Indocyanine green fluorescence imaging as a predictor of long-term testicular atrophy in testicular torsion: a pilot study.

PURPOSE: This pilot study evaluated indocyanine green-guided near-infrared fluorescence (ICG-NIRF) imaging of testicular blood flow to predict long-term testicular atrophy after testicular torsion (TT) surgery. METHODS: The subjects of this retrospective study were patients who underwent surgery for TT at our hospital between December, 2020 and July, 2022. After detorsion, testicular blood flow was evaluated by ICG-NIRF imaging and classified into three categories: fluorescence detected, no fluorescence detected, and fluorescence detected only in the tunica albuginea vessels. Testicular volume was measured by ultrasonography up to 12 months after surgery to evaluate long-term outcomes. RESULTS: Twelve patients were included in this analysis. We found a 100% correlation between the absence of ICG-NIRF signals and subsequent testicular atrophy. In three patients without an ICG-NIRF signal, the median testis size 12 months postoperatively was significantly smaller (16.5% of the contralateral testis; range 13-20%) than that in six patients with an ICG-NIRF signal (96%; 89-115%) (p = 0.013). Mild atrophy (74.5%; 73-76%) was also observed in the three patients for whom an ICG-NIRF signal was detected only in the tunica albuginea vessels. CONCLUSIONS: Our pilot study highlights the potential of ICG-NIRF imaging as a prognostic tool for guiding surgical decision-making for patients with TT, by predicting postoperative testicular atrophy.

Effect of emergent nephrostomy on long-term total and split renal function in patients with upper urinary tract obstruction due to pelvic malignant tumors.

PURPOSE: This study aimed to investigate the impact of nephrostomies on the outcome of total renal function (TRF) and split renal function (SRF) in patients with malignant pelvic tumors associated with upper urinary tract obstruction (UUTO). METHODS: Patients with pelvic tumors suffering severe unilateral hydronephrosis treated at our hospital from 2000 to 2022 were included. Data for nephrostomy placement, short- and long-term renal function, and radiological and nuclear imaging studies were collected. The TRF and SRF of patients who underwent nephrostomy were compared to those who did not. RESULTS: Seven patients were included (rhabdomyosarcoma: 5, ovarian germ cell tumor: 1, malignant rhabdoid tumor: 1). Nephrostomies were placed in four, which were successfully managed without severe infections. Estimated glomerular filtration rate (eGFR) was significantly improved at the end of treatment in patients with nephrostomy. In contrast, eGFR in patients who did not undergo nephrostomy was not improved. Nuclear imaging studies (renograms or renal scintigrams) revealed impaired SRF of the affected kidney compared to the contralateral kidney, even in patients whose eGFR was within normal levels. Notably, SRF showed a trend to improve over time in one patient treated with nephrostomy. CONCLUSION: Nephrostomy for UUTO caused by pelvic tumors may improve renal outcome.

Clinical significance of sarcopenia in children with neuroblastic tumors.

PURPOSE: To elucidate the clinical significance of sarcopenia in children with neuroblastic tumors (NTs). METHODS: We conducted a retrospective observational study and analyzed the z-scores for height, body weight, body mass index, and skeletal muscle index (HT-z, BW-z, BMI-z, and SMI-z) along with the clinical characteristics of 36 children with NTs. SMI-z was calculated from 138 computed tomography scans at diagnosis, during treatment, and at follow-up. The International Neuroblastoma Risk Group classification was used to identify high-risk groups. We analyzed the data at diagnosis for prognostic analysis and changes over time after diagnosis in the HT-z, BW-z, BMI-z, and SMI-z groups. RESULTS: Among the four parameters at diagnosis, only SMI-z predicted overall survival (hazard ratio, 0.58; 95% confidence interval, 0.34-0.99). SMI-z, HT-z, and BW-z significantly decreased over time after diagnosis (P < 0.05), while BMI-z did not (P = 0.11). In surviving high-risk NT cases without disease, SMI-z, HT-z, and BW-z significantly decreased over time (P < 0.05), while BMI-z did not (P = 0.43). CONCLUSION: In children with NT, the SMI-z at diagnosis was a significant prognostic factor and decreased during treatment and follow-up along with HT-z and BW-z. Monitoring muscle mass is important because sarcopenia may be associated with growth impairment.

Outcomes of adult native liver survivors with biliary atresia: the current situation in Japan.

PURPOSE: This study aimed to elucidate the difficulties faced by adult native liver survivors with biliary atresia (BA) in Japan. METHODS: A single-center, retrospective, observational study of 57 adult patients with BA was conducted. The clinical course of BA was compared between native liver survivors and non-survivors who reached adulthood. Indications and outcomes of liver transplantation (LT) among non-survivors were assessed. RESULTS: A significantly larger portion of non-survivors (n = 10) met the criteria for LT (p < 0.001) and received treatment for portal hypertension after reaching 20 years of age (p < 0.01) compared with the survivors. Causes of death included liver cirrhosis (n = 8), graft failure of living donor liver transplantation (LDLT) (n = 1), and hepatocarcinoma (n = 1). Two of the non-survivors who died of liver cirrhosis had no indication for LT because of alcohol dependence and uncontrolled infection. An appropriate donor candidate could not be found for the five patients who opted for LDLT. All six patients waitlisted for deceased donor liver transplantation (DDLT) died after a median waiting period of 17 months. CONCLUSION: Adult BA patients in Japan have limited options for LT, mainly owing to low donor candidate availability for LDLT and a low prevalence of DDLT.

Functional Restoration of Bacteriomes and Viromes by Fecal Microbiota Transplantation.

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI). However, the overall mechanisms underlying FMT success await comprehensive elucidation, and the safety of FMT has recently become a serious concern because of the occurrence of drug-resistant bacteremia transmitted by FMT. We investigated whether functional restoration of the bacteriomes and viromes by FMT could be an indicator of successful FMT. METHODS: The human intestinal bacteriomes and viromes from 9 patients with rCDI who had undergone successful FMT and their donors were analyzed. Prophage-based and CRISPR spacer-based host bacteria-phage associations in samples from recipients before and after FMT and in donor samples were examined. The gene functions of intestinal microorganisms affected by FMT were evaluated. RESULTS: Metagenomic sequencing of both the viromes and bacteriomes revealed that FMT does change the characteristics of intestinal bacteriomes and viromes in recipients after FMT compared with those before FMT. In particular, many Proteobacteria, the fecal abundance of which was high before FMT, were eliminated, and the proportion of Microviridae increased in recipients. Most temperate phages also behaved in parallel with the host bacteria that were altered by FMT. Furthermore, the identification of bacterial and viral gene functions before and after FMT revealed that some distinctive pathways, including fluorobenzoate degradation and secondary bile acid biosynthesis, were significantly represented. CONCLUSIONS: The coordinated action of phages and their host bacteria restored the recipients' intestinal flora. These findings show that the restoration of intestinal microflora functions reflects the success of FMT.

Usefulness of hepatobiliary scintigraphy for predicting late complications in patients with choledochal cysts.

PURPOSE: Hepatobiliary scintigraphy is a minimally invasive imaging method that evaluates bile flow dynamics. At our hospital, it has been performed for postoperative evaluation of patients with choledochal cysts (CC). This study evaluated the usefulness of biliary scintigraphy for predicting late complications in patients with CCs. METHODS: The study included pediatric patients with CC who underwent surgery at Chiba University Hospital from 1978 to 2020, followed by postoperative biliary scintigraphy and subsequent radiologic evaluation. The patients were divided into two groups according to the presence or absence of "biliary cholestasis" on biliary scintigraphy. RESULTS: The study included 108 patients, with a median age at surgery of 2 years and 11 months. The median follow-up period was 5203 days, with 11 hepatolithiasis cases and 8 cholangitis cases. No patients had cholangiocarcinoma. Twelve patients were considered to have "cholestasis" following biliary scintigraphy evaluation. There was no significant difference in the occurrence of hepatolithiasis between the cholestasis and non-cholestasis groups (p = 0.47), but cholangitis was significantly more common in the cholestasis group (p = 0.016). CONCLUSION: Biliary cholestasis on postoperative hepatobiliary scintigraphy was a risk factor for cholangitis in patients with CCs. These particular patients should be monitored carefully.

Antigen-Specific Mucosal Immunity Regulates Development of Intestinal Bacteria-Mediated Diseases.

BACKGROUND & AIMS: Dysregulation of the microbiome has been associated with development of complex diseases, such as obesity and diabetes. However, no method has been developed to control disease-associated commensal microbes. We investigated whether immunization with microbial antigens, using CpG oligodeoxynucleotides and/or curdlan as adjuvants, induces systemic antigen-specific IgA and IgG production and affects development of diseases in mice. METHODS: C57BL/6 mice were given intramuscular injections of antigens (ovalbumin, cholera toxin B-subunit, or pneumococcal surface protein A) combined with CpG oligodeoxynucleotides and/or curdlan. Blood and fecal samples were collected weekly and antigen-specific IgG and IgA titers were measured. Lymph nodes and spleens were collected and analyzed by enzyme-linked immunosorbent assay for antigen-specific splenic T-helper 1 cells, T-helper 17 cells, and memory B cells. Six weeks after primary immunization, mice were given a oral, nasal, or vaginal boost of ovalbumin; intestinal lamina propria, bronchial lavage, and vaginal swab samples were collected and antibodies and cytokines were measured. Some mice were also given oral cholera toxin or intranasal Streptococcus pneumoniae and the severity of diarrhea or pneumonia was analyzed. Gnotobiotic mice were gavaged with fecal material from obese individuals, which had a high abundance of Clostridium ramosum (a commensal microbe associated with obesity and diabetes), and were placed on a high-fat diet 2 weeks after immunization with C ramosum. Intestinal tissues were collected and analyzed by quantitative real-time polymerase chain reaction. RESULTS: Serum and fecal samples from mice given injections of antigens in combination with CpG oligodeoxynucleotides and curdlan for 3 weeks contained antigen-specific IgA and IgG, and splenocytes produced interferon-gamma and interleukin 17A. Lamina propria, bronchial, and vaginal samples contained antigen-specific IgA after the ovalbumin boost. This immunization regimen prevented development of diarrhea after injection of cholera toxin, and inhibited lung colonization by S pneumoniae. In gnotobiotic mice colonized with C ramosum and placed on a high-fat diet, the mice that had been immunized with C ramosum became less obese than the nonimmunized mice. CONCLUSIONS: Injection of mice with microbial antigens and adjuvant induces antigen-specific mucosal and systemic immune responses. Immunization with S pneumoniae antigen prevented lung infection by this bacteria, and immunization with C ramosum reduced obesity in mice colonized with this microbe and placed on a high-fat diet. This immunization approach might be used to protect against microbe-associated disorders of intestine.

Impaired Aortic Growth in Neuroblastoma Patients After Intensive Treatment.

PURPOSE: This study evaluated the abdominal aortic diameter in high-risk neuroblastoma (NB) patients and the risk of aortic narrowing following intensive treatment. METHODS: We measured the aortic diameter at four specific levels of the abdominal aorta (diaphragmatic crus, celiac axis, and the root of the superior (SMA) and inferior (IMA) mesenteric arteries) on contrast CT scans. The control group consisted of 56 children with non-oncologic disorders, while the NB group included 35 patients with high-risk abdominal NB. We used regression analysis of age and aortic diameter to determine the regression formula for each level in each group and performed intergroup comparisons using t-test. RESULTS: We evaluated a total of 160 contrast-enhanced CTs performed in the 35 eligible cases. The aortic diameter of pretreated NB patients was not significantly different from the controls. After receiving any treatment, the aortic diameter was significantly smaller in the NB group (p < 0.01 each). Patients who underwent radical surgery, particularly gross total resection (n = 26), had smaller aortic diameters at all levels compared to controls (p < 0.01 each). Patients treated with radiotherapy (RT) had smaller aortic diameters than controls. External beam radiotherapy (EBRT) patients (n = 24) had smaller aortic diameters at all levels except the celiac axis (crus, SMA, IMA; p < 0.01 each), and intraoperative radiotherapy (IORT) ± EBRT patients (n = 5) had smaller aortic diameters at all levels (p < 0.01 each). CONCLUSION: Patients with NB may experience impaired development of the abdominal aorta after multimodal therapy, particularly after RT. Close observation and long-term follow-up is essential to monitor for catastrophic vascular complications. LEVEL OF EVIDENCE: LEVEL III.

Gastric tumor mimicking bronchial tissue associated with a laryngotracheoesophageal cleft: a case report.

BACKGROUND: Laryngotracheoesophageal cleft (LTEC) is a rare disease in which the larynx and trachea communicate posteriorly to the esophagus. It is often associated with other congenital malformations, particularly gastrointestinal anomalies. Herein, we report a case of LTEC associated with a gastric polypoid lesion in bronchial tissue. CASE PRESENTATION: A gastric mass was detected in a male fetus since week 21 of gestation using fetal ultrasonography. Esophagogastroduodenoscopy performed after birth revealed a pedunculated polypoid lesion of the gastric fornix. The patient experienced frequent vomiting and aspiration pneumonia, which persisted after nasoduodenal tube feeding. Communication between the airway and esophagus was suspected. Laryngoscopy performed 30 days later revealed an LTEC (type III). Partial gastrectomy was performed when the patient was 93 days of age. Histopathological examination revealed tumor consisting of cartilage tissue covered with a layer of respiratory epithelium. CONCLUSION: The gastric tumor associated with LTEC exhibited structures mimicking bronchial tissue. LTEC occurs because of foregut maldevelopment, and the tumorous respiratory tissue in the stomach may have been formed from the same abnormal foregut development event as LTEC.

Combined Use of Three-Dimensional Construction and Indocyanine Green-Fluorescent Imaging for Resection of Multiple Lung Metastases in Hepatoblastoma.

It is essential to accurately and safely resect all tumors during surgery for multiple lung metastases. Here, we report a case of hepatoblastoma (HB) with multiple pulmonary nodules that ultimately underwent complete resection using combined three-dimensional image reconstruction and indocyanine green (ICG) fluorescence guidance. A 1-year-old boy was diagnosed with HB and multiple lung metastases. After intensive chemotherapy, complete resection with subsegmentectomy (S5 + 6) and partial resection (S3, S8) were performed. More than 100 pulmonary nodules, which remained visible on computed tomography (CT) despite additional postoperative chemotherapy, were subjected to pulmonary resection. We used the SYNAPSE VINCENT software (Fujifilm Medical, Tokyo, Japan) to obtain three-dimensional images of the nodules. We numbered each nodule, and 33 lesions of the right lung were resected by multiple wedge resections through a right thoracotomy, with the aid of palpation and ICG fluorescence guidance. One month after the right metastasectomy, resection of 64 lesions in the left lung was performed via left thoracotomy. Postoperative CT showed complete clearance of the lung lesions, and the patient remained disease-free for 15 months after the treatment. This case study confirms that the combination of three-dimensional localization and ICG fluorescence guidance allows for accurate and safe resection of nearly 100 lung metastases.

Proton pump inhibitors enhance intestinal permeability via dysbiosis of gut microbiota under stressed conditions in mice.

BACKGROUND: Intestinal permeability and psychological stress are considered the key mechanism(s) in functional dyspepsia (FD). Although proton pump inhibitors (PPIs) are commonly used for the treatment of FD, the effect of PPIs on intestinal permeability has not been elucidated. This study investigated the effect of PPI on intestinal permeability under stressed conditions. METHODS: C57BL/6J mice were subjected to water avoidance stress (WAS) and administered rabeprazole (40 mg/kg) or vehicle treatment (VT). We then evaluated intestinal permeability both in vivo and ex vivo using plasma fluorescein isothiocyanate-dextran and by assessing the paracellular permeability and transepithelial electrical resistance (TEER) in an Ussing chamber, respectively. Furthermore, we evaluated the effect of PPI-treated fecal microbiota transplant (FMT) on intestinal permeability in vivo. Microbiota profiles of donor feces were assessed by 16S rRNA gene analysis using MiSeq and QIIME2. KEY RESULTS: In the WAS treatment, PPI significantly enhanced intestinal permeability in vivo compared to that in VT. Moreover, PPI significantly increased paracellular permeability and decreased TEER in the duodenum and jejunum, respectively, compared to those in VT under stressed conditions. Moreover, both vasoactive intestinal peptide (VIP) receptor antagonist and ketotifen significantly reversed the effect of PPI on intestinal permeability. Furthermore, PPI-treated FMT significantly increased the intestinal permeability in vivo compared to that in vehicle-treated FMT. Proton pump inhibitors treatment altered the gut microbiota composition, indicating that PPI induced dysbiosis. CONCLUSIONS AND INFERENCES: Under stressed conditions, PPI enhances intestinal permeability via dysbiosis of gut microbiota. Vasoactive intestinal peptide and mast cells are also implicated in the underlying mechanisms.

Metagenome Data on Intestinal Phage-Bacteria Associations Aids the Development of Phage Therapy against Pathobionts.

The application of bacteriophages (phages) is proposed as a highly specific therapy for intestinal pathobiont elimination. However, the infectious associations between phages and bacteria in the human intestine, which is essential information for the development of phage therapies, have yet to be fully elucidated. Here, we report the intestinal viral microbiomes (viromes), together with bacterial microbiomes (bacteriomes), in 101 healthy Japanese individuals. Based on the genomic sequences of bacteriomes and viromes from the same fecal samples, the host bacteria-phage associations are illustrated for both temperate and virulent phages. To verify the usefulness of the comprehensive host bacteria-phage information, we screened Clostridioides difficile-specific phages and identified antibacterial enzymes whose activity is confirmed both in vitro and in vivo. These comprehensive metagenome analyses reveal not only host bacteria-phage associations in the human intestine but also provide vital information for the development of phage therapies against intestinal pathobionts.

Prediction of respiratory collapse among pediatric patients with mediastinal tumors during induction of general anesthesia.

PURPOSE: Fatality resulting from respiratory collapse (RC) during general anesthesia (GA) induction in children with mediastinal tumors has been reported. We explored potentially useful parameters for predicting the risk of RC based on objective imaging results. METHODS: We retrospectively reviewed the records of 31 patients (median age: 4years; range: 4months-15years) with mediastinal tumors treated between 2000 and 2015. Comparing those with RC under GA induction to those without (RC group vs. non-RC group), we analyzed a variety of factors that might predict respiratory obstruction during GA induction, including our new parameter, the standardized tumor volume (STV), which is adapted from the formula for the volume of an ellipsoid. RESULTS: All eight patients in the RC group had large tumors in the anterior mediastinum, including lymphoma, teratoma, and germ cell tumor. The mean STV value of the RC group was significantly larger than that of the non-RC group (3.6±1.4 vs. 1.4±1.0, p=0.006). Using an STV cut-off value of 2.5, the sensitivity and specificity for predicting RC under GA induction were both 0.86, making STV more useful than previously reported risk factors. CONCLUSION: Anterior mediastinal tumors in children can often cause airway obstruction under GA induction. Measuring STV can help predict the respiratory risk during GA among pediatric patients with anterior mediastinal tumors. LEVEL OF EVIDENCE: III.