytoplasmic mucin.