The impact of the recipient intestinal site on the differentiation of transplanted enteric neural crest cells.

PURPOSE: It has long been established that the failure of enteric neural crest cells (ENCCs) to colonize the entire gut results in aganglionosis at the distal colon in Hirschsprung disease (HD). However, it is still unclear how the intestinal microenvironment of the distal aganglionic gut differs from that of the proximal ganglionic gut in HD versus normal gut. We have recently succeeded in transplanting ENCC into aganglionic gut in endothelin receptor B (Ednrb) knockout (KO) mice. to advance the development of cell therapy for HD, it is essential to determine if the transplanted ENCCs differentiate normally in aganglionic gut. Therefore, we designed this study to investigate the impact of the environment of the recipient intestinal tract, at various sites of aganglionic gut, on the differentiation of transplanted ENCCs. METHODS: ENCCs were isolated from Sox10 Venus transgenic (Tg) mouse gut on embryonic day 18.5 (E18.5) and neurospheres (NS) were generated. Then, NS were transplanted into aganglionic KO and wildtype (WT) gut that had been transected just distal to the ENCC wavefront (KO-wf: n = 6, WT: n = 7), and into distal KO gut transected at a site equivalent to that of the WT (KO-d: n = 6) on E12.5. ENCC differentiation was evaluated using whole-mount immunohistochemistry with Tuj-1 (neuronal marker) and GFAP (glial marker) antibodies. RESULTS: The transplanted ENCCs migrated to form the myenteric and submucosal plexus in all groups. The ratio of the area of Tuj-1-positive cells/GFAP-positive cells in migrated cells in the recipient gut was found to be significantly lower in KO-d compared to KO-wf and WT, while there was no significant difference between KO-wf and WT groups. This suggests that neuronal/glial differentiation was decreased in KO-d compared to that in KO-wf and WT groups. CONCLUSION: Our study highlights the differences in ENCC differentiation depending on the site of transplantation. To further develop cell therapy for HD, it is important to consider the impact of the recipient intestinal environment on transplanted ENCCs.

Increased enteric neural crest cell differentiation after transplantation into aganglionic mouse gut.

PURPOSE: In recent years, many studies have made considerable progress in the development of stem cell-based therapies for Hirschsprung's disease (HD). However, the question of whether enteric neural crest-derived cells (ENCCs) that are transplanted into the aganglionic gut can migrate, proliferate, and differentiate in a normal manner remains unanswered. Thus, we designed this study to compare the behavior of ENCCs transplanted into the aganglionic gut of endothelin receptor B knockout (Ednrb-KO) mice versus wild-type (WT) mice. METHODS: ENCCs were isolated from the fetal guts of Sox10 transgenic mice, in which ENCCs were labeled with an enhanced green fluorescent protein, Venus, on an embryonic day 18.5 (E18.5). Neurospheres were generated and transplanted into the aganglionic region of either Ednrb-KO mice gut, or WT mice gut that had not yet been colonized, on E12.5. Time-lapse imaging of the transplanted ENCCs was performed after 24, 48, and 72 h of culture. Neuronal differentiation was evaluated using whole-mount immunohistochemistry. RESULTS: Sox10-positive ENCCs were seen to successfully migrate into the myenteric region of the aganglionic gut following transplantation in both the Ednrb-KO and WT mice. The ratio of Tuj1-positive/Sox10-positive cells was significantly increased after 72 h of culture compared to 24 h in the Ednrb-KO mice, which suggests that the transplanted ENCCs differentiated over time. In addition, at the 72 h timepoint, neuronal differentiation of transplanted ENCC in the aganglionic gut of Ednrb-KO mice was significantly increased compared to that of WT mice. CONCLUSIONS: The results of our study demonstrated that transplanted ENCCs migrated into the myenteric region of the aganglionic recipient gut in mice. The increased neuronal differentiation of transplanted ENCC in Endrb-KO mice gut suggests that the microenvironment of this region affects ENCC behavior following transplantation. Further research to explore the characteristics of this microenvironment will improve the potential of developing cell therapy to treat HD patients.

Japan's comprehensive undescended testis screening program: incidence of ascending testis after screening.

PURPOSE: Screening for undescended testis (UDT) in Japan is performed as a neonate, then at 1, 3, 10, and 18 months old, and 3 years old. Incidence of ascending testis (AT) after screening was reviewed. METHODS: All orchiopexy/orchiectomy at a single institute between July 2005 and June 2022 were reviewed retrospectively. RESULTS: 376 boys had 422 procedures; 54/422 (12.8%) were in 48 boys ≥ 4 years old (mean age: 6.7 years; range: 4-13); testes were normal (n = 22; 40.7%), small (n = 25; 46.2%), or atrophied (n = 7; 1.3%). There were 47 orchiopexies and 7 orchiectomies for atrophy. Incidence of AT in boys ≥ 4 years old was 24/422 (5.7%). Of these, 16/422 (3.8%) developed after normal descent and 8/422 (1.9%) were associated with retractile testis (AT + RET). Other indications included delayed treatment for UDT (n = 13), late referral by pediatricians (n = 10), and iatrogenic UDT (n = 6). Surgical intervention in boys ≥ 4 years old (12.8%) was less than that reported in the West (range: 30-50%) as was AT: (5.7% versus 15.4%) and AT + RET (1.9% versus 13.8%). CONCLUSIONS: Comprehensive UDT screening probably contributed to the lower incidence of surgery and AT (especially AT + RET) in boys ≥ 4 years old.

Decreased incidence of intussusception during the COVID-19 pandemic. Trends in pediatric surgical emergencies.

PURPOSE: Recent reports suggest that the COVID-19 pandemic may be influencing disease morbidity. The purpose of this study was to investigate pandemic-related changes in the incidence of pediatric surgical emergencies. METHODS: Data from patients with one of 8 typical conditions considered to be pediatric emergencies who presented at 3 hospitals close to central Tokyo were collated retrospectively from accident and emergency (AE) department records for 2020 and compared with data for 3 years prior to 2020. RESULTS: All subjects had similar demographic profiles. The total number of pediatric AE attendances from 2017 to 2020 was 2880 (2017: n = 600, 2018: n = 736, 2019: n = 817, and 2020: n = 727). Annual attendances were similar. Of the 8 conditions, there were significantly less cases of intussusception in 2020 than previously (23/727; 3.1% versus 132/2153; 6.1%) p < 0.01 and the number of emergency surgical interventions for intussusception was also significantly less in 2020 (0/23; 0% versus 13/132; 9.8%) p < 0.01. CONCLUSION: The implementation of preventative measures to combat the COVID-19 pandemic in 2020 would appear to have influenced the etiopathogenesis of intussusception enough to significantly decrease its overall incidence and the requirement for emergency surgical intervention.

Decreased expression of ß1 integrin in enteric neural crest cells of the endothelin receptor B null mouse model.

BACKGROUND: Interactions between enteric neural crest-derived cells (ENCC) and the surrounding intestinal microenvironment, such as the extracellular matrix (ECM), are critical for regulating enteric nervous system (ENS) development. Integrins are the major receptors for ECM molecules, such as laminin, which have been reported to be involved in the pathogenesis of Hirschsprung's disease. In this study, we examined the expression of ß1 integrin in the endothelin receptor B (Ednrb) knock out (KO) mouse gut, which presents with an aganglionic colon. METHODS: A Sox10-Venus-positive Ednrb KO mouse, where ENCC is labeled with fluorescent protein, 'Venus', was created. Sox10-Venus-positive Ednrb wild type (WT) were used as controls. Small intestine, proximal colon and distal colon were dissected on E13.5 and E15.5 and ß1 integrin expression of the gut tissue was examined by immunohistochemistry and real time RT-PCR. The cells of the gut dissected on E11.5 were isolated and cultured for 2 days. Venus-positive ENCC were immunostained with ß1 integrin and Tuj-1, which is a marker for neurons. RESULTS: The expression of ß1 integrin was not significantly different between KO and WT in all parts of the gut examined. However, the ß1 integrin expression in the isolated ENCC was significantly decreased in KO compared to WT. The average threshold area was 42.98 ± 17.47% in KO and 73.53 ± 13.77 in WT (p < 0.001). CONCLUSIONS: We demonstrated that ß1 integrin expression was specifically decreased in ENCC in Ednrb KO mice. Our results suggest that impaired interaction between integrin and its ligands may disturb normal ENS development, resulting in an aganglionic colon.

Perforation in pediatric non-complicated appendicitis treated by antibiotics: the real incidence.

PURPOSE: The incidence of perforation during antibiotic therapy (AT) of children triaged as non-complicated acute appendicitis (NC-Ap) was investigated. METHODS: Abdominal ultrasonography (US) and/or computed tomography (CT) scans from cases of perforation identified at appendectomy for failed AT were reassessed blindly by a panel of board-certified specialists for any evidence of pre-AT morbidity suggestive of perforation. RESULTS: Of 521 cases triaged as NC-Ap, symptoms resolved with AT in 452 cases (86.8%). All 69/521 (13.2%) cases with persistent symptoms had urgent appendectomy, and 12/521 (2.3%) were found to have perforated. Blind reassessment of US and/or CT scans from these cases identified seven with evidence of perforation when they were triaged as NC-Ap. Thus, the actual incidence of perforation during AT for NC-Ap was actually 12-7 = 5/521 (0.95%). CONCLUSIONS: Perforation is generally believed to be a complication of AT, but inappropriate triaging of cases for AT can bias results by artificially inflating the number of perforations, in this study, by more than double. We are the first to assess the unbiased incidence of perforation during AT for NC-Ap, by reassessing pre-AT US and/or CT scans. The incidence of perforation during AT is actually negligible.

Hirschsprung's disease in the laparoscopic transanal pull-through era: implications of age at surgery and technical aspects.

AIM: Detailed implications of age at laparoscopic transanal pull-through (LTAPT) on postoperative bowel function (POBF) in Hirschsprung's disease (HD) are somewhat obscure because of a spectrum of factors. METHODS: Age at surgery was used to categorize 106 consecutive postoperative HD cases treated by our modified LTAPT (JLTPAT) between 1997 and 2015; group A: < 3 months old (n = 31); group B: 3-11 months old (n = 44); group C: 1-3 years old (n = 19); and group D: ≥ 4 years old (n = 12). POBF was assessed by reviewing outpatient records 1, 3, 5, 7, and 10 years after JLTAPT prospectively and scoring each of 5 criteria on a scale of 0-2; best score = 10. RESULTS: Only operative time was statistically longer in group D versus groups A, B, and C. Differences in gender ratios, blood loss, duration of follow-up, and POBF scores were not statistically significant. Mean POBF scores over time were: group A: 6.8, 7.6, 8.4, 8.6, and 8.4; group B: 7.1, 7.8, 8.3, 8.5, and 9.0; group C: 6.9, 7.9, 8.1, 8.3, and 8.6; group D: 7.0, 7.4, 8.2, 8.1, and 8.5, respectively. CONCLUSION: Age at JLTAPT was not correlated with POBF in HD.

Three- and four-dimensional analysis of altered behavior of enteric neural crest derived cells in the Hirschsprung's disease mouse model.

BACKGROUND/AIM: The behavior of enteric neural crest-derived cells (ENCC) during enteric nervous system (ENS) development is being gradually understood with the introduction of live-cell imaging. However, many of the analyses to date are two-dimensional and the precise multidirectional migration of ENCC has been challenging to interpret. Mice lacking the endothelin-B receptor gene, Ednrb (-/-) mice, are widely used as a model for Hirschsprung's disease (HD). We have recently developed a Sox10 transgenic (Tg) mouse to visualize ENCC with enhanced green fluorescent protein (Venus). By breeding these two models, we have created a Venus-positive, Sox10 Tg mouse with a deletion of the Ednrb gene, Sox10-Venus(+)/Ednrb (-/-) mouse, to investigate the ENS in HD. The aim of this study was to investigate the behavior of migrating ENCC in the hindgut of the Sox10-Venus(+)/Ednrb (-/-) mouse using three-dimensional and four-dimensional image analysis software. METHODS: To compare the ENCC behavior when the wavefront of ENCC reaches the mid-hindgut between HD mouse and control, we harvested the fetal hindguts of Sox10-Venus(+)/Ednrb (-/-) mice on embryonic day 15.5 (E15.5) and Sox10-Venus(+)/Ednrb (+/+) mice on E12.5, which was used as control. Dissected hindguts were cultured for 360 min and the time-lapse images were obtained using a confocal laser-scanning microscope. Each ENCC at the wavefront was tracked after adjusting the longitudinal axis of the gut to the Y axis and analyzed using Imaris software. RESULTS: Track displacement (TD)-Y indicates ENCC advancement in a rostral-caudal direction. TD-X and TD-Z indicate ENCC advancement perpendicular to the rostral-caudal axis. Mean TD-Y was 34.56 µm in HD, but 63.48 µm in controls. TD-Y/TD-XZ was not significantly different in both groups. However, the mean track speeds were significantly decreased in HD (72.87 µm/h) compared to controls (248.29 µm/h). CONCLUSIONS: Our results showed that the track speed of ENCC advancement was markedly decreased in the HD mice compared to controls. This technique provides added information by tracking ENCC with depth perception, which has potential for further elucidating the altered behavior of ENCC in HD.

Comprehensive assessment of prognosis after laparoscopic portoenterostomy for biliary atresia.

PURPOSE: Total bilirubin (T-bil) is used universally for monitoring post-portoenterostomy (PE) biliary atresia (BA) patients although other biochemical markers [BM; AST/ALT and platelet count (PC)] are also prognostic. We compared open PE (OPE) with laparoscopic PE (LPE) using T-bil, AST/ALT, and PC (3BM) as more comprehensive indicators of postoperative clinical status. METHODS: Subjects were 31 PE cases (LPE: n = 17; OPE: n = 14). BA classification was type III (n = 16), type II (n = 1) in LPE and type III (n = 12), type I (n = 1), type II (n = 1) in OPE. RESULTS: Mean ages and weights at PE were similar: 65.5 days, 4.4 kg (LPE) versus 69.3 days, 4.1 kg (OPE); and mean follow-up was 2.5 years for both LPE and OPE. Jaundice clearance (T-bil ≤1.2 mg/dL) was achieved in 16/17 (94.1 %) after LPE versus 10/14 (71.4 %) after OPE (p = NS), but 3BM were closer to normal after OPE. At the time of review, 13/17 LPE cases (76.5 %) were alive with native livers and 4/17 had received LTx (23.5 %) and 10/14 OPE cases (71.4 %) were alive with native livers and 4/14 had received LTx (28.6 %). CONCLUSIONS: Although JC was better after LPE, 3BM were better after OPE. Further follow-up will prove the comprehensive prognostic value of 3BM.

Does pneumoperitoneum adversely affect growth, development and liver function in biliary atresia patients after laparoscopic portoenterostomy?

PURPOSE: We assessed the effect of high partial pressure of arterial carbon dioxide (PaCO2) due to pneumoperitoneum (PP) on growth (height/weight) and development (gross/fine motor function, receptive/expressive communication, and social interaction), by comparing outcome after portoenterostomy (PE) for biliary atresia (BA) using laparoscopic PE (LPE: n = 13) and open PE (OPE: n = 13) cases performed between 2005 and 2014. METHODS: Our PE is based on Kasai's original PE. All data were collated prospectively. RESULTS: Differences in duration of follow-up (LPE: 38.8 months; OPE: 38.1 months), jaundice clearance (LPE: 12/13 = 92.3 %; OPE: 9/13 = 69.2 %), survival with the native liver (LPE: 10/13 = 76.9 %; OPE: 9/13 = 69.2 %), incidence of cholangitis, hypersplenism, and incidence of esophageal varices were not significant. Mean intraoperative PaCO2 was significantly higher in LPE (LPE: 50.1 mmHg; OPE: 40.7 mmHg, p < 0.05). Liver function impairment was not statistically different, although LPE results were slightly worse. There was no overall delay in growth observed, although height/weight gain was more consistent in LPE. The pattern of developmental delay observed was similar for LPE and OPE suggesting that developmental delay is not PE-related; in other words, PP is not implicated in developmental delay. CONCLUSIONS: PP during LPE would appear to have no adverse effects on overall growth/development and liver function in BA patients.

Experience of treating biliary atresia with three types of portoenterostomy at a single institution: extended, modified Kasai, and laparoscopic modified Kasai.

PURPOSE: Generally, open portoenterostomy (PE) involves a wide extended anastomosis and all sutures are deep [extended PE (EP)]. In contrast, the anastomosis in Kasai's PE (KP), our modified open Kasai PE (MK), and our laparoscopic modified Kasai PE (lapMK) involve shallow suturing, especially at the 2 and 10 o'clock positions where the right and left bile ducts would be normally. We compared outcomes of 36 consecutive biliary atresia (BA) patients treated by three types of PE at a single institution during the period 2005-2014; EP (n = 13), MK (n = 11), and lapMK (n = 12). METHODS: We compared age at PE, time taken to become jaundice-free (total bilirubin ≤1.2 mg/dL; JF time), proportion of JF subjects [JF ratio (JFR)], steroid dosage, incidence of cholangitis, postoperative liver function and CRP, presence of hypersplenism, requirement for liver transplantation (LTx), and JF survival with the native liver (JF+NL) as indicators of outcome. RESULTS: Patient demographics, steroid dosage, JF time, incidence of cholangitis, presence of hypersplenism, operating time, blood loss and postoperative biochemistry were similar for all groups. However, JFR was significantly higher for lapMK (100 %) versus EP (46.2 %) (p < 0.05), but not for MK (81.8%) versus EP. Kaplan-Meier analysis showed survival with NL was significantly higher for lapMK (10/12: 83.3%: JF in 9; not JF in 1) and MK (9/11: 81.8 %: JF in all) versus EP (3/13: 23.1%: JF in all) (p < 0.05, respectively), but not for lapMK versus MK. JF+NL in both lapMK (9/12: 75.0%) and MK (9/11: 81.8%) were significantly higher compared with EP (3/13: 23.1%) (p < 0.05, respectively). Intraperitoneal adhesions were less pronounced at LTx in lapMK compared with MK or EP. CONCLUSIONS: This study would suggest that depth of suturing during PE would appear to influence post-PE outcome. LapMK should be reconsidered as a valid treatment option for BA.

Assessment of laparoscopic inguinal hernia repair using the classification for single port laparoscopy in adolescents and young adults.

BACKGROUND: Inguinal hernia repair is one of the most common operations performed worldwide. No consensus currently exists regarding the most appropriate operation for inguinal hernia in adolescent and young adult (AYA) patients. This study aimed to evaluate the outcomes in AYA patients undergoing high ligation or mesh repair under laparoscopy by examining the location and size of the hernia orifice defect. METHODS: We retrospectively reviewed all patients aged 15 to 40 years old who underwent laparoscopic hernia repair. Under single port laparoscopy, we classified the anatomic location (lateral, medial, or femoral) and size of the hernia orifice according to the classification by the European Hernia Society (EHS). A laparoscopic percutaneous extraperitoneal closure (LPEC) was performed on the patients with a lateral hernia with a hernia orifice defect size of ≤1.5 cm (L1). Transabdominal preperitoneal (TAPP) repair was performed on the patients with a lateral hernia with a hernia orifice defect size of >1.5 cm (L2 or 3). RESULTS: Overall, 40 patients underwent the mentioned surgical procedures. We performed LPEC on 22 patients, and TAPP on 18 patients. There were no intraoperative or postoperative complications and recurrences. CONCLUSIONS: This is the first report that evaluated the outcomes of AYA patients who underwent high ligation or mesh repair under laparoscopy by examining the location and size of the hernia orifice defect. Our data indicated that LPEC were effective and safe for AYA patients with small hernia orifice defect.

Do Parameatal Urethral Cysts in Children Need Surgical Excision?

OBJECTIVE: To examine pathophysiology of parameatal urethral cyst (PUC) with comparison between the surgical excision group and the spontaneous resolution group. METHODS: We retrospectively reviewed all patients diagnosed with PUC and aged ≤15 years. Initially, all the patients received observation without any treatment. The indication of surgical excision was family preference. The patients were analyzed according to their sex, age, symptoms, clinical course, and pathological examination findings. RESULTS: Among the 54 boys visited our hospital for PUC. The median age at presentation was 35 (IQR: 12-50) months, including 7 (13.0%) neonates cases. In total, 38 (70.4%) patients were underwent surgical excision, 12 (22.2%) had spontaneous resolution during observation, 1 (1.9%) had observation without resolution, and 3 (5.6%) were lost to follow-up. The median size of PUC at the first visit was significantly larger in the surgical excision group (5 mm median, IQR 3-5) than in the spontaneous resolution group (1.5 mm median, IQR 1-2.5) (P <.0001). In this study, PUC ≥5 mm in diameter did not have spontaneous resolution. CONCLUSION: This is the largest study of PUC conducted at a single institute. This study indicated that 22% of PUCs had spontaneous resolution, and PUCs <5 mm had potential for spontaneous resolution. The results recommend an observation of at least 5.5 months for patients with asymptomatic PUC <5 mm. By contrast, we recommend the surgical excision for symptomatic PUC ≥5 mm according to the family preference.

Biochemical Evaluation of Laparoscopic Portoenterostomy for Treating Biliary Atresia and Redo for Failed Portoenterostomy.

Background: Postoperative outcomes of portoenterostomy (PE) and redo-PE were evaluated using selected biochemical markers (SBM) and biochemical status categories (BSC). Methods: Subjects were 70 consecutive PE performed for biliary atresia. SBM were aspartate aminotransferase (AST)/alanine aminotransferase (ALT), cholinesterase (ChE), and platelet count (PLT) assessed at 1, 2, 3, 6, and 12 months, and thence, annually for a maximum of 10 years. BSC were as follows: all SBM normal (N-SBM), normal AST/ALT (N-SLT), normal ChE (N-ChE), normal PC (N-PLT), all abnormal (A-SBM), abnormal AST/ALT (A-SLT), abnormal ChE (A-ChE), and abnormal PC (A-PLT). Subjects achieving jaundice clearance (JC) and surviving with native livers (SNL) also had gamma glutamyl transpeptidase assessed. Redo-PE indicated for failed PE was assessed postoperatively using the same SBM/BSC protocol. Results: PE were laparoscopic (LPE; n = 40) or open (OPE; n = 30). Mean age/weight at PE and duration of follow-up were similar. For JC, LPE = 34/40 (85.0%) and OPE = 22/30 (73.3%); P = .23. For SNL, LPE = 29/40 (72.5%) and OPE = 16/30 (53.3%); P = .10. LPE and OPE were similar for SBM/BSC, except for a single significant increase in ALT in OPE at 6 months. Redo-PE was performed 17-180 days (mean 67.1 days) after primary PE. AST was significantly increased at the last preredo assessment 3 months after primary PE; P < .05. After redo, AST decreased and SBM/BSC results were equivalent to nonredo subjects. Conclusion: Postoperative biochemical data for all PE cases were comparable; redo-PE would appear to be viable for restoring SBM, and AST could be valuable as a single marker of deterioration in redo cases.

How valuable is ductal plate malformation as a predictor of clinical course in postoperative biliary atresia patients?

PURPOSE: We assessed ductal plate malformation (DPM) as a prognostic factor for mid-/long-term outcome in post-hepatoportoenterostomy (HPE) biliary atresia patients. METHODS: Of 78 cases of HPE performed between 1989 and 2009, biopsy specimens were available for 43. Cytokeratin 19 was used to identify DPM and preoperative status, postoperative serum total bilirubin, time taken to become jaundice-free, duration of jaundice-free period, steroid usage, incidences of cholangitis, bile lakes, and varices, and requirement for reoperation and liver transplantation were compared. RESULTS: DPM was detected in 21/43 (48.8%) subjects [DPM-positive (DPM+)]. Differences were identified for maximum postoperative serum total bilirubin: DPM+ (12.28 ± 1.00 mg/dL) versus DPM-negative (DPM-) (9.67 ± 0.71 mg/dL) (P < 0.05) and total steroid usage: DPM+ (98.3 ± 11.8 mg/kg) versus DPM- (83.4 ± 15.9 mg/kg) (P = NS). However, total steroid dose in jaundice-free cases was significantly higher in DPM+ [75.3 ± 10.0 mg/kg (n = 14) vs. 48.1 ± 6.4 mg/kg (n = 19); P < 0.05)]. There were no differences for complications. Mean duration of follow-up was significantly shorter for DPM+ (60.9 ± 38.4 vs. 113.8 ± 56.9 months; P < 0.05). CONCLUSION: Postoperative total bilirubin was higher in DPM+ cases, thus higher doses of steroids were required. However, DPM+ did not appear to influence the incidence of complications mid-/long-term.

Duration from the first pale stool to portoenterostomy is prognostic in biliary atresia. Comparison with age at portoenterostomy.

OBJECTIVE: Three criteria (age at first pale stool, age at portoenterostomy, and duration from the first pale stool to portoenterostomy) were assessed for prognostic value in biliary atresia. METHODS: The medical records of 116 consecutive biliary atresia patients treated by portoenterostomy after liver transplantation became available in Japan in 1989 were identified and data from 96 were analyzed retrospectively for this study. The impact of each criterion on clearance of jaundice to normal levels (total serum bilirubin ≤1.2 mg/dL) and survival with the native liver as indicators of outcome were compared according to time (≤30 days, 31-60 days, and ≥61 days). RESULTS: Age at first pale stool was ≤30 days in 53, 31-60 days in 26, ≥61 days in 17; age at portoenterostomy was ≤30 days in 7, 31-60 days in 35, ≥61 days in 54, and duration pre-portoenterostomy was ≤30 days in 50, 31-60 days in 36, ≥61 days in 10. Survival with the native liver was not significantly influenced by age at first pale stool or age at portoenterostomy, but prolonged duration (≥61 days) reduced survival with the native liver significantly (p = 0.003). Clearance of jaundice to normal levels was not affected by any criterion at any time.

Lessons learned from lower urinary tract complications of anorectoplasty for imperforate anus with rectourethral/rectovesical fistula: Laparoscopy-assisted versus posterior sagittal approaches.

PURPOSE: To report the sequelae of and preventive strategies for selected lower urinary tract (LUT) complications, i.e., posterior urethral diverticulum (PUD), intraoperative LUT injuries, postoperative dysuria, and fistula recurrence in male imperforate anus (IA) with rectourethral/rectovesical (RU/RV) fistula after laparoscopy-assisted anorectoplasty (LAARP) or posterior sagittal anorectoplasty (PSARP). METHODS: 153 boys with IA and RU/RV fistula treated 1986-2019 by LAARP (n = 56) or PSARP (n = 97) at two unrelated institutes were studied retrospectively. RESULTS: After mean follow-up of 17.0 years (range: 36.5 days-32.0 years), the overall incidences of LUT complications were: LAARP (6/56; 10.7%); PSARP (7/97; 7.2%); p = 0.55, comprising PUD: LAARP (n = 5), PSARP (n = 0); p = 0.006; injuries: LAARP (n = 0), PSARP (n = 5); p = 0.16; dysuria: LAARP (n = 1), PSARP (n = 1); p>0.999; and recurrence: LAARP (n = 0), PSARP (n = 1); p>0.999. Mean onset of PUD was 5.1 years (range: 1.0-15.1 years). TREATMENT: PUD: surgery (n = 2/5), conservative (n = 3/5); injuries: intraoperative repair (n = 5/5); dysuria: conservative (n = 2/2), and recurrence: redo PSARP (n = 1/1). CONCLUSIONS: Strategies devised to improve dissection accuracy resolved the specific technical issues causing LUT complications (remnant RU fistula dissection in LAARP and blind posterior access in PSARP). Currently, the incidence of new cases of PUD and LUT injuries is zero. LEVEL OF EVIDENCE: Level III.

Dysgerminoma with Estrogen-Producing Functioning Stroma Presenting Precocious Puberty.

Dysgerminoma is a malignant ovarian germ cell tumor, and unlike sex-cord stromal tumors, endocrine manifestation is considered rare. Here, we report the first case of dysgerminoma presenting precocious puberty. The patient is a 7-year-old girl who presented with a breast development in Tanner stage 3. Serum estradiol (E2) was markedly elevated while luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were suppressed below the detection limit. Microscopically, the right ovarian mass displayed nests of large polygonal cells and fibrous septa which were focally concentrated by theca-like plump spindle cells. Immunohistochemistry revealed that the spindle cells expressed various steroidogenic enzymes involved in estrogen biosynthesis including P450 aromatase. The tumor was diagnosed with pure dysgerminoma with estrogen-producing functioning stroma. After the operation, serum E2 declined below the detection limit; LH and FSH returned within the normal range. This case demonstrates that even a conventional dysgerminoma can present endocrine manifestation through functioning stroma.

Forty-Year Experience Alleviating Postoperative Hirschsprung-Associated Enterocolitis by Complete Full-Thickness Posterior Rectal Cuff Excision. The Anorectal Line Eliminates Problematic Anastomoses.

Introduction: A modified pull-through (PT) distinguished by complete full-thickness removal of the posterior rectal cuff, initially developed as an open procedure in 1980, has been performed with laparoscopic assistance since 1997. Postoperative bowel dysfunction improved when the anatomic landmark for PT surgery was revised from the dentate line (DL) to the anorectal (or Herrmann's) line (ARL) in 2007. A 40-year (1980-2019) review of 153 consecutive rectal/rectosigmoid type Hirschsprung's disease (HD) patients is presented. Methods: Data for postoperative bowel dysfunction and Hirschsprung-associated enterocolitis (HAEC) classified according to the American Pediatric Surgical Association (APSA) scale were obtained retrospectively. Results: PT was open (n = 43) and laparoscopic (n = 110). Dissection was DL (n = 57) and ARL (n = 96). Over 40 years, 5/153 patients (3.3%) had postoperative obstructive symptoms (POS), and 10/153 patients (6.5%) had 13 episodes of postoperative HAEC; APSA grades were: I (n = 4); II (n = 8); and III: (n = 1) presenting with explosive diarrhea (10/13; 76.9%), fever (10/13; 76.9%), abdominal distension (9/13; 69.2%), or bloody stools/shock (1/13 with grade III; 7.7%). The grade III case had histologically-proven transitional zone PT. Postoperative HAEC developed in 3/5 (60.0%) POS+ patients and 7/148 (4.7%) POS- patients (P = .002). Symptom duration and treatment were not correlated with APSA grades. Conclusions: Complete full-thickness posterior rectal cuff excision and using the ARL reduced postoperative HAEC significantly in this series. Despite being anatomically distinct, the DL is inadequate as a precise landmark for PT surgery because it lacks functional relevance. The APSA scale could benefit from timely review to improve its clinical and prognostic value.

Can Intraoperative Video Recordings Contribute to Improving Laparoscopic Percutaneous Extraperitoneal Closure in Children with Inguinal Hernia and Prevent Recurrence? A Pilot Study.

Aim: We reviewed intraoperative video recordings (IVRs) of laparoscopic percutaneous extraperitoneal closure (LPEC) for inguinal hernia in children blindly to assess performance. Methods: IVRs of 183 LPEC performed between April 2013 and March 2016, graded by the operating surgeon as difficult (D; n = 8), straightforward (S; n = 96), or easy (E; n = 79), were scored by a panel of reviewers with advanced (group A; >400 LPEC cases; n = 5), intermediate (group I; 50-150 cases; n = 5), and basic (group B; <10 cases; n = 5) experience, according to suturing, dissection plane, vas/vessel dissection, bleeding, and peritoneal injury. They also allocated a recurrence risk rank (RRR; highest = 6; lowest = 1) for each IVR. Mean score variance for each IVR was also compared between reviewers. Results: There was one recurrence (R; 4-year-old male; level E). RRR were: 1, 2, and 2 for reviewers A, I, and B, respectively. Reviewer A scores for "suturing" and "bleeding," and reviewer I scores for "dissection plane" and "peritoneal injury" correlated significantly with RRR. No reviewer B scores correlated with RRR. Score variance between A and I and A and B for cases D1 and D2 were statistically significant. Conclusion: Advanced reviewers showed greatest variance, questioning the validity of whether experience alone improves surgical technique.