照井 慶太

PURPOSE: The prenatal diagnosis of the stomach position in congenital diaphragmatic hernia (CDH) has been a reliable prognostic factor, but few studies have focused on the postnatal position. We therefore evaluated the significance of the nasogastric (NG) tube position just after birth. METHODS: The Japanese CDH Study Group database enrolled 1037 CDH neonates over 15 years. In our multicenter retrospective study, 464 cases of left-sided isolated CDH with prenatal diagnoses were divided into two groups: NG tube below the diaphragm (BD; n = 190) or above the diaphragm (AD; n = 274). The primary outcome was the 90-day survival rate, and the secondary outcomes were mechanical ventilation duration, hospitalization duration, and recurrence rate. RESULTS: The BD group had a significantly higher 90-day survival rate (98.4 vs. 89.4%, p < 0.001), shorter mechanical ventilation (11 vs. 19 days, p < 0.001), shorter hospitalization (38 vs. 59 days, p < 0.001), and lower recurrence rate (p = 0.002) than the AD group. A multivariate analysis showed that BD (adjusted odds ratio, 3.68; 95% confidence interval 1.02-13.30) was a favorable prognostic factor for the 90-day survival. CONCLUSION: The assessment of the NG tube position revealed it to be a reliable prognostic factor of left-sided isolated CDH. Therefore, it should be included as a routine assessment.

PURPOSE: This study aimed to evaluate prenatal predictors of mortality in fetuses with congenital diaphragmatic hernia (CDH). METHODS: A systematic literature search was performed to identify relevant observational studies that evaluated the ability of lung-to-head ratio (LHR), observed-to-expected LHR (o/e-LHR), observed-to-expected total fetal lung volume (o/e-TFLV), lung-to-thorax transverse area ratio (L/T ratio), intrathoracic herniation of the liver and the stomach, and side of diaphragmatic hernia, using a threshold for the prediction of mortality in fetuses with CDH. Study quality was assessed using the QUADAS-2 tool. Hierarchical summary receiver operating characteristic curves were constructed. RESULTS: A total of 50 articles were included in this meta-analysis. The QUADAS-2 tool identified a high risk of bias in more than one domain scored in all parameters. Among those parameters, the diagnostic odds ratio of mortality with o/e-LHR < 25%, o/e-TFLV < 25%, and L/T ratio < 0.08 were 11.98 [95% confidence interval (CI) 4.65-30.89], 11.14 (95% CI 5.19-23.89), and 10.28 (95% CI 3.38-31.31), respectively. The predictive values for mortality were similar between the presence of liver herniation and retrocardiac fetal stomach position. CONCLUSIONS: This systematic review suggests that o/e-LHR, o/e-TFLV, and L/T ratio are equally good predictors of neonatal mortality in fetuses with isolated CDH.

BACKGROUND: Treatment modalities for neonates with congenital diaphragmatic hernia (CDH) have greatly improved in recent years, with a concomitant increase in survival. However, long-term outcomes restrict the identification of optimal care pathways for CDH survivors in adolescence and adulthood. Therefore, we evaluated the long-term outcomes within the Japanese CDH Study Group (JCDHSG). METHODS: Participants were born with CDH between 2006 and 2018 according to the JCDHSG. Participants were enrolled in the database at 1.5, 3, 6, and 12 years old. Follow-up items included long-term complications, operations for long-term complication, and home medical care. RESULTS: A total of 747 patients were included in this study, with 626 survivors (83.8%) and 121 non-survivors (16.2%). At 1.5, 3, 6, and 12 years old, 45.4%, 36.5%, 34.8%, and 43.6% developed complications, and 20.1%, 14.7%, 11.5%, and 5.1% of participants required home care, respectively. Recurrence, pneumonia, pneumothorax, gastroesophageal reflux disease, and intestinal obstruction decreased with age, and thoracic deformity increased with age. CONCLUSIONS: As CDH survival rates improve, there is a need for continued research and fine-tuning of long-term care to optimize appropriate surveillance and long-term follow-up.

PURPOSE: Anorectal malformations are associated with other organ malformations. Proximodistal elongation of the cloacal plate and anal opening at its distal end are essential for anal development. However, the anal developmental stage in which Wnt5a is directly involved remains unelucidated. Here, we attempted to identify this developmental stage; since Wnt5a is expressed in the mesoderm, and the striated muscle complex (SMC) in mice develops from the mesoderm, we also examined Wnt5a contribution to SMC development. METHODS: We established conditional knockout (CKO) mice in which Wnt5a could be knocked out using an appropriate tamoxifen dose. We evaluated the macroscopic appearance and histopathological features of Wnt5aCKO and wild-type mouse embryos. RESULTS: Wnt5aCKO mice showed phenotypes typical of Wnt5a constitutional knockout mice when Wnt5a was knocked out at E8-E11. Furthermore, the anus failed to open when Wnt5a was knocked out at E8 but opened when it was knocked out at E9 or thereafter. The caudal end of the SMC was dysplastic in Wnt5aCKO mice induced at E8, but was unaffected when mice were induced at E9 or thereafter. CONCLUSION: We suggest a critical role for Wnt5a in anal opening and SMC formation at a very early stage of embryonic development.

Omphalomesenteric cysts are an exceedingly rare type of embryologic remnant of the omphalomesenteric duct. Owing to its rarity and unspecific imaging findings, it is occasionally difficult to diagnose preoperatively. Herein, we report the case of a 15-month-old female with an omphalomesenteric cyst that presented as a painful abdominal mass. Imaging showed a 4 cm cystic lesion just beneath the umbilicus, which also contained a 1 cm enhanced lesion. On the immediate right side of this cyst, a 7 cm hematoma was found within the abdominal wall. Aspiration revealed bloody fluid with an amylase level of 38,250 U/L. She was then diagnosed with an omphalomesenteric cyst, with aberrant pancreas and associated hematoma of the abdominal wall. These findings were confirmed with laparotomy and subsequent pathological examinations. The high level of amylase in the cyst led us to speculate the existence of ectopic pancreatic tissue. Thus, amylase measurement may be considered for the diagnosis of an omphalomesenteric cyst.

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

The clinical features and risk factors of acute appendicitis in infants are unclear. Our aim was to evaluate the association between anthropometrics and the occurrence of infantile appendicitis. This was a retrospective study of infants (<6 years of age) and school-age children (6-10 years of age) of Asian ethnicity who required hospitalization for appendicitis at our two participating institutions between 2004 and 2018. The Z-score for height, body weight, and body mass index (BMI) was compared between the two groups, as well as between patients presenting with perforated and non-perforated appendicitis. The analysis included data from 73 infants and 362 school-age children. Z-scores were greater in infants than in school-age children for height (0.37 versus -0.03, p = 0.003) and body weight (0.12 versus -0.36, p = 0.023), with no between-group difference for the Z-score of BMI. There was no difference in Z-scores for height, weight, and BMI between the perforated and non-perforated appendicitis infant groups. Infants presenting with acute appendicitis were characterized by a larger physique but with normal proportion. This trend was not observed in school-age children. Therefore, larger infants presenting with abdominal pain should be screened for appendicitis.

The Kif26a protein-coding gene has been identified as a negative regulator of the GDNF-Ret signaling pathway in enteric neurons. The aim of this study was to investigate the influence of genetic background on the phenotype of Kif26a-deficient (KO, -/-) mice. KO mice with both C57BL/6 and BALB/c genetic backgrounds were established. Survival rates and megacolon development were compared between these two strains of KO mice. Functional bowel assessments and enteric neuron histopathology were performed in the deficient mice. KO mice with the BALB/c genetic background survived more than 400 days without evidence of megacolon, while all C57BL/6 KO mice developed megacolon and died within 30 days. Local enteric neuron hyperplasia in the colon and functional bowel abnormalities were observed in BALB/c KO mice. These results indicated that megacolon and enteric neuron hyperplasia in KO mice are influenced by the genetic background. BALB/c KO mice may represent a viable model for functional gastrointestinal diseases such as chronic constipation, facilitating studies on the underlying mechanisms and providing a foundation for the development of treatments.

PURPOSE: Predicting lethal pulmonary hypoplasia in infants with congenital diaphragmatic hernia (CDH) before extracorporeal membrane oxygenation (ECMO) initiation is difficult. This study aimed to predict lethal pulmonary hypoplasia in patients with CDH prior to ECMO. METHODS: This was a multicenter cohort study involving neonates prenatally diagnosed with isolated unilateral CDH (born 2006-2020). Patients who required ECMO due to respiratory insufficiency were included in this study. Patients who underwent ECMO due to transient disorders were excluded from analysis. Blood gas analysis data within 24 h of birth were compared between survivors and non-survivors. Predictive abilities were assessed for factors with significant differences. RESULTS: Overall, 34 patients were included (18 survivors and 16 non-survivors). The best pre-ductal PaO2 was significantly lower in non-survivors than in survivors (50.4 [IQR 30.3-64.5] vs. 67.5 [IQR 52.4-103.2] mmHg, respectively; p = 0.047). A cutoff PaO2 of 42.9 mmHg had a sensitivity, specificity, and positive predictive value of 50.0%, 94.4%, and 88.9%, respectively, to predict mortality. CONCLUSION: The best PaO2 within 24 h after birth predicted mortality following ECMO initiation. This should be shared to families and caregivers to optimize the best interests of the infants with CDH.

OBJECTIVE: To evaluate the optimal timing of neonates with prenatally diagnosed congenital diaphragmatic hernia (CDH). METHODS: Data from a retrospective cohort study conducted by the Japanese CDH Study Group between 2011 and 2018 were divided into two groups according to delivery timing: 36-37 and 38-41 weeks of gestation (wg). Death before 90 days as the primary outcome and the duration of hospitalization, oxygen therapy and tube feeding at discharge as the secondary outcomes were analyzed with generalized linear model applying inverse probability of treatment weighting method. We also performed layered analysis according to stomach position. RESULT: Among 493 neonates with prenatally diagnosed, isolated and left CDH, 237 were born at 38-41wg. The duration of hospitalization was significantly shorter in those born at 38-41wg, especially among those with stomach malposition, and the other outcomes showed no difference. CONCLUSIONS: Delivery at 38-41wg could be beneficial for those with high grade stomach position.

PURPOSE: We compared the efficacy of thoracoscopic repair (TR) with that of open repair (OR) for neonatal congenital diaphragmatic hernia (CDH). METHODS: The subjects of this multicenter retrospective cohort study were 524 infants with left-sided isolated CDH, diagnosed prenatally, and treated at one of 15 participating hospitals in Japan between 2006 and 2018. The outcomes of infants who underwent TR and those who underwent OR were compared, applying propensity score matching. RESULTS: During the study period, 57 infants underwent TR and 467 underwent OR. Ten of the infants who underwent TR required conversion to OR for technical difficulties and these patients were excluded from the analysis. The survival rate at 180 days was similar in both groups (TR 98%; OR 93%). Recurrence developed after TR in 3 patients and after OR in 15 patients (TR 7%, OR 3%, p = 0.40). The propensity score was calculated using the following factors related to relevance of the surgical procedure: prematurity (p = 0.1), liver up (p < 0.01), stomach position (p < 0.01), and RL shunt (p = 0.045). After propensity score matching, the multivariate analysis adjusted for severity classification and age at surgical treatment revealed a significantly shorter hospital stay (odds ratio 0.50) and a lower incidence of chronic lung disease (odds ratio 0.39) in the TR group than in the OR group. CONCLUSIONS: TR can be performed safely for selected CDH neonates with potentially better outcomes than OR.

Congenital diaphragmatic hernia (CDH) is a birth defect of the diaphragm in which abdominal organs herniate through the defect into the thoracic cavity. The main pathophysiology is respiratory distress and persistent pulmonary hypertension because of pulmonary hypoplasia caused by compression of the elevated organs. Recent progress in prenatal diagnosis and postnatal care has led to an increase in the survival rate of patients with CDH. However, some survivors experience mid- and long-term disabilities and complications requiring treatment and follow-up. In recent years, the establishment of clinical practice guidelines has been promoted in various medical fields to offer optimal medical care, with the goal of improvement of the disease' outcomes, thereby reducing medical costs, etc. Thus, to provide adequate medical care through standardization of treatment and elimination of disparities in clinical management, and to improve the survival rate and mid- and long-term prognosis of patients with CDH, we present here the clinical practice guidelines for postnatal management of CDH. These are based on the principles of evidence-based medicine using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The recommendations are based on evidence and were determined after considering the balance among benefits and harm, patient and society preferences, and medical resources available for postnatal CDH treatment.

PURPOSE: The optimal timing of surgery for congenital diaphragmatic hernia (CDH) is controversial. We aimed to validate our protocol for the timing of CDH repair using the quantified patent ductus arteriosus (PDA) flow pattern. METHODS: This retrospective comparative study analyzed patients with a prenatal diagnosis of isolated CDH between 2007 and 2020. We defined the "LR ratio" as the percentage of velocity-time integral (VTI) of the left-to-right flow of PDA against overall VTI on echocardiography. Since 2010, we followed the decision criterion of performing surgery when LR ratio of > 50% has been achieved in the patients (protocol group). The protocol group (2010-2020) was compared with the historical control group (2007-2009). RESULTS: The average age at surgery was 104.1 ± 175.9 and 37.3 ± 30.6 h in the control and protocol groups, respectively (p = 0.11). Survival rate (88.9% vs. 95.0%, p = 0.53) and the rate of worsening of pulmonary hypertension within 24 h after surgery (22.2% vs. 10.0%, p = 0.57) were not different between the groups. The protocol group had a significantly shorter duration of tracheal intubation (26.9 ± 21.1 vs. 13.3 ± 9.5 days, p = 0.03). CONCLUSION: Our decision criterion might have the advantage of facilitating early and safe surgery for patients with CDH.