TMEM25 is a Par3-binding protein that attenuates claudin assembly during tight junction development.

The tight junction (TJ) in epithelial cells is formed by integral membrane proteins and cytoplasmic scaffolding proteins. The former contains the claudin family proteins with four transmembrane segments, while the latter includes Par3, a PDZ domain-containing adaptor that organizes TJ formation. Here we show the single membrane-spanning protein TMEM25 localizes to TJs in epithelial cells and binds to Par3 via a PDZ-mediated interaction with its C-terminal cytoplasmic tail. TJ development during epithelial cell polarization is accelerated by depletion of TMEM25, and delayed by overexpression of TMEM25 but not by that of a C-terminally deleted protein, indicating a regulatory role of TMEM25. TMEM25 associates via its N-terminal extracellular domain with claudin-1 and claudin-2 to suppress their cis- and trans-oligomerizations, both of which participate in TJ strand formation. Furthermore, Par3 attenuates TMEM25-claudin association via binding to TMEM25, implying its ability to affect claudin oligomerization. Thus, the TJ protein TMEM25 appears to negatively regulate claudin assembly in TJ formation, which regulation is modulated by its interaction with Par3.

Long-term cosmetic outcomes of the slit-slide procedure for umbilical hernia repair in children.

PURPOSE: To assess the long-term cosmetic outcomes of the "slit-slide procedure", designed to provide a more natural appearance for umbilical hernia repair, as perceived by the patients and their parents. METHODS: A total of 149 patients with umbilical hernia underwent the slit-slide procedure at our hospital. The slit-slide procedure allows for the creation of an umbilicus with a more natural and integrated appearance. The patient satisfaction survey questionnaire was mailed to the families (n = 139), and there were 74 (53.2%) respondents. A questionnaire survey on postoperative appearance was also distributed to pediatric surgeons. RESULTS: The median age at the time of operation was 2.5 years (range, 2 months to 14 years) and the average median age at the time of answering the questionnaire was 6.25 years old (range, 2.5-14.8 years). The average median period of observation was 3.2 years (range, 4 months to 8.97 years). Most patients (89.2%) and parents (93.2%) were satisfied with the appearance of the umbilicus. Twenty-seven patients reported improved satisfaction after surgery (36.2%). Surgeons tended to score the elongated-oval shape highly; however, there was no difference in satisfaction among the shapes. CONCLUSION: The slit-slide procedure is not only effective and safe, but it achieves a satisfactory aesthetic outcome.

Thoracoscopic repair for late-presenting congenital diaphragmatic hernia with thoracic kidney in a child.

Congenital diaphragmatic hernia (CDH) with a hernia sac and thoracic kidney is a very rare congenital anomaly. Recently, the usefulness of endoscopic surgery for CDH has been reported. We herein report a patient who underwent thoracoscopic repair of CDH with a hernia sac and thoracic kidney. A 7-year-old boy was referred to our hospital due to a diagnosis of CDH without clinical symptoms. Computed tomography showed herniation of the intestine into the left thorax and left-sided thoracic kidney. The key points of operation are resection of the hernia sac and identification of the suturable diaphragm under the presence of the thoracic kidney. In the present case, after repositioning the kidney to the subdiaphragmatic area completely, the border of the diaphragmatic rim was clearly visualized. Good visibility allowed resection of the hernia sac without damaging the phrenic nerve and closure of the diaphragmatic defect.

The degree of satisfaction and level of learning in male and female surgical residents: a nationwide questionnaire survey of graduating residents in Japan.

PURPOSE: Since 2002, the Japan Surgical Society has established a board certification system for surgeons to be certified for a specialty. Surgery remains a male-dominated field in Japan. This study aimed to clarify if the Japanese surgical residency training system is equally suitable for female and male residents. METHODS: The Japan Surgical Society conducted the first questionnaire survey regarding the system of surgical training for the residents in 2016. The questionnaire included the degree of satisfaction with 7 aspects of the training system, including the number and variety of cases experienced and duration and quality of instruction, and the learning level for 31 procedures. The degree of satisfaction and level of learning were compared between female and male residents. RESULTS: The degree of satisfaction was similar for all items between female and male residents. Female residents chose breast surgery as their subspecialty more frequently than male residents and were more confident in breast surgery procedures than male residents. Conversely, fewer female residents chose gastrointestinal surgery and were less confident in gastrointestinal surgery procedures than male residents. CONCLUSION: Female residents were as satisfied with the current surgical training system as male residents. However, there may be room for improvement in the surgical system, considering that fewer applications for gastrointestinal surgery come from female residents than from males.

Feasibility of Laparoscopic Fundoplication Without Removing the Preceding Gastrostomy in Severely Neurologically Impaired Patients: A Multicenter Evaluation of the Traction Technique.

Purpose: Severely neurologically impaired patients sometimes require anti-reflux surgery with preceding gastrostomy. We apply a traction technique for laparoscopic fundoplication (LF) without gastrostomy takedown (GTD) in such cases. We conducted a multicenter review to assess the feasibility of our approach. Materials and Methods: In brief, the traction technique involves left-lateral-traction of the stomach body, right-lateral-traction of the round ligament of the liver, and elevation of the left liver lobe to create a sufficient field for manipulating the forceps. Patients who underwent LF with Nissen's procedures in 2010-2022 were retrospectively reviewed. Data were analyzed by a one-way analysis of variance. Results: The operative approaches included the traction technique (n = 16; Group 1), GTD and reconstruction (n = 5; Group 2), and LF followed by gastrostomy (n = 92; Group 3). In comparison with Group 1, significant differences were only found in pneumoperitoneum time (Group 1 versus Group 2 versus Group 3: 174.4 minutes versus 250.4 minutes versus 179.5 minutes; P = .0179). Operating time (222.7 minutes versus 303.0 minutes versus 239.7 minutes; P = .0743), duration to full-strength enteral nutrition (10.4 days versus 17.2 days versus 11.0 days; P = .0806), and length of hospital stay (17.2 days versus 31.0 days versus 18.5 days; P = .3247) were equivalent. No re-fundoplication was required in Group 1. Conclusion: The traction technique secures the operative quality and outcome of LF without GTD.

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.

The experiences of interval appendectomy for inflammatory appendiceal mass.

BACKGROUND: Interval appendectomy (IA) is a common treatment of acute appendicitis (AA) with inflammatory appendiceal mass (IAM). However, the management of patients with IAM is still controversial. The aim of this study was to assess the outcomes in patients with this condition. METHODS: We retrospectively evaluated 244 patients with AA for their clinical characteristics and outcomes. RESULTS: Forty-three patients had IAM at the first medical examination. The mean age was significantly younger and the C-reactive protein level significantly higher (12.6 vs 3.1 mg/dL) in patients with IAM. Thirty-four patients received IA, and nine received emergency appendectomy (EA). In the IA group, the diameter of the abscess was larger than in the EA group (31.4 vs 16.1 mm). The total length of hospitalization was longer in the IA group than the EA group (20.6 vs 7.0 days), although the operative time was longer in the EA group because of adhesion (101.1 vs 192.1 min). Furthermore, most IA patients received a reduced-port appendectomy (74% vs 11%). Recurrence occurred in approximately 15% of patients awaiting IA. There were no complications in either group. CONCLUSIONS: Although each treatment approach has its advantages and disadvantages, both IA and EA can be the first option for the treatment of AA with IAM.

Is there disparity between regions and facilities in surgical resident training in Japan? Insights from a national survey.

PURPOSE: This study sought to assess the disparity between regions and facilities in surgical resident training in Japan via a national level needs-assessment. METHODS: A survey was sent to all 909 graduating residents of 2016. Residents trained in the six prefectures with a population of 7 million or more were included in the large prefecture (LP) group. Residents trained in the other 41 prefectures were included in the small prefecture (SP) group. Each group was further divided into a university hospital (UH) group and a non-university hospital (NUH) group. RESULTS: The response rate was 56.3% (n = 512). Excluding nine residents who did not report their prefectures and facilities, surveys from 503 residents were analyzed. The UH group received significantly more years of training. In the SP and UH groups, there were significantly fewer residents who had performed 150 procedures or more under general anesthesia in comparison to the LP and NUH groups, respectively. Self-assessed competencies for several procedures were significantly lower in the SP and UH groups. CONCLUSION: Disparity in surgical resident training was found between regions and facilities in Japan. The surgical residency curriculum in Japan could be improved to address this problem.

Are graduating residents sufficiently competent? Results of a national gap analysis survey of program directors and graduating residents in Japan.

PURPOSE: To evaluate the self-assessed competency of graduating residents (GRs) in Japan upon completion of their residency and to identify the gap between their competency and the competency expected by their program directors (PDs). METHOD: A list of 31 essential surgical procedures was compiled according to the consensus of surgical educators from around the country. A survey with this list was sent to all 909 GRs and their 611 PDs in 2016. The GRs rated their competency to perform these procedures and the PDs were asked to evaluate the expected competency of their GRs using the Zwisch Scale. RESULT: The response rate was 56.3% for the GRs and 76.8% for the PDs. Fewer than half of the GRs who responded felt confident performing ten (32%) of the surgical procedures evaluated. For most procedures, the GRs' self-reported competency was lower than the expectation reported by their PDs. This gap was more than 10% for 13 of the procedures. CONCLUSION: More than half of the GRs in Japan lacked the confidence in their skill to perform one-third of the surgical procedures selected for evaluation in this study. These findings should be used to update the surgical education curriculum in Japan.

The outcome of real-time evaluation of biliary flow using near-infrared fluorescence cholangiography with Indocyanine green in biliary atresia surgery.

BACKGROUND: Indocyanine green (ICG) fluorescence imaging is a promising tool for intraoperative decision-making. The aim of this study was to evaluate the utility of near-infrared fluorescence cholangiography (NIR-FCG) with ICG in primary surgery for biliary atresia (BA). METHODS: We performed NIR-FCG with ICG in 10 BA patients and observed the fluorescence of their hilar micro-bile ducts and hilar exudate in order to assess the appropriate level at which to dissect the hilar fibrous corn. We compared the jaundice outcome of 10 patients using NIR-FCG (Group A) to that of 35 historical patients in whom NIR-FCG had not been used (Group B). RESULTS: The mean age of patients was 74.8 days. The classification of BA was type I in two cases and type-III in eight cases. NIR-FCG visualized the hilar micro-bile ducts, and the incidence of positive fluorescence was 80%. The ratio of postoperative normalization of hyperbilirubinemia in Group A was significantly higher than that in Group B (1.0 vs. 0.65, p < 0.05). CONCLUSION: NIR-FCG provided important objectifiable information about the biliary structures in surgery of BA. Although the number of cases was small, our results suggest that NIR-FCG may be useful for improving the outcome of primary surgery for BA. TYPE OF STUDY: Study of Diagnostic Test. LEVEL OF EVIDENCE: Level III.

A snapshot of surgical resident training in Japan: results of a national-level needs assessment survey.

PURPOSE: To evaluate the status of surgical training in Japan through a national-level needs assessment. METHODS: A survey was sent to all 909 graduating residents (GRs) and their 611 program directors (PDs) for the year 2016. A working group of surgical educators from around the country was formed under the education committee of the Japan Surgical Society. The survey items were developed by consensus of this working group. The survey investigated the knowledge and problems of the current curriculum, and the status of the current residency training. RESULTS: The response rates were 56.3% of the GRs and 76.8% of the PDs. Among the participants, 47.6% of the GRs and 29.4% of the PDs believed that the residency curriculum did not match the clinical experience. Over 80% of the GRs and PDs agreed on the importance of training outside of the OR, whereas only 13% of the GRs had received such training regularly. Trainees also reported a lower satisfaction rate about the opportunity to train outside of the OR. CONCLUSION: This national-level needs assessment of surgical training in Japan identified several gaps in the curriculum. These results provide valuable data to assist the ongoing efforts for surgical residency curriculum improvement.

Acquired isolated hypoganglionosis as a distinct entity: results from a nationwide survey.

PURPOSE: Acquired isolated hypoganglionosis (A-IH) is a late-onset intestinal pseudo-obstruction disorder and shows different pathophysiological findings from congenital isolated hypoganglionosis (C-IH). In this study, we retrospectively examined five cases of A-IH and investigated the features of A-IH. METHODS: Five cases of A-IH were extracted from a nationwide retrospective cohort study in 10 years, from which totally 355 cases of Allied Disorders of Hirschsprung's Disease (ADHD) were collected. RESULTS: Ages of onset were between 13 and 17 years in three cases, and 4 years and 4 months in ones. Initial symptoms were abdominal distension and/or chronic constipation in 4 cases, whereas one exhibited intestinal perforation. Affected lesions varied from case to case, extending various length of intestinal tracts. All cases underwent multiple operations (average: 4.6 times), such as enterostomy, resection of dilated intestines, and/or pull-through. Pathological findings showed the decreased numbers of ganglion cells and degeneration of ganglion cells, whereas the size of the plexus was normal. Currently, all cases were alive and almost all eat regular food without requiring parenteral feeding. CONCLUSION: A-IH is rare, but distinct entity characterized by different clinical courses and pathological findings from those of C-IH. The outcome is considered to be favorable after a resection of affected intestine.

Extensive spinal epidural immature teratoma in an infant: case report.

Here, the authors present an extremely rare case of an extensive spinal epidural teratoma (SET) in an infant and provide a review of the cases in the literature. In this report, the authors focused on the clinical manifestation and management of extensive SET. A 64-day-old girl presented with severe dyspnea and paraparesis caused by a large thoracic mass. Imaging studies revealed that the mass originated from the epidural space of the thoracic spine and extended from C7 to L1. The tumor extended bilaterally through the intervertebral foramina and formed a large posterior mediastinal mass. The tumor was partially resected via laminotomy after an emergency thoracotomy. The remnant grade I immature teratoma grew rapidly. After a re-laminotomy and bilateral thoracotomy, the residual tumor stopped growing. However, the patient's paraparesis improved very little, and her scoliosis progressed gradually. Therefore, SET should be included in the differential diagnosis when an infant patient with paraparesis of the lower extremities is encountered. Timely diagnosis, aggressive treatment, and close monitoring are of critical importance to successful recovery in such patients.

The evaluation of rectal mucosal punch biopsy in the diagnosis of Hirschsprung's disease: a 30-year experience of 954 patients.

PURPOSE: For 30 years, we have consecutively performed rectal mucosal punch biopsy to diagnose Hirschsprung's disease. The aim of this study was to evaluate the safety of our technique. METHODS: Patients with suspected Hirschsprung's disease who underwent punch biopsy, including our original "K-PUNCH" method using an S-moid forceps and non-specific blood-collecting tube at our department and branch hospital between April 1986 and March 2016 were included in the present study. Our punch biopsy technique is characterized by excellent visibility and a direct grasping sensation. The backgrounds and complications of the patients were retrospectively investigated. RESULTS: During this period, 954 patients (median age 4 months; range 1 day-73 years) underwent punch biopsy. Although there were no cases of severe complications (i.e., rectal perforation, infection or full-thickness biopsy), one (0.1%) of the 954 cases in the early period showed liver dysfunction and required transfusion due to bleeding. In addition, inappropriate specimens were obtained in 37 patients (3.9%). CONCLUSION: Punch biopsy including the "K-PUNCH" method is considered safe and feasible and is associated with a low rate of complications and inappropriate specimen harvesting among patients of all ages. Comorbidities, including the potential for hemorrhage, should always be considered.

Testicular ascent after laparoscopic percutaneous extraperitoneal closure for inguinal hernias.

AIM: Laparoscopic percutaneous extraperitoneal closure (LPEC) has been widely performed for the repair of pediatric inguinal hernias in Japan. This study aimed to evaluate the testicular ascent and orchiopexy after LPEC in males with inguinal hernias. METHODS: The medical records of male patients who underwent LPEC procedures for the repair of an inguinal hernia from January 2010 to December 2013 at our institution were reviewed. The patients who underwent orchiopexy after the LPEC procedure were investigated, the characteristics studied were the birth weight of the patients, the age when they underwent LPEC, the mean time from LPEC to orchiopexy, and the location of the affected testes. The LPEC procedure was performed by extraperitoneal circuit suturing around the internal inguinal ring with a long straight special needle (Lapaherclosure; Hakko Medical Co., Tokyo, Japan). RESULTS: During the 4-year period of this study, 438 LPECs were performed on 367 male patients. Orchiopexy was performed on 14 testes (3.2%) in 10 patients who had previously undergone LPEC. Five of the 10 patients were extremely low-birth-weight infants. The mean time from LPEC to orchiopexy was 13.2 months. In 7 of these 10 patients, both testes were initially identified in the scrotum at 3 months after LPECs, but they later showed ascending or retractile testes. In another three patients, the ipsilateral testes were elevated early after LPECs, and they were thought to be missed congenital undescended testes. At orchiopexy, 10 of the 14 testes were located in the inguinal region, and the other four testes were retractile. During the orchiopexy, the remaining processus vaginalis was found to adhere to the spermatic cord in all of the patients with ascending testes. CONCLUSION: The postoperative testicular ascent should be carefully examined after the LPEC procedure in patients with pediatric inguinal hernias, especially in extremely low-birth-weight infants.

The WD40 protein Morg1 facilitates Par6-aPKC binding to Crb3 for apical identity in epithelial cells.

Formation of apico-basal polarity in epithelial cells is crucial for both morphogenesis (e.g., cyst formation) and function (e.g., tight junction development). Atypical protein kinase C (aPKC), complexed with Par6, is considered to translocate to the apical membrane and function in epithelial cell polarization. However, the mechanism for translocation of the Par6-aPKC complex has remained largely unknown. Here, we show that the WD40 protein Morg1 (mitogen-activated protein kinase organizer 1) directly binds to Par6 and thus facilitates apical targeting of Par6-aPKC in Madin-Darby canine kidney epithelial cells. Morg1 also interacts with the apical transmembrane protein Crumbs3 to promote Par6-aPKC binding to Crumbs3, which is reinforced with the apically localized small GTPase Cdc42. Depletion of Morg1 disrupted both tight junction development in monolayer culture and cyst formation in three-dimensional culture; apico-basal polarity was notably restored by forced targeting of aPKC to the apical surface. Thus, Par6-aPKC recruitment to the premature apical membrane appears to be required for definition of apical identity of epithelial cells.

Diagnostic value of lectin reactive alpha-fetoprotein for neoinfantile hepatic tumors and malignant germ cell tumors: preliminary study.

BACKGROUND AND PURPOSE: The serum alpha-fetoprotein (AFP) level has been used as a tumor marker for hepatoblastoma, and malignant germ cell tumors in pediatric patients. The AFP has 3 isoforms (L1, L2, L3), and the usefulness of the L3 fraction as a diagnostic marker for the adult hepatocellular carcinoma is well known. However, there are few reports dealing with various pediatric malignant tumors. In the current study, we analyzed the diagnostic value of AFP fractions for pediatric diseases, in particular, those occurring in the neoinfantile period. MATERIALS AND METHODS: From 2003 to 2006, two cases of hepatoblastoma, and 5 cases of germ cell tumor, all of which were neoinfantile, were treated in our department. In our analytical system (LiBASys), the level of the L3 fraction contains the majority of the L2 fraction. The total AFP (ng/mL) level and the L3 fraction (%) were measured to assess the usefulness of the L3 fraction as a diagnostic marker. RESULTS: In all cases of hepatoblastoma and yolk sac tumor, both the total AFP and the L3 fraction were high, either before treatment or in the presence of malignant tumors. Most of the cases of neonatal immature teratoma showed a high total AFP level during the neoinfantile period, however, the L3 fraction was around 10%, and decreased after surgical treatment. Only 1 case of the immature teratoma demonstrated malignant transformation, when the patient was 8 months old. As the total AFP and the AFP-L3 fraction were proportionally elevated, the patient was treated with additional surgical resection and chemotherapy. In the case of neonatal mature teratoma, the L3 fraction was below 0.5%, even when the total AFP level was high. DISCUSSION: Our results indicated that the level of the L3 fraction accurately confirmed the existence, or the malignant potential of hepatic tumor or germ cell tumor. The L3 fraction is useful as a tumor marker during the neoinfantile period.