Localization of macrophages and dendritic cells in human thoracic lymph nodes: An immunohistochemical study using surgically obtained specimens.

Both dendritic cells (DCs) and macrophages are bone marrow-derived cells that perform antigen presentation. The distribution of DCs and CD68-positive macrophages were immunohistochemically examined in 103 thoracic nodes obtained from 23 lung cancer patients (50-84 years old) without metastasis. Among three antibodies tested initially-CD209/DCsign, fascin, and CD83-DCsign was chosen as the DC marker. For comparison, 137 nodes from 12 patients with cancer metastasis were also examined histologically. In patients without metastasis, DCs were found as (1) clusters along the subcapsular sinus and in a border area between the medullary sinus and cortex (mean sectional area of multiple nodes at one site, 8.4%) and, (2) rosette-like structures in the cortex (mean number in multiple nodes at one site, 20.5). Notably, DC clusters and rosettes contained no or few macrophages and were surrounded by smooth muscle actin (SMA)-positive, endothelium-like cells. The subcapsular linear cluster corresponded to 5%-85% (mean, 34.0%) of the nodal circumferential length and was shorter in older patients (p = 0.009). DC rosettes, solitary, or communicating with a cluster, were usually connected to a paracortical lymph sinus. Few differences were found between nodes with or without metastasis, but DC cluster sometimes contained abundant macrophages in cancer metastasis patients. The subcapsular DC cluster is not known in the rodent model, in which the subcapsular sinus is filled with macrophages. This quite different, even complementary, distribution suggests no, or less, cooperation between DCs and macrophages in humans.

[Thoracic Endovascular Aortic Repair for Mycotic Thoracic Aortic Aneurysm After BCG Intravesical Therapy].

Bacille Calmette-Guérin( BCG) intravesical therapy is an effective and safe treatment for bladder cancer; however, mycotic aneurysms have been reported as a rare complication. Case 1:A 64-year-old man with a history of BCG intravesical therapy underwent emergent thoracic endovascular aortic repair (TEVAR) for a ruptured thoracic aortic aneurysm (TAA). He was diagnosed with BCG infection by hemosputum specimen culture five months later;then, antituberculous therapy was initiated. However, his follow-up computed tomography scan revealed stent-graft infection and new aneurysm formation. Therefore, we performed a repeated TEVAR with abdominal 4-vessel debranching. There was no recurrence of infection for six years while continuing postoperative antituberculous therapy. Case 2:A 72-year-old man who had undergone BCG intravesical therapy underwent TEVAR for a rapidly enlarging mycotic TAA. He received anti-tuberculous therapy for one year with no recurrent infection for one year. TEVAR may be an effective alternative to the open surgical procedure;however, multidisciplinary treatment including anti-tuberculous therapy and careful long-term follow up are required.

The clinical value of texture analysis of dual-time-point 18F-FDG-PET/CT imaging to differentiate between 18F-FDG-avid benign and malignant pulmonary lesions.

OBJECTIVES: To examine whether the texture analysis of dual-time-point (DTP) F-18-fluorodeoxyglucose (18F-FDG)-PET/CT imaging can differentiate between 18F-FDG-avid benign and malignant pulmonary lesions. METHODS: We compared standardized uptake value (SUV)-related (SUVmax [g/ml] and SUVmean [g/ml]), volumetric (metabolic tumor volume [MTV] [cm3] and total lesion glycolysis [TLG] [g]), and texture (entropy, homogeneity, dissimilarity, intensity variability [IV], size-zone variability [SZV], and zone percentage [ZP]) (MTV ≥ 5.0 cm3 and SUV ≥ 2.5 g/ml) parameters between 13 benign and 46 malignant lesions using the Mann-Whitney U test. Diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis. Stepwise logistic regression analysis was performed to identify and use the independent variables that correctly differentiate between benign and malignant lesions. RESULTS: Malignant pulmonary lesions showed significantly higher SUVmax, SUVmean, MTV, TLG, entropy, dissimilarity, IV, and SZV and significantly lower homogeneity and ZP than benign pulmonary lesions (all p < 0.05) in both early and delayed images. Their areas under the ROC curves (AUCs) ranged between 0.69 and 0.94, and diagnostic accuracies between 64.4% and 93.2%. Entropy-early (p = 0.014), SUVmean-delay (p = 0.039), and dissimilarity-delay (p = 0.027) were independent parameters, and combined use of them yielded the highest AUC (0.98) with 100% sensitivity (46/46), 84.6% specificity (11/13), and 96.7% (57/59) accuracy for distinguishing between benign and malignant lesions. CONCLUSIONS: The individual early and delayed SUV-related, volumetric, and texture parameters showed a wide range of accuracy. Combined use of independent parameters extracted from DTP imaging might yield a high diagnostic accuracy with balanced sensitivity and specificity to differentiate between benign and malignant 18F-FDG-avid pulmonary lesions. KEY POINTS: • Malignant pulmonary lesions showed significantly higher SUV-related (SUVmax and SUVmean) and volumetric (MTV and TLG) parameters than benign pulmonary lesions in both early and delayed images. • Malignant pulmonary lesions showed significantly more heterogeneous18F-FDG uptake than benign pulmonary lesions in both early and delayed images. • Combined use of independent parameters extracted from DTP imaging might yield a high diagnostic accuracy to differentiate between benign and malignant18F-FDG-avid pulmonary lesions.

The Pharmacokinetics of Sildenafil May Be Affected by Intestinal Absorption Rate in Children Admitted to the Intensive Care Unit.

This study was performed for a better understanding of the pharmacokinetics of sildenafil (SIL) and N-desmethyl sildenafil (DMS) in 13 children treated in the intensive care unit (ICU). Blood samples were taken periodically after the first oral administration of SIL (0.5 mg/kg). Plasma concentrations were analyzed by tandem LC/MS. Of the 13 patients, apparent peaks in the plasma concentration of SIL were observed in four patients, with the other nine patients showing reduced or delayed drug absorption of SIL. The maximum plasma concentrations of SIL after administration varied in range from 7.8 to 101.0 ng/mL. The parent drug-to-metabolite (SIL/DMS) ratios of the nine patients with reduced or delayed drug absorption of SIL were relatively lower than those in the four patients with rapid absorption of the drug. These observations suggested that the inter-individual variability of intestinal absorption and/or first-pass extraction of SIL was involved in the pharmacokinetic variability of the drug. Next, we evaluated the impact of changes in the gastrointestinal absorption rate on the pharmacokinetics of the drug. That is, SIL (2.5 mg/body) was administered at two different rates in the duodenum of rats. When SIL was administered for 10 min, the Cmax and bioavailability were 3.46 ± 1.65 µg/mL and 23.2 ± 11.1%, respectively. When SIL was administered for 60 min, the Cmax and bioavailability were 0.990 ± 0.352 µg/mL and 9.91 ± 3.79%, respectively. These findings suggest that the drug absorption rate was at least partly responsible for the pharmacokinetic variability of SIL in the ICU children.

Congenital vascular ring.

A vascular ring is a rare congenital cardiovascular anomaly, which encircles and compresses the trachea or esophagus, or both. In this review we discuss the pathophysiology, theoretical embryopathogenesis, diagnostic modalities, and surgical treatment of the different types of vascular ring. Knowledge of the normal embryonic development of the aortic arch and related structures is important for understanding and classifying the various forms of vascular ring. The development of a vascular ring begins with the embryonic aortic arch system. The persistence, involution, or regression of the arches determines the multiple variations of vascular ring. With the development of new technologies, multi-detector computed tomography (MDCT) has become a good diagnostic modality for pre- and postoperative evaluation. MDCT provides an excellent image of aortic arch abnormalities and the related anatomy, as well as the tracheal pathology. For patients with symptoms, surgical division of the vascular ring usually achieves excellent outcomes with marked resolution of symptoms and a low risk of morbidity and mortality. Symptomatic vascular rings require early surgical intervention to prevent prolonged vascular compression of the airway and serious complications.

[Redo Right Ventricular Outflow Tract Reconstruction in Adult Patients with Congenital Heart Disease].

Between April 2005 and February 2019, 11 adult patients underwent redo reconstruction of the right ventricular outflow tract. The primary malformation was Fallot's tetralogy in 8, transposition of the great arteries in 2, and pulmonary atresia with intact ventricular septum in 1. Mean age at redo operation was 27.4 years. Right ventricular outflow tract was reconstructed with expanded polytetrafluoroethylene conduits with bulging sinuses and a fan-shaped valve in 9, transannular patch in 1, and right ventricular outflow patch in 1. There were no early and late deaths. One patient had residual branch pulmonary stenosis, while other 10 patients had no significant pulmonary stenosis and no significant pulmonary regurgitation. Signs and symptoms were improved in these 10 patients. Re-operation should be done before the development of right ventricular dysfunction, while it can be performed with satisfactory results in adult patients.

Detection of alternative subpleural lymph flow pathways using indocyanine green fluorescence.

PURPOSE: Pulmonary lymphatic fluid predominately flows along the bronchi. However, there are reports suggesting that an alternative lymphatic pathway exist, which may result in skip metastases. The aim of this study was to evaluate the subpleural lymph flow in vivo using indocyanine green (ICG) fluorescence. METHODS: One hundred cases were enrolled. ICG was injected into the macroscopically healthy subpleural space. Intraoperative fluorescence images were then observed in real time. RESULTS: ICG fluorescence was observed moving through subpleural channels in 58/100 cases. ICG flowed into adjacent lobes over interlobar lines in 18 cases and flowed from the visceral pleura directly into the mediastinum in 5 cases. The frequency of mediastinal detection without hilar lymph node detection was significantly higher in the left lung compared to the right (p < 0.05). The subpleural lymph flow detection rates were significantly lower in patients with smoking pack-years ≥ 40 than those with < 40 (p < 0.05). CONCLUSIONS: The flow of lymphatic fluid directly into the mediastinum suggests one mechanism of skip metastasis. In addition, the reduction of the subpleural lymph flows in smokers with ≥ 40 pack-years suggests that smoking might modify lymph flow patterns. These findings may assist in selecting the optimal therapy for patients with possible skip metastasis.

Current topics in surgery for multiple ventricular septal defects.

In this review article, we describe several topics, including the sandwich technique, the transatrial re-endocardialization technique, the limited apical left ventriculotomy approach and device closure. The sandwich technique was introduced for the closure of muscular ventricular septal defects (VSD) by sandwiching the septum between two felt patches placed in the left and right ventricle. This technique requires neither the transection of muscular trabeculae nor ventriculotomy. Although the sandwich technique has resulted in the improvement of surgical outcomes, cases of postoperative cardiac dysfunction have been reported. Multiple smaller VSDs have been closed with transatrial re-endocardialization. Septal dysfunction may be avoided through this technique, in which the septal trabeculae are approximated in two layers of superficial, endocardial running sutures. Recently, a number of reports have recommended a limited apical left ventriculotomy approach. With this technique, a much shorter incision of around 1 cm at the apex of the left ventricle may be sufficient for achieving the complete closure of apical muscular VSDs. The transcatheter or perventricular device closure of muscular VSDs has increasingly been performed with good results. Although favorable early and mid-term results of device closure have been reported, this method is not always safer or less invasive than surgical closure. Long-term evaluations should be performed to determine whether the right and left ventricular functions are affected by treatment with relatively large devices in the heart.

[Esophageal Injury Treated with a Covered Expandable Metallic Stent].

We report a case of iatrogenic esophageal injury treated with a covered expandable metallic stent after thoracoscopic chest drainage. A 70-year-old man who had stricture of the esophagus after endoscopic submucosal dissection underwent balloon dilation. Chest computed tomography revealed esophageal rupture. Initially, continuous intra-esophageal drainage was carried out, however, due to the development of mediastinitis with enlarged abscess around the descending aorta and the left pneumothorax, thoracoscopic chest drainage was performed. Since direct closure was thought to be in appropriate, an intra-esophageal approach was chosen and a covered expandable metallic stent was mounted under fluorography on the next day. After the treatment, the patient was able to eat, and was able to discharge 42 days later. Intra-esophageal covered expandable metallic stent can be an alternative treatment for esophageal rupture.

[Metastatic Lung Tumor Diagnosed as Primary Lung Cancer due to its Accompanying Lesion Mimicking Atypical Adenomatous Hyperplasia by Intraoperative Needle Biopsy Findings;Report of a Case].

We reported a case of metastatic lung tumor, which was suspected as being a primary lung cancer because of its accompanying lesion mimicking atypical adenomatous hyperplasia(AAH) based on intraoperative needle biopsy findings. AAH is a preinvasive lesion or marginal lesion of primary lung cancer that is not accompanied by metastatic tumor. However, it needs to be distinguished pathologically from secondary changes of inflammation or fibrosis. In our case, the needle biopsy revealed AAH-like pathological findings, which indicates a primary lung cancer, and the standard lobectomy with lymph node dissection was performed, however, the final diagnosis turned out to be metastatic tumor. The rapidly enlarging tumor led to surrounding obstructive pneumonitis, which may have caused pathological changes mimicking AAH findings. In the case of obstructive pneumonitis, we must be careful to diagnose AAH, in addition to decisions about the surgical procedure especially when based on frozen section diagnosis.

Current topics in surgery for isolated total anomalous pulmonary venous connection.

Surgical correction of total anomalous pulmonary venous connection (TAPVC) remains a challenge, with reported early mortality rates of up to 20%. In this review article, we describe several topics, including surgery for neonates, diagnoses with multidetector computed tomography (MDCT), and primary sutureless repair. Several studies have reported mortality rates of around 10%, and demonstrated unchanged hospital mortality in neonates, despite improvement of the overall mortality of cohorts including older patients. Previous reports identified a low body weight at the time of the operation, preoperative pulmonary venous obstruction (PVO), and a prolonged cardiopulmonary bypass time as risk factors for hospital mortality. With the development of new technologies, MDCT has become a good diagnostic modality for use in the pre- and post-operative evaluation. MDCT delineates the drainage site of the vertical vein and the atypical vessel into the systemic vein, and it can also evaluate the existence of obstruction in the vertical vein. Following favorable experiences with post-repair PVO, the indications for sutureless repair as a primary operation have been expanded for infants, including those at risk of developing PVO after the repair of TAPVC. Primary sutureless repair has proven especially useful for difficult patient groups, such as those with congenital PVO, infracardiac TAPVC with small pulmonary veins, or mixed-type TAPVC.

Functional evaluation in cruciate-retaining-type TKA: anatomical relationship between tibial osteotomy level and PCL attachment.

INTRODUCTION: The level and morphology of posterior cruciate ligament (PCL) attachment vary greatly among individuals, and the function of the PCL after tibial osteotomy performed during total knee arthroplasty (TKA) surgery remains unclear. Therefore, we evaluated the resection amount of PCL attachment and the function of the residual PCL in cruciate-retaining (CR)-type TKA. METHODS: We examined 76 patients with knee osteoarthritis who had undergone CR-type TKA. The level of the tibial PCL attachment was measured by preoperative MRI and the amount resected into the tibial PCL attachment from the osteotomy level as well as the longitudinal diameter of the residual PCL by postoperative radiography. The relationships between these and joint gap tension value at flexion or amount of tibial posterior transfer by postoperative stress radiography were examined. RESULTS: The longitudinal diameter of the PCL attachment and the attachment level varied widely among patients. There were 39 patients (51%) with tibial osteotomy level caudal to the PCL attachment. Flexion gap tension in patients with residual PCL (residual PCL group) was slightly higher than those without residual PCL (fully-resected group). There was no correlation between amount of PCL residual and joint gap tension at the flexion position. Even in those without residual PCL, no correlation was observed between the resected amount and flexion joint gap tension value. Comparison of amount of posterior transfer by postoperative stress radiography between those with and without residual PCL revealed no significant difference. CONCLUSIONS: It was confirmed that the level and morphology of the PCL attachment vary greatly among individuals and the amount of PCL resected at tibial osteotomy during TKA surgery varies depending on the patient. The tension due to flexion position tended to decrease if the tibial osteotomy line was caudal to the PCL attachment; however, the amount of tibial posterior transfer due to stress was not changed.

Prognostic Outcome of Pulmonary Resection for Pulmonary Metastases from Gastric Cancer.

PURPOSE: Regardless of the devastating outcomes of pulmonary resection for metastases from gastric cancer, a handful of patients survive long after pulmonary metastasectomy. This study aimed to identify a good candidate for pulmonary resection for metastases from gastric cancer. METHODS: Between 2005 and 2023, 564 patients underwent pulmonary metastasectomy in our department, of which 12 patients underwent pulmonary resection for metastases from gastric cancer. Variables evaluated were the number and size of metastatic lesions, surgical procedure, disease-free interval (DFI), and the serum carcinoembryonic antigen at pulmonary metastasectomy. RESULTS: The DFI following gastrectomy ≤12.5 months group had a significantly worse overall survival (OS) than the other group (p = 0.005). A comparison between DFI following gastrectomy ≤12.5 months group and DFI following gastrectomy >12.5 months group showed a significant difference in serum carcinoembryonic antigen (CEA) value at pulmonary metastasectomy (p = 0.048). The serum CEA value at pulmonary metastasectomy >5.8 ng/ml group had a significantly worse OS than the other group (p = 0.001). CONCLUSION: Pulmonary metastasectomy can be indicated in some patients with metastasis from gastric cancer who have longer DFI from gastrectomy and lower serum CEA at pulmonary metastasectomy.

Fulminant myocarditis during postoperative adjuvant chemotherapy for lung cancer with atezolizumab: a case report.

BACKGROUND: Postoperative adjuvant systemic therapy with atezolizumab for lung cancer has been reported to be effective. Although myocarditis is a rare immune adverse event associated with atezolizumab, it can have a serious course and should be treated with caution. We herein report a case of fulminant myocarditis during adjuvant systemic therapy with atezolizumab. CASE PRESENTATION: The patient was a 49-year-old Asian woman. She was diagnosed with pT2aN1M0 stage IIB (Programmed Death Ligand 1(PD-L1), 50%) after surgery for right upper lobe lung adenocarcinoma. Atezolizumab was administered following platinum-based adjuvant chemotherapy. On day 14, the patient was hospitalized because of deterioration in her general condition caused by fever. On day 16, she developed dyspnea, which worsened, and on day 17, she experienced shock. Blood tests, echocardiography, and cardiac catheterization were performed, and the patient was diagnosed with cardiogenic shock due to myocarditis. Initial measures did not improve the patient's shock state. The patient was transferred to hospital for the use of an assistive circulatory system. Pulse steroid therapy was administered, and myocarditis showed a tendency toward improvement. A retrospective review of the patient's history revealed a decreased lymphocyte count and an increase in the neutrophil/lymphocyte ratio, which may be useful for detecting severe immune-related adverse events. The troponin levels were elevated, but creatine phosphokinase level remained within the normal range. CONCLUSION: Myocarditis can be fatal due to the rapid progression of symptoms. Close follow-up, a prompt diagnosis, and therapeutic intervention are important. Decreased lymphocyte counts, increased neutrophil/lymphocyte ratios, and the measurement of multiple myocardial biomarkers are considered useful for the early diagnosis of myocarditis.

A case of attempted transbronchial spigot insertion for fistulous pyothorax in the residual pleural airspace after pleurectomy/decortication for malignant pleural mesothelioma.

Pleurectomy/decortication for malignant pleural mesothelioma is a relatively recent surgical approach for which there is a dearth of information on complications, especially in the late postoperative period. A 70-year-old man was diagnosed with right epithelioid malignant pleural mesothelioma and underwent pleurectomy/decortication. Computed tomography at 6 months after surgery revealed nodules on the surface of the right lung. These nodules gradually increased in size and were diagnosed as recurrent disease. Immunotherapy was started, but treatment was discontinued a few days after the first course due to pneumonitis. Subsequent oral prednisolone therapy for about 2 months ameliorated pneumonitis, but fistulous pyothorax developed. During attempted transbronchial occlusion of the responsible bronchus, some spigots penetrated the empyema cavity. Open window thoracotomy was performed on the following day. This case suggests that if there is no change in diameter between the proximal and distal parts of the responsible bronchus, transbronchial occlusion should not be chosen.

Effect of Tegafur-Uracil in Resected Stage IB Lung Adenocarcinoma According to Presence or Absence of Epidermal Growth Factor Receptor Gene Mutation: A Retrospective Cohort Study.

PURPOSE: Tegafur-uracil (UFT) is the standard postoperative adjuvant therapy for stage IB lung adenocarcinoma (LUAD) in Japan. This study aimed to determine whether UFT is effective in stage IB LUAD with and without epidermal growth factor receptor (EGFR) mutations. METHODS: This retrospective study included 169 patients with stage IB LUAD who underwent complete resection at our department between 2010 and 2021. We investigated the clinicopathological and prognostic impact of EGFR mutations as well as the postoperative use of UFT. RESULTS: EGFR mutation-positive cases tended to show a higher cumulative recurrence rate than EGFR mutation-negative cases (p = 0.081), while overall survival was comparable between the groups (p = 0.238). In the entire cohort, UFT administration was not an independent prognostic factor in the multivariate regression analysis (p = 0.112). According to a stratification analysis, UFT administration was independently associated with favorable overall survival (p = 0.031) in EGFR mutation-negative cases, while it was not associated with recurrence-free survival (p = 0.991) or overall survival (p = 0.398) in EGFR mutation-positive cases. CONCLUSION: UFT administration can improve the prognosis of EGFR mutation-negative LUAD but not EGFR mutation-positive LUAD. Thus, clinical trials of adjuvant-targeted therapy for EGFR mutation-positive stage IB LUAD should also be conducted in Japan.

SF6 is a useful expander for post-pneumonectomy syndrome in the long-term course: a case report.

BACKGROUND: Post-pneumonectomy syndrome (PPS) is a rare but serious condition that can occur after pneumonectomy. It is characterized by a mediastinal shift towards the vacated hemithorax, which can potentially lead to respiratory failure. The management of PPS poses a clinical challenge, especially in the context of the limited availability of certain therapeutic devices due to regulatory restrictions in Japan. CASE PRESENTATION: A 36-year-old female with stage IB non-small cell lung cancer underwent left pneumonectomy. Approximately 2 years later, she developed dyspnea. After consulting with our hospital, subsequent imaging revealed an extreme mediastinal shift causing bronchial obstruction. Emergency thoracotomy and subsequent sulfur hexafluoride (SF6) injections were successfully used to manage her condition. Over the course of follow-up, the interval between SF6 injections was extended from 3 to 11 months, indicating an improvement in the intrathoracic condition. CONCLUSIONS: This case illustrates the efficacy of SF6 gas in treating PPS and in reducing the frequency of medical interventions. SF6 gas administration is safe and effective for the treatment of patients with PPS.

Prognostic significance of preoperative to postoperative serum carcinoembryonic antigen ratio after lobectomy for lung adenocarcinoma.

INTRODUCTION: Lung adenocarcinoma with a preoperatively elevated serum carcinoembryonic antigen (CEA) value has a relatively poor postoperative prognosis. Although surgical resection generally results in a reduction in the CEA value, the significance of the change in the CEA value on the prognostic outcome remains unclear. METHODS: Our study included 133 patients who underwent lobectomy with curative intent for lung adenocarcinoma representing a preoperative CEA value > 5.0. Statistical analysis was performed using a receiver operating characteristic analysis and a stepwise Cox proportional hazards analysis. RESULTS: Both the postoperative CEA value and postoperative-to-preoperative CEA ratio (CEA ratio) significantly affected the survival. Although the CEA ratio was not predictive of the survival in patients with postoperative CEA ≤ 6.2 ng/ml (n = 105), it was predictive in the remaining patients with postoperative CEA > 6.2 ng/ml (n = 28). Patients with postoperative CEA > 6.2 ng/ml and a CEA ratio ≥ 0.39 (n = 7) showed the worst survival outcome. According to the multivariate analysis, the CEA ratio and postoperative nodal status were significant predictors of the survival in overall patients. CONCLUSION: The CEA ratio may be a useful prognostic marker in patients who undergo lobectomy for lung adenocarcinoma and show postoperative CEA > 6.2 ng/ml. A high CEA ratio may indicate the presence of a subclinical residual tumor, which may lead to the development of subsequent recurrence.

Adjuvant Chemotherapy in Addition to Neoadjuvant Chemotherapy for Locally Advanced Non-small Cell Lung Cancer.

BACKGROUND/AIM: The prognostic impact of adjuvant cytotoxic chemotherapy for patients with resectable locally advanced non-small cell lung cancer (NSCLC) who underwent surgery after neoadjuvant chemotherapy remains unclear. PATIENTS AND METHODS: A retrospective chart review was performed to identify patients who underwent surgery following neoadjuvant therapy for clinical T3N0 or N1-N2 resectable NSCLC between 2011 and 2016 at our hospital. Survival outcomes were analyzed with the Kaplan-Meier method and a Cox proportional hazard model. RESULTS: Thirty-eight patients were identified. The median recurrence-free survival (RFS) was 50.6 months and overall survival (OS) was 75.2 months. Patients who had undergone adjuvant chemotherapy were not associated with a favorable RFS (hazard ratio=1.01, p=0.98) or OS (hazard ratio=0.72, p=0.55), as compared with those who had not. However, subgroup analysis revealed that hazard ratio based on RFS and OS varied greatly between subgroups, suggesting that selected patients might benefit from adjuvant therapy, while others might be harmed by it. For example, in surgical-pathological stage III disease, adjuvant therapy showed a favorable RFS (HR=0.22, 95%CI=0.02-2.57, p=0.23) and OS (HR=0.36, 95%CI=0.03-4.01, p=0.40). Conversely, in surgical-pathological stage 0-II disease, adjuvant therapy showed an unfavorable RFS (HR=1.40, 95%CI=0.49-3.96, p=0.53) and OS (HR=0.95, 95%CI=0.29-3.12, p=0.93). CONCLUSION: Regardless of the negative findings in our overall patient cohort, our results may be beneficial in identifying patients who may likely benefit from adjuvant therapy. This contribution could assist the planning of large-scale prospective studies.

Probiotics may alleviate intestinal damage induced by cardiopulmonary bypass in children.

OBJECTIVES: Intestinal ischaemia-reperfusion injury induced by cardiopulmonary bypass causes intestinal epithelial barrier dysfunction, leading to dysbiosis and bacterial translocation. We conducted a randomized prospective study with 2 objectives: (i) to investigate epithelial barrier dysfunction and bacterial translocation induced by cardiopulmonary bypass and changes in the gut microbiota and (ii) to verify whether probiotics can improve these conditions. METHODS: Between 2019 and 2020, patients 0-15 years old scheduled to undergo cardiac surgery using cardiopulmonary bypass were enrolled and randomly allocated to 2 groups: the intervention group received probiotics and the control group did not receive probiotics. We analysed the microbiota in faeces and blood, organic acid concentrations in faeces, plasma intestinal fatty acid-binding protein and immunological responses. RESULTS: Eighty-two patients were enrolled in this study. The characteristics of the patients were similar in both groups. The total number of obligate anaerobes was higher in the intervention group than in the control group after postoperative day 7. We identified 4 clusters within the perioperative gut microbiota, and cluster changes showed a corrective effect of probiotics on dysbiosis after postoperative day 7. Organic acid concentrations in faeces, incidence of bacterial translocation, intestinal fatty acid-binding protein levels and immunological responses, except for interleukin -17A, were not markedly different between the 2 groups. CONCLUSIONS: Administration of probiotics was able to correct dysbiosis but did not sufficiently alleviate the intestinal damage induced by cardiopulmonary bypass. More effective methods should be examined to prevent disturbances induced by cardiac surgery using cardiopulmonary bypass. CLINICAL TRIAL REGISTRATION NUMBER: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037174 UMIN000035556.