Okayama University Medical SchoolActa Medica Okayama0386-300X8042026Post-Tracheostomy Fistula Formation Between the Trachea and Left Common Carotid Artery in a Pediatric Patient with Trisomy 18247252ENTsuyoshiShiinaDepartment of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirokazuWatanabeDepartment of Pediatrics, Fukuyama City HospitalJunkoYoshimotoDepartment of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakeshiSatoDepartment of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDaisakuMorimotoDepartment of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomokaOkamuraDepartment of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTerutakaTanimotoDepartment of Pediatric Surgery, Okayama University HospitalYosukeWashioDepartment of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakanoriOyamaDepartment of Pediatric Surgery, Fukuyama City HospitalHirokazuTsukaharaDepartment of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakuoNodaDepartment of Pediatric Surgery, Japanese Red Cross Society Himeji HospitalCase Report10.18926/AMO/71068The long-term survival of individuals with trisomy 18 has improved, and the need for tracheostomy in this population has thus increased. We describe the case of a 3-year-old Japanese boy with trisomy 18 who developed a tracheoarterial fistula involving the left common carotid artery (LCCA). He underwent an emergency tracheostomy for respiratory failure secondary to pneumonia. Massive hemorrhage from the tracheostoma occurred on postoperative day 31, leading to his death. The autopsy revealed that the LCCA originated from the brachiocephalic trunk and coursed medially, forming a fistulous connection with the trachea. This case highlights the clinical importance of preoperative vascular mapping in patients with chromosomal abnormalities.No potential conflict of interest relevant to this article was reported.International Institute of Anticancer ResearchActa Medica Okayama0250-70054642026P53-armed Oncolytic Adenovirus Enhances the Efficacy of PD-1 Blockade in Neuroblastoma by Inducing Immunogenic Cell Death17691784ENMORIMICHITANIDepartment of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHIROSHITAZAWADepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTERUTAKATANIMOTODepartment of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHIROSHINOUSODepartment of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHINAKOWATANABEDepartment of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTAKANORIOYAMADepartment of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYASUOURATAOncolys BioPharma, Inc.SHUNSUKEKAGAWADepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTAKUONODADepartment of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSHINJIKURODADepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTOSHIYOSHIFUJIWARADepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground/Aim: Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system. Although immunotherapy with immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) has emerged as novel antitumor therapy, high-risk NB tumors are refractory to ICI therapy. Oncolytic virotherapy is expected to potentiate the antitumor immune response by inducing immunogenic cell death (ICD). In the present study, we assessed the therapeutic potential of OBP-301 and OBP-702, telomerase-specific oncolytic adenoviruses, for the induction of ICD and combined effect with PD-1 blockade against NB cells.<br>
Materials and Methods: The cytopathic activity of OBP-301 and OBP-702 was assessed using three human MYCN-amplified NB cell lines (IMR-32, LA-N-5, and NB-1) and a murine non-MYCN-amplified NB cell line (Neuro-2a). Virus-mediated antitumor effect was assessed by analyzing cell viability, secretion of extracellular adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1), apoptosis, autophagy, and PD-L1 levels. A subcutaneous Neuro-2a tumor model was used to evaluate the in vivo antitumor effect of combination therapy with OBP-702 and anti-PD-1 antibody.<br>
Results: OBP-702 exhibited stronger cytopathic activity, inducing ICD with secretion of ATP and HMGB1, compared to OBP-301 in human and murine NB cells. OBP-301 and OBP-702 increased apoptosis, autophagy, and PD-L1 expression in murine NB cells. Moreover, OBP-702 significantly prolonged the survival of tumor-bearing mice compared to monotherapy with PD-1 blockade.<br>
Conclusion: OBP-702 is a promising antitumor strategy to promote the antitumor effect of ICIs by inducing ICD against NB tumors.No potential conflict of interest relevant to this article was reported.International Institute of Anticancer ResearchActa Medica Okayama0250-70054612025Near-infrared Photoimmunotherapy Targeting High-risk Human Neuroblastoma Cells Expressing GD22538ENHIROSHINOUSODepartment of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHIROSHITAZAWADepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTERUTAKATANIMOTODepartment of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMORIMICHITANIDepartment of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHINAKOWATANABEDepartment of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTAKANORIOYAMADepartment of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKAZUHIRONOMADepartment of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSHUNSUKEKAGAWADepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHISATAKAKOBAYASHIMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthTAKUONODADepartment of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSHINJIKURODADepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTOSHIYOSHIFUJIWARADepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground/Aim: Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system in infancy. Despite advances in treatment, the prognosis remains poor for high-risk NB patients. Although immunotherapy using anti-GD2 antibodies is available for high-risk NB, the therapeutic efficacy is insufficient. Near-infrared photoimmunotherapy (NIR-PIT) is an antitumor strategy that induces tumor-specific cytotoxicity by combining an antibody-photoabsorber conjugate (APC) with NIR light irradiation. In this study, we investigated the therapeutic efficacy of GD2-targeted NIR-PIT against human NB cells.<br>
Materials and Methods: GD2 expression was analyzed on the surface of high-risk human NB cells (CHP-134, LA-N-5, IMR-32) and non-high-risk human NB cells (SK-N-SH) by flow cytometry. The APC was synthesized by incubating anti-GD2 antibody and IR700. The cytotoxic effect of GD2-targeted NIR-PIT was evaluated using the XTT assay. The distribution of dead cells within tumor spheres was evaluated using a live/dead assay. The in vivo antitumor effect of GD2-targeted NIR-PIT was assessed using a subcutaneous human NB xenograft tumor model.<br>
Results: GD2 protein was expressed on the surface of CHP-134, LA-N-5, and IMR-32 cells but not SK-N-SH cells. GD2-targeted NIR-PIT significantly suppressed the viability of GD2-positive NB cells but not GD2-negative NB cells, compared to the control and monotherapy groups. GD2-targeted NIR-PIT significantly reduced the volume of GD2-positive CHP-134 tumor spheres by inducing the accumulation of dead cells. Subcutaneous CHP-134 xenograft tumor models demonstrated that GD2-targeted NIR-PIT significantly inhibited tumor growth compared with the control and monotherapy groups.<br>
Conclusion: GD2-targeted NIR-PIT is a promising antitumor strategy for treating high-risk NB tumors expressing GD2.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama22135766772022A case of esophageal atresia complicated by a right-sided aortic arch with right ductus arteriosus and inferior vena cava interruption with hemiazygos continuation102167ENTerutakaTanimotoDepartment of Pediatric Surgery, Okayama University HospitalTakuoNodaDepartment of Pediatric Surgery, Okayama University HospitalHiroshiNousoDepartment of Pediatric Surgery, Okayama University HospitalYukinoriMiyataDepartment of Pediatric Surgery, Okayama University HospitalDuring the repair of esophageal atresia with tracheoesophageal fistula (EA/TEF), cardiovascular malformations occasionally create a technical challenge. We report a novel case of a 4-day-old girl with EA/TEF and multiple cardiovascular malformations, including right-sided aortic arch (RAA), right ductus arteriosus (RDA), single ventricle with single atrium, common atrioventricular valve, pulmonary atresia, bilateral superior vena cava, and interruption of the inferior vena cava (IVC) with hemiazygos continuation. In this case, a right-sided approach would require the mobilization of the RAA and RDA, which were supplying the pulmonary blood flow due to pulmonary atresia. Alternatively, the left-sided approach would require the mobilization of the hemiazygos vein, which was essential for venous return from the lower body due to IVC interruption. We performed the less intrusive left-sided approach, and the postoperative course was uneventful. Right-sided EA/TEF repair should be avoided because RDA spasm or injury caused by RAA mobilization would be fatal. In cases of interrupted IVC with azygos or hemiazygos vein continuation, care must be taken not to ligate these vessels or block the venous return. Preoperative evaluation is important to prevent complications in such complicated cases. If sufficient information is not available, the left-sided approach may be preferred.No potential conflict of interest relevant to this article was reported.SpringerActa Medica Okayama2198-7793812022A case of esophageal atresia with the bronchial-like lower esophagus which originates from the left lower lobe bronchus156ENTerutakaTanimotoDepartment of Pediatric Surgery, Okayama University HospitalTakuoNodaDepartment of Pediatric Surgery, Okayama University HospitalReisukeImajiDepartment of Pediatric Surgery, Hiroshima City Hiroshima Citizens HospitalHiroshiNousoDepartment of Pediatric Surgery, Okayama University HospitalBackground Esophageal atresia with or without a trachea-esophageal fistula occurs due to the failure of separation or incomplete development of the foregut. Therefore, esophageal atresia is often associated with various forms of tracheobronchial anomalies. We report an extremely rare case of esophageal atresia. Case presentation A female infant was born at 37 weeks of gestation and weighed 2596 g. A diagnosis of esophageal atresia and total anomalous pulmonary vein return type III were confirmed. The infant had respiratory distress that required tracheal intubation and ventilatory support soon after birth. Temporary banding of the gastroesophageal junction and gastrostomy were performed on the second day of life. However, her respiratory condition deteriorated due to atelectasis of the left lung and compensatory hyperinflation of the right lung. Preoperative examinations showed the unilobe and atelectatic left lung. The trachea was trifurcated in three directions, and the branch that was expected to be the left main bronchus was blind-ended. The dorsal branch was cartilaginous and bifurcated into the left lower lobe bronchus and lower esophagus approximately 1 cm distal from the tracheal trifurcation. The cartilaginous tissue continued to the lower esophagus. The diagnosis of esophageal atresia with the lower esophagus which originated from the left lower lobe bronchus was made. Esophageal atresia repair was performed when the patient was 4 months of age. The esophagus was dissected distally to the bifurcation of the left lower lobe bronchus via right thoracotomy. The lower esophagus was bronchial-like in appearance, transitioning to the normal esophageal wall approximately 7 mm distal to the transected edge. The cartilage tissue was completely resected during surgery, and a primary end-to-end anastomosis of the esophagus was successfully performed. Histopathological findings revealed that the extracted specimen was surrounded by tracheal cartilage and that the inner surface was covered by stratified squamous epithelium that originated from the esophagus. Conclusions In cases of esophageal atresia with an atypical clinical presentation, there may be unique structural abnormalities of the foregut. We emphasize the importance of a preoperative surgical planning since an inadequate operation can lead to fatal complications.No potential conflict of interest relevant to this article was reported.Lippincott, Williams & WilkinsActa Medica Okayama0025-797499382020Pediatric growing teratoma syndrome of the ovary A case report and review of the literaturee22297ENTakanoriOyamaDepartment of Pediatric Surgery,Okayama University HospitalTakuoNodaDepartment of Pediatric Surgery,Okayama University HospitalKanaWashioDepartment of Pediatrics, Okayama University HospitalAkiraShimadaDepartment of Pediatrics, Okayama University HospitalRationale: </br>
Growing teratoma syndrome is defined as an increase in tumor size during or after systemic chemotherapy for germ cell tumors. These cases involve normal tumor maker levels and histological features of only mature teratoma. We report a rare case of an ovarian immature teratoma in a Japanese child that was diagnosed as growing teratoma syndrome.</br>
Patient concerns: </br>
A 12-year-old girl presented a painful abdominal mass. She underwent left salpingo-oophorectomy for grade 1 immature teratoma in the left ovary. She did not undergo additional chemotherapy or radiotherapy. Four months later, she presented with grade 3 immature teratoma disseminated into the abdomen and pelvis. Chemotherapy resulted in the tumor maker levels returning to their normal ranges, although the tumors had grown slightly.</br>
Diagnosis: </br>
The specimens resected by laparotomy after the chemotherapy consisted of mature tissue predominantly, although primitive neuroepithelium was observed in a small part of the specimen. The pathological diagnosis was grade 1 immature teratoma, notwithstanding the clinical diagnosis was growing teratoma syndrome based on the clinical features and pathogenesis.</br>
Interventions: </br>
Laparotomy was performed at 7 months after the first operation, with resection of various tumors as well as the rectum, sigmoid colon, residual left fallopian duct, and a small part of the ileum and omentum. Some small tumors at the parietal peritoneum were ablated, although many tiny tumors around the uterus were left untreated.</br>
Outcomes: </br>
The patient has been free from recurrence for 5 years.</br>
Lessons: </br>
Growing teratoma syndrome can develop in children, and their tumor size is comparable to that in adolescents and adults. Furthermore, development of growing teratoma syndrome from a primary germ cell tumor is presumably faster in children than in adolescents and adults. Complete resection of all growing teratoma tissue is recommended, although fertility-sparing surgery should be considered when possible.No potential conflict of interest relevant to this article was reported.Cell PressActa Medica Okayama2372-7705182020Elimination of MYCN-Amplified Neuroblastoma Cells by Telomerase-Targeted Oncolytic Virus via MYCN Suppression1423ENTerutakaTanimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiTazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakeshiIedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiNousoDepartment of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMorimichiTaniDepartment of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakanoriOyamaDepartment of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuoUrataOncolys BioPharma, Inc.ShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuoNodaDepartment of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNeuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system. High-risk NB is characterized by MYCN amplification and human telomerase reverse transcriptase (hTERT) rearrangement, contributing to hTERT activation and a poor outcome. For targeting hTERT-activated tumors, we developed two oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in which the hTERT promoter drives expression of the viral E1 gene for tumor-specific virus replication. In this study, we demonstrate the therapeutic potential of the hTERT-driven oncolytic adenoviruses OBP-301 and OBP-702 using four human MYCN-amplified NB cell lines (IMR-32, CHP-134, NB-1, LA-N-5) exhibiting high hTERT expression. OBP-301 and OBP-702 exhibited a strong antitumor effect in association with autophagy in NB cells. Virus-mediated activation of E2F1 protein suppressed MYCN expression. OBP-301 and OBP-702 significantly suppressed the growth of subcutaneous CHP-134 tumors. Thus, these hTERT-driven oncolytic adenoviruses are promising antitumor agents for eliminating MYCN-amplified NB cells via E2F1-mediated suppression of MYCN protein.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812612014膵・胆管合流異常症―その概念と治療―1724ENTakuoNodaNo potential conflict of interest relevant to this article was reported.