A short-term three dimensional culture-based drug sensitivity test is feasible for malignant bone tumors.

The feasibility of a short-term, three-dimensional (3D) culture-based drug sensitivity test (DST) for surgically resected malignant bone tumors, including osteosarcoma (OS), was evaluated utilizing two OS cell line (KCS8 or KCS9)-derived xenograft (CDX) models. Twenty-three (KCS8) or 39 (KCS9) of 60 tested drugs were likely effective in OS cells derived from a cell line before xenografting. Fewer drugs (19: KCS8, 26: KCS9) were selected as effective drugs in cells derived from a CDX tumor, although the drug sensitivities of 60 drugs significantly correlated between both types of samples. The drug sensitivity of a CDX tumor was not significantly altered after the depletion of non-tumorous components in the sample. In a surgically resected metastatic tumor obtained from a patient with OS, for whom a cancer genome profiling test detected a pathogenic PIK3CA mutation, DST identified mTOR and AKT inhibitors as effective drugs. Of two CDX and six clinical samples of OS and Ewing's sarcoma, DST identified proteasome inhibitors (bortezomib, carfilzomib) and CEP-701 as potentially effective drugs in common. This unique method of in vitro drug testing using 3D-cell cultures is feasible in surgically resected tissues of metastatic malignant bone tumors.

Severe RAS-Associated Lymphoproliferative Disease Case with Increasing αß Double-Negative T Cells with Atypical Features.

Autoimmune lymphoproliferative syndrome (ALPS) is a disease of lymphocyte homeostasis caused by FAS-mediated apoptotic pathway dysfunction and is characterized by non-malignant lymphoproliferation with an increased number of TCRαß+CD4-CD8- double-negative T cells (αßDNTs). Conversely, RAS-associated leukoproliferative disease (RALD), which is caused by gain-of-functional somatic variants in KRAS or NRAS, is considered a group of diseases with a similar course. Herein, we present a 7-year-old Japanese female of RALD harboring NRAS variant that aggressively progressed to juvenile myelomonocytic leukemia (JMML) with increased αßDNTs. She eventually underwent hematopoietic cell transplantation due to acute respiratory distress which was caused by pulmonary infiltration of JMML blasts. In general, αßDNTs have been remarkably increased in ALPS; however, FAS pathway gene abnormalities were not observed in this case. This case with RALD had repeated shock/pre-shock episodes as the condition progressed. This shock was thought to be caused by the presence of a high number of αßDNTs. The αßDNTs observed in this case revealed high CCR4, CCR6, and CD45RO expressions, which were similar to Th17. These increased Th17-like αßDNTs have triggered the inflammation, resulting in the pathogenesis of shock, because Th17 secretes pro-inflammatory cytokines such as interleukin (IL)-17A and granulocyte-macrophage colony-stimulating factor. The presence of IL-17A-secreting αßDNTs has been reported in systemic lupus erythematosus (SLE) and Sjögren's syndrome. The present case is complicated with SLE, suggesting the involvement of Th17-like αßDNTs in the disease pathogenesis. Examining the characteristics of αßDNTs in RALD, JMML, and ALPS may reveal the pathologies in these cases.

Case report: Hepatectomy with Rex bypass for a child with hepatoblastoma and portal vein thrombosis.

Pediatric liver tumors with portal vein obstruction are often candidates for liver transplantation. However, lifelong use of immunosuppressants and invasiveness to healthy donors in the case of living-donor liver transplantation is inevitable. Moreover, when lung metastasis is involved, the lung recurrence rate after liver transplantation is still high. Therefore, transplantation should be avoided as much as possible. In cases of tumors in the right lobe of the liver, complete resection of the portal vein trunk may be possible by creating a Rex bypass, but with the original method, end-to-side anastomosis to the umbilical portal vein is difficult in small children. We report a case of a 2-year-old girl with hepatoblastoma in whom a Rex shunt was created by end-to-end anastomosing the recanalized umbilical vein to the portal vein stump with interposing a vein graft, and the right lobe was successfully resected along with the tumor.

Infantile hepatic hemangioma and hepatic mesenchymal hamartoma in an infant associated with placental mesenchymal dysplasia: a case report.

BACKGROUND: Although infantile hepatic hemangioma and hepatic mesenchymal hamartoma are relatively common in benign pediatric liver tumors, coexistence of the two tumors is rare. Placental mesenchymal dysplasia is also a rare disorder. We report the case of a baby girl born after a pregnancy complicated by placental mesenchymal dysplasia, who developed both infantile hepatic hemangioma and hepatic mesenchymal hamartoma. CASE PRESENTATION: The patient was born at 32 weeks and 5 days of gestation for impending placental abruption, weighing 1450 g. Liver tumors, composed of both hypervascular solid and large cystic lesions, were detected after birth and markedly increased to create abdominal distention within 9 months. Diagnostic imaging suspected the coexistence of infantile hepatic hemangioma and cystic hepatic mesenchymal hamartoma. Following propranolol therapy for infantile hepatic hemangioma and needle puncture of a large cyst, the cystic lesions and adjacent hypervascular lesions were partially resected via laparotomy. Pathological findings confirmed the coexistence of hepatic mesenchymal hamartoma and infantile hepatic hemangioma, which had no association with androgenetic/biparental mosaicism. The postoperative course was uneventful, and the tumor had not regrown after 3 years. CONCLUSIONS: Although the coexistence of infantile hepatic hemangioma and hepatic mesenchymal hamartoma associated with placental mesenchymal dysplasia is extremely rare, the pathological and pathogenetic similarities between these disorders suggest that they could have derived from similar embryologic origins rather than being a mere coincidence. Further follow-up is required, with careful attention to the potential for malignant hepatic mesenchymal hamartoma transformation.

A novel risk stratification model based on the Children's Hepatic Tumours International Collaboration-Hepatoblastoma Stratification and deoxyribonucleic acid methylation analysis for hepatoblastoma.

INTRODUCTION: Hepatoblastoma (HB) is the most common paediatric liver tumour, and epigenetic aberrations may be important in HB development. Recently, the Children's Hepatic Tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) developed risk stratification based on clinicopathological factors. This study aimed to construct a more accurate model by integrating CHIC-HS with molecular factors based on DNA methylation. METHODS: HB tumour specimens (N = 132) from patients treated with the Japanese Pediatric Liver Tumors Group-2 protocol were collected and subjected to methylation analysis by bisulfite pyrosequencing. Associations between methylation status and clinicopathological factors, overall survival (OS), and event-free survival (EFS) were retrospectively analysed. We investigated the effectiveness of the evaluation of methylation status in each CHIC-HS risk group and generated a new risk stratification model. RESULTS: Most specimens (82%) were from post-chemotherapy tissue. Hypermethylation in ≥2 of the four genes (RASSF1A, PARP6, OCIAD2, and MST1R) was significantly associated with poorer OS and EFS. Multivariate analysis indicated that ≥2 methylated genes was an independent prognostic factor (hazard ratios of 6.014 and 3.684 for OS and EFS, respectively). Two or more methylated genes was also associated with poorer OS in the CHIC-very low (VL)-/low (L)-risk and CHIC-intermediate (I) risk groups (3-year OS rates were 83% vs. 98% and 50% vs. 95%, respectively). The 3-year OS rates of the VL/L, I, and high-risk groups in the new stratification model were 98%, 90%, and 62% (vs. CHIC-HS [96%, 82%, and 65%, respectively]), optimising CHIC-HS. CONCLUSIONS: Our proposed stratification system considers individual risk in HB and may improve patient clinical management.

Clinicopathological study of surgery for pulmonary metastases of hepatoblastoma with indocyanine green fluorescent imaging.

BACKGROUND: The prognosis of metastatic hepatoblastoma remains poor; to improve it, pulmonary metastasis must be controlled. Indocyanine green (ICG) fluorescent imaging has been used recently for lung metastasectomy. The objective of our study was to clarify the usefulness of ICG imaging for lung metastasectomy of hepatoblastoma using detailed clinicopathological analysis. PROCEDURE: Patients with hepatoblastoma who underwent resection of pulmonary metastases with ICG fluorescent imaging were studied using a retrospective analysis of clinical information, a review of their surgical records, and a histological analysis of their metastatic nodules. RESULTS: Sixteen patients were enrolled. In total, 61 ICG imaging-guided pulmonary metastasectomies were performed, and 350 ICG-positive and 23 ICG-negative specimens were identified. Tumors were confirmed in 250 of the ICG-positive specimens, including eight nonpalpable nodules, on microscopic examination. ICG-positive and tumor-negative specimens showed histological changes suggesting the regression of a tumor or bloodstream disturbance. CONCLUSIONS: Surgical resection is one of the few treatment strategies available to patients with hepatoblastoma with multiple relapses of pulmonary metastasis resistant to chemotherapy. This study demonstrates the high sensitivity of ICG imaging and that thorough metastasectomy can be achieved with ICG imaging. Because a number of false-positive specimens were detected, further optimization of the dose of ICG and the timing of its administration, and establishment of detection of ICG-positive, tumor-negative nodules during surgery are important issues. Several false-negative specimens were also detected, suggesting the presence of ICG-negative metastatic tumors. Palpation during surgery and imaging studies remain essential for detecting metastatic lesions, even in the era of ICG imaging.

Characteristics and treatment of congenital esophageal stenosis: A retrospective collaborative study from three Japanese children's hospitals.

BACKGROUND/PURPOSE: There is no consensus on treatment strategy of congenital esophageal stenosis (CES). This study aimed to assess appropriateness of the treatment we have provided to patients with CES over the past four decades. METHODS: We carried out a retrospective chart review of 83 CES patients treated at three children's hospitals between 1973 and 2015. Each patient underwent an initial treatment with either surgery or a series of dilation that was followed by surgery if dilation failed to improve esophageal transit. Demographic data, course of treatment, outcomes, and complications were analyzed. RESULTS: During this initial treatment, 19 and 64 patients underwent surgery and dilation, respectively. Out of the 64 patients who underwent dilations as an initial treatment, 26 patients eventually required surgery. Out of all patients who required surgery (19 initial treatments + 26 failed dilations), 29 had tracheobronchial remnants and 16 had fibromuscular hypertrophy. Six patients experienced esophageal perforation during dilation and ten experienced anastomotic leakage after surgery. No patients had swallowing difficulties at the latest follow up, 141(9-324) months. CONCLUSIONS: Dilation is recommended as an initial therapy, especially if histological diagnosis of CES is uncertain. Persistent swallowing difficulties after 2 series of dilation may be an indication for surgery. LEVELS OF EVIDENCE: level IV.

A novel method for isolating lymphatic endothelial cells from lymphatic malformations and detecting PIK3CA somatic mutation in these isolated cells.

PURPOSE: Tissue disaggregation and the cell sorting technique by surface markers has played an important role in isolating lymphatic endothelial cells (LECs) from lymphatic malformation (LM). However, this technique may have the drawback of impurities or result in isolation failure because it is dependent on surface marker expressions, the heterogeneity of which has been found in the lymphatic system. We developed a novel method for isolating LM-LECs without using whole tissue disaggregation. METHODS: Seven LM surgical specimens were collected from seven patients with LMs. LM-LECs were detached from the LM cyst wall by "lumen digestion" and irrigating the cystic cavity with trypsin, and maintained in culture. RESULTS: The cells formed a monolayer with a cobblestone-like appearance. Immunohistochemistry and quantitative RT-PCR of these cells revealed high expression of lymphatic-specific genes, confirming their identity as LM-LECs. The whole-exome sequencing and PIK3CA sequencing of these cells revealed somatic mutations in PIK3CA in all cases. CONCLUSIONS: We established a novel technique for isolating LM-LECs from LM tissue by "lumen digestion" without whole-tissue disaggregation. The limited incorporation of non-LM LECs in the isolate in our method could make it an important tool for investigating the heterogeneity of gene expression as well as mutations in LM-LECs.

A MicroRNA Cluster in the DLK1-DIO3 Imprinted Region on Chromosome 14q32.2 Is Dysregulated in Metastatic Hepatoblastomas.

Hepatoblastoma (HB) is the most common malignant liver neoplasm in children. Despite progress in HB therapy, outcomes for patients with metastatic disease remain poor. Dysregulation of miRNA expression is one of the potential epigenetic mechanisms associated with pathogenesis of HB. However, miRNA profiles related to the different stages of HB tissues and cells, in particular of lung metastatic tumor cells, are unknown. In the present study, using array-based miRNA expression and DNA methylation analysis on formalin-fixed paraffin-embedded tissues, we aimed to identify miRNA changes that can discriminate between lung metastatic tumors, primary tumors (fetal and embryonal subtypes), and nontumorous surrounding livers. Our analysis demonstrated that a large cluster of microRNAs and snoRNAs located within the 14q32.2 DLK1-DIO3 region showed a strikingly upregulated expression pattern in HB tumors, especially metastatic tumors, compared to normal liver tissues. This revealed dysregulation of miRNAs similar to that seen in a malignant stem-like subtype of hepatocellular carcinoma associated with poor prognosis. These findings in HB mirror similar findings made in multiple other cancer types. With further analysis this may in future allow stratification of different stages and types of HB tumors based on their miRNA profiles, which could lead to new approaches to diagnosis and treatment in progressive HB patients.

Pilot study of the combination of sorafenib and fractionated irinotecan in pediatric relapse/refractory hepatic cancer (FINEX pilot study).

BACKGROUND: Preclinical observations suggested a synergistic effect of sorafenib (SFN) and irinotecan (CPT-11) in hepatoblastoma (HB). Thus, we conducted a feasibility study of fractionated CPT-11 combined with SFN to develop a new therapy against relapsed/refractory pediatric hepatic cancer (HC). PROCEDURE: The study was originally designed as a phase I, standard 3+3 dose-finding study to evaluate dose-limiting toxicities (DLTs) for the regimen and the optimal CPT-11 dose in combination with SFN against relapsed/refractory pediatric HC, including HB and hepatocellular carcinoma (HCC). The enrolled patients received SFN at 200 mg/m2 every 12 hours or 400 mg/m2 every 24 hours daily combined with CPT-11 at 20 mg/m2 /day on days 1 to 5 as an initial level 1 dose. RESULTS: Six patients with HB (n = 4) or HCC (n = 2) were enrolled and treated with CPT-11 dose level 1. The median age at enrollment was 8.7 (6.2-16.3) years. All patients received platinum-containing chemotherapy, and five or two patients received CPT-11 or SFN before enrollment, respectively. Regimen toxicities were evaluable in all patients. One of six patients experienced a grade 4 transaminase levels increase, which was defined as a DLT per protocol. Grade 3/4 neutropenia and a grade 3 transaminase level increase occurred in three patients and one patient, respectively. All patients reported grade 1/2 toxicities such as anemia, skin toxicity, gastrointestinal symptoms, and hypoalbuminemia. CONCLUSIONS: Although the study was terminated before determining the maximum-tolerated CPT-11 dose, SFN and CPT-11 at the level 1 dose were concluded to be tolerable in pediatric patients with HC.

Lymphatic malformations compromising the upper airway in children: ultrasound-guided intralesional focal sclerotherapy with bleomycin targeting culprit lesions.

PURPOSE: Lymphatic malformations (LMs) compromising the upper airway is a life-threatening and intractable disease. Here, we establish a novel method to perform intralesional focal sclerotherapy targeting the culprit for airway stenosis. METHODS: Between July 2015 and February 2020, 11 patients with airway-compromising LMs were enrolled. To yield maximal effects on the compromised airway with minimal adverse effects, ultrasound-guided intralesional bleomycin sclerotherapy assisted by balloon was performed, aimed at the most responsible lesion around the airway. A retrospective analysis was performed. RESULTS: Ten patients presented with respiratory symptoms, eight of whom required airway support. The last asymptomatic patient showed airway compression on magnetic resonance imaging. The dose of bleomycin injected ranged from 1.3-9 mg per patient per course. A median of one course was required for withdrawal from airway support, and the median time was 15 days. A median of two courses was required to eliminate the lesion adjacent to the airway, which would have potential risk of airway stenosis. No complications were observed. CONCLUSIONS: Our intralesional focal sclerotherapy technique with bleomycin targeting the culprit lesion is dose-sparing, safe, and effective in achieving rapid shrinkage of LMs compromising the upper airway in children, thereby avoiding tracheostomy.

Laparoscopic partial circular myectomy for congenital esophageal stenosis due to tracheobronchial remnant.

Congenital esophageal stenosis (CES) is a rare anomaly, and its appropriate management is not well established. This may be the first report describing laparoscopic partial circular myectomy of the esophageal wall in an infant with CES caused by tracheobronchial remnant (TBR). The narrow segment of the esophagus was laparoscopically detected 1 cm above the esophagogastric junction because the segment was whiter and narrower than the other parts of the esophagus. The narrow segment was approximately 1.5 cm in length. Partial anterior 270° circular muscle layers were dissected using hook electrocautery. Small cartilage-like tissues were identified during the procedure. The muscular layers of both ends were interruptedly sutured. Intraoperative complications were not detected. After undergoing balloon dilation for slight residual stenosis, the patient could eat solid foods without vomiting. Laparoscopic partial circular myectomy is safe and effective for short-segment lower esophageal stenosis in patients with CES caused by TBR.

The Collagen Gel Droplet-embedded Culture Drug Sensitivity Test in Relapsed Hepatoblastoma.

There are few treatment options for patients with unresectable or refractory hepatoblastoma which has failed to respond to the standard treatment. The rarity of the disease and lack of experimental materials have hampered the development of new treatments. In this study, the collagen gel droplet-embedded culture drug sensitivity test was used to evaluate the effectiveness of the multikinase inhibitors sorafenib and sunitinib, and other drugs, in relapsed hepatoblastoma tumor tissues. Tumor samples from 6 patients with relapsed hepatoblastoma were tested for drug sensitivity by the collagen gel droplet-embedded culture drug sensitivity test; evaluable results were obtained from 5 of them. All samples were judged to be sensitive to sorafenib with a 50% growth inhibitory concentration (IC50) of 0.5 to 3.1 µg/mL. Sunitinib did not achieve IC50 in 2 of 3 samples within the tested concentration range based on clinically observed serum concentrations. In the drug combination assay using a hepatoblastoma cell line, sorafenib showed synergistic effects with SN-38, an active metabolite of irinotecan. Our results provide the basic science background warranting future clinical trials of a combination of sorafenib and irinotecan for relapsed or refractory hepatoblastoma.

Continuous transanal decompression for infants with long- and total-type Hirschsprung's diseases as a bridge to curative surgery: a single-center experience.

BACKGROUND: The purpose of this study is to assess the usefulness of continuous bowel decompression using an indwelling transanal tube (ITT) for preoperative management in infants with long-segment (L)- or total (T)-type Hirschsprung's disease (HD). CASE PRESENTATION: Between 2012 and 2015, seven patients with L- or T-type HD underwent preoperative bowel management by continuous bowel decompression using an ITT during waiting period for curative surgery. Continuous bowel decompression was done using an ITT, a 10-12F flexible dual lumen tube placed through the rectum up to the dilated colon under fluoroscopic guidance and secured to the bilateral buttocks. The ITT tips were located at least in a dilated colon or the cecum if there was no radiographic transitional zone. The ITT was left open for continuous drainage, and its patency was checked by regular suction until the curative operation. The patient status and complications of this preoperative management were reviewed retrospectively. RESULTS: The median duration of decompression management was 65 (17-137) days. During decompression period, neither abdominal distention, enterocolitis, nor other complications occurred and six patients could stay at home until the curative operation. The weight-for-age Z-score at curative surgery was the same as or higher than that at birth in five patients. ITT replacement was needed three times per patient on an average for accidental ITT removal, ITT stenosis, or ITT hardening. CONCLUSIONS: Bowel management by continuous bowel decompression using an ITT is easy, safe, and effective for preoperative management in patients with L- or T-type HD and may permit single-stage surgery rendering colostomy or enterostomy unnecessary.

Usefulness of a recanalized umbilical vein for vascular reconstruction in pediatric hepatic surgery.

PURPOSE: Pediatric surgeons currently engage in various abdominal vascular surgeries, which sometimes require vascular conduits or grafts. Herein, we report our experience with patients undergoing vascular reconstruction using a recanalized umbilical vein (rUV) and their long-term outcome. METHOD: Five patients with extrahepatic portal vein obstruction (EHPVO) underwent mesenterico-/porto-left portal vein (PV) bypass surgery using a short rUV conduit with an interposition vein graft. A sixth neonate with a huge hepatic tumor underwent PV reconstruction with anastomosis of rUV to the proximal PV stump following right hepatectomy with partial PV resection. A seventh patient underwent living donor liver transplantation for recurrent hepatoblastoma. The hepatic inferior vena cava (IVC) was resected because of tumor involvement and reconstructed by transposition of the infrahepatic IVC and interposition of rUV obtained from the donor liver graft. RESULTS: Sufficient flow through rUV was achieved and maintained in all patients without any complications during follow-up (0.7-6.9 years). Esophageal varices, splenomegaly, and other laboratory test abnormalities because of portal hypertension disappeared after surgery in patients with EHPVO. CONCLUSION: Our experience confirmed the usefulness and long-term patency of rUV as an entry to the intrahepatic PV and as a free vascular graft to reconstruct PV or IVC.

Standard values of rapid turnover proteins and zinc in Japanese children.

Measurement of rapid-turnover proteins has an established place in nutrition assessment and is partly dependent on the zinc metallo-enzymes involved. We investigated the reference values of rapid turnover proteins and zinc in Japanese children. This cross-sectional study was conducted at a single center. We collected data from children aged 0 to 12 years with inguinal hernia, umbilical hernia, or hydrocele of the spermatic cord, who had body mass index z scores of -2 to 2. The standard references (mean±2 SD) of transthyretin were 11.5-21.5 mg/dL in infants (<=1.5 years), 13.6-21.5 mg/dL in preschool children (1.6-6 years), and 12.3-23.4 mg/dL in preadolescent children (6.1-12 years). The standard references of retinol binding protein were 1.27-2.55 mg/dL, 1.28-2.54 mg/dL, and 1.27-2.44 mg/dL in each age group, respectively. Rapid turnover proteins did not differ significantly in each group. The transthyretin level was weakly correlated with aging (r=0.284, p=0.003) and estimated lean body mass (r=0.274, p=0.004). Retinol-binding protein was not correlated with aging and anthropometric parameters. We established reference values for rapid turnover proteins with known zinc status in Japanese children. These values were not, or only weakly, correlated with anthropometric parameters for assessing protein energy malnutrition.

Chylothorax associated with child abuse.

We report a case of right chylothorax associated with physical abuse in a 10-month-old boy who presented with respiratory decompensation. Chylothorax was improved by thoracic drainage and nutrition management, such as fasting followed by medium-chain triglyceride milk. Chest computed tomography on admission showed bilateral old rib fractures. Accordingly, physical abuse was suspected. Chylothorax of unknown cause in infancy, especially in those with coexisting rib fractures, must be scrutinized for child abuse.

Impact of an external lengthening procedure on the outcome of long-gap esophageal atresia at our hospitals.

PURPOSE: To demonstrate the outcome of external lengthening for long-gap esophageal atresia (LGEA) at our hospitals. METHODS: Five patients with LGEA underwent external lengthening between 2010 and 2014 (group A), and 11 patients with LGEA underwent other lengthening techniques between 1990 and 2011 (group B). We compared the procedure and outcome between these two groups. RESULTS: The mean birth weight was 2001 g in group A and 2485 g in group B (p = 0.06). The mean age at esophageal reconstruction was 28 days in group A and 227 days in group B (p = 0.03). Although primary esophageal anastomosis without myotomy was feasible in all patients in group A, a myotomy was needed for primary esophageal anastomosis in half of the patients in group B. Anastomotic leakage occurred in none in group A and in six patients in group B (p = 0.03). The mean age at the establishment of full oral feeding was 76 days in group A and 686 days in group B (p = 0.009). CONCLUSION: External traction for LGEA can effectively lengthen the esophagus to enable primary anastomosis at an earlier age. This may facilitate oral intake.

A case of alpha-fetoprotein-producing gastric cancer in a child presenting with rupture of multiple liver metastases.

We report a 14-year-old boy with alpha-fetoprotein-producing gastric cancer (AFPGC) who was found with ruptured metastatic tumor in the liver. AFPGC is exceedingly rare in pediatric age. It often shows metastases to the liver and should be included in differential diagnoses of liver tumors with increased serum AFP.

Navigation using indocyanine green fluorescence imaging for hepatoblastoma pulmonary metastases surgery.

To achieve precise and sensitive detection of chemotherapy-resistant hepatoblastoma pulmonary metastases, we performed surgery using indocyanine green (ICG) fluorescence imaging navigation. Lung metastasectomies were performed in 10 patients aged from 1 to 11 years. ICG (0.5 mg/kg) was injected intravenously 24 h before the operation. After a thoracotomy had been performed, a 760-nm infrared ray was applied to the lung using a generator and the 830-nm evoked fluorescence was collected and visualized on a real-time display. In total, 250 fluorescence-positive lesions were extirpated in 37 operations. All of the pathologically positive lesions were clearly fluorescence positive. The diameter of the smallest detectable lesion was 0.062 mm. In two patients, there were 29 extirpated lesions that were pathologically proven not to be hepatoblastoma metastases. Although a problem of false positive remains, this method is very useful for the detection of small pulmonary metastases.