Notable Clinical Differences Between Neonatal and Post-Neonatal Intestinal Malrotation: A Multicenter Review in Southern Japan.

BACKGROUND: Most cases of intestinal malrotation appear in neonates with bilious vomiting due to midgut volvulus, whereas in cases that develop beyond infancy, the initial symptoms vary. This study investigated the clinical features of these two populations and identified issues that should be considered in daily practice. METHODS: A retrospective chart review was conducted from January 1, 2010, to December 31, 2022. Data on patients with intestinal malrotation were collected in an anonymized fashion from five pediatric surgical hub facilities in the Southern Kyushu and Okinawa areas of Japan. RESULTS: Of the 80 subjects, 57 (71.3%) were neonates (Group N) and 23 (28.7%) were infants and schoolchildren (Group I). The frequencies of initial symptoms, such as abdominal distention (Group N: 19.3% vs. Group I: 13.0%), bilious vomiting (59.6% vs. 43.5%), and hematochezia (8.8% vs. 21.7%), were not skewed by the age of onset (p = 0.535, 0.087, and 0.141, respectively). Midgut volvulus was significantly more frequent in Group N (71.9% [41/57] vs. 34.8% [8/23]; p = 0.005), while the degree of torsion was greater in group I (median 360° [interquartile range: 180-360°] vs. 450° [360-540°]; p = 0.029). Although the bowel resection rate was equivalent (7.0% [4/57] vs. 4.3% [1/23]; p = 1.000), half of the patients in Group N presented with 180° torsion. The neonatal intestine has been highlighted as being more susceptible to ischemia than that in older children. CONCLUSIONS: The incidence of midgut volvulus is higher in neonates than in older children. Even relatively mild torsion can cause ischemic bowel changes during the neonatal period. LEVEL OF EVIDENCE: LEVEL III.

Proctoring System of Pediatric Laparoscopic Surgery for Choledochal Cyst.

Background: Endoscopic surgery also has been becoming widespread in the field of pediatric surgery. However, most disease treated by pediatric surgery in a single institution are small number of cases. Besides, the variety of operative procedures that need to be performed in this field is quite wide. For these reasons, pediatric surgeons have limited opportunities to perform endoscopic surgery. Therefore, it is difficult to introduce advanced endoscopic surgery at a single local hospital. To educate pediatric surgeons in local hospitals, for widespread advanced pediatric endoscopic surgery safely, and to eliminate the need for patient centralization, we have introduced a proctoring system. We compared the surgical results of our institution, a center hospital, with other local institutions, to investigate the feasibility of our proctoring system. Methods: The experienced pediatric surgeon of our institution visits local hospitals to provide onsite coaching and supervises pediatric surgeons on the learning curve. All patients who underwent laparoscopic cyst excision and hepaticojejunostomy for choledochal cysts, one of the advanced pediatric endoscopic surgeries was retrospectively reviewed. Results: Thirty-four cases were evaluated (14 cases in our institution, 20 cases in 9 other institutions). The procedures of all 34 cases were performed by surgeons with 0-2 cases of experience in the procedure. There were no open conversion cases. There was no significant difference in the operative date. There was 1 case (6.7%) of postoperative complications during hospitalization at our institution and 3 cases (14.3%) at other institutions (P = .47). Two cases of late complications (13.3%) occurred at our institution, whereas 6 cases (28.6%) occurred at other institutions (P = .28). Conclusion: With the proctoring system, the performance and completion of advanced pediatric endoscopic surgery at local institutions was feasible. This has important implications given the ever-growing demand for pediatric endoscopic surgery and the increasing need for competent pediatric endoscopic surgeons.

Successful management of pyriform sinus cyst and fistula using endoscopic electrocauterization.

Objectives: Pyriform sinus cyst (PSC) and pyriform sinus fistula (PSF) is a rare congenital malformation that arises from the third or fourth branchial structure. In our study, we describe the safety and the utility of endoscopic electrocauterization against PSC/PSF. Methods: We retrospectively reviewed the records of patients who underwent endoscopic electrocauterization for PSC/PSF at our hospital. The internal opening of the fistula was identified under general anesthesia using a flexible endoscope (XQ-260 or H-290; Olympus, Tokyo, Japan), and the DualKnifeJ (KD-655L; Olympus) was used to ablate the internal opening. Results: We experienced three PSF and three PSC patients. The postoperative course was uneventful in all cases. The patients declared no pain in the neck, and there were no cases showing recurrent nerve paralysis. Five in six cases (83%), the closure of fistula was archived in the first cauterization. One case (16.6%) required repeated cauterization. No recurrence was found during the follow-up period ( median: 1 year) in any cases. Conclusions: Owing to its rarity in neonates, the diagnosis and treatment of PSC remains complicated and not clearly described. Complete removal of the fistula and the cyst with or without affected thyroid tissue was previously the most commonly used treatment. From our experience, we believe that endoscopic electrocauterization can be the first choice not only for PSF but also for neonatal PSC. In conclusion, endoscopic electrocauterization is feasible even for neonatal PSC. Further investigations including multicenter analyses are needed.

"A salvage technique using a fibrous sheath to avoid the loss of the central veins in cases of pediatric intestinal failure".

PURPOSE: The number of accessible central veins (CVs) affects the prognosis of patients with intestinal failure (IF). The loss of residual CVs should be avoided. We, therefore, evaluated the efficacy of a new CV catheter-exchange technique using a subcutaneous fibrous sheath (FS) in pediatric IF patients. METHODS: We retrospectively collected the CV catheter (CVC) data of pediatric IF patients managed from January 2009 to December 2019. The data were divided into two groups; Groups 1 (CVCs placed with the FS method) and Group 2 (CVCs placed by the primary or another insertion). The main outcome was the CVC indwelling time. RESULTS: Eighty-five CVCs were analyzed. The FS method was attempted in 47 cases and succeeded in 40 (85%). No significant difference was observed between the groups regarding characteristics. A log-rank test revealed an equivalent CVC indwelling time between the two groups (Group 1: 268 [126-588] days vs. Group 2: 229 [126-387] days, p = 0.256). CONCLUSIONS: The FS method is highly recommended for pediatric IF patients, as its attempt showed a high success rate with an indwelling time equivalent to primary insertion. The FS method leads to the prolonged use of a single CV and thereby contributes to improving the outcomes of pediatric IF patients.

Laparoscopic repositioning of an aberrant right hepatic artery and hepaticojejunostomy for pediatric choledochal cyst: A case report.

INTRODUCTION: The right hepatic artery crossing the ventral side of the common hepatic duct is a relatively frequent abnormality. This aberrant right hepatic artery not only interferes with dissection of the common bile duct and hepaticojejunostomy for choledochal cyst but can also cause postoperative anastomotic stenosis. CASE PRESENTATION: A 14-year-old patient presented with upper abdominal pain and was diagnosed with a choledochal cyst (Type IVA in Todani Classification) and pancreaticobiliary maljunction. Abdominal enhanced computed tomography showed aberrant right hepatic artery located at the ventral side of the common hepatic duct. Laparoscopic choledochal cyst resection and hepaticojejunostomy were planned. Intraoperative findings also showed the aberrant right hepatic artery crossing the common hepatic duct ventrally as detected on preoperative computed tomography. Laparoscopic dorsal side repositioning of the aberrant right hepatic artery was performed because it appeared to compress the common hepatic duct and risked causing postoperative anastomotic stenosis. We performed laparoscopic hepaticojejunostomy by replacing the aberrant right hepatic artery dorsally to facilitate suturing and prevent postoperative anastomotic stenosis. The postoperative course was uneventful, with no findings suggestive of anastomotic stenosis. DISCUSSION: The abnormality of the right hepatic artery is reported to be a primary cause of anastomotic stenosis after hepaticojejunostomy. Once anastomotic stenosis or stricture develops, it is often difficult to treat. The prevention of the stenosis is important. CONCLUSIONS: In choledochal cyst with aberrant right hepatic artery, dorsal repositioning is effective for preventing postoperative anastomotic stenosis and cholestasis.

Glypican-3 expression in malignant small round cell tumors.

Malignant small round cell tumors usually progress rapidly and show resistance to chemotherapy, and it is often difficult to make a definitive diagnosis based on their histological morphology. Glypican-3 (GPC3) is a highly tumor-specific antigen, and the overexpression of GPC3 was reported in many pediatric and adult malignancies. In the present study, we investigated the GPC3 expression in pediatric malignant small round cell tumors to assess its role in the differential diagnosis of the tumors. Immunohistochemistry was performed to assess the expression of GPC3 in samples from 84 rhabdomyosarcomas (RMSs; 44 alveolar and 40 embryonal RMSs), 62 Ewing sarcomas (EWSs), 35 neuroblastomas (NBs) and two desmoplastic small round cell tumors (DSRCTs). We performed a reverse transcription-quantitative polymerase chain reaction for GPC3 to determine the GPC3 mRNA expression in samples from 66 frozen tumors (23 RMSs, 28 EWSs and 15 NBs). The serum expression levels of GPC3 were analyzed in pre-operative blood samples from two RMS and eight NB patients. In total, 25% (21/84) of the RMSs and 3% (1/35) of the NBs exhibited a focal expression of GPC3, whereas, the other specimens showed no GPC3 expression. The GPC3 mRNA expression level of the RMSs with positive GPC3 expression (n=6) was significantly higher compared with the RMSs without such expression (n=17). A total of two cases of NB showed high serum levels of GPC3, but neither tumor showed immunoreactivity for GPC3. The immunohistochemical overexpression of GPC3 may be a candidate ancillary parameter in the differential diagnosis of RMS from EWS and DSRCT.

The Utility of Muscle-Sparing Axillar Skin Crease Incision with Thoracoscopic Surgery in Children.

BACKGROUND: Thoracoscopic surgery for pediatric benign tumors is a common procedure. However, a large incision is needed to remove large tumors from the thoracic cavity. And, for intrapulmonary sequestration in lower lobe, it sometimes needs a large incision to ligate the aberrant vessels. A muscle-sparing axillar skin crease incision (MSASCI) has been introduced for thoracic open surgery, resulting in excellent aesthetic outcomes compared with a standard incision. We herein report the utility of this MSASCI technique in thoracoscopic surgery to remove large tumors from the thoracic cavity and to ligate the aberrant vessels in intrapulmonary sequestration in lower lobe. MATERIALS AND METHODS: From 2014 April to 2016 March, we performed the MSASCI technique in thoracoscopic surgeries for 5 children. RESULT: Five cases were diagnosed as mediastinal masses (mature teratoma for 1 case, ganglioneuroblastoma for 2 cases, and extrapulmonary sequestration and intrapulmonary sequestration for 1 case each). The age at surgery was 32.0 ± 25.0 months (range 5-58 months). The size of the mediastinal mass was 9 × 5 × 5 cm, 4 × 3 × 3 cm, 5 × 5 × 2.5 cm, and 3 × 2.5 × 2 cm. For 4 other cases, except for the intrapulmonary sequestration case, the mass was resected under thoracoscopic surgery using only three or four 5-mm trocars and the mass was removed from the thoracic cavity using the MSASCI technique. For the intrapulmonary sequestration case, the aberrant vessels were resected under thoracoscopic surgery using only two 5-mm and one 12-mm trocars and the left lower lobectomy was performed using the MSASCI technique. All lesions were resected completely. No cases had surgical complications, none showed recurrence, and all cases demonstrated good cosmetic outcomes. CONCLUSIONS: Performing thoracoscopic surgery using a MSASCI technique is associated with good cosmetic outcome.

Re-evaluation of lung to thorax transverse area ratio immediately before birth in predicting postnatal short-term outcomes of fetuses with isolated left-sided congenital diaphragmatic hernia: A single center analysis.

We aimed to investigate whether the lung-to-thorax transverse area ratio (LTR) immediately before birth is of diagnostic value for the prediction of postnatal short-term outcomes in cases of isolated left-sided congenital diaphragmatic hernia (CDH). We retrospectively reviewed the cases of fetal isolated left-sided CDH managed at our institution between April 2008 and July 2016. We divided the patients into two groups based on LTR immediately before birth, using a cut-off value of 0.08. We compared the proportions of subjects within the two groups who survived until discharge using Fisher's exact test. Further, using Spearman's rank correlation, we assessed whether LTR was correlated with length of stay, duration of mechanical ventilation, and supplemental oxygen. Twenty-nine subjects were included (five with LTR < 0.08, and 24 with LTR ≥ 0.08). The proportion of subjects surviving until discharge was 40% (2/5) for patients with LTR < 0.08, as compared with 96% (23/24) for those with LTR ≥ 0.08. LTR measured immediately before birth was negatively correlated with the postnatal length of stay (Spearman's rank correlation coefficient, rs = -0.486), and the duration of supplemental oxygen (rs = -0.537). Further, the duration of mechanical ventilation was longer in patients with a lower LTR value. LTR immediately before birth is useful for the prediction of postnatal short-term outcomes in fetuses with isolated left-sided CDH. In particular, patients with prenatal LTR value less than 0.08 are at increased risk of postnatal death.

Immunostaining for Hu C/D and CD56 is useful for a definitive histopathological diagnosis of congenital and acquired isolated hypoganglionosis.

Isolated hypoganglionosis (IHG) has been proposed as a distinct entity with two subtypes: congenital IHG (CIHG) and acquired IHG (AIHG). However, due to the rarity of the disease and the lack of defining histological criteria, the concept of IHG is not widely accepted. We studied paraffin-embedded intestinal specimens from 79 patients diagnosed with Hirschsprung's disease (HD) (n = 49), CIHG (n = 25), and AIHG (n = 5) collected between January 1996 and December 2015. Histopathological diagnosis of HD, CIHG, and AIHG was confirmed by hematoxylin and eosin staining and immunohistochemical staining using Hu C/D and CD56. We evaluated (immuno)histopathological findings, counted the number of ganglion cells, and measured the size of Auerbach's plexus. Hu C/D labeled neuronal cell bodies, whereas CD56 was detected in all neuronal components. In HD, all ganglion cells in Auerbach's plexus in the normoganglionic segment (NGS) were immunoreactive for Hu C/D, whereas in the aganglionic segment (AGS), these were replaced by CD56-positive extrinsic nerve fibers and bundles. The number of ganglion cells in AIHG and CIHG was significantly lower than in the NGS of HD (p < 0.05). Auerbach's plexus was significantly smaller in CIHG (p < 0.05) but in AIHG equivalent to the NGS in HD. In summary, immunostaining for Hu C/D and CD56 is useful for definitive histopathological diagnosis of IHG.

The incidence and outcome of allied disorders of Hirschsprung's disease in Japan: Results from a nationwide survey.

BACKGROUND: Allied disorders of Hirschsprung's disease (ADHD) have been proposed to be the concept of the functional obstruction of the intestine with the presence of ganglion cells in the terminal rectum. They are classified into two categories based on pathology: (1) abnormal ganglia, including immaturity of ganglia, hypoganglionosis (HG), and intestinal neuronal dysplasia; (2) normal ganglia, including megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS), segmental dilatation (SD), internal anal sphincter achalasia (IASA), and chronic idiopathic intestinal pseudo-obstruction (CIIP). Some of these show poor prognosis, therefore, the establishment of criteria and appropriate treatment strategies is required. METHODS: The questionnaires were sent to the 161 major institutes of pediatric surgery or gastroenterology in Japan, in order to collect the cases of ADHD during 10 years from 2001 and 2010. RESULTS: In total, 355 cases were collected. They included 28 immaturity of ganglia, 130 HG (121 congenital, 9 acquired), 18 intestinal neuronal dysplasia, 33 MMIHS, 43 SD, three IASA, and 100 CIIP. Of the 95 institutes, 69 (72.6%) had their own criteria for ADHD. Criteria were based on clinical symptoms and signs, and conventional pathological examinations. Prognosis was poor in congenital HG, MMIHS, and CIIP, while the others showed good survival rates. CONCLUSION: Almost all Japanese cases of ADHD in the past 10 years were collected. Congenital HG and CIIP showed relatively high incidence, whereas acquired HG and IASA were extremely rare in Japan. The criteria of each disorder were also collected and summarized. Prognosis was poor in congenital HG, MMIHS, and CIIP.

Current clinical features in diagnosis and treatment for immaturity of ganglia in Japan: analysis from 10-year nationwide survey.

BACKGROUND: To identify the current clinical features in diagnosis and treatment for immaturity of ganglia (IG) in Japan, we retrospectively analyzed data for patients with IG from the nationwide surveys in Japan. This survey was performed by Japanese Study Group of allied disorders of Hirschsprung's disease (ADHD). METHODS: In primary research, data on totally 355 cases of ADHD were collected for 10 years (2001-2010). Fifteen patients were IG. All IG patients were confirmed by pathological examination. In secondary research, detail questionnaires were sent and collected. RESULTS: Male/female ratio was 9/6 and mean birth weight was 2474 g. All cases (100 %) were onset in neonatal period. Primary symptoms were abdominal distention (86.7 %), vomiting (53.3 %), and late egestion of meconium (26.7 %). An abnormal distention of intestine was recognized in 86.7 % on X-ray, and microcolon was recognized in 58.3 % on contrast enema. Caliber change was recognized in 58.3 % on laparotomy. An enterostomy was made in 13 patients (86.7 %), and an ileostomy was made in 69.2 %. Pathological diagnosis was performed in 100 %. Enterostomy was closed in 100 %. CONCLUSIONS: Totally, 15 definitive cases of IG in 10 years were collected and analyzed. All cases were onset in the neonatal period and almost all underwent enterostomy, but no mortalities occurred.

Glypican 3 expression in pediatric malignant solid tumors.

PURPOSE: Glypican 3 (GPC3) is one of the cell surface heparan sulfate proteoglycans that binds to the cell membrane, and it is known as an oncofetal protein in adult malignant tumors. Clinical trials using a GPC3 peptide vaccine have already been started in Japan as a new immunotherapy for hepatocellular carcinoma in adult patients. To investigate the possibility of GPC3 immunotherapy for pediatric malignant tumors, we assessed the expression of GPC3 in pediatric malignant tumors. METHODS: Immunohistochemically, the GPC3 expression was examined in 159 pediatric solid tumors, including 35 cases of neuroblastoma, 30 cases of Wilms tumor, 10 cases of hepatoblastoma, 25 cases of germ cell tumors, 56 cases of rhabdomyosarcoma, and 3 cases of other tumors. In addition, to clarify the physiological expression during the fetal to neoinfantile period, autopsy specimens of subjects without any neoplastic diseases were assessed in 9 fetal cases and 21 neoinfantile cases. The serum levels of GPC3 were also analyzed using specimens obtained from 53 subjects by the sandwich enzyme-linked immunosorbent assay method. RESULTS: Histologically, a high rate of GPC3 expression was noted in 10 (90.9%) of the 11 subjects with yolk sac tumors and 6 (60.0%) of the 10 subjects with hepatoblastoma. In addition, 9 (30.0%) of the 30 subjects with Wilms tumors and 14 (25.0%) of the 56 subjects with rhabdomyosarcoma were positive for the expression of GPC3. Concerning autopsy specimens, most of the 23 subjects younger than 7 months showed positive findings in the liver (94.7%) and kidney (81.8%). Two subjects (100%) with yolk sac tumors and six (75.0%) of the eight subjects with hepatoblastoma serologically demonstrated a high rate of positive expression. Concerning the distribution of the serum GPC3 level according to age, 8 (80.0%) of the 10 subjects younger than 1 year showed a positive finding, while only 16 (37.3%) of the 43 subjects older than 1 year showed a positive finding. CONCLUSION: Most cases of hepatoblastoma and yolk sac tumor, and some cases of other tumors were found to express GPC3 either histologically or serologically. On the other hand, GPC3 was physiologically expressed during the fetal and neoinfantile period under 1 year of age. Although, more preliminary data and experience are required, patients older than 1 year that show a positive finding for GPC3 are considered to be appropriate candidates to receive the new immunotherapy using GPC3 peptide vaccination.

Close correlation between CXCR4 and VEGF expression and frequent CXCR7 expression in rhabdomyosarcoma.

CXC chemokine receptor 4 (CXCR4) expression is reportedly correlated with both vascular endothelial growth factor (VEGF) expression and poor prognosis in a variety of cancers. Its relation to CXC chemokine receptor 7 (CXCR7) is also noted in several malignancies, including rhabdomyosarcoma (RMS) cell lines. However, the correlations between these chemokine receptors and angiogenic factors have not yet been adequately investigated in RMS clinical specimens. By immunohistochemistry, we assessed CXCR4, CXCR7, CC chemokine receptor 6, CC chemokine receptor 7, VEGF expression, microvessel density, and MIB-1 labeling index in 82 formalin-fixed RMS specimens, including 34 primary alveolar RMS and 44 primary embryonal RMS (ERMS). Twenty-six frozen samples were available for investigation by quantitative reverse transcription polymerase chain reaction to detect the messenger RNA expression levels of these molecules. We also evaluated their significance with respect to clinicopathological factors and patient survival rates. Primary RMS showed high expression of CXCR7 (83.1%) regardless of the histologic subtype. High cytoplasmic CXCR4 and high VEGF expression revealed significant correlations in both ERMS and alveolar RMS (P = .0051 and P = .0003, respectively). By univariate analysis of ERMS cases, the tumors with high VEGF expression showed significantly poor prognoses (P = .0017). High VEGF expression also was the independent adverse prognostic factor for ERMS. Because CXCR4, CXCR7, and VEGF are widely expressed in RMS, the combination of these antagonists may provide a potential target for molecular therapy.