RESUMEN
PURPOSE: Surgical procedures for anorectoplasty for anorectal malformations (ARMs), particularly rectourethral fistula (RUF), depend on the institution. We investigated the diagnosis and treatment of RUF in male patients with ARMs in Japan using a questionnaire survey. METHODS: An online survey inquiring about the diagnosis and treatment (diagnostic modalities, surgical approaches, fistula dissection devices, and fistula closure techniques) of each type of ARM in male patients was conducted among institutional members of the Japanese Study Group of Anorectal Anomalies. Fisher's exact test was used to compare surgical methods between posterior sagittal anorectoplasty (PSARP) and laparoscopy-assisted anorectoplasty (LAARP). RESULTS: Sixty-one institutions (100%) completed the survey. LAARP was the preferred approach for high-type ARM (75.4%). PSARP was preferred for intermediate-type ARM (59.0%). Monopolar devices were most commonly used (72.1%) for RUF dissection. Blunt dissection was more frequent in the PSARP group (PSARP vs. LAARP: 55.6 vs. 20.0%, p < 0.005). Cystoscopy/urethroscopy to confirm the extent of dissection was used more frequently in the LAARP group (70.0% vs. 25.0%, p < 0.005). Clips and staplers were used more frequently in the LAARP group (p < 0.05). CONCLUSION: Distinct fistula management strategies for PSARP and LAARP were revealed. Further studies are needed to investigate the postoperative outcomes associated with these practices.
Asunto(s)
Malformaciones Anorrectales , Fístula Rectal , Enfermedades Uretrales , Fístula Urinaria , Humanos , Masculino , Fístula Rectal/cirugía , Fístula Rectal/diagnóstico , Japón , Malformaciones Anorrectales/cirugía , Fístula Urinaria/cirugía , Fístula Urinaria/diagnóstico , Encuestas y Cuestionarios , Enfermedades Uretrales/cirugía , Enfermedades Uretrales/diagnóstico , Ano Imperforado/cirugía , Ano Imperforado/diagnóstico , Laparoscopía/métodosRESUMEN
PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic limited the delivery of medical resources. Although surgeries are triaged according to disease severity and urgency, a delay in diagnosis and surgery can be detrimental. We conducted this study to analyze data on the impact of the COVID-19 pandemic on pediatric surgery for different diseases or disorders. METHODS: We compiled and compared data on pediatric surgical cases from 2018 to 2020, using the National Clinical Database. The number of diseases, severity, complication rates, mortality rates by disease/disorder, and the COVID-19 pandemic areas were analyzed. RESULTS: The total number of cases of pediatric surgery in 2018, 2019, and 2020 was 50,026, 49,794, and 45,621, respectively, reflecting an 8.8% decrease in 2020 from 2018 and an 8.4% decrease in 2020 from 2019. A decrease was observed when the number of patients with COVID-19 was high and was greater in areas with a low infection rate. There was a marked decrease in the number of inguinal hernia cases. The number of emergency room visits and emergency surgeries decreased, but their relative proportions increased. CONCLUSIONS: The COVID-19 pandemic decreased the number of pediatric surgeries, reflecting the limitations of scheduled surgeries and infection control measures.
Asunto(s)
COVID-19 , Bases de Datos Factuales , Procedimientos Quirúrgicos Operativos , Humanos , COVID-19/epidemiología , Niño , Procedimientos Quirúrgicos Operativos/estadística & datos numéricos , Pandemias , Índice de Severidad de la Enfermedad , Pediatría , Preescolar , Servicio de Urgencia en Hospital/estadística & datos numéricos , Adolescente , LactanteRESUMEN
BACKGROUND: We performed the first autologous oral mucosa-derived epithelial cell sheet transplantation therapy in a patient with refractory postoperative anastomotic stricture in congenital esophageal atresia (CEA) and confirmed its safety. In this study, patients with CEA and congenital esophageal stenosis were newly added as subjects to further evaluate the safety and efficacy of cell sheet transplantation therapy. METHODS: Epithelial cell sheets were prepared from the oral mucosa of the subjects and transplanted into esophageal tears created by endoscopic balloon dilatation (EBD). The safety of the cell sheets was confirmed by quality control testing, and the safety of the transplantation treatment was confirmed by 48-week follow-up examinations. RESULTS: Subject 1 had a stenosis resected because the frequency of EBD did not decrease after the second transplantation. Histopathological examination of the resected stenosis revealed marked thickening of the submucosal layer. Subjects 2 and 3 did not require EBD for 48 weeks after transplantation, during which time they were able to maintain a normal diet by mouth. CONCLUSIONS: Subjects 2 and 3 were free of EBD for a long period of time after transplantation, confirming that cell sheet transplantation therapy is clearly effective in some cases. In the future, it is necessary to study more cases; develop new technologies such as an objective index to evaluate the efficacy of cell sheet transplantation therapy and a device to achieve more accurate transplantation; identify cases in which the current therapy is effective; and find the optimal timing of transplantation; and clarify the mechanism by which the current therapy improves stenosis. TRIAL REGISTRATION: UMIN, UMIN000034566, registered 19 October 2018, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039393 .
Asunto(s)
Atresia Esofágica , Neoplasias Esofágicas , Estenosis Esofágica , Humanos , Estenosis Esofágica/etiología , Estenosis Esofágica/cirugía , Atresia Esofágica/cirugía , Atresia Esofágica/complicaciones , Constricción Patológica/complicaciones , Mucosa Bucal/trasplante , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Resultado del Tratamiento , Células Epiteliales/trasplante , Estudios RetrospectivosRESUMEN
BACKGROUND: Congenital esophageal atresia postoperative anastomotic stricture occurs in 30-50% of cases. Patients with severe dysphagia are treated with endoscopic balloon dilatation (EBD) and/or local injection of steroids, but many patients continue to experience frequent stricture. In this study, we investigated the transplantation of autologous oral mucosa-derived cell sheets (epithelial cell sheets) as a prophylactic treatment for congenital esophageal atresia postoperative anastomotic stricture. METHODS: Epithelial cell sheets were fabricated from a patient's oral epithelial tissue, and their safety was confirmed by quality control tests. The epithelial cell sheets were transported under controlled conditions from the fabrication facility to the transplantation facility and successfully transplanted onto the lacerations caused by EBD using a newly developed transplantation device for pediatric patients. The safety of the transplantation was confirmed by follow-up examinations over 48 weeks. RESULTS: The dates that EBD was performed were recorded for one year before and after epithelial cell sheet transplantation, and the intervals (in days) were evaluated. For about 6 months after transplantation, the intervals between EBDs were longer than in the year before transplantation. The patients were also aware of a reduction in dysphagia after transplantation. CONCLUSIONS: These results suggest that cell sheet transplantation may be effective in preventing anastomotic stricture after surgery for congenital esophageal atresia, but the effect was temporary and limited in this case. Although we chose a very severe case for the first human clinical study, it may be possible to obtain a more definitive effect if the transplantation is performed before the disease becomes so severe. Future studies are needed to identify cases in which cell sheet transplantation is most effective and to determine the appropriate timeframes for transplantation. TRIAL REGISTRATION: UMIN, UMIN000034566, registered 19 October 2018, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039393 .
Asunto(s)
Atresia Esofágica , Estenosis Esofágica , Niño , Constricción Patológica/complicaciones , Constricción Patológica/terapia , Atresia Esofágica/complicaciones , Atresia Esofágica/cirugía , Estenosis Esofágica/prevención & control , Estenosis Esofágica/cirugía , Humanos , Mucosa Bucal/trasplante , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Hemorrhoids are an extremely rare condition in children, and data on its incidence and treatment in the pediatric population remains scarce. We retrospectively reviewed children who underwent sclerotherapy for internal hemorrhoids, and analyzed patients' characteristics and outcomes. METHODS: A total of 14 pediatric patients who underwent sclerotherapy were included. Patients' ages and the required amount of polidocanol, depending on the grade of hemorrhoids, and the correlation between age and volume of sclerosant, were statistically analyzed. RESULTS: Patients had a male predominance with a ratio of 2.5:1 (grade 2:6 patients, grade 3:8 patients). Four children had underlying conditions including portal hypertension and Klippel-Trenaunay syndrome. Of the 14 patients, 43% had constipation requiring medication or enema. Only one minor complication, a perianal ulceration, was found to be associated with sclerotherapy. Patients with grade 3 hemorrhoids required a significantly larger amount of polidocanol than those with grade 2 hemorrhoids. Two patients with grade 3 hemorrhoids required a second session of treatment for recurrence. The success rate of sclerotherapy with polidocanol was 86%. CONCLUSIONS: Sclerotherapy with polidocanol is a safe, effective, and less invasive treatment option for internal hemorrhoids in children. Further studies are needed to investigate this treatment approach.
Asunto(s)
Hemorroides , Escleroterapia , Niño , Hemorroides/tratamiento farmacológico , Humanos , Masculino , Polidocanol , Polietilenglicoles/efectos adversos , Estudios Retrospectivos , Soluciones Esclerosantes/uso terapéutico , Escleroterapia/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Postoperative recurrence of tracheoesophageal fistula (TEF) is a frequent complication in the repair of esophageal atresia (EA). Based on the recent etiologic classification, a TEF that develops in a different new pathway from the original one is categorized as an acquired TEF. The TEFs that fall into this category have been reported to be refractory and their mechanisms have not been fully understood. Here, we report the complicated case of an acquired TEF derived from mediastinitis after the original TEF repair developed an anastomotic stricture. The TEF contained double fistulas, both towards the right lobe bronchi, and was repaired by gastric transposition through a retrosternal route. CASE PRESENTATION: The patient was diagnosed with Gross C esophageal atresia after birth and underwent tracheoesophageal fistula banding during the neonatal period. He experienced an intractable anastomotic stenosis after surgery which was treated with repeated balloon dilation therapy. By the age of 11 months, he developed a mediastinal abscess that improved with conservative treatment. At 18 months old, a fistula from the esophagus to the right superior lobe bronchus was identified. The patient underwent a right upper lobectomy to resect the fistula. However, at 21 months old, another fistula to the right lower lobe was revealed. An esophageal banding was done to relieve the respiratory symptoms. This was followed by esophagectomy and gastric transposition through the retrosternal route at 26 months old. The patient started rehabilitation and oral intake gradually after surgery. By 3 years after gastric transposition, he could already take blended food orally with the support of small amounts of enteral feeding. CONCLUSION: Cases of TEF derived from severe inflammation have the potential to form a complicated network and lead to recurrence. Surgeons should consider the possibility of multiple tiny fistulas in cases of severe acquired TEF. These may be repaired successfully by gastric transposition through the retrosternal route.
RESUMEN
INTRODUCTION: Decellularized tissue exhibits cell matrix-like properties, along with reduced antigenicity. We explored the potential of decellularized allogeneic trachea to restore the upper respiratory tract, focusing on pediatric application. This study specifically aimed at long-term observation of tissue regeneration using a micro-miniature pig model. METHODS: Artificial defects (15 × 15 mm) in the subglottis and trachea of micro-miniature pigs were repaired by transplantation of either allogeneic decellularized or fresh (control) tracheal patches. Pigs were evaluated in situ, by bronchoscopy, every three months, and sacrificed for histological examination at six and twelve months after transplantation. RESULTS: No airway symptom was observed in any pig during the observation period. Bronchoscopy revealed the tracheal lumen to be restored by fresh grafts, showing an irregular surface with remarkable longitudinal compression; these changes were mild after restoration with decellularized grafts. Histologically, while fresh graft patches were denatured and replaced by calcified tissue, decellularized patches remained unchanged throughout the observation period. There were regeneration foci of cartilage adjacent to the grafts, and some foci joined the decellularized graft uniformly, suggesting the induction of tracheal reconstitution. CONCLUSION: Allogeneic decellularized tracheal tissue could serve as a promising biomaterial for tracheal restoration, especially for pediatric patients at the growing stage.
RESUMEN
Fluorescence-guided surgery with indocyanine green (ICG) for malignant hepatic tumors has been gaining more attention with technical advancements. Since hepatoblastomas (HBs) possess similar features to hepatocellular carcinoma, fluorescence-guided surgery can be used for HBs, as aggressive surgical resection, even for distant metastases of HBs, often contributes positively to R0 (complete) resection and subsequent patient survival. Despite a few caveats, fluorescence-guided surgery allows for the more sensitive identification of lesions that may go undetected by conventional imaging or be invisible macroscopically. This leads to precise resection of distant metastatic tumors as well as primary liver tumors.
RESUMEN
The curability of chemotherapy-resistant hepatoblastoma (HB) largely depends on the achievement of radical surgical resection. Navigation techniques utilizing indocyanine green (ICG) are a powerful tool for detecting small metastatic lesions. We herein report a patient who underwent a second living donor liver transplantation (LDLTx) for multiple recurrent HBs in the liver graft following metastasectomy for peritoneal dissemination with ICG navigation. The patient initially presented with ruptured HB at 6 years of age and underwent 3 liver resections followed by the first LDLTx with multiple sessions of chemotherapy at 11 years of age. His alpha-fetoprotein (AFP) level increased above the normal limit, and metastases were noted in the transplanted liver and peritoneum four years after the first LDLTx. The patient underwent metastasectomy of the peritoneally disseminated HBs with ICG navigation followed by the second LDLTx for multiple metastases in the transplanted liver. The patient has been recurrence-free with a normal AFP for 30 months since the second LDLTx. To our knowledge, this report is the first successful case of re-LDLTx for recurrent HBs. Re-LDLTx for recurrent HB can be performed in highly select patients, and ICG navigation is a powerful surgical tool for achieving tumor clearance.
RESUMEN
BACKGROUND/PURPOSE: Differences in clinical features between congenital pulmonary airway malformation (CPAM) and bronchial atresia (BA) have not yet been clearly described. METHODS: We retrospectively reviewed 112 patients with a pathological diagnosis of CPAM or BA. The clinical parameters were statistically analyzed between these diseases. RESULTS: Seventy-one patients received prenatal diagnosis and 41 received postnatal diagnosis. The percentage of prenatal diagnosis was significantly higher in CPAM patients (84% vs 50%, pâ¯<â¯0.001). Among patients with prenatal diagnosis, the backgrounds were not different between the two diseases except for the number of Caesarean sections (81% vs 9%, pâ¯<â¯0.0001). The numbers of patients that underwent fetal interventions and emergent neonatal surgery were higher in CPAM (51% vs 15%, pâ¯<â¯0.01 and 76% vs 12%, pâ¯<â¯0.0001), although there was no statistical difference in survival rate (86% vs 97%, pâ¯=â¯0.2). In patients receiving postnatal diagnosis, pneumonia was the primary symptom in most BA patients, whereas respiratory distress was the major symptom in patients with CPAM. Age at presentation of the primary symptom was significantly older in BA patients (4.2â¯years vs 1.2â¯years, pâ¯<â¯0.005). CONCLUSION: CPAM and BA have distinct clinical features in terms of therapeutic and natural history. Careful imaging evaluation and pathological analysis can lead to an accurate diagnosis of BA. TYPE OF STUDY: Prognostic study. LEVEL OF EVIDENCE: Level II. This study is categorized as a "Prognostic Study" with LEVEL III of Evidence.
Asunto(s)
Enfermedades Bronquiales/diagnóstico , Malformación Adenomatoide Quística Congénita del Pulmón/diagnóstico , Enfermedades Bronquiales/congénito , Enfermedades Bronquiales/terapia , Malformación Adenomatoide Quística Congénita del Pulmón/terapia , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Diagnóstico Prenatal/estadística & datos numéricos , Pronóstico , Estudios RetrospectivosRESUMEN
PURPOSE: The purpose of this study was to clarify the relationship between congenital pulmonary airway malformation volume ratio (CVR) of bronchial atresia (BA), CVR of congenital cystic adenomatoid malformations (CCAM), and time of surgery after birth. METHOD: We retrospectively analyzed data of 36 BA and CCAM cases, prenatally diagnosed as CPAM from 2009 through 2014. RESULTS: Within 2â¯h after birth, 12 neonatal patients underwent emergent (EMG) lobectomy. Five cases of lobectomy were performed urgently (UG) from 12 to 48â¯h after birth. Four cases of lobectomy were required within 30â¯days after birth (earlyâ¯=â¯EAG). We performed lobectomy in 15 other patients at 11â¯months after birth (lateâ¯=â¯LG). Of the EMG cases, 11 were macrotype CCAM (maximal CVR >2.0), and 4 of 5 UG cases were microtype CCAM (CVR >2.0). Of the EAG cases, 3 of 4 were macrotype CCAM with CVR of <1.5. Of 15 LG, 13 were BA and showed a CVR of 0.13-3.0 (median, 0.78). The CVR of the cases operated on within 48â¯h after birth was significantly larger than that of the cases operated on after 2â¯weeks (pâ¯=â¯0.001). CONCLUSION: EMG or UG lobectomy was usually required after birth in CCAM, indicating maximal CVR >2.0. By contrast, elective surgery was performed in most BA cases. LEVEL OF EVIDENCE: IV.
Asunto(s)
Enfermedades Bronquiales/cirugía , Malformación Adenomatoide Quística Congénita del Pulmón/cirugía , Neumonectomía/métodos , Medición de Riesgo/métodos , Enfermedades Bronquiales/congénito , Enfermedades Bronquiales/diagnóstico , Malformación Adenomatoide Quística Congénita del Pulmón/diagnóstico , Tratamiento de Urgencia/métodos , Humanos , Recién Nacido , Neumonectomía/estadística & datos numéricos , Diagnóstico Prenatal/métodos , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND/PURPOSE: This study aimed to assess the significance of tumor debulking surgery by using immune checkpoint inhibitors for advanced pediatric solid tumors in a murine model of advanced osteosarcoma. METHODS: In C3H mice, 5â¯×â¯106 LM8 (osteosarcoma cell line with a high metastatic potential in the lungs originating from the C3H mouse) cells were transplanted subcutaneously. Thereafter, the mice were divided into 4 groups as follows: the control group received no intervention (CG, nâ¯=â¯5), the surgery group underwent subcutaneous tumor resection (tumor debulking surgery) 11â¯days after transplantation (SG, nâ¯=â¯10), the immunotherapy group received a cocktail consisting of 200⯵g each of three antibodies (anti-Tim-3, anti-PD-L1, and anti-OX-86) intraperitoneally on posttransplantation days 11, 14, 18, and 21 (IG, nâ¯=â¯10), and the combination therapy group, tumor debulking surgery on day 11 and the cocktail intraperitoneally on days 11, 14, 18, and 21 (COMBG, nâ¯=â¯10). Survival curves were plotted by using the Kaplan-Meier method and compared with those plotted using the log-rank test. Next, the lungs of mice in the 4 groups were pathologically evaluated. RESULTS: The COMBG showed significantly longer survival than the other three groups (Pâ¯≤â¯0.002), whereas the SG and IG revealed no difference in survival rate compared to CG. Pathological evaluations revealed no lung metastasis 16â¯weeks after tumor transplantation in the survivors of COMBG. CONCLUSIONS: The results of this study suggest that tumor debulking surgery combined with immune checkpoint inhibitors could be a curative treatment for advanced pediatric solid tumors.
Asunto(s)
Neoplasias Óseas/cirugía , Procedimientos Quirúrgicos de Citorreducción/métodos , Inmunoterapia/métodos , Osteosarcoma/cirugía , Animales , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/mortalidad , Línea Celular Tumoral , Terapia Combinada , Modelos Animales de Enfermedad , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Endogámicos C3H , Trasplante de Neoplasias , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/mortalidad , Análisis de SupervivenciaRESUMEN
BACKGROUND: Multiple studies have failed to reveal an effective method for preventing the recurrence of primary sclerosing cholangitis (PSC) after liver transplantation (LTx). A national study conducted in Japan revealed several risk factors for the recurrence after living donor LTx (LDLTx); however, recipients of ABO-blood type incompatible (ABO-I) LTx were excluded from the previous analysis. In the present study, we investigated the efficacy of an immunosuppressive protocol in ABO-I LTx on the recurrence of PSC after LDLTx. METHODS: We conducted a national survey and analyzed the outcome of recipients who underwent ABO-I LDLTx for PSC (n = 12) between 1994 and 2010 in 9 centers and compared the outcome with that of ABO-compatible LDLTx for PSC (n = 96). The key elements of the immunosuppressive regimen in ABO-I LTx are plasma exchange sessions to remove existing antibodies, and the use of immunosuppression to control humoral immunity. Rituximab was added to the immunosuppression regimen from 2006 onward; 5 patients received rituximab perioperatively. RESULTS: All 7 recipients who underwent ABO-I LDLTx before 2006 (who did not receive rituximab) died of infection (n = 3), antibody-mediated rejection (n = 1), ABO-incompatibility associated cholangiopathy (n = 1) or recurrence of PSC (n = 2). In contrast, we found that all 5 recipients from 2006 (who were treated with rituximab) retained an excellent graft function for more than 7 years without any recurrence of PSC. CONCLUSIONS: The findings of this study shed light on the efficacy of a novel strategy to prevent the recurrence of PSC and the possible mechanisms provided by rituximab treatment are discussed.
RESUMEN
Children with single ventricle physiology have complete mixing of the pulmonary and systemic circulations, requiring staged procedures to achieve a separation of these circulations, or Fontan circulation. The single ventricle physiology significantly increases the risk of mortality in children undergoing non-cardiac surgery. As liver transplantation for patients with single ventricle physiology is particularly challenging, only a few reports have been published. We herein report a case of successful LDLTx for an 8-month-old pediatric patient with biliary atresia, heterotaxy, and complex heart disease of single ventricle physiology. The cardiac anomalies included total anomalous pulmonary venous return type IIb, intermediate atrioventricular septal defect, tricuspid regurgitation grade III, coarctation of aorta, interrupted inferior vena cava, bilateral superior vena cava, and polysplenia syndrome. Following LDLTx, the patient sequentially underwent total cavopulmonary shunt + Damus-Kaye-Stansel at 3 years of age and extracardiac total cavopulmonary connection (EC-TCPC) completion at 5 years of age; 7 years have now passed since LDLTx (2 years post-EC-TCPC). We describe the details of the management of LTx in the presence of cardiac anomalies and report the long-term cardiac and liver function, from peri-LDLTx through EC-TCPC completion.
Asunto(s)
Anomalías Múltiples/cirugía , Atresia Biliar/cirugía , Puente Cardíaco Derecho , Cardiopatías Congénitas/cirugía , Ventrículos Cardíacos/anomalías , Trasplante de Hígado/métodos , Donadores Vivos , Niño , Preescolar , Ventrículos Cardíacos/cirugía , Humanos , Lactante , MasculinoRESUMEN
Growing evidence suggests a relationship between antibody-mediated rejection (AMR) and early graft failure due to a previously unknown etiology in liver transplantation (LTx). We herein report a 3-year-old boy who developed rapid graft failure due to de novo donor-specific antibody (DSA)-driven AMR a week after living donor LTx, requiring a second transplant on the 10th day after the first LTx. The pathology of the first graft showed massive necrosis in zone 3 along with positive C4d and inflammatory cell infiltrates in portal areas. The mean fluorescence intensity against human leukocyte antigen (HLA)-DR15, which was possessed by both the first and the second donor, peaked at 12 945 on the day before the second LTx. Antithymocyte globulin, plasma exchange along with i.v. immunoglobulin, rituximab, and the local infusion of prostaglandin E1, steroids, and Mesilate gabexate through a portal catheter were provided to save the second graft. To our knowledge, this is the first report to show a clear association between de novo DSA and acute AMR within 7 days of a LTx. Furthermore, we successfully rescued the recipient with a second graft despite possessing the same targeted HLA. The rapid decision to carry out retransplantation and specific strategies overcoming AMR were crucial to achieving success in this case of immunologically high-risk LTx.
RESUMEN
BACKGROUND/PURPOSE: The prognosis of patients with metastases remains unsatisfactory in certain pediatric solid tumors. In this study, we evaluated the efficacy of immune checkpoint inhibitors against such metastases using a murine model of osteosarcoma. METHODS: Murine osteosarcoma LM8 cells were transplanted subcutaneously into C3H mice. The primary tumor lesion was surgically resected 11 days after transplantation. Two hundred micrograms of three antibodies (anti-PD-1, anti-PD-L1, and anti-OX-86) or an isotype antibody were administered intraperitoneally on post-transplantation days 11, 14, 18, and 21. Survival curves were plotted by the Kaplan-Meier method and compared with the log-rank test. Computed tomography (CT) scans were performed on day 11 after tumor transplantation (pre-therapy) and on day 25 (post-therapy). For pathology, 3 mice from each group were euthanized on days 11, 22, and 33 after tumor transplantation. RESULTS: The antibody-treated group had a significantly longer survival time compared with the control group (p = 0.002). Both the CT scan and pathological results revealed suppression of metastatic tumor proliferation in the treatment group as compared with the control group. CONCLUSIONS: These results suggest that immune checkpoint inhibitors may be an innovative therapy for lung metastases of advanced pediatric solid tumors.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inmunoterapia , Neoplasias Pulmonares/secundario , Osteosarcoma/secundario , Animales , Antígeno B7-H1/antagonistas & inhibidores , Modelos Animales de Enfermedad , Inmunohistoquímica , Estimación de Kaplan-Meier , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Glicoproteínas de Membrana/antagonistas & inhibidores , Ratones , Ratones Endogámicos C3H , Trasplante de Neoplasias , Ligando OX40 , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Pronóstico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Tomografía Computarizada por Rayos X , Inhibidores del Factor de Necrosis TumoralRESUMEN
PURPOSE: Tracheal cartilage reconstruction is an essential approach for the treatment of tracheal congenital abnormalities or injury. Here, we evaluated the use of allogeneic decellularized tracheas as novel support scaffolds. METHODS: Six weaned pigs (4-week-old domestic males) were transplanted with allogeneic tracheal graft patches (three decellularized and three fresh tracheal scaffolds) onto artificial defects (approximately 15 × 15 mm). After 11 weeks, the tracheas were evaluated by bronchoscopy and histological studies. RESULTS: No pigs displayed airway symptoms during the observation period. Tracheal lumen restored by fresh graft patches showed more advanced narrowing than that treated with decellularized grafts by bronchoscopy. Histologically, fresh grafts induced typical cellular rejection; this was decreased with decellularized grafts. In addition, immunohistochemistry demonstrated regenerating foci of recipient cartilage along the adjacent surface of decellularized tracheal grafts. CONCLUSION: Decellularized allogeneic tracheal scaffolds could be effective materials for restoring impaired trachea.
Asunto(s)
Aloinjertos/cirugía , Tráquea/cirugía , Animales , Masculino , Modelos Animales , Porcinos , Ingeniería de Tejidos/métodos , Andamios del TejidoRESUMEN
BACKGROUND: Biliary atresia commonly leads to liver fibrosis and cirrhotic complications, including esophageal varices. OBJECTIVE: To evaluate liver and spleen stiffness measurements using acoustic radiation force impulse (ARFI) imaging for diagnosing grade of liver fibrosis and predicting the presence of esophageal varices in patients treated for biliary atresia. MATERIALS AND METHODS: ARFI imaging of the spleen and native liver was performed in 28 patients with biliary atresia. We studied the relation between ARFI imaging values and liver histology findings (n=22), upper gastrointestinal endoscopy findings (n=16) and several noninvasive test results. Diagnostic accuracy was assessed using receiver operating characteristic curve analyses. RESULTS: Liver stiffness measurements exhibited a significant difference among the different grades of liver fibrosis (P=0.009), and showed higher values in patients with high-risk esophageal varices than in the other patients (P=0.04). The areas under the receiver operating characteristic curves of liver stiffness measurements for liver fibrosis grades ≥ F2, ≥F3 and = F4 were 0.83, 0.93 and 0.94, respectively. Patients with high-risk esophageal varices were preferentially diagnosed by the combined liver and spleen stiffness measurements (area under the curve, 0.92). CONCLUSION: Liver and spleen stiffness measurements using ARFI imaging are potential noninvasive markers for liver fibrosis and esophageal varices in patients treated for biliary atresia.
Asunto(s)
Atresia Biliar/complicaciones , Diagnóstico por Imagen de Elasticidad , Várices Esofágicas y Gástricas/diagnóstico por imagen , Cirrosis Hepática/diagnóstico por imagen , Adolescente , Adulto , Atresia Biliar/cirugía , Niño , Preescolar , Várices Esofágicas y Gástricas/etiología , Femenino , Humanos , Lactante , Cirrosis Hepática/etiología , Masculino , Proyectos Piloto , Bazo/diagnóstico por imagenRESUMEN
AIM: The current study aimed to assess the perinatal risk of congenital cystic lung diseases (CCLD) and to establish a suitable surgical strategy in consideration of postoperative lung growth and problems during adulthood. METHODS: Among 874 CCLD patients identified in a nationwide survey, 428 patients were born between 1992 and 2012 and treated at 10 high-volume centers were retrospectively reviewed with statistical analysis. RESULTS: In the 194 patients who were prenatally diagnosed to have CCLD, 16.7% presented with fetal hydrops as observed using ultrasonography. The Apgar score (5 minutes) was lower than 5 in 5.4%. As of postnatal day 30, 14.0% of the neonatal patients required respiratory support, and 3.3% (8/243) had died because of pulmonary hypoplasia. Among those who were asymptomatic immediately after birth, 33.6% of the patients developed the respiratory infectious symptoms during their first year of life, and 22.1% did so between the age of 1 and 2 years. The postoperative percent vital capacity among the prenatally diagnosed patients was significantly higher than that among the postnatally diagnosed patients (98.3 ± 11.9 vs. 81.7 ± 9.7, p < 0.0222). Late complications included thoracic deformity in 30 patients and persistent lung cyst in 4 patients, whereas malignancy was not observed in the present series. CONCLUSIONS: Approximately 10 to 15% of prenatally diagnosed CCLD patients may carry a high risk of perinatal respiratory distress. Early operation before developing episodes of lung infection, seem to be associated with a better development of the reserved lung during later life. The incidence of carcinogenesis among patients with CCLD may be extremely low.