Reduction en masse of Inguinal Hernia in a 2-Month-Old Male Infant.

Reduction en masse is the reduction of the hernial sac into the preperitoneal space, with a loop of bowel remaining trapped at the neck of the hernial sac. This complication is rare, usually associated with inguinal hernias, and is characterized by the absence of a noticeable bulge in the groin. The patient was a 2-month-old male infant and presented with a nonreducible bulge in his left groin, and incarceration of the left inguinal hernia was diagnosed. Manual reduction was performed, and the hernia bulge became less noticeable. He was admitted, and laparoscopic percutaneous extraperitoneal closure was scheduled for the next day. The laparoscopy revealed remarkably dilated intestines, serous ascites, and an ischemic intestine in the left groin. A laparotomy was performed and revealed reduction en masse of the left inguinal hernia with a strangulated ileum at its neck. We made an incision at the neck, followed by the resection of 20-cm long strangulated ileum. The patient's condition was unstable on the day of operation, but the postoperative period was uneventful, and the left inguinal hernia was repaired, 11 months after the operation. Reduction en masse in pediatrics is significantly rare but when it occurs, the diagnosis can be delayed and occasionally the patient will be life-threatening. To avoid reduction en masse, it is crucial to perform the reduction gently and confirm the absence of a hernia sac in the preperitoneal space containing a loop of bowel by ultrasound scanning. Moreover, contrary to common practice, overnight observation and close monitoring will avoid missing a late presentation, leading to timely interventions.

Achaete-scute family bHLH transcription factor 2 activation promotes hepatoblastoma progression.

Achaete-scute family bHLH transcription factor 2 (ASCL2) is highly expressed in hepatoblastoma (HB) tissues, but its role remains unclear. Thus, biological changes in the HB cell line HepG2 in response to induced ASCL2 expression were assessed. ASCL2 expression was induced in HepG2 cells using the Tet-On 3G system, which includes doxycycline. Cell viability, proliferation activity, mobility, and stemness were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony-formation, migration, invasion, and sphere-formation assays. Quantitative reverse-transcription polymerase chain reaction was used to assess the expression of markers for proliferation (CCND1 and MYC), epithelial-mesenchymal transition (EMT; SNAI1, TWIST1, and ZEB1), mesenchymal-epithelial transition (CDH1), and stemness (KLF4, POU5F1, and SOX9). Compared with the non-induced HepG2 cells, cells with induced ASCL2 expression showed significant increases in viability, colony number, migration area (%), and sphere number on days 7, 14, 8, and 7, respectively, and invasion area (%) after 90 h. Furthermore, induction of ASCL2 expression significantly upregulated CCND1, MYC, POU5F1, SOX9, and KLF4 expression on days 2, 2, 3, 3, and 5, respectively, and increased the ratios of SNAI1, TWIST1, and ZEB1 to CDH1 on day 5. ASCL2 promoted the formation of malignant phenotypes in HepG2 cells, which may be correlated with the upregulation of the Wnt signaling pathway-, EMT-, and stemness-related genes. ASCL2 activation may therefore be involved in the progression of HB.

Single-cell next-generation sequencing of circulating tumor cells in patients with neuroblastoma.

Circulating tumor cells (CTCs) derived from any tumor tissue could contribute to metastasis and resistance to cancer treatments. In this study, we performed single-cell next-generation sequencing of CTCs and evaluated their usefulness for characterizing tumor biology and the mechanisms of metastasis in neuroblastomas (NB). We aimed to isolate CTCs from 10 patients with NB at diagnosis before any treatments and four patients at relapse. GD2+ CD90+ CD45- CD235a- DAPI- cells were isolated as neuroblastoma CTCs using fluorescence-activated cell sorting. In five patients with advanced stages (M stage), DNA and RNA sequencing of CTCs at single-cell level were performed. NB CTCs were isolated from eight of the 10 patients at diagnosis and three of the four patients at relapse. More CTCs could be isolated from patients with advanced stages. In one patient, ALK mutation (p.F1174L), was identified in both tumor tissue and a CTC. In patients with MYCN amplification, this gene was amplified in 12 of 13 CTCs. Using single-cell RNA sequencing, angiogenesis-related and cell cycle-related genes together with CCND1 and TUBA1A genes were found to be upregulated in CTCs. In one patient, CTCs were divided into two subgroups showing different gene expression profiles. In one subgroup, cell cycle-related and proliferation-related genes were differentially upregulated compared with the other group. In conclusion, next-generation sequencing of CTCs at single-cell level might help to characterize the tumor biology and the mechanisms of metastasis in NB.

Determination of the umbilicus position in Japanese children.

BACKGROUND: Although there have been many reports concerning the normal position of the umbilicus, the measurements were performed from the surface of the body in all cases. We examined computed tomography (CT) images to determine the accurate position of the umbilicus in children. METHODS: We retrospectively examined the CT data of 120 Japanese children (60 boys, 60 girls). The angle between both iliac crests to the umbilicus (IU angle), the angle between both anterior superior iliac spines and the umbilicus (AU angle), and the ratio of the length from the xiphoid process to the umbilicus and length from the umbilicus to the pubic symphysis were measured. RESULTS: The mean AU angle was 33.7° ± 5.1°, showing the least data variations. A significant difference was noted in the AU angle between boys and girls (32.7° ± 4.6° and 34.6° ± 5.4° respectively; p = 0.04). When we defined the position of the umbilicus as an AU angle of 33° in boys and 35° in girls, 115 children (95.8%) fell within ±10°. CONCLUSIONS: The AU angle is the preferable predictor of the umbilicus position in children.

A new surgical technique for short bowel syndrome.

OBJECTIVE: Short bowel syndrome (SBS) is a severe intestinal disease that causes malabsorption. Long-term parental nutrition therapy induces infection and liver failure. For the surgical management of intestinal rehabilitation, the intestinal loop lengthening method and serial transverse enteroplasty (STEP) method have been reported, although their effects have proven limited. We herein report a new surgical technique, Saeki-Spiral-Shark (3S) method for SBS using biomimetics of shark intestine. METHODS: In the 3S method, a spiral valve is formed inside the intestine by external sutures. Using a 25 cm length intestinal organ model, we performed both the 3S method and STEP procedure. We then compared the length and fluid passage times of the subsequently formed intestine. RESULTS: After the 3S method was performed, the length of the intestinal model changed to 22 cm, and after the STEP procedure, that was elongated to 30 cm. Although the water passage times did not change markedly, the semi-digestive nutritional supplement passage time slowed down in the model with the 3S method. There was slight leakage in the STEP procedure model. CONCLUSIONS: The 3S method is a unique method of treating SBS based on biomimetics. This procedure does not require an incision of the intestine, which thereby enabling clean and less-invasive surgery. We plan to conduct animal experiments in the future.

Feasibility of Real-Time Central Surgical Review for Patients with Advanced-Stage Hepatoblastoma in the JPLT3 Trial.

In the JPLT3 study, a real-time central surgical reviewing (CSR) system was employed aimed at facilitating early referral of candidates for liver transplantation (LTx) to centers with pediatric LTx services. The expected consequence was surgery, including LTx, conducted at the appropriate time in all cases. This study aimed to review the effect of CSR on institutional surgical decisions in cases enrolled in the JPLT3 study. Real-time CSR was performed in cases in which complex surgeries were expected, using images obtained after two courses of preoperative chemotherapy. Using the cloud-based remote image viewing system, an expert panel consisting of pediatric and transplant surgeons reviewed the images and commented on the expected surgical strategy or the necessity of transferring the patient to a transplant unit. The results were summarized and reported to the treating institutions. A total of 41 reviews were conducted for 35 patients, and 16 cases were evaluated as possible candidates for LTx, with the treating institutions being advised to consult a transplant center. Most of the reviewed cases promptly underwent definitive liver surgeries, including LTx per protocol.

Single-cell DNA and RNA sequencing of circulating tumor cells.

Single-cell sequencing of circulating tumor cells can precisely represent tumor heterogeneity and provide useful information for cancer treatment and research. After spiking TGW neuroblastoma cells into blood derived from healthy volunteer, the cells were isolated by fluorescence-activated cell sorting. DNA and mRNA were amplified by four different whole-genome amplifications (WGA) and three whole-transcriptome amplifications (WTA) methods, followed by single-cell DNA and RNA sequencing. Multiple displacement amplification (MDA)-based WGA methods showed higher amplification efficiency than other methods with a comparable depth of coverage as the bulk sample. The uniformity of coverage greatly differed among samples (12.5-89.2%), with some samples evaluated by the MDA-based WGA method using phi29 DNA polymerase and random primers showing a high (> 80%) uniformity of coverage. The MDA-based WTA method less effectively amplified mRNA and showed non-specific gene expression patterns. The PCR-based WTA using template switching with locked nucleic acid technology accurately amplified mRNA from a single cell. Taken together, our results present a more reliable and adaptable approach for CTC profiling at the single-cell level. Such molecular information on CTCs derived from clinical patients will promote cancer treatment and research.

Design of taste-masked swellable drug particles using dry-coating technology with mechanical curing.

A novel dry coating technique for fine particles that does not require any liquids has been developed. Swellable ordered-mixed drug particles (Swell-OM-spheres, SOS), using a modified starch as the core particle and a drug coating layer have been previously developed. In the present work, SOS particles were further processed to generate 100-µm taste-masking particles using an all dry coating processes. SOS particles were coated with a gastric-soluble powder using a mechanical powder processor. The coated particles (CPs) were subsequently heated while rotating in the same powder processor, completing film formation by a process termed dynamic curing. As a control, conventional film formation (static curing) was performed using a drying oven. The CPs obtained by these two curing processes had distinct appearances, but exhibited equivalent dissolution suppression effects in a medium at pH 6.8 (the pH of the oral cavity). The suppression effect was further improved by adding a plasticizer to the coating powder, even though a lower heating temperature was required. Orally disintegrating tablets incorporating these CPs exhibited excellent taste-masking performance, i.e., suppressing taste in saliva while accelerating dissolution in gastric juice. The dissolution behavior indicated that the CPs can provide an ON/OFF switching function in drug release.

The "Twitching Technique": A New Space-Irrespective Laparoscopic Ligation Technique Using a JAiMY Needle Holder.

Background: Laparoscopic intracorporeal sutures and knots require advanced techniques in children. The JAiMY® needle holder (Endocontrol Company, Grenoble, France), a flexible jaw with both clockwise and anticlockwise revolving functions, enables the placement of sutures in very small working spaces. Using this tool, a novel new ligation method, which we named "twitching technique," can be performed. Methods: To perform the "twitching technique," first grasp the long tail of the thread with the JAiMY and the forceps on the needle side. Then, rotate the tip of the needle holder halfway in either direction and bring the forceps closer to the needle holder to make a ring using the thread. Grasp the thread at the crossing point with the forceps, and then catch the short tail through the ring with the needle holder. Results (Case Presentation): A 1-year-old boy presented with vomiting because of esophageal hiatal hernia. He was being treated for single ventricle and asplenia at our hospital. Laparoscopic esophageal hiatus plication was performed. Although the working space was extremely limited, the JAiMY and the "twitching technique" enabled steady suture placement and ligation. Conclusions: The "twitching technique" is an easy, steady, and safe method for performing ligation in difficult situations and may facilitate the performance of many laparoscopic surgeries in pediatric fields.

Features and Techniques of Laparoscopic Percutaneous Extraperitoneal Closure for Ovarian Hernia.

PURPOSE: The purpose of this report was to evaluate the safety and efficacy of the simple laparoscopic percutaneous extraperitoneal closure (LPEC) method for treating ovarian hernia patients, including newborns and low-birth-weight infants. METHODS: We retrospectively reviewed the cases of ovarian hernia that were treated in our institution from May 2012 to September 2017. RESULTS: Thirty-four infants were included in this study (right side, n = 8; left side, n = 22; bilateral, n = 4). The mean corrected age was 2.3 ± 2.8 months and the mean body weight was 4.4 ± 1.6 kg. The contralateral positive rate was 53%, and 34% of the cases showed sliding of the fallopian tube. Umbilical hernias were observed in 24 cases (71%). The mean operative time was 53 ± 20 minutes. The LPEC procedure was successful in 32 cases; two cases were converted to open surgery. CONCLUSION: Small infants with ovarian hernia have some specific features such as a shortened round ligament and the presence of peritoneum cavities that require skillful techniques when being surgically repaired. The simple LPEC procedure can be performed safely with a low risk of recurrence, even in infants with sliding of the fallopian tube.

Transumbilical Surgery for Duodenal Stenosis in a Child with Situs Inversus: The First Report.

Background. Situs inversus is a rare congenital anomaly with a reported incidence of only 1 in 5,000 to 10,000 live births. Congenital duodenal stenosis complicated with situs inversus is an even rarer entity. Case Presentation. A 1-year-old girl with situs inversus who had undergone a hemi-Fontan procedure against a single ventricle in our hospital was referred to our department for vomiting and failure to thrive. An upper gastrointestinal contrast study and endoscopy revealed duodenal stenosis. A transumbilical radical operation as a minimally invasive surgery was successfully performed. After the surgery, she stopped vomiting, and the postoperative course was uneventful with good cosmetic results. Conclusions. To our knowledge, this is the first report of transumbilical surgery for congenital duodenal stenosis with situs inversus as minimally invasive surgery. Transumbilical surgery to situs inversus patient can be performed safely and lead to good cosmetic outcome.

A morphological study of the removed livers from patients receiving living donor liver transplantation for adult biliary atresia.

BACKGROUND: In liver transplantation (LT) for adult biliary atresia (BA), we often encounter a cirrhotic deformation of the native liver. We aimed to investigate a morphological study of the removed livers and the patient's clinical status. METHODS: We examined 8 BA patients who had undergone LT in adulthood at our hospital. The presence of hypertrophic or atrophic areas of the removed liver was recorded macroscopically. We graded the microscopic findings in the porta hepatis area, a hypertrophic area, and an atrophic area, respectively. Moreover, we investigated the relationship between these morphological findings and the pre-transplant clinical status (MELD score). RESULTS: Macroscopically, a hypertrophic area existed in central liver in all cases (8/8 cases), while an atrophic area was existed in peripheral liver (7/8 cases). Microscopically, an atrophic area was the most severely impaired, while the porta hepatis and hypertrophic area were relatively intact. The pathological score in a compensatory hypertrophic area was strongly correlated with the MELD score. CONCLUSIONS: This study suggests that the partial shrinking is not uncommon in BA cirrhotic liver. It may be due to the imbalance of bile drainage by the different segment. The patient's pre-transplant status depends on the compensatory hypertrophic liver.

Neonatal appendicitis mimicking intestinal duplication: a case report.

INTRODUCTION: Acute appendicitis is a common disease in older children but rare in neonates. CASE PRESENTATION: We report the case of a 2-day-old Asian baby who suffered from neonatal appendicitis mimicking intestinal duplication. Laparoscopic appendectomy was successfully performed after the trans-umbilical division of adhesions, and the postoperative course was uneventful. CONCLUSION: There are few reports describing abdominal masses caused by appendicitis mimicking intestinal duplication. The laparoscopic approach for neonatal appendicitis is considered to be a safe and useful therapeutic modality with good cosmetic results.

Intracranial hemorrhage associated with vitamin K-deficiency bleeding in patients with biliary atresia: focus on long-term outcomes.

BACKGROUND AND AIM: The prophylactic oral administration of vitamin K to newborns has markedly reduced the incidence of vitamin K deficiency (VKD); however, intracranial hemorrhage (ICH) is still one of the complications found in biliary atresia (BA) patients and is associated with VKD bleeding. Therefore, we aimed to investigate the incidence and long-term outcome of ICH in patients with BA who previously received prophylactic vitamin K during the neonatal period. METHODS: Eighty-eight consecutive infants with BA were treated and followed up at Kyushu University Hospital from 1979 to 2009. The clinical records and imaging study results were retrospectively reviewed in the infants with BA who presented with ICH. RESULTS: ICH occurred in 7.95% of patients with BA. The onset of ICH occurred at 47 to 76 days after birth, before the patients underwent surgery for BA (9-37 days after the onset of ICH). Coagulopathy was found upon admission in all of the cases with available data and improved after intravenous administration of vitamin K. A craniotomy was required in 2 cases before the surgery for BA. During the 22 to 278 months of follow-up, some neurologic sequelae persisted in 5 of 7 cases. Follow-up head computed tomography scans showed a low-density area in the left hemisphere in 5 cases. CONCLUSIONS: Although vitamin K prophylaxis had been given during the neonatal period, ICH-associated VKD bleeding was still found in 7.95% of patients with BA. Persistent neurologic sequelae were found in 5 of 7 cases, with low-density area in the left hemisphere.

A formula for determining the standard liver volume in children: a special reference for neonates and infants.

Accurately evaluating the ratio of GV to the SLV (GV/SLV) is important in successful pediatric liver transplantation. However, the formula used to calculate the SLV of children, including neonates and infants, has not yet been established. The aim of the current study was to estimate the SLV of children, including neonates, and to establish an accurate formula. The LV of 100 children (including 7 neonates and 15 infants) were measured using thin slice (3-5 mm) helical CT images. Their BSA was calculated from height and weight. A new formula to estimate the SLV was established as follows: SLV (mL) =689.9 × BSA (m(2)) -24.7. The SLV of children was significantly lower than that in previous reports (p < 0.001). A formula for calculating the SLV of children including neonates was established. This new formula will be useful in pediatric liver transplantation.

Synchronized expressions of hepatic stellate cells and their transactivation and liver regeneration during liver injury in an animal model of cholestasis.

BACKGROUND: There is much known about hepatic stellate cells (HSCs) during liver injury. However, some aspects remain unclear, such as the natural expression levels of HSCs during the days to weeks after liver injury. Does liver regeneration start the same time as the injury process? METHODS: Fifty-four male Wistar rats aged 7 to 8 weeks, weighing 200 to 320 g each were subjected to bile duct ligation (BDL). After surgery, they were killed at different times post-BDL. Collagen deposition was analyzed, and immunohistochemical staining of α-smooth muscle actin (α-SMA), vimentin, matrix metalloproteinase-2 (MMP-2), tissue inhibitor matrix metalloproteinase-1, and proliferating cell nuclear antigen antibody (PCNA) was performed to evaluate HSCs and liver regeneration. RESULTS: The expression of α-SMA was seen as early as day 3 post-BDL, which started from peribiliary to perisinusoidal, and was seen throughout the whole liver sections on day 28 post-BDL. Similar expression patterns were seen in MMP-2 staining. The PCNA expression was strongest around the perisinusoidal area. These expression patterns were not observed in the sham-operated rats. CONCLUSIONS: The activation of HSCs showed a synchronized fibrogenic process and liver regeneration from days to weeks after liver injury. Matrix degradation was thus found to increase in accordance with chronic liver injury, which thus led to an excessive collagen deposition.

Outcome of modified portal vein anastomosis for recipients with portal vein thrombosis or stenosis before living donor liver transplantation.

BACKGROUND: Portal vein thrombosis (PVT) or stenosis (PVS) often requires challenging techniques for reconstruction in living donor liver transplantation (LDLT). MATERIALS AND METHODS: A total of 57 LDLTs were performed between October 1996 and December 2010. There were 16 cases (28%) with PVT/PVS that underwent modified portal vein anastomosis (m-PVa). The m-PVa techniques were classified into 3 groups: patch graft (Type-1), interposition graft (Type-2), and using huge shunt vessels (Type-3). The reconstruction patterns were evaluated with regard to age, graft vessels, PV flow, and complication rate. RESULTS: The m-PVas were Type-1 in 10 cases, Type-2 in 3 cases, and Type-3 in 3 cases. The vessel graft in Type-1 was the inferior mesenteric vein (IMV) in 8 and the jugular vein in 2 cases, whereas the vessel graft in Type-2 was IMV in 2 and the saphenous vein in 1 case; in Type-3, the vessel grafts were renoportal, gonadal-portal, and coronary-portal anastomoses, respectively. The postoperative PV flow was sufficient in all types and slightly higher in Type-3. The postoperative complications occurred in 20% of the patients who underwent Type-1, in 33% who underwent Type-2, and in 0% who underwent Type-3. CONCLUSION: The m-PVa was effective to overcome the surgical difficulty during transplantation. Pretransplant planning for the selection of the type of reconstruction is important for recipients with PVT/PVS.