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The lung is a complex organ comprising a branched airway that connects the large airway and millions of terminal gas-exchange units. Traditional pulmonary biomedical research by using cell line model system have limitations such as lack of cellular heterogeneity, animal models also have limitations including ethical concern, race-to-race variations, and physiological differences found in vivo. Organoids and on-a-chip models offer viable solutions for these issues.Organoids are three-dimensional, self-organized construct composed of numerous cells derived from stem cells cultured with growth factors required for the maintenance of stem cells. On-a-chip models are biomimetic microsystems which are able to customize to use microfluidic systems to simulate blood flow in blood channels or vacuum to simulate human breathing. This review summarizes the key components and previous biomedical studies conducted on lung organoids and lung-on-a-chip models, and introduces potential future applications. Considering the importance and benefits of these model systems, we believe that the system will offer better platform to biomedical researchers on pulmonary diseases, such as emerging viral infection, progressive fibrotic pulmonary diseases, or primary or metastatic lung cancer.
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We systematically reviewed the literature on the co-occurrence of squamous cell carcinoma (SCC) and Warthin’s tumor (WT), thought to be quite rare, to help reduce misdiagnosis and improve treatment planning. For this systematic review, we searched for articles in the Web of Science and PubMed databases, analyzed relevant studies for forward and backward citations, and identified only articles reporting on the “co-occurrence” of WT and SCC.Of the 237 studies identified, 12 comprising 18 patients met the inclusion criteria, to which we added one study from our institution. Most WTs were associated with SCC in the parotid gland or cervical lymph nodes. Most patients (89.5%) underwent selective or radical neck dissection due to identification of lesions separate from the primary SCC. Despite its frequent co-occurrence with other neoplasms, WT in the parotid or cervical lymph nodes tends to be misdiagnosed as a metastatic node when SCC is observed as the primary tumor. Factors to consider in diagnosis and neck management include identification of an association other than growth or development by lymphangiogenesis and whether the patient is a smoker, a strong risk factor.
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Nontuberculous mycobacteria (NTM) represent a broad spectrum of acid-fast bacilli, excluding the pathogens responsible for tuberculosis and leprosy. Over 200 species have been identified and classified as NTM, based on shared phenotypic characteristics. These bacteria are prevalent in diverse environments and are implicated in NTM pulmonary disease (NTM-PD), resulting from interactions between the host, the environment, and the microorganism.Current Concepts: Diagnosing NTM-PD necessitates a comprehensive approach. It is essential to identify the risk factors, including underlying lung conditions, compromised immune responses, and other host-specific factors. The clinical diagnosis considers pulmonary or systemic symptoms aligned with the disease and the exclusion of alternative pulmonary disorders. Radiological evaluations, such as chest X-rays and computed tomography scans reveal patterns indicative of the disease, including fibrocavitary and nodular bronchiectatic forms. Microbiological criteria are fundamental to the diagnostic process and require a minimum of two positive cultures from separate sputum samples or a single positive result from invasive techniques, such as bronchoscopy or biopsies.Discussion and Conclusion: As there are multiple phenotypes of NTM-PD, it is necessary to assess the likelihood of the disease in individuals with increased risk factors. A combination of the clinical, radiological, and microbiological criteria is essential for the accurate diagnosis of NTM-PD. Once diagnosed, a thorough assessment is necessary to guide appropriate management decisions.
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This article aims to summarize the available information and present treatment recommendations. The scope of this discussion is limited to physeal and metaphyseal fractures of the pediatric distal radius.Current Concepts: Pediatric distal radial fractures are common among children and adolescents. The mechanism of injury is usually a fall on an outstretched hand, and fractures typically occur during sports-related activities. Children with distal radial fractures initially present with pain, swelling, and distal forearm deformities. Plain radiographs are essential for evaluating the fracture type and degree of displacement. Complete wrist, forearm, and elbow views should also be assessed, especially for high-energy injuries, to identify ipsilateral fractures. Fractures typically involve the distal radial metaphysis or physis. Metaphyseal fractures are classified as torus, buckle, and bicortical fractures. Most displaced Salter-Harris types I and II and non-displaced metaphyseal fractures can be treated with closed reduction and casting. Operative treatment is recommended if irreducibility or soft-tissue neurovascular compromise is suspected. Operative options include closed reduction, percutaneous pinning, or open reduction, followed by pin or plate fixation. Malunion, nonunion, physeal arrest, ulnocarpal impaction, and nerve injury are possible complications of distal radial fractures in pediatric patients.Discussion and Conclusion: Metaphyseal and physeal fractures of the distal radius are common in children. Most cases are best treated with closed reduction and cast immobilization. Clinicians should be aware of delayed complications and understand how to manage them to ensure successful long-term outcomes.
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Preterm birth (PTB), a pregnancy-related disease, is defined as a birth before 37 weeks of gestation. It is a major cause of maternal mortality and morbidity worldwide, and its incidence rate is steadily increasing. Various genetic factors can contribute to the etiology of PTB. Vascular endothelial growth factor A (VEGFA) gene is an important angiogenic gene and its polymorphisms have been reported to be associated with PTB development. Therefore, we conducted a case-control study to evaluate the association between VEGFA rs699947, rs2010963, and rs3025039 polymorphisms and PTB in Korean women. A total of 271 subjects (116 patients with PTB and 155 women at ≥38 weeks of gestation) were analyzed in this study. The genotyping of VEGFA gene polymorphisms was performed using polymerase chain reaction– restriction fragment length polymorphism. No significant association between the patients with PTB and the control groups was confirmed. In the combination analysis, we found a significant association between PTB and VEGFA rs699947 CC-rs2010963 GG-rs3025039 CC combination (odds ratio, 3.77; 95% confidence interval, 1.091 to 13.032; p = 0.031). The VEGFA rs699947, rs2010963, and rs3025039 polymorphisms might have no genetic association with the pathogenesis of PTB in Korean women. However, the combination analysis indicates the possibility that VEGFA acts in PTB pathophysiology. Therefore, larger sample sets and replication studies are required to further elucidate our findings.
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Background@#Administration of adequate antibiotics is crucial for better outcomes in sepsis. Because no uniform tool can accurately assess the risk of multidrug-resistant (MDR) pathogens, a local antibiogram is necessary. We aimed to describe the antibiogram of MDR bacteria based on locations of sepsis onset in South Korea. @*Methods@#We performed a prospective observational study of adult patients diagnosed with sepsis according to Sepsis-3 from 19 institutions (13 tertiary referral and 6 universityaffiliated general hospitals) in South Korea. Patients were divided into four groups based on the respective location of sepsis onset: community, nursing home, long-term-care hospital, and hospital. Along with the antibiogram, risk factors of MDR bacteria and drug-bug match of empirical antibiotics were analyzed. @*Results@#MDR bacteria were detected in 1,596 (22.7%) of 7,024 patients with gram-negative predominance. MDR gram-negative bacteria were more commonly detected in long-termcare hospital- (30.4%) and nursing home-acquired (26.3%) sepsis, whereas MDR grampositive bacteria were more prevalent in hospital-acquired (10.9%) sepsis. Such findings were consistent regardless of the location and tier of hospitals throughout South Korea. Patients with long-term-care hospital-acquired sepsis had the highest risk of MDR pathogen, which was even higher than those with hospital-acquired sepsis (adjusted odds ratio, 1.42; 95% confidence interval, 1.15–1.75) after adjustment of risk factors. The drug-bug match was lowest in patients with long-term-care hospital-acquired sepsis (66.8%). @*Conclusion@#Gram-negative MDR bacteria were more common in nursing home- and long-term-care hospital-acquired sepsis, whereas gram-positive MDR bacteria were more common in hospital-acquired settings in South Korea. Patients with long-term-care hospitalacquired sepsis had the highest the risk of MDR bacteria but lowest drug-bug match of initial antibiotics. We suggest that initial antibiotics be carefully selected according to the onset location in each patient.
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Recently, the efficacy of immuno-oncologic agents for advanced hepatocellular carcinoma (HCC) has been proven in several trials. In particular, atezolizumab with bevacizumab (AteBeva), as a first-line therapy for advanced HCC, has shown tremendous advances in the IMBrave150 study. However, second or third-line therapy after treatment failure with AteBeva has not been firmly established. Moreover, clinicians have continued their attempts at multidisciplinary treatment that includes other systemic therapy and radiotherapy (RT). Here, we report a case that showed a near complete response (CR) of lung metastasis to nivolumab with ipilimumab therapy after achieving a near CR of intrahepatic tumor using sorafenib and RT in a patient with advanced HCC who had experienced treatment failure of AteBeva.
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The use of digital technology in fixed prosthetic treatment using implants enables predictive treatment through diagnosis and virtual surgery by integrating clinical and radiological information of patients. Existing digital scanning methods require several components to be removed, such as removing the healing abutment and connecting the scan body. In the scannable healing abutment developed in consideration of this point, scanning is performed directly on the healing abutment, maintaining soft tissue sealing and simplifying scanning. Digital technology can also be used when obtaining the intermaxillary relationship. Recently, various digital technologies have been reported to acquire the intermaxillary relationship of edentulous patients using surgical guides, patient-specific scanning devices, or scans of the inside of temporary dentures. In this case, the implant-supported fixed prosthesis treatment was performed through scanning the scannable healing abutment and the inner side of the temporary denture to obtain the intermaxillary relationship, thereby simplifying the treatment process and obtaining aesthetically and functionally excellent clinical results.
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In order to fabricate stable dentures in patients with severe resorption of residual ridges, various factors must be considered. One of them is the neutral zone, which is defined as the potential region in which the pressure of the tongue outward in the oral cavity and the pressure of the cheeks and lips directed inward from the outside of the oral cavity equalize during functioning. In patients with severe ridge resorption, if the teeth are usually arranged above the residual ridge, the teeth are located on the lingual side rather than the original position. Therefore, the functional space of the tongue is invaded, the tongue is positioned backward, and the sealing of the lingual border is broken, which acts as a factor reducing the maintenance of denture. In addition, it is also important for the stability of dentures to assume an interalveolar crest line connecting the maxillary and mandibular ridge crests, and to arrange the maxillary and mandibular artificial teeth to match the masticatory force to the interalveolar crest line. Therefore, good clinical results were obtained by fabricating dentures for the patient with poor alveolar residual ridge using neutral zone impression and ridge relationship analysis.
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A new bicyclic megastigmane derivative, (3S,6S)-amoreol (1), was isolated and determined along with twenty known compounds, dihydrosinapic acid (2), 2,6-dimethoxyterephthalic acid (3), 4-methoxybenzoic acid (4), 4-ethylbenzene-1,2-diol (5), ethylparaben (6), vanillic acid (7), ferulic acid (8), 3-(4-hydroxy-3-methoxyphenyl)propionic acid (9), ethyl dihydroferulate (10), dihydroconiferyl alcohol (11), 1,2-dihydrodendroarboreol B (12), 1,2-dihydropanaxydiol (13), panaxydiol (14), panaxytriol (15), (S)-cis-abscisic acid (16), (R)-trans-abscisic acid (17), (6R,9S)-blumenol C (18), (3S,5R,6S,7E)-5,6-epoxy-3-hydroxy-7-megastigmene-9-one (19), (+)-salicifoliol (20), imperatorin (21), indole-3-carboxaldehyde (22) from the by-product of ginseng berry extract. The structures of the isolated compounds were determined through spectroscopic techniques including UV, 1D-, and 2D NMR, CD, MS and optical rotation. The absolute configuration of 1 was elucidated based on the experimental and calculated electronic circular dichroism (ECD) spectra.
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Background@#and Purpose Migraine is reportedly associated with several cardio-cerebrovascular diseases (CCDs), but some of these diseases have not received sufficient attention. We thus attempted to determine the associations of migraine with peripheral arterial disease (PAD), ischemic heart disease (IHD), atrial fibrillation/flutter (AF), ischemic stroke (IS), and hemorrhagic stroke (HS). @*Methods@#The study population was recruited by applying International Classification of Diseases, Tenth Revision (ICD-10) codes to the database of the Korean National Health Insurance Service from 2002 to 2018. Cumulative incidence curves were plotted to compare the incidence rates of CCDs between the migraine (ICD-10 code G43; n=130,050) and nonmigraine (n=130,050) groups determined using 1:1 propensity-score matching. Cox proportional-hazards regression models were used to obtain adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CCDs in patients with any migraine, migraine with aura (n=99,751), and migraine without aura (n=19,562) compared with nonmigraine controls. @*Results@#For all CCDs, the cumulative incidence rates were higher in the migraine group than the nonmigraine group (p<0.001 in log-rank test). Any migraine, irrespective of the presence of aura, was associated with PAD (aHR 2.29, 95% CI 2.06–2.53), IHD (aHR 2.17, 95% CI 2.12– 2.23), AF (aHR 1.84, 95% CI 1.70–1.99), IS (aHR 2.91, 95% CI 2.67–3.16), and HS (aHR 2.46, 95% CI 2.23–2.71). aHR was higher in female than in male migraineurs for all of the CCDs. @*Conclusions@#Associations of migraine with CCDs have been demonstrated, which are stronger in females than in males.
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This study aimed to investigate the association between Bacille Calmette-Guérin (BCG) vaccination and nontuberculous mycobacterial pulmonary disease (NTM-PD). Patients in the prospective NTM-PD cohort were matched to healthy controls to measure the association between BCG and NTM-PD development. The clinical course of NTM-PD patients was also evaluated to investigate the association between BCG and NTM-PD progression. BCG scars were not associated with NTM-PD development (adjusted odds ratio [OR], 2.04; 95% confidence interval [CI], 0.96–4.34) or progression (adjusted OR, 1.61; 95% CI, 0.92–2.81).In conclusion, BCG vaccination was not associated with the development or progression of NTM-PD.
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Background/Aims@#Acute eosinophilic pneumonia (AEP) is common among military smokers; however, bronchoscopy is required for the diagnosis. We aimed to derive and validate a scoring system to diagnose AEP without bronchoscopy. @*Methods@#We conducted a retrospective study including patients diagnosed with AEP or any other pneumonia among military smokers hospitalized in the Armed Forces Capital Hospital from 15 November 2016 through 25 December 2019. The patients were divided into derivation and validation groups according to their admission day. Patient symptoms, laboratory findings, and computed tomography findings were candidate variables. Least absolute shrinkage and selection operator (LASSO) regression was used to calculate the scores for each variable. @*Results@#Among 414 patients, AEP was confirmed in 54 of 279 patients (19.4%) in the derivation group and in 18 of 135 patients (13.3%) in the validation group. Ten variables were selected using LASSO regression: new-onset or a recently increased smoking (≤ 4 weeks) (8 points), interlobular septal thickening (5 points), absence of sputum (3 points), ground glass opacity (3 points), acute onset (≤ 3 days) (2 points), dyspnea (2 points), chest pain (2 points), leukocytosis (2 points), bronchovascular bundle thickening (2 points), and bilateral involvement (2 points). The area under the receiver-operating characteristic curve of the score to diagnose AEP was 0.997 (95% confidence interval, 0.992 to 1.000) in the derivation group and 0.985 (95% confidence interval, 0.965 to 1.000) in the validation group. @*Conclusions@#We introduce a scoring system that can distinguish AEP from other types of pneumonia in military smokers without the need for bronchoscopy.
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Purpose@#We previously developed learning models for predicting the need for intensive care and oxygen among patients with coronavirus disease (COVID-19). Here, we aimed to prospectively validate the accuracy of these models. @*Materials and Methods@#Probabilities of the need for intensive care [intensive care unit (ICU) score] and oxygen (oxygen score) were calculated from information provided by hospitalized COVID-19 patients (n=44) via a web-based application. The performance of baseline scores to predict 30-day outcomes was assessed. @*Results@#Among 44 patients, 5 and 15 patients needed intensive care and oxygen, respectively. The area under the curve of ICU score and oxygen score to predict 30-day outcomes were 0.774 [95% confidence interval (CI): 0.614–0.934] and 0.728 (95% CI:0.559–0.898), respectively. The ICU scores of patients needing intensive care increased daily by 0.71 points (95% CI: 0.20–1.22) after hospitalization and by 0.85 points (95% CI: 0.36–1.35) after symptom onset, which were significantly different from those in individuals not needing intensive care (p=0.002 and <0.001, respectively). Trends in daily oxygen scores overall were not markedly different; however, when the scores were evaluated within <7 days after symptom onset, the patients needing oxygen showed a higher daily increase in oxygen scores [1.81 (95% CI: 0.48–3.14) vs. -0.28 (95% CI: 1.00–0.43), p=0.007]. @*Conclusion@#Our machine learning models showed good performance for predicting the outcomes of COVID-19 patients and could thus be useful for patient triage and monitoring.
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Background@#and Purpose Previous studies have assessed the relationship between cerebral vessel tortuosity and intracranial aneurysm (IA) based on two-dimensional brain image analysis. We evaluated the relationship between cerebral vessel tortuosity and IA according to the hemodynamic location using three-dimensional (3D) analysis and studied the effect of tortuosity on the recurrence of treated IA. @*Methods@#We collected clinical and imaging data from patients with IA and disease-free controls. IAs were categorized into outer curvature and bifurcation types. Computerized analysis of the images provided information on the length of the arterial segment and tortuosity of the cerebral arteries in 3D space. @*Results@#Data from 95 patients with IA and 95 controls were analyzed. Regarding parent vessel tortuosity index (TI; P<0.01), average TI (P<0.01), basilar artery (BA; P=0.02), left posterior cerebral artery (P=0.03), both vertebral arteries (VAs; P<0.01), and right internal carotid artery (P<0.01), there was a significant difference only in the outer curvature type compared with the control group. The outer curvature type was analyzed, and the occurrence of an IA was associated with increased TI of the parent vessel, average, BA, right middle cerebral artery, and both VAs in the logistic regression analysis. However, in all aneurysm cases, recanalization of the treated aneurysm was inversely associated with increased TI of the parent vessels. @*Conclusions@#TIs of intracranial arteries are associated with the occurrence of IA, especially in the outer curvature type. IAs with a high TI in the parent vessel showed good outcomes with endovascular treatment.
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Objectives@#We aimed to collect and report data from all patients who have been diagnosed with mucosal malignant melanoma to obtain the epidemiology and principles of current treatments. @*Materials and Methods@#Between January 2008 and December 2018, 20 patients underwent surgery or follow-up observations at Yonsei University Dental Hospital. The patients’ clinical information was reviewed retrospectively. @*Results@#Seventeen of 20 patients had undergone definitive surgery, while only 6 patients received adjuvant radiotherapy or systemic therapy. Eight of 20 patients, including those that had recurrent lesions, were provided immunotherapy. The 3-year survival for all stages was 50%, with a local recurrence rate of 75% and a metastasis rate of 65%. @*Conclusion@#The overall survival of patients receiving surgical treatment was longer than that of patients who did not undergo surgical resection.Eight of 20 patients received immunotherapy as the first-line regimen at our clinic, and those patients exhibited longer overall survival compared to patients in reported keynote studies.
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Carbon-ion radiotherapy (CIRT) is on the rise as a treatment choice for malignant tumor. Compared to conventional radiotherapy, particle beams have different physical and biological properties. Particle beam provides a low entry dose, deposits most of the energy at the endpoint of the flight path, and forms an asymptotic dose peak (the “Bragg peak”). Compared to protons, carbon with its larger mass decreases beam scattering, resulting in a sharper dose distribution border. We report a 50-year-old male who underwent CIRT without surgical resection on osteosarcoma of the mandible. After CIRT, the patient’s pain was gone, and the malignant mass remained stable with accompanying necrosis. Nine months later, however, magnetic resonance imaging demonstrated progression of the left mandibular osteosarcoma with pulmonary metastases. After multidisciplinary discussion, concurrent chemoradiotherapy was conducted. While necrotic bone segments came out of the mandible during subsequent periodic outpatient visits, the tumor itself was stable. Thirty months after his first visit and diagnosis, the patient is waiting for chemotherapy. Although CIRT is superior in treating radioresistant hypoxic disease, CIRT is in its infancy, so care must be taken for its indications and complications.
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Background@#and Purpose Previous studies have assessed the relationship between cerebral vessel tortuosity and intracranial aneurysm (IA) based on two-dimensional brain image analysis. We evaluated the relationship between cerebral vessel tortuosity and IA according to the hemodynamic location using three-dimensional (3D) analysis and studied the effect of tortuosity on the recurrence of treated IA. @*Methods@#We collected clinical and imaging data from patients with IA and disease-free controls. IAs were categorized into outer curvature and bifurcation types. Computerized analysis of the images provided information on the length of the arterial segment and tortuosity of the cerebral arteries in 3D space. @*Results@#Data from 95 patients with IA and 95 controls were analyzed. Regarding parent vessel tortuosity index (TI; P<0.01), average TI (P<0.01), basilar artery (BA; P=0.02), left posterior cerebral artery (P=0.03), both vertebral arteries (VAs; P<0.01), and right internal carotid artery (P<0.01), there was a significant difference only in the outer curvature type compared with the control group. The outer curvature type was analyzed, and the occurrence of an IA was associated with increased TI of the parent vessel, average, BA, right middle cerebral artery, and both VAs in the logistic regression analysis. However, in all aneurysm cases, recanalization of the treated aneurysm was inversely associated with increased TI of the parent vessels. @*Conclusions@#TIs of intracranial arteries are associated with the occurrence of IA, especially in the outer curvature type. IAs with a high TI in the parent vessel showed good outcomes with endovascular treatment.
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Objectives@#We aimed to collect and report data from all patients who have been diagnosed with mucosal malignant melanoma to obtain the epidemiology and principles of current treatments. @*Materials and Methods@#Between January 2008 and December 2018, 20 patients underwent surgery or follow-up observations at Yonsei University Dental Hospital. The patients’ clinical information was reviewed retrospectively. @*Results@#Seventeen of 20 patients had undergone definitive surgery, while only 6 patients received adjuvant radiotherapy or systemic therapy. Eight of 20 patients, including those that had recurrent lesions, were provided immunotherapy. The 3-year survival for all stages was 50%, with a local recurrence rate of 75% and a metastasis rate of 65%. @*Conclusion@#The overall survival of patients receiving surgical treatment was longer than that of patients who did not undergo surgical resection.Eight of 20 patients received immunotherapy as the first-line regimen at our clinic, and those patients exhibited longer overall survival compared to patients in reported keynote studies.
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Carbon-ion radiotherapy (CIRT) is on the rise as a treatment choice for malignant tumor. Compared to conventional radiotherapy, particle beams have different physical and biological properties. Particle beam provides a low entry dose, deposits most of the energy at the endpoint of the flight path, and forms an asymptotic dose peak (the “Bragg peak”). Compared to protons, carbon with its larger mass decreases beam scattering, resulting in a sharper dose distribution border. We report a 50-year-old male who underwent CIRT without surgical resection on osteosarcoma of the mandible. After CIRT, the patient’s pain was gone, and the malignant mass remained stable with accompanying necrosis. Nine months later, however, magnetic resonance imaging demonstrated progression of the left mandibular osteosarcoma with pulmonary metastases. After multidisciplinary discussion, concurrent chemoradiotherapy was conducted. While necrotic bone segments came out of the mandible during subsequent periodic outpatient visits, the tumor itself was stable. Thirty months after his first visit and diagnosis, the patient is waiting for chemotherapy. Although CIRT is superior in treating radioresistant hypoxic disease, CIRT is in its infancy, so care must be taken for its indications and complications.