Balloon dilatation for congenital esophageal stenosis associated with esophageal atresia.

PURPOSE: Congenital esophageal stenosis (CES) associated with esophageal atresia (EA) is rare, and no standard treatment has been established. We reviewed cases of EA-associated CES to assess the clinical characteristics and treatment outcomes, especially the feasibility of endoscopic dilatation. METHODS: We retrospectively examined patients with EA-associated CES. We also compared treatment outcomes of EA-associated CES with those of EA patients without CES who developed postoperative anastomotic stricture. RESULTS: Among 44 patients with EA, ten had CES (23%). Postoperative complications were not significantly different between EA patients with CES and those without CES but with anastomotic stricture. All CES patients underwent balloon dilatation as initial treatment. Eight of nine patients (89%) were successfully treated by dilatation only, and one patient underwent surgical resection. The median number of balloon dilatations for CES was five (2-17), which was higher than that for anastomotic stricture in patients without CES (p = 0.012). Esophageal perforation occurred in five patients with CES (5/9, 56%) after dilatation, but all perforations were successfully managed conservatively with an uneventful post-dilatation course. CONCLUSIONS: Twenty-three percent of patients with EA had CES. Although balloon dilatation for EA-associated CES required multiple treatments and carried a risk of perforation, balloon dilatation showed an 89% success rate and all perforations could be managed conservatively.

Tension-free thoracoscopic repair of congenital diaphragmatic hernia combined with a percutaneous extracorporeal closure technique: how to do it.

PURPOSE: Thoracoscopic repair (TR) of congenital diaphragmatic hernia (CDH) is associated with a higher recurrence rate than the conventional open method. We evaluated the effectiveness of our strategy for quality improvement, named "tension-free TR of CDH". METHODS: The subjects of this retrospective analysis were 11 consecutive patients with CDH who underwent TR at our hospital between 2017 and 2021. Tension-free TR of CDH included the proactive use of an oversized patch for dome-shaped reconstruction and gapless suturing. We developed a percutaneous extracorporeal closure technique for secure suturing using a commercially available needle. RESULTS: Patch repair was performed in 8 (73%) patients and none required conversion to open surgery because of technical difficulties. Recurrence developed in one patient (9%), who underwent successful reoperation via TR. All patients had an uneventful postoperative course. CONCLUSION: Tension-free TR combined with extracorporeal closure could reduce the difficulty of suturing and the risk of recurrence of CDH.

Treatment and follow-up of late onset intra hepatic bile duct stones in congenital biliary dilatation.

PURPOSE: The postoperative course after surgery for congenital biliary dilatation (CBD) has some complications. Intrahepatic bile duct (IHBD) stones were known as a late complication. We report on the treatment and long-term follow-up of postoperative IHBD stones in our department. METHODS: Patients who underwent CBD surgery at age 15 years or younger in our department were identified. Those followed up for 5 years or more were enrolled. Annual blood chemistry tests and abdominal ultrasonography were performed. Each patient's surgical procedure, IHBD stone diagnosis, treatments, and outcomes were retrospectively assessed. RESULTS: Fifty-one patients were analyzed. The median age at the last visit was 24 years (range 7-45 years), and the median age at CBD surgery was 3 years. Eight patients (16%) developed late-onset IHBD stones. The median age at onset was 25 years, and the median duration after surgery was 20 years. The initial treatment was double-balloon enteroscopy (DBE) in 4 cases, which resulted in stone removal in 3 of the 4 patients (75%). CONCLUSION: Since CBD may cause late-onset IHBD stones, continuous follow-up is required even in adulthood. In this study, DBE was effective and minimally invasive, and it is recommended as the initial treatment.

Early detection of liver fibrosis with serum Mac-2 binding protein glycosylation-modified isomer (M2BPGi) during follow-up intestinal failure patients without intestinal failure-associated liver disease (IFALD).

PURPOSE: Mac-2 binding protein glycosylation-modified isomer (M2BPGi) is a new marker for hepatic fibrosis progression. We examined the relationship between serum M2BPGi levels and liver histological findings in intestinal failure (IF) patients without IF-associated liver disease (IFALD). METHODS: This study included IF patients without IFALD followed at our hospital. All patients underwent routine liver biopsies per protocol every 1-2 years. We examined M2BPGi levels and histological findings in relation to aspartate aminotransferase (AST) to platelet ratio index, fibrosis-4 index, and AST/ALT ratio. Liver fibrosis was evaluated based on the METAVIR score. RESULTS: Total 18 liver biopsies out of eight patients were included. The median age was 11.5 years. Mean M2BPGi was 0.44 cutoff index (COI) in patients with F0 fibrosis, 0.78 COI in patients with F1 fibrosis and 1.63 COI in patients with F2 fibrosis. Mean M2BPGi was significantly higher in patients with F2 versus F1 or F0 fibrosis (P < 0.016 and P < 0.028, respectively). M2BPGi levels were more strongly correlated with fibrosis stage than with other conventional fibrosis markers. CONCLUSION: Serum M2BPGi is a novel marker of liver fibrosis in patients with IF. It is useful for follow-up prior to IFALD. Serum M2BPGi levels can support the interpretation of liver status.

Effect of microscopy-assisted portoenterostomy (MAPE) for biliary atresia.

PURPOSE: Portoenterostomy (PE) is the standard treatment for biliary atresia (BA). However, micro-bile ducts are difficult to identify with surgical loupes and dissect systematically. We report the effects of our attempts to dissect hilar tissue using a surgical microscope. METHODS: Microscopy-assisted portoenterostomy (MAPE) was initiated in 2014. Patients born between 2000 and 2013 who underwent PE until day 70 without a surgical microscope for BA were gathered as historical control. MAPE in re-do PE cases (Re-MAPE) was evaluated in the same manner. RESULTS: Ten patients underwent MAPE for BA during the study period. 17 patients in the conventional PE group were gathered. In the MAPE group, the jaundice clearance rate was 80%, compared with 53% in the conventional PE group. Re-MAPE was performed in four patients, who had a jaundice clearance rate of 75%, essentially identical to the rate with initial MAPE. At age 4 years, the native liver survival rate was 58% in the MAPE group and 38% in the conventional PE group. The native liver survival rate in the Re-MAPE group was 75%. CONCLUSION: MAPE is useful for sharing the surgical field during open PE in patients with BA. It may improve the rate of jaundice clearance.

Computed tomography-guided marking using a dye-staining method for preoperative localization of tiny pulmonary lesions in children.

PURPOSE: It is important to confirm the existence of pulmonary metastases in pediatric patients with malignancies. Therefore, we aimed to investigate if computed tomography CT-guided marking is a feasible and safe method for the identification and resection of tiny pulmonary lesions in pediatric cancer patients. METHODS: We retrospectively reviewed the medical records of pediatric cancer patients who underwent CT-guided marking procedures in our institutions between Jan 2011 and Apr 2020. After 2015, these procedures were combined with an indocyanine green (ICG) navigation-guided surgery for hepatoblastoma cases. RESULTS: We targeted a total of 22 nodules in 12 patients. Of these, marking was successful in 18 (81.8%) nodules, 10 of which contained viable malignant cells. Complications caused by the marking procedures included mild pneumothorax and mild atelectasis in two patients, respectively. Of the eight resected nodules in patients with hepatoblastoma, four were ICG-positive and contained viable malignant cells. Two additional ICG-positive nodules, which were unidentified before surgery, were observed intraoperatively. CONCLUSION: CT-guided marking is a feasible and safe method that can be used to identify and resect tiny pulmonary lesions in pediatric cancer patients. An ICG navigation-guided surgery is useful when combined with CT-guided marking, particularly in hepatoblastoma cases.

Results of mass screening for neuroblastoma in 18-month-old infants in Osaka area, Japan.

PURPOSE: In 2004, the Japanese government halted nationwide mass screening for neuroblastoma in 6-month-old infants as it led to overdiagnosis of localized tumors with favorable prognoses and failed to reduce neuroblastoma-related mortality. However, a new mass screening program for neuroblastoma in 18-month-old infants (18MS) was conducted in the Osaka prefecture. We assessed the efficacy of the 18MS in screening unfavorable cases. METHODS: Public health centers in Osaka prefecture, excluding the Osaka city area, provided test kits to the guardians of infants who received a check-up at 18 months of age between 2004 and 2017. For patients whose standardized urinary levels of vanillylmandelic acid or homovanillic acid exceeded the threshold, they were further examined and treated in two specific hospitals Osaka University Hospital and Osaka Women's and Children's Hospital. Screening-positive patients with and without neuroblastoma were retrospectively reviewed. RESULTS: Among 142,423 children screened during the 18MS, 85 tested positive, and 14 were diagnosed with neuroblastoma. Twelve patients were classified as very low risk, while 2 were classified as high risk, based on the International Neuroblastoma Risk Group risk classification. CONCLUSION: The 18MS did not screen unfavorable cases with neuroblastoma efficiently, although few participants benefited from it.

Thoracoscopic repair of esophageal atresia.

Thoracoscopic repair (TR) of esophageal atresia (EA) has been performed with increasing frequency over the last two decades, with the expectation of improved outcomes by avoiding thoracotomy. To understand the current practice and outcomes of TR of EA, we reviewed the relevant literature, including 15 case series, 7 comparative studies, and 3 meta-analysis comparing TR with conventional open repair (COR). Most of the studies had a retrospective design and small numbers of patients. Although the evidence level is low because of the lack of prospective studies, this review found that TR is as safe as COR, with comparative outcomes. Moreover, there were several advantages of TR over COR, such as less blood loss and a shorter hospital stay. The long-term outcomes of TR remain unclear because of limited data. Moreover, there is a significant learning curve over the first 10-20 TRs performed. We conclude that TR of EA, when conducted by experienced surgeons, is a safe and minimally invasive alternative to COR and may yield better results than COR in appropriately selected patients.

Potential role of the PD-L1 expression and tumor-infiltrating lymphocytes on neuroblastoma.

PURPOSE: The programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway has garnered much attention for its roles in clinical oncology. The aim of this study was to examine the clinical impact of the PD-L1 expression and tumor-infiltrating lymphocytes (TILs) on neuroblastoma. METHODS: We evaluated the PD-L1 expression and TIL status in 31 patients with neuroblastoma who underwent a biopsy or resection by an immunohistochemical analysis. Furthermore, we performed the serial analysis of the PD-L1 status before and after chemotherapy in 15 patients. RESULTS: Among the 31 cases, 11 (35%) showed a positive PD-L1 expression. The survival analysis showed a trend toward an association between PD-L1 positivity and a decreased overall survival. PD-L1 positivity tended to be associated with higher levels of tumor markers. In the serial analysis of the PD-L1 status, positivity was noted in 8 of 15 patients before chemotherapy and 6 after chemotherapy. Notably, all four patients with a positive PD-L1 status both before and after chemotherapy had recurrence, and 3 of them died during the follow-up period. CONCLUSION: Our findings suggest that the PD-L1 tumor expression might be a good biomarker for the treatment of neuroblastoma patients, especially for advanced neuroblastoma.

Serum Mac-2-binding protein (M2BPGi) as a marker of chronological liver fibrosis in biliary atresia patients with cirrhosis.

PURPOSE: Biliary atresia (BA) is characterized by progressive liver fibrosis, but it is difficult to assess the progression after the patient develops cirrhosis. Mac-2-binding protein glycosylation isomer (M2BPGi) is a new marker for hepatic fibrosis. We examined the chronological changes in M2BPGi levels in BA patients with cirrhosis. METHODS: Patients with cirrhosis were selected from among pediatric BA patients who had their native livers. Serum M2BPGi levels and Child-Pugh classification were evaluated. A total of 11 pediatric BA patients with cirrhosis were recruited. RESULTS: Initial M2BPGi level after diagnosis of liver cirrhosis based on liver biopsy was on average 3.4, and the most recent M2BPGi level under observation was on average 4.3. The follow-up period from the initial M2BPGi measurement averaged 22.6 months. The ratio of the initial and most recent values (M2BPGi ratio) was on average 1.3 (0.5-2.4). Three cases with improved fibrosis (M2BPGi ratio < 1.0) remained in Child A, as did six cases (1.0 ≤ M2BPGi ratio < 2.0), but two cases with marked fibrosis progression (2.0 ≤ M2BPGi ratio) advanced to decompensated cirrhosis Child B. CONCLUSION: M2BPGi is useful as a prognostic factor for BA patients with liver cirrhosis. In addition, fibrosis improved even after the development of cirrhosis.

Cancer's Achilles' Heel: Apoptosis and Necroptosis to the Rescue.

Apoptosis, and the more recently discovered necroptosis, are two avenues of programmed cell death. Cancer cells survive by evading these two programs, driven by oncogenes and tumor suppressor genes. While traditional therapy using small molecular inhibitors and chemotherapy are continuously being utilized, a new and exciting approach is actively underway by identifying and using synergistic relationship between driver and rescue genes in a cancer cell. Through these synthetic lethal relationships, we are gaining tremendous insights into tumor vulnerabilities and specific molecular avenues for induction of programmed cell death. In this review, we briefly discuss the two cell death processes and cite examples of such synergistic manipulations for therapeutic purposes.

Impact of Total Parenteral Nutrition on Preoperative Management of Pediatric Living-Donor Liver Transplantation for Biliary Atresia Under 2 Years Old.

BACKGROUND: Liver failure and gastrointestinal bleeding occur in the end-stage of biliary atresia (BA). Living-donor liver transplantation (LDLT) is a standard treatment in Japan. Our program actively provides pre-transplant total parenteral nutrition (TPN) for such patients, and here we report its efficiency and safety. METHODS: Patients with BA for whom LDLT was indicated were identified. Those with a long-term external central venous catheter and TPN, longer than 4 weeks before LDLT, were analyzed. Ascites was controlled with diuretics. TPN indications, efficacy, and complications were assessed along with patient growth, biochemical markers, and gastrointestinal bleeding. RESULTS: Fourteen patients were included in the study, of whom 8 were girls and 6 were boys. The median age at LDLT was 0.9 years. Body weight (BW) at TPN initiation averaged 6799 g, and the median serum total bilirubin was 9.5 mg per dL. The median catheterization duration was 54 days, and 1 patient received home TPN. Indications for TPN were gastrointestinal bleeding and/or massive esophageal varices in 4 patients and poor nutritional status in 10 patients. No complications were observed except for 1 catheter infection and 1 catheter occlusion. The median final body weight before LDLT was 7906 g. The mean rate of BW gain was significantly higher after TPN than before (149 vs 32 g/wk, respectively, P = .0002). Mean prothrombin time and levels of albumin, cholinesterase, and total bilirubin were not significantly different at the start and end of TPN. CONCLUSIONS: Pre-transplant TPN was safe and effective for patients with end-stage BA.

Plasma Concentration of Antifungal Agent Micafungin for Pediatric Living Donor Liver Transplantation.

BACKGROUND: Pediatric living-donor liver transplantation (LDLT) candidates often receive long-term antibiotic treatment. Micafungin has been used as an antifungal agent after LDLT, but the adequate dose after pediatric LDLT was unknown. Here, we report micafungin blood concentrations after pediatric LDLT and discuss its safety and adequate dosing. METHODS: Pediatric patients with data on micafungin concentrations after LDLT were identified. Those with surgical complications were excluded. All patients received standard tacrolimus-based immunosuppression. A micafungin dose of 1 mg/kg was administered once daily for 10 days starting on postoperative day (POD) 1. The trough and peak micafungin blood concentrations were evaluated on PODs 1, 4, 7, and 10. Beta D glucan levels and liver function tests were assessed to determine micafungin effectiveness and safety. RESULTS: Ten patients were enrolled, with a median age of 1.2 years. The median graft vs body weight ratio was 2.7%. The primary diseases were biliary atresia (n = 7), Alagille syndrome (n = 2), and progressive familial intrahepatic cholestasis type 2 (n = 1). Mean peak micafungin levels were 4.47, 6.27, 5.47, and 5.47 µg/mL on PODs 1, 4, 7, and 10, respectively. Mean trough levels were 2.03, 1.88, and 2.66 µg/mL on PODs 4, 7, and 10, respectively. The micafungin half-lives were 13.7, 14.7, and 14.0 hours on PODs 4, 7, and 10, respectively. Beta D glucan levels were 4.4 pg/mL and 3.7 pg/mL before and after transplantation, respectively, indicating no significant difference (P = .3). No clinical fungal infections were observed. CONCLUSION: Micafungin administration is safe and effective after pediatric LDLT.

Clinical Implications of Serum Mac-2 Binding Protein in Patients After Living Donor Liver Transplantation for Biliary Atresia.

BACKGROUND: Patients who undergo pediatric living donor liver transplantation (LDLT) sometimes develop graft fibrosis. Recently, Mac-2 binding protein glycosylation-modified isomer (M2BPGi) was developed as a new marker of hepatic fibrosis progression. We performed this study to examine the relationship between serum M2BPGi levels and liver histologic findings in patients after LDLT for biliary atresia. METHODS: Patients aged <19 years who underwent LDLT for biliary atresia at our institution and followed up for at least 1 year after LDLT were eligible. There were 56 patients in this study. Pathologic findings of the last available biopsy were assessed. Portal vein (PV) stenosis was confirmed with angiography. M2BPGi levels were compared with pathologic fibrosis scores and PV stenosis findings. RESULTS: The mean age at transplant was 4.3 years. The mean observation period was 8.6 years. In terms of the degree of liver fibrosis, F0 was observed in 7 patients, F1 in 36, and F2 in 13. The median serum M2BPGi value was 0.8 cut-off index (COI) overall and 0.60 COI for F0, 0.74 COI for F1, and 1.07 COI for F2. The mean M2BPGi value in F2 was higher than that in F0 (P = .016) and F1 (P = .012). Mean serum M2BPGi values were 1.57 COI (0.29 COI) in patients with PV complications (n = 5) and 0.72 COI in patients without PV complications (n = 51) (P = .0001). CONCLUSION: M2BPGi is a novel marker for liver fibrosis in patients after pediatric LDLT. It is especially useful for follow-up of pediatric patients after LDLT to support liver biopsy interpretation.

13-Cis retinoic acid can enhance the antitumor activity of non-replicating Sendai virus particle against neuroblastoma.

Hemagglutinating virus of Japan-envelope (HVJ-E) is a drug delivery vector based on inactivated Sendai virus. Recently, antitumor activities were found for HVJ-E itself and clinical trials of HVJ-E for some malignant tumors are now ongoing. We investigated the in vitro and in vivo antitumor effects of HVJ-E against neuroblastoma, which is one of the most common malignant solid tumors in childhood. The sensitivity of human neuroblastoma cell lines to HVJ-E correlated with the expression level of gangliosides, Sialylparagloboside (SPG) and GD1a, receptors for HVJ. Among the cell lines, SK-N-SH was the most sensitive to HVJ-E in vitro and total SPG and GD1a expression was the highest. Complete eradication of subcutaneous tumors derived from SK-N-SH cells was achieved by intratumoral injection of HVJ-E in SCID mice and no recurrence was observed for more than 300 days after HVJ-E inoculation. In contrast, NB1 cells expressed the lowest amount of GD1a and SPG and were resistant to HVJ-E in vitro. The expression of GD1a increased by 13-cis retinoic acid (13cRA), which is a therapeutic drug for high risk neuroblastoma, thus leading to an improved sensitivity to HVJ-E in vitro. Only growth inhibition of the subcutaneous tumors derived from NB1 cells was achieved by HVJ-E in the SCID mice, but the combination of 13cRA and HVJ-E could achieve partial eradication of the xenograft and also lead to an improved prognosis. In conclusion, HVJ-E is a promising therapeutic modality for neuroblastoma and 13cRA can be used as an adjuvant to HVJ-E.

Hedgehog signal inhibitors suppress the invasion of human rhabdomyosarcoma cells.

PURPOSE: In the treatment of rhabdomyosarcoma (RMS), invasion and metastasis remain the most critical determinants of resectability and survival. The objective of this study was to determine whether Hedgehog (Hh) signaling plays a role in the invasion of RMS. METHODS: Two kinds of specific Hh signaling inhibitors, cyclopamine and forskolin, were used to suppress activated Hh signals in three RMS cell lines. The effects of the Hh signaling inhibitors on tumor cell invasion and motility were investigated using Matrigel invasion assays and wound closure assays, respectively. RESULTS: The number of invaded cells counted in six random microscopic fields in the Matrigel chambers was significantly decreased by both cyclopamine and forskolin in every RMS cell line. Furthermore, the wound closure assays revealed that a blockade of the Hh signaling pathway by the Hh inhibitors strongly impairs RMS cell motility, as visualized by the delayed closure of the gaps generated in the cultured cell monolayers of the three RMS cell lines. CONCLUSIONS: Both the invasive capacity and motility of RMS cells are significantly suppressed by Hh signaling inhibitors, demonstrating that the Hh pathway plays an important role in the invasion of RMS. Hh inhibitors may provide a new paradigm for the treatment of RMS.

Stapleless thoracoscopic lobectomy for congenital pulmonary airway malformation: a simple technique in thoracoscopic surgery.

Congenital pulmonary airway malformation (CPAM) is a developmental malformation that affects the lung parenchyma, especially terminal respiratory bronchioles. This paper reports a case of an infant diagnosed with CPAM who underwent stapleless thoracoscopic lobectomy using Hem-o-Lok clips®. Computed tomography showed cystic pulmonary lesions in the left lower lobe. Thoracoscopic lobectomy was performed at the age of 1 year and 3 months. During surgery, the hilar vasculature was treated using either Hem-o-Lok® clips or a LigaSure vessel sealing system. The lower lobe bronchus was divided using double Hem-o-Lok® clips proximally. The surgery was successfully completed. The patient's postoperative course was uneventful, and there were no complications. This technique can be easily performed as a thoracoscopic lobectomy with the potential benefits of safe and effective procedures for bronchus closure and vascular sealing in the small working space of pediatric patients.

Factors reducing psychological satisfaction after the Nuss procedure in pediatric patients.

PURPOSE: We examined patient satisfaction with postoperative chest appearance after Nuss procedure and analyzed the factors for postoperative low satisfaction. METHODS: We retrospectively reviewed data of 133 patients who underwent the Nuss procedure from 2000 to 2016. Their medical records, X-rays, and computed tomography scans were evaluated. Haller index and concave rate were used as objective indices of the deformity. The questionnaires were used to evaluate satisfaction with the chest appearance by a linear scale including five markers (1: dissatisfaction, 5: satisfaction). The patients were divided into two groups: the low satisfaction (score = 1, 2) and the high satisfaction (score = 3-5). RESULTS: The median age during the Nuss procedure was 7.6 (interquartile range, 5.8-12.8) years. Out of 133, 65 patients replied, and the mean postoperative satisfaction score was 3.8 ± 0.2. Out of the 65 respondents, 16 patients (24.6%) were classified as low satisfaction group. Haller index and concave rate were significantly higher and the previous instances of chest operation history were more frequent in the low satisfaction group than in the high satisfaction group, although there was no significant intergroup difference in terms of the postoperative concave rate. CONCLUSIONS: Severe deformity and previous chest operation history were considered to be factors for low satisfaction.

Liver-Spleen Volume Ratio as a Predictor of Native Liver Survival in Patients with Biliary Atresia.

BACKGROUND: The appropriate timing of liver transplantation (LT) in patients with biliary atresia (BA) who survived with their native livers until adolescence remains controversial. The liver-spleen volume ratio (LSR) has been reported to be efficacious in predicting the prognosis of chronic liver disease. We investigated whether LSR could predict long-term native liver prognosis and serve as an indication for LT in patients with BA. METHODS: Patients with BA who survived with their native liver until the age of 15 years were included. These patients were classified into 2 groups. The unfavorable prognosis group included patients who underwent or were awaiting LT or developed complications such as refractory cholangitis or gastrointestinal bleeding due to esophagogastric or intestinal varices. The favorable prognosis group included patients who survived with their native liver without complications. We compared the 2 groups regarding LSR, hematological, and histologic data. RESULTS: Of 19 patients, 8 were in the unfavorable prognosis group, and 11 were in the favorable prognosis group. LSR was significantly lower in the unfavorable prognosis group (P = .009). Analysis of the receiver operating characteristic curve showed that the area under the curve of the LSR was 0.891, which was higher than the area under the curve of liver fibrosis markers. The optimal LSR cut-off value for predicting poor native liver prognosis was 1.97, with a sensitivity of 75.0% and a specificity of 87.5%. CONCLUSIONS: The LSR reflects splenomegaly and liver atrophy. The LSR might be a reliable predictor of native liver prognosis and could guide decisions about LT in patients with BA.

Inhibition of cIAP1 in the effective suppression of chemotherapy­resistant hepatoblastoma.

Cellular inhibitor of apoptosis protein­1 (cIAP1) is a key regulator of programmed cell death and is known to be associated with chemotherapeutic resistance. The present study aimed to investigate the antitumor efficacy of birinapant, a novel selective inhibitor of cIAP1, against cisplatin (CDDP)­resistant hepatoblastoma (HB) cells. Western blot analysis was used to investigate the antitumor effect of birinapant on cIAP1 expression in Huh6 cells at the protein level. A WST­8 assay was performed to evaluate the tumor growth inhibitory effect of birinapant on the human HB cell lines, Huh6 and HepG2. Huh6 cells were exposed to CDDP and/or birinapant in order to confirm tumor growth inhibition. The antitumor efficacy of birinapant plus CDDP combination therapy was significantly higher than that of CDDP monotherapy in a dose­dependent manner (P=0.035). The study also investigated the antitumor efficacy of birinapant plus CDDP combination therapy in an established xenograft model of SCID mice. Compared with CDDP monotherapy, birinapant combined with CDDP showed better inhibition of tumor growth (P=0.121). It was observed that the mRNA expression of cIAP1 in tumors was significantly enriched in the CDDP monotherapy group compared with that in the untreated group. Furthermore, immunohistochemical staining was performed to compare cIAP1 expression in pre­ and post­chemotherapy specimens in patients with HB, and a significant increase was observed in the post­chemotherapy specimens (P<0.001). CDDP­resistant Huh6 (Huh6­CDDPR) cells were also established following repeated exposure to CDDP. Birinapant was substantially more effective against the Huh6­CDDPR cells than against the Huh6 wild­type cells. Taken together, these findings suggest that repeated exposure to CDDP enhances cIAP1 expression in HB cells and that birinapant is a promising therapeutic drug for CDDP­resistant HB.