Published papers

Purpose: This study aimed to compare respiratory functions of patients after thoracoscopic lobectomy (TS) with those after thoracotomy (TR). Methods: This retrospective study was conducted in two centers, one of which adapted TS as a standard procedure in 2009 and the other performs it via TR. Data on patients who underwent lobectomy for congenital lung disease between 2009 and 2021 and underwent pulmonary function test (spirometry) were collected. Results: Ten patients underwent TS and 36 underwent TR. Distribution based on sex, prenatal diagnosis, pathological diagnosis, and resected lobe were similar between the two groups. The median [interquartile range] age at procedure in the TR group was significantly smaller than that in the TS group (13 [11-18] months versus 38 [13-79] months, P = .03). The procedure duration in the TR group was significantly shorter than that in the TS group (230 [171-264] minutes versus 264 [226-420] minutes, P = .02). Pulmonary function test was conducted at the age of eight in both groups, but the interval between the procedure, and the test was significantly shorter in the TS group (TR: 7 [5-8] years versus TS: 5 [2-7] years, P = .03). The ratio of forced vital capacity compared to predicted one (TR: 86.6 [76.6-95.3] versus TS: 88.7 [86.8-89.1], P = .58) and the ratio of forced expiratory volume in 1 second against that predicted (TR: 84.0 [80.5-88.7] versus TS: 88.7 [86.8-89.1], P = .08) were not significantly different between the two groups. Conclusions: Although TR was performed earlier than TS, respiratory function was similar between the two groups.

Recent studies have shown that the PI3K signaling pathway plays an important role in the pathogenesis of slow-flow vascular malformations (SFVMs). Analysis of genetic mutations has advanced our understanding of the mechanisms involved in SFVM pathogenesis and may identify new therapeutic targets. We screened for somatic variants in a cohort of patients with SFVMs using targeted next-generation sequencing. Targeted next-generation sequencing of 29 candidate genes associated with vascular anomalies or with the PI3K signaling pathway was performed on affected tissues from patients with SFVMs. Fifty-nine patients with SFVMs (venous malformations n = 21, lymphatic malformations n = 27, lymphatic venous malformations n = 1, and Klippel–Trenaunay syndrome n = 10) were included in the study. TEK and PIK3CA were the most commonly mutated genes in the study. We detected eight TEK pathogenic variants in 10 samples (16.9%) and three PIK3CA pathogenic variants in 28 samples (47.5%). In total, 37 of 59 patients (62.7%) with SFVMs harbored pathogenic variants in these three genes involved in the PI3K signaling pathway. Inhibitors of this pathway may prove useful as molecular targeted therapies for SFVMs.

We report a case of a one-year-old boy with a congenital dermal sinus situated at the lateral buttock. The exact pathway of the sinus was shown by magnetic resonance imaging, contrast medium examination and computed tomographic examination. The sinus was not connected to the spinal canal and the sinus ended near the anterior surface of the sacral bone in a blind manner. Complete surgical resection of the sinus was achieved after these imaging examinations.

Background: Hemorrhoids are an extremely rare condition in children, and data on its incidence and treatment in the pediatric population remains scarce. We retrospectively reviewed children who underwent sclerotherapy for internal hemorrhoids, and analyzed patients' characteristics and outcomes. Methods: A total of 14 pediatric patients who underwent sclerotherapy were included. Patients' ages and the required amount of polidocanol, depending on the grade of hemorrhoids, and the correlation between age and volume of sclerosant, were statistically analyzed. Results: Patients had a male predominance with a ratio of 2.5:1 (grade 2:6 patients, grade 3:8 patients). Four children had underlying conditions including portal hypertension and Klippel–Trenaunay syndrome. Of the 14 patients, 43% had constipation requiring medication or enema. Only one minor complication, a perianal ulceration, was found to be associated with sclerotherapy. Patients with grade 3 hemorrhoids required a significantly larger amount of polidocanol than those with grade 2 hemorrhoids. Two patients with grade 3 hemorrhoids required a second session of treatment for recurrence. The success rate of sclerotherapy with polidocanol was 86%. Conclusions: Sclerotherapy with polidocanol is a safe, effective, and less invasive treatment option for internal hemorrhoids in children. Further studies are needed to investigate this treatment approach.

Background: We performed the first autologous oral mucosa-derived epithelial cell sheet transplantation therapy in a patient with refractory postoperative anastomotic stricture in congenital esophageal atresia (CEA) and confirmed its safety. In this study, patients with CEA and congenital esophageal stenosis were newly added as subjects to further evaluate the safety and efficacy of cell sheet transplantation therapy. Methods: Epithelial cell sheets were prepared from the oral mucosa of the subjects and transplanted into esophageal tears created by endoscopic balloon dilatation (EBD). The safety of the cell sheets was confirmed by quality control testing, and the safety of the transplantation treatment was confirmed by 48-week follow-up examinations. Results: Subject 1 had a stenosis resected because the frequency of EBD did not decrease after the second transplantation. Histopathological examination of the resected stenosis revealed marked thickening of the submucosal layer. Subjects 2 and 3 did not require EBD for 48 weeks after transplantation, during which time they were able to maintain a normal diet by mouth. Conclusions: Subjects 2 and 3 were free of EBD for a long period of time after transplantation, confirming that cell sheet transplantation therapy is clearly effective in some cases. In the future, it is necessary to study more cases; develop new technologies such as an objective index to evaluate the efficacy of cell sheet transplantation therapy and a device to achieve more accurate transplantation; identify cases in which the current therapy is effective; and find the optimal timing of transplantation; and clarify the mechanism by which the current therapy improves stenosis. Trial registration: UMIN, UMIN000034566, registered 19 October 2018, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039393.

Background: Congenital esophageal atresia postoperative anastomotic stricture occurs in 30–50% of cases. Patients with severe dysphagia are treated with endoscopic balloon dilatation (EBD) and/or local injection of steroids, but many patients continue to experience frequent stricture. In this study, we investigated the transplantation of autologous oral mucosa-derived cell sheets (epithelial cell sheets) as a prophylactic treatment for congenital esophageal atresia postoperative anastomotic stricture. Methods: Epithelial cell sheets were fabricated from a patient’s oral epithelial tissue, and their safety was confirmed by quality control tests. The epithelial cell sheets were transported under controlled conditions from the fabrication facility to the transplantation facility and successfully transplanted onto the lacerations caused by EBD using a newly developed transplantation device for pediatric patients. The safety of the transplantation was confirmed by follow-up examinations over 48 weeks. Results: The dates that EBD was performed were recorded for one year before and after epithelial cell sheet transplantation, and the intervals (in days) were evaluated. For about 6 months after transplantation, the intervals between EBDs were longer than in the year before transplantation. The patients were also aware of a reduction in dysphagia after transplantation. Conclusions: These results suggest that cell sheet transplantation may be effective in preventing anastomotic stricture after surgery for congenital esophageal atresia, but the effect was temporary and limited in this case. Although we chose a very severe case for the first human clinical study, it may be possible to obtain a more definitive effect if the transplantation is performed before the disease becomes so severe. Future studies are needed to identify cases in which cell sheet transplantation is most effective and to determine the appropriate timeframes for transplantation. Trial registration: UMIN, UMIN000034566, registered 19 October 2018, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039393.

A giant omphalocele was successfully treated with a two-step procedure. The first step was a three-staged operation with Gore-tex® sheet to elongate the abdominal muscular layer, and the second step was conservative treatment using the artificial dermis (Terudermis®) to attain effective epithelization at the residual skin defect areas. The proper combination therapy of surgical and conservative treatments may be effective for giant omphalocele because some novel materials and methods including silver-containing materials, povidone-iodine, artificial dermis and negative pressure wound therapy have become available. We report one optional treatment here. The best combination of these strategies for the treatment of giant omphalocele should be sought in the future.

Congenital H-type fistula is a rare congenital rectourogenital anomaly and is less common in males than in females. A one-year-and-eight-month-old boy with an ectopic perineal fistula was incidentally diagnosed with H-type fistula when he underwent voiding cystourethrography for vesicoureteral reflux. Further examination revealed that the H-type fistula was an ano-bulbar urethral fistula. At two years of age, the patient underwent fistulectomy and also anterior sagittal anorectoplasty for the ectopic perineal fistula during the same surgery.

No standard diagnostic method or surgical treatment for congenital isolated hypoganglionosis (CIHG) has been established. This study aimed to analyze the clinical outcomes of patients with CIHG and identify the best surgical interventions provided thus far. Data on surgical interventions in 19 patients were collected between 1992 and 2020, including the type of enterostomy, type of revision, and length of the intestines. Ganglion cells in the myenteric plexus were enumerated using Hu C/D staining. The ratio of the length of the small intestine to its height was defined as the intestinal ratio (IR). The outcomes were assessed using the stoma output, growth parameters including the body mass index (BMI), and parenteral nutrition (PN) dependency. All patients required a diverting enterostomy. The IR ranged from 0.51 to 1.75 after multiple non-transplant surgeries. The stoma types were tube-stoma, end-stoma, Santulli-type, and Bishop–Koop (BK)-type. Patients with Santulli- or BK-type stomas had better BMIs and less PN dependency in terms of volume than those with end-stomas or tube-stomas. Two patients with BK-type stomas were off PN, and three who underwent an intestinal transplantation (Itx) achieved enteral autonomy. The management of CIHG involves a precise diagnosis using Hu C/D staining, neonatal enterostomy, and stoma revision using the adjusted IR and Itx if other treatments do not enable enteral autonomy.

Neonatal omphalitis is a postpartum infection of periumbilical superficial soft tissues that usually has a good prognosis in developed countries. In rare cases, it could progress to periumbilical necrotizing fasciitis (NF), which is an infection of the deep soft tissues, including muscle fascia, and has a high mortality rate. However, the signs and timing of developing NF secondary to omphalitis are unclear. We encountered a neonatal case of NF following omphalitis. In the initial days of the clinical course, general symptoms and condition of the patient were good, and abdominal physical findings were mild; however, the patient rapidly developed NF. The patient was successfully treated by emergent surgical debridement, broad-spectrum antibiotics, and intensive care. To determine the area of blood perfusion, we intravenously injected indocyanine green by intraoperative angiography, and then extensively removed necrotic and hypoperfused tissues. In neonatal omphalitis, the deterioration can suddenly occur despite good initial conditions; intensive monitoring should be required during the first few days of the clinical course.

Nodular fasciitis occurring at the anterior abdominal wall in a 12-year-old female is reported. Nodular fasciitis has recently been recognized as a kind of neoplasm and its characteristic fusion genes such as MYH9-USP6 have been reported. The mass reported here occurred in a pediatric patient and the mass originated at the abdominal wall, whose clinical features were extremely rare.

Outflow obstruction of a catheter for peritoneal dialysis (PD) is one of the most common complications in patients who are undergoing PD for renal failure. Although the cause of catheter obstruction is variable, a choked catheter caused by a fallopian tube fimbria is quite rare and only five pediatric cases were reported. We report a case of a five-month-old female who suffered from recurrent catheter obstruction by a fallopian tube fimbria. Laparoscopic surgery was performed to recanalize the catheter, but the catheter obstruction recurred three days after the surgery. We abandoned the use of the catheter that had been inserted into the Douglas fossa and a new catheter was inserted into the left para-colonic groove. After the second surgery, catheter obstruction did not occur and PD has been continued without any complications.

Background: Biliary atresia (BA) is a progressive obstructive hepatic disease that requires early diagnosis and the prompt initiation of treatment. Although portoenterostomy (PES) is usually performed as the initial surgical procedure, the liver damage may subsequently progress, such that liver transplantation (LTx) may be required. In this study, we comprehensively evaluated the histopathology of liver samples collected during PES and retrospectively evaluated its relationship with prognosis. Methods: Forty-seven patients with BA who underwent PES between 2002 and 2021 were included. Their biopsy samples were semi-quantitatively graded according to the severity of liver fibrosis, bile duct proliferation, cholestasis, ductal plate malformation, and inflammatory cell infiltration; and the expression of cluster of differentiation (CD)3, CD20, human leukocyte antigen II-DR, and α-smooth muscle actin (α-SMA). The relationships of each with the prevalence of survival with native liver (SNL) were evaluated to identify prognostic markers. Results: The median postoperative duration of follow-up was 11.8 years (maximum, 18.0 years; minimum, 3.5 years). There were no deaths during this period, but LTx was performed in 31 patients and the final prevalence of SNL was 34.0% (16/47). There were negative correlations of liver fibrosis and α-SMA with SNL, and a positive correlation between CD20 and SNL. Multivariate analysis using a proportional hazards regression model showed that only CD20 expression was significant. Conclusions: Comprehensive histopathological analysis of liver biopsy samples obtained at the time of PES showed a positive correlation between CD20 expression and SNL, suggesting that this may represent a useful prognostic marker. Level of evidence: III

Objectives: Atrophy of the left lateral segment (LLS) is often encountered in liver transplantation (LT) for biliary atresia (BA). Toclarify themeaning of the heterogeneous atrophy, we compared the pathological characteristics of the LLS with the right posterior segment (RPS) of BA livers obtained during LT. Methods: Among the 116 patients with BA who underwent LT at our hospital between 2014 and 2018, 63 patients with persistent cholestasis after the Kasai portoenterostomy (KP) were selected. Three pathologists evaluated tissues from the LLS and RPS for 5 pathological parameters. Positive areas in whole-slide image observed as portal inflammation, fibrosis, cholestasis, and ductular reaction, were analyzed with automated image quantitation. Moreover, we examined the relationship between the pathological score and the Pediatric End-stage Liver Disease (PELD) score. Results: The median age at LT was 7 months (range 4-26 months). Inflammation and fibrosis were significantly greater in the LLS than in the RPS (P<0.001, for both); however, there were no differences in cholestasis, ductular reaction, and hepatocellular damage (P0.3, 0.3, and 0.82). The same results were obtained in automated image quantitation. Moreover, the sums of the 5 pathological scores in the LLS showed a significant positive correlation with the PELD score (P0.016, rs0.3). Conclusions: More severe inflammation and fibrosis without cholestasis were observed in the LLS. The segmental atrophy may not be associated with poor bile drainage, but with etiopathogenesis of BA. Moreover, the proper site for biopsy during KP could be the LLS

Introduction: Intractable lymphatic anomalies (LAs) include cystic lymphatic malformation (LM; macrocystic, microcystic, or mixed), generalized lymphatic anomaly, and Gorham–Stout disease. LAs can present with severe symptoms and poor prognosis. Thus, prospective studies for treatments are warranted. We conducted a prospective clinical trial of sirolimus for intractable LAs. Methods: This was an open-label, single-arm, multicenter, prospective trial involving five institutions in Japan. All patients with LAs received oral sirolimus once daily, and the dose was adjusted to ensure that the trough concentration remained within 5–15 ng/mL. We prospectively assessed the drug response (response rate for radiological volumetric change in target lesion), performance state, change in respiratory function, visceral impairment (pleural effusion, ascites, bleeding, pain), laboratory examination data, quality of life (QOL), and safety at 12, 24, and 52 weeks of administration. Results: Eleven patients with LAs (9 generalized lymphatic anomaly, 1 cystic LM, 1 Gorham–Stout disease) were treated with sirolimus, of whom 6 (54.5%; 95% confidence interval: 23.4–83.3%) demonstrated a partial response on radiological examination at 52 weeks of administration. No patients achieved a complete response. At 12 and 24 weeks of administration, 8 patients (72.7%) already showed a partial response. However, patients with stable disease showed minor or no reduction after 12 weeks. Adverse events, such as stomatitis, acneiform dermatitis, diarrhea, and fever, were common with sirolimus. Sirolimus was safe and tolerable. Conclusion: Sirolimus can reduce the lymphatic tissue volume in LAs and may lead to improvements in clinical symptoms and QOL.

Background: The natural history of venous malformation (VM) and Klippel–Trenaunay Syndrome (KTS) has not been quantitatively studied. To obtain benchmarks to guide designing clinical trials to assess safety and efficacy of novel drug candidates, the clinical course of the patients was followed for 6 months. Methods and Results: This is a multicenter prospective observational study evaluating the change rate in lesion volume from baseline with magnetic resonance images, as the primary endpoint. In addition, disease severities, performance status (PS), pain visual analog scale (VAS) score, quality of life (QoL), infections, and coagulation markers were also evaluated. Thirty-four patients (VM = 17, KTS = 17, 1–53 of age; median 15.9 years) with measurable lesion volume were analyzed. There was no statistically significant difference in the lesion volume between baseline and day 180, and the mean change rate (standard deviation) was 1.06 (0.28). There were no baseline characteristics that affected the change in lesion volume over 6 months. However, there were patients who showed more than 20% volume change and it was suggested that the lesion volume was largely impacted by local infection. There were no statistically significant changes in pain VAS score, severity, PS, QoL score, D-dimer, and platelet count over 6 months within all patients analyzed. Conclusion: The results showed the representative natural course of VM and KTS for a 6-month period with objective change of lesion volume and other factors, suggesting that it is scientifically reasonable to conduct a Phase 2 proof-of-concept study without a placebo arm, using the results of this study as the control.

Triple duodenal obstruction is an extremely rare disorder—apparently only two cases were reported in the English literature. We present a third case complicated with some cardiovascular anomalies (interrupted inferior vena cava, left-sided inferior vena cava, preduodenal portal vein, and ventricular septal defect) and intestinal malrotation. Operative procedure to reconstruct continuity of the duodenal lumen was a combination of longitudinal incision, partial web resection, and transverse closure at the first obstruction site together with diamond-shaped duodeno-duodenostomy between the oral side of the second obstruction and the anal side of the third obstruction.

We report a very rare case of large fetal mediastinal cystic lymphatic malformation (cLM), formerly called lymphangioma, that was managed with prenatal serial thoracocentesis and postnatal sclerotherapy. A fetal pericardial effusion-like lesion gradually increased the size until it occupied more than half of the thoracic cavity. Thoracocentesis was performed three times, namely at 31 and 35 weeks of gestation, and also just before the delivery for decompression. The characteristic shape changes of the lesion were observed after thoracocentesis. A boy delivered by planned cesarian section at term required respiratory support after birth. Postnatal magnetic resonance imaging (MRI), which showed a large cystic lesion with septa and hemorrhage without solid components, led to the diagnosis of cLM. The fluid from the cyst continued to be drained. Neonatal sclerotherapy using OK-432 was effective and the infant recovered well. Fetal thoracocentesis may be useful for the diagnosis and management of a large mediastinal cLM.