PURPOSE:Trisomy 21 is associated with neonatal surgical disorders, such as duodenal atresia, Hirschsprung's disease, and anorectal malformation (ARM). Therefore, the purpose of this study was to compare postoperative complications in patients with vs. without trisomy 21 who underwent neonatal gastrointestinal surgery and to identify risk factors for postoperative complications after these surgeries in the Japanese population. METHODS:From the National Clinical Database-Pediatric, we selected patients with duodenal atresia/stenosis, Hirschsprung's disease, and ARM operated in the neonatal period from 2016 to 2020 and analyzed the risk factors for postoperative complications. RESULTS:Duodenal atresia/stenosis, Hirschsprung's disease, and ARM were diagnosed in 4052 patients, of which 2486 patients were operated on in the neonatal period. These patients comprised 801 with duodenal atresia/stenosis, 289 with Hirschsprung's disease, and 1446 with ARM. The numbers of patients with complicated trisomy 21 were 212 (26.5%), 16 (5.5%), and 102 (7.1%) for duodenal atresia/stenosis, Hirschsprung's disease, and ARM, respectively. Regarding duodenal atresia/stenosis, multivariable logistic regression analysis showed that trisomy 21 were risk factors for postoperative complications. CONCLUSION:In this analysis of Japanese data, trisomy 21 was an independent risk factor for postoperative complications in patients with duodenal atresia/stenosis.

Objective: In extremely low-birthweight infants with stomas following neonatal intestinal perforation, early stoma closure is desirable to avoid complications associated with prolonged stoma management. However, from a surgical standpoint, closure after sufficient weight gain is considered safer due to improved tolerance of general anesthesia and intestinal anastomosis. To assess the optimal body weight for stoma closure, we used the National Clinical Database in Japan. Study design: This nationwide retrospective study included 420 neonates with intestinal perforations who weighed <1000 g at the time of enterostomy and subsequently underwent stoma closure between 2017 and 2022. A multivariate analysis was conducted using the preoperative items of stoma closure as variables and the postoperative 90-day status, rate of unexpected reoperation within 30 days postoperatively, and rate of postoperative complications as outcomes. Results: The median body weight at stoma closure in all eligible patients was 1950 g [1500-2350]. Data indicated that patients with liver failure (p = 0.002) and growth failure (p = 0.016) were more likely to undergo stoma closure at lower body weights. Multivariate analysis revealed that cardiovascular disease (OR = 3.41 (1.06-10.81, p = 0.040)) and stoma closure weight <1000 g (OR = 10.65 (2.27-54.98, p = 0.003)) were independently associated with postoperative mortality within 90 days, and preoperative liver failure was a significant predictor of postoperative complications (OR = 2.17 (1.19-3.87, p = 0.010)). Conclusion: Stoma closure in infants weighing <1000 g may be associated with an increased risk of mortality. To mitigate this risk, efforts should focus on preventing the progression of liver failure and promoting weight gain through appropriate nutritional interventions, such as recycling stoma effluent or administering intravenous omega-3 fatty acid emulsions. (c) 2025 Asian Surgical Association and Taiwan Society of Coloproctology. Publishing services by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/ 4.0/)

Biliary obstruction due to compression by a B-cell solid tumor occurs rarely. A few reports have described biliary reconstruction surgery for obstructive jaundice caused by Burkitt’s lymphoma. However, there are no detailed reports on pediatric cases. We report a pediatric case of obstructive jaundice due to malignant lymphoma treated with biliary reconstruction surgery. A 5-year-old girl presented to our hospital with a massive abdominal tumor that caused biliary stricture. Chemotherapy was initiated after an open tumor biopsy. However, endoscopic biliary stent placement was performed owing to elevated bilirubin levels. We treated the patient with chemotherapy for 9 months while endoscopically replacing the biliary stent every few months. She achieved complete tumor remission. However, sclerotic lymph nodes were persistent on the dorsal side of the cholecystic duct junction, and biliary stricture at the same site had changed to stent-dependent biliary obstruction. Therefore, we performed choledochojejunostomy and retrocolic Roux-en-Y reconstruction 15 months after initial admission. There were no postoperative complications or tumor recurrences, and the bilirubin level remained low. Histopathologically, the resected bile duct wall was fibrotic and thick, and the bile duct lumen narrowed. Biliary reconstruction is effective to achieve long-term biliary patency in pediatric patients with stent-dependent biliary obstruction due to malignant lymphoma. However, the decision on when to stop biliary stent replacement and proceed to biliary reconstruction surgery is a matter of debate. Further case studies are required to address this issue.

To the Editors: Streptococcus constellatus is a Gram-positive coccus that resides in the intestinal tract. Faden and Mohmand1 reported that approximately 80% of 37 children with infections involving S. constellatus had acute appendicitis with perforation. Additionally, half of the patients with acute appendicitis and perforation developed intra-abdominal abscesses. We describe a pediatric case of acute appendicitis complicated with bacteremia of S. constellatus. A 3-year-old girl presented with fever, vomiting and abdominal pain. Blood examination revealed a white blood cell count of 10,800/µL, a C-reactive protein (CRP) level of 11.9 mg/dL and a procalcitonin level of 81.38 ng/mL. Contrast-enhanced computed tomography revealed the perforation of the appendix with findings indicating free air and purulent ascites (with no abscess formation). S. constellatus was detected in 2 sets of blood cultures. She was diagnosed with acute perforated appendicitis complicated with bacteremia of S. constellatus. Piperacillin/tazobactam was administered without surgery. On the 4th day, the fever gradually subsided, and the CRP level decreased to 3.85 mg/dL. However, the abdominal pain did not improve, the fever recurred and the CRP level increased again. On the 8th day, ultrasonography suggested intra-abdominal abscess formation due to perforation. A large amount of pus was aspirated through drainage. Enterococcus avium and S. constellatus were detected in the pus culture. After switching to sulbactam/ampicillin, which is effective to both S. constellatus and E. avium, both the clinical symptoms and laboratory findings improved. In a study by García-Marín et al.,2 more S. constellatus were detected in complicated acute appendicitis than in uncomplicated acute appendicitis. In these studies, bacteremia caused by S. constellatus was absent. This is the first case report of acute appendicitis with bacteremia caused by S. constellatus. Pediatricians and surgeons should consider that perforation and abscess formation are more likely in children with acute appendicitis associated with S. constellatus. ACKNOWLEDGMENTS We would like to thank Editage (www.editage.com) for the English language editing.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have increased worldwide in people without underlying diseases. CA-MRSA can often cause serious bacterial infections, especially skin and soft tissue infections (SSTI). Here, we describe a case of severe subcutaneous abscess due to Panton-Valentine leucocidin (PVL)-positive CA-MRSA in an infant without underlying diseases. A 4-month-old girl presented with a 4-day history of fever, with extensive redness and swelling of the lumbar region and buttocks. She was diagnosed with extensive subcutaneous abscess of the lumbar region and buttocks. Surgical drainage was performed, and a substantial volume of pus was drained. MRSA was detected in the pus on culture. Antibiotic therapy that covered MRSA was also administered for 3 weeks, and the abscess healed. As it was a severe SSTI due to MRSA, analysis of MRSA revealed PVL-positive MRSA. This patient had no underlying disease or history of antibiotic administration, and as MRSA was present in the nasopharyngeal cavity, it was considered a case of CA-MRSA. Furthermore, the prevalence of PVL-positive CA-MRSA in MRSA isolated from patients with SSTI has also increased in Japan. The Infectious Diseases Society of America recommends surgical intervention and empirical antibiotic therapy for MRSA-complicated SSTI cases in an era of CA-MRSA. Pediatricians must strongly consider the possibility of MRSA in children with severe SSTIs.

BACKGROUND:Lymphatic malformation (LM) is a congenital disease caused by lymphatic vessel malformation. Although standard therapies for LMs are sclerotherapy and/or surgical excision, a new therapy using Japanese herbal medicine Eppikajutsuto (TJ-28) has been recently reported as clinically effective. We aimed to experimentally confirm the therapeutic effectiveness of TJ-28 for LMs.METHODS:LM lesions were generated in the mesentery and peritoneum of mice by intraperitoneal injection of Freund's incomplete adjuvant. Mice with LMs were treated by gavage or dietary administration of TJ-28 for 2 months. Formalin-fixed paraffin-embedded tissue sections of mesentery and peritoneum tissues were histologically and immunohistochemically examined by focusing on lymph nodes and perinodal lymph vessels.RESULTS:Multiple Freund's incomplete adjuvant-associated foreign-body granulomas were formed in the mesentery and peritoneum, resulting in congestion of lymph fluid and dilatation of lymph vessels. The numbers and sizes of lymph nodes were not significantly different between TJ-28-treated and control groups. However, the luminal areas of lymphatic vessels were reduced significantly in the TJ-28 treatment group by both gavage and dietary administrations.CONCLUSION:TJ-28 conspicuously reduced congestion of lymph fluid. This is the first histopathological evaluation of LM model mice to study the effectiveness of oral TJ-28 treatment.

The clinical utility of plasma cell-free DNA in precision cancer medicine has not been established. A pilot study was conducted to investigate the clinical utility of comprehensive genomic profiling by liquid biopsy in a Japanese population. In this PROFILE study, 102 patients with advanced solid tumors who showed progression with standard systemic therapy underwent liquid biopsy between August 2017 and February 2020. Liquid biopsy was performed using Guardant360. Of the 102 patients, 56 were women, and the median age was 65 years. Regarding the types of cancer, 31 were hepatobiliary and pancreatic cancer, 17 were gastrointestinal cancer, and 13 were breast cancer. Frequently altered genes were TP53 (53.9%, 46/102), KRAS (25.5%, 26/102), PIK3CA (19.6%, 20/102), and EGFR (17.6%, 18/102). At least one genetic aberration was detected in 92 patients (90.2%). Actionable mutation was discovered in 88 patients (86.3%), and 67 patients (65.7%) were clinical trial candidates. Of the 102 patients, 22 (21.6%) were able to receive biomarker-matched therapy. Their best responses were as follows: 1 complete response, 3 partial responses, 7 stable diseases, and 11 progressive diseases. Additionally, the treated patients were divided on the basis of matching scores (≥ 50% vs. < 50%). The patients were divided into high and low groups. The high group had a higher disease control rate (DCR) of 75% compared with 20% in the low group (P = 0.010). The results indicate that liquid biopsy is useful for identifying actionable mutations associated with the clinical response of selected patients.

Background: Comprehensive genomic profiling (CGP) was widely adopted in Japan after its coverage by national healthcare insurance began in June 2019. We investigated the clinical utility of CGP in pediatric and adolescent young adults (AYA) solid tumor patients. Procedure: Between November 2017 and December 2019, 13 patients who progressed with or who were likely to progress with standard therapies were recruited to the PROFILE-F study to undergo CGP using either FoundationOne® CDx or FoundationOne® Heme. Results: The median age was 28 years old. Tumor types were as follows: neuroblastoma (n=1), Wilms’ tumor (n=1), rhabdomyosarcoma (n=2), Ewing sarcoma (n=1), gastric cancer (n=1), rectal cancer (n=1), osteosarcoma (n=1), neuroendocrine tumor (n=2), salivary gland carcinoma (n=1), tracheal adenoid cystic carcinoma (n=1), and thymic cancer (n=1). In 92% of cases, at least one genomic alteration was identified, including CDKN2A (four cases), TP53 (three cases), and MYC (two cases). Actionable aberrations were found in 10 cases (77%), and a clinical trial candidate was found in seven cases (54%). However, no patients were able to receive biomarker-matched therapy according to their genomic alterations. Conclusions: Further efforts to increase basket trials and collection of clinical genomic data to predict response are necessary to advance precision cancer medicine in pediatric and AYA populations.

Because of their rarity, the treatment strategy for pediatric ovarian epithelial tumors is controversial, especially for a giant cystadenoma. We report the largest mucinous cystadenoma (MCA) case in the pediatric literature thus far. A 12-year-old girl had abdominal distention and visited our hospital. She had a multilocular cyst with some protuberance on the inside and high values of CA 19-9 and CA-125. We diagnosed her with a left MCA and performed a left oophorectomy. The tumor was the stage IA borderline malignant MCA and weighed 11.8 kg. Five years have passed, the patient has not experienced recurrence or metastasis. The resection of giant tumors can affect respiration and circulation. However, pre- or intra-operative drainage may lead to dissemination and adhesion. When we treat pediatric giant ovarian epithelial tumors, we must understand the findings that suggest the possibility of malignancy to decide appropriately as to whether drainage should be performed.

Waardenburg syndrome (WS) has the characteristic clinical features caused by the embryologic abnormality of neural crest cells. WS patients sometimes suffer from functional intestinal obstruction. When it is Hirschsprung disease (HD), the WS is diagnosed as type 4 WS. We report a case of WS which did not have myenteric ganglion cells in the sigmoid colon and rectum. Whether to diagnosis this case as type 1 or 4 WS is controversial. Moreover, this is the third report which has peristalsis failure caused by abnormal myenteric plexus. In all three cases, the eosinophils had aggregated in the myenteric layer of the transition zone. During embryonic life, enteric ganglion cells migrate to the myenteric layer from the proximal to the distal side sequentially and, subsequently, to the submucosal layer through the circular muscle. Therefore, we hypothesize that myenteric ganglion cells that had already migrated were eliminated by an eosinophil-mediated mechanism in these three cases. We believe this report may be helpful to elucidate the pathogenesis of some types of HD.

We report here a very rare case of de novo inversion-duplication chromosomal abnormality with a pure 3qter duplication syndrome. Interestingly, the 3q duplication includes an overlap of the syndromes critical region. Although there have only been 9 cases of this syndrome reported in the past, our patient had more severe neurological abnormalities than anticipated. In this regard, we have gathered the 3q chromosomal duplication abnormalities known to cause pure 3q duplication syndrome to date as a reference for comparisons and we discuss the particulars of our case.