Miyuki Kohno

Hepatocellular carcinoma complicating biliary cirrhosis caused by biliary atresia : report of a case

A case of hepatocellular carcinoma complicating biliary cirrhosis caused by biliary atresia is reported. The patient had persistent severe jaundice with hepatosplenomegaly. A liver tumor was suspected because of the elevated serum alpha-fetoprotein and was shown by ultrasonography at 6 years of age. The tumor was treated with percutaneous ethanol injection therapy (PEIT). Nine months after initiation of PEIT, the patient died of massive bleeding from a metastatic tumor.

Laparoscopic enucleation of a gastroenteric duplication cyst arising in a pancreatic tail that did not communicate with the pancreatic duct: report of a case.

Gastroenteric duplication rarely occurs in locations such as the pancreas. We report a case of gastroenteric duplication of the pancreatic tail, which was noncontiguous with the stomach and had no communication with the pancreatic duct, in a 3-year-old girl. The cyst was enucleated by laparoscopy, without the need for pancreatic resection. The optimal treatment procedures vary considerably, depending on where the gastroenteric duplication is located in the pancreas and, most importantly, whether there is communication with the pancreatic duct.

Solitary intrapulmonary cystic lymphangioma in an infant: A case report with literature review

Lymphangioma rarely presents as a solitary pulmonary lesion. We encountered a case of solitary cystic lymphangioma and present its clinicopathologic and immunohistochemical findings. A 2-month-old boy was referred to the hospital after developing a persistent cough. Chest X-ray showed a large cyst in the right lung. Under the preoperative diagnosis of bronchogenic cyst, he underwent right lower lobectomy at the age of 11 months. The resected specimen contained a 5.5-cm septate cystic lesion. Microscopically, the lesion consisted of a large cystic space and interconnected slit-like spaces surrounding bronchovascular islands. The cyst was lined by a monolayer of flat cells with focal multinucleated giant cells. Immunohistochemically, the cells lining the cystic lesion were positive for D2-40, Prox1, CD34, and CD31, and weakly positive for VEGFR-3, but were negative for AE1/3, HMB45, VEGF-A, VFGF-C, VEGFR-1. Differential diagnoses included lobar or interstitial emphysema, bronchogenic cyst, congenital pulmonary airway malformation and alveolar adenoma. D2-40 and Prox1 were useful in differentiation and in determining the extent of the lesion. A review of the literature found only 15 cases of solitary pulmonary lymphangioma. In younger patients, the lesions tend to occupy more of the lung. Focal giant cell reaction has not been described in the reported papers.

Comparison of the postoperative bowel function between transanal endorectal pull-through and transabdominal pull-through for Hirschsprung's disease: a study of the feces excretion function using an RI-defecogram

PurposeHerein, we compared the bowel function after a transabdominal and a transanal procedure for Hirschsprung’s disease (HD) using the clinical score and a quantitative evaluation of the feces excretion function based on the findings of an RI-defecogram.Materials and methodsThe subjects included 35 patients with short segment aganglionosis. In the two groups with transabdominal Z-shaped anastomosis (open group) and transanal endorectal pull-through (TEPT) (transanal group), the postoperative bowel function were evaluated based on the clinical score. In the RI-defecogram study, a time-activity curve was drawn for the 99mTc remaining in the rectum on defecation. The feces excretion function was thus quantified, with the time until the 99mTc in the rectum became 50% as T0.5 and the time until 90% of the feces were excreted from the rectum as T0.9.ResultsThe clinical score could be evaluated in 9 cases in the open group and in 15 cases in the transanal group. No significant difference was observed in the total clinical score between the two groups, but the urge to defecate and the constipation scores in the subcategories were significantly lower in the open group. The defecogram was performed included seven cases in the open group and five cases in the transanal group. When an analysis of covariance of the two groups was conducted for the T0.5 and T0.9 values using the postoperative months as a covariate, there was a significantly negative slope, and moreover, there was a significant difference between the two groups.ConclusionsThe RI-defecogram showed that feces excretion time improves with the postoperative months in both the groups, but the transanal group has higher feces excretion function in the early postoperative period compared with the open group. We consider the RI-defecogram to therefore be a useful examination method for evaluating the feces excretion function.

FGFR1 is critical for the anti-endothelial mesenchymal transition effect of N -acetyl-seryl-aspartyl-lysyl-proline via induction of the MAP4K4 pathway

Endothelial-to-mesenchymal transition (EndMT) has been shown to contribute to organ fibrogenesis, and we have reported that the anti-EndMT effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is associated with restoring expression of diabetes-suppressed fibroblast growth factor receptor (FGFR), the key anti-EndMT molecule. FGFR1 is the key inhibitor of EndMT via the suppression of the transforming growth factor β (TGFβ) signaling pathway, and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) inhibits integrin β1, a key factor in activating TGFβ signaling and EndMT. Here, we showed that the close proximity between AcSDKP and FGFR1 was essential for the suppression of TGFβ/smad signaling and EndMT associated with MAP4K4 phosphorylation (P-MAP4K4) in endothelial cells. In cultured human dermal microvascular endothelial cells (HMVECs), the anti-EndMT and anti-TGFβ/smad effects of AcSDKP were lost following treatment with a neutralizing FGFR1 antibody (N-FGFR1) or transfection of FRS2 siRNA. The physical interaction between FGFR1 and P-MAP4K4 in HMVECs was confirmed by proximity ligation analysis and an immunoprecipitation assay. AcSDKP induced P-MAP4K4 in HMVECs, which was significantly inhibited by treatment with either N-FGFR1 or FRS2 siRNA. Furthermore, MAP4K4 knockdown using specific siRNAs induced smad3 phosphorylation and EndMT in HMVECs, which was not suppressed by AcSDKP. Streptozotocin-induced diabetic CD-1 mice exhibited suppression of both FGFR1 and P-MAP4K4 expression levels associated with the induction of TGFβ/smad3 signaling and EndMT in their hearts and kidneys; those were restored by AcSDKP treatment. These data demonstrate that the AcSDKP–FGFR1–MAP4K4 axis has an important role in combating EndMT-associated fibrotic disorders.

A ketogenic amino acid rich diet benefits mitochondrial homeostasis by altering the AKT/4EBP1 and autophagy signaling pathways in the gastrocnemius and soleus

Muscle biology is important topic in diabetes research. We have reported that a diet with ketogenic amino acids rich replacement (KAAR) ameliorated high-fat diet (HFD)-induced hepatosteatosis via activation of the autophagy system. Here, we found that a KAAR ameliorated the mitochondrial morphological alterations and associated mitochondrial dysfunction induced by an HFD through induction of the AKT/4EBP1 and autophagy signaling pathways in both fast and slow muscles. The mice were fed with a standard HFD (30% fat in food) or an HFD with KAAR (HFDKAAR). In both the gastrocnemius and the soleus, HFDKAAR ameliorated HFD-impaired mitochondrial morphology and mitochondrial function, characterized by decreased mitofusin 2, optic atrophy 1, peroxisome proliferator-activated receptor (PPAR) γ coactivator-1α and PPARα levels and increased dynamin-related protein 1 levels. The decreased levels of phosphorylated AKT and 4EBP1 in the gastrocnemius and soleus of HFD-fed mice were remediated by HFDKAAR. Furthermore, the HFDKAAR ameliorated the HFD-induced autophagy defects in the gastrocnemius and soleus. These findings suggest that KAAR may be a novel strategy to combat obesity-induced mitochondrial dysfunction, likely through induction of the AKT/4EBP1 and autophagy pathways in skeletal muscle.

Surgical approach for fecal incontinence with a patulous anus after transanal pull-through for Hirschsprung disease

BACKGROUND We have performed transanal pull-through (TAPT) for Hirschsprung disease since 1998. Some of our patients after TAPT showed a patulous anus and suffered from severe true fecal incontinence. We performed anal canal plasty for these patients and evaluated its efficacy in restoring anorectal function. METHODS Thirty-one patients who were ≥5years old were previously operated on for Hirschsprung disease, and seven (22.5%) of these were indicated for this procedure. Anorectal function was evaluated using the Japanese Study Group of Anorectal Anomalies (JSGA) clinical assessment of defecation function score. For surgery, the patients were positioned in the prone jackknife posture. The posterior half of the anal canal was exposed and folded inward until the anal canal lumen was as narrow as the surgeons index finger. External anal sphincter muscles were repaired, and the wound was closed vertically. RESULTS The mean preoperative JSGA score was 1.42±0.4. The mean JSGA scores at 2-6months and 2years after this procedure were 5±2.1 and 5.8±2.1, respectively. Postoperatively, the JSGA score significantly improved at both times (p<0.05). CONCLUSIONS Anal canal plasty may be effective for true fecal incontinence and a patulous anus after TAPT. This surgical approach may be useful for these conditions. LEVEL OF EVIDENCE Type of study: Treatment study, Level IV.

Patent ductus arteriosus flow patterns in the treatment of congenital diaphragmatic hernia

Background:  Congenital diaphragmatic hernia (CDH) mortality still remains high, due to lung hypoplasia and persistent pulmonary hypertension of the neonate (PPHN). Effective management of PPHN and time of operation are quite important to the improvement of CDH treatment. In order to determine the optimal time for operation, we monitored PPHN with cardiac ultrasound.

Spinal muscular atrophy with respiratory distress type 1 associated with novel compound heterozygous mutations in IGHMBP2: Differential diagnosis in a case with congenital diaphragm eventration: SMARD1 with novel mutations

Spinal muscular atrophy with respiratory distress type 1 (SMARD1, OMIM #604320) is a rare motor neuron disease caused by autosomal recessive mutations in the immunoglobulin mu binding protein 2 (IGHMBP2) gene (Grohmann 2001). SMARD1 is characterized by respiratory failure requiring mechanical ventilation, initial distal and later generalized muscular weakness, and autonomic nerve dysfunction (Eckart 2015).

Congenital duodenal and multiple jejunal atresia with malrotation in a patient with Down syndrome

Congenital duodenal atresia (CDA) is a relatively common anomaly affecting an estimated 1 in 3000 to 10 000 births and is strongly associated with Down syndrome (Coran et al. 2011a, b; Adams and Stanton, 2014; Alnosair et al. 2014; Zaghal et al. 2015). Intrinsic CDA is thought to result from failure of recanalization of the duodenum (Alnosair et al. 2014). Congenital jejunoileal atresia (CJIA) affects approximately 1 in 5000 to 14 000 births (Adams and Stanton 2014; Zaghal et al. 2015). More than one-third of affected children are born prematurely, and associated chromosomal abnormalities are rare (<1 % of cases) (Adams and Stanton 2014). CJIA is thought to result from an intrauterine vascular accident (Coran et al. 2011a, b; Adams and Stanton 2014; Alnosair et al. 2014; Zaghal et al. 2015). No reports have described the simultaneous occurrence of duodenal and multiple jejunal atresia, malrotation, an annular pancreas, and the absence of branches of the superior mesenteric artery in a patient with Down syndrome. To our knowledge, this is the first such case report. The patient was referred to our institute because two intraabdominal cysts exhibiting the “double-bubble” sign were detected by fetal ultrasonography at 29 gestational weeks. This finding was confirmed at our institution by fetal magnetic resonance imaging, which revealed a dilated stomach and first portion of the duodenum. The patient, a female infant, was delivered at 35 gestational weeks with a body weight of 2352 g. She had the typical features of Down syndrome. Based on the radiologic and ultrasonic findings, she was preoperatively diagnosed with CDA, malrotation without volvulus, and a ventricular septal defect. She underwent laparotomy at 0 days of age. She had type III duodenal atresia (i.e., the third and fourth parts of the duodenum were absent), type IV multiple jejunal atresia, malrotation, an annular pancreas, and the absence of branches of the superior mesenteric artery (Fig. 1a, b). The small intestine and freely mobile jejunal end were supplied by a marginal artery (Fig. 1c). The type IV multiple jejunal atresia comprised three areas of type II atresia, the blind ends of which were separated by a fibrous cord 6, 8, and 11 cm from the jejunal end, respectively; and two areas of type I (mucosal) atresia with an intact bowel wall and mesentery 27 and 30 cm from the jejunal end, respectively (Fig. 1d). The biliary and pancreatic ducts were inserted into the duodenum proximal to the annular pancreas. The patient underwent resection from the jejunal end to 30 cm from the jejunal end, including all areas affected by jejunal atresia; side-to-end duodenojejunostomy; appendectomy; and replacement of the intestine in the peritoneal cavity. Reconstruction of the mesentery was easily performed because both margins of the mesentery were close in proximity to each other after the side-to-end duodenojejunostomy. The specimen (almost 10 cm from the jejunal end) showed >10 intestinal villi/mm, some goblet cells in each villus, and no Peyer’s patches. These findings suggest that the specimen was jejunum. The postoperative course was uneventful. She was diagnosed with Down syndrome by chromosomal testing. The duodenum has an abundant dual vascular supply originating from the celiac axis and superior mesenteric artery. These vessels form the pancreaticoduodenal arcade, an important collateral between the celiac artery and the superior mesenteric artery. Some authors have suggested that the vascular accidents involving the pancreaticoduodenal arcade might have been the underlying cause of the duodenal atresia (Weber and Freeman 1999). Furthermore, some authors have suggested that Down syndrome cell adhesion molecule (DSCAM), located at 21q22.2, is associated with gastrointestinal problems, although it is evident that no single critical region of genes is sufficient to cause all Down syndrome phenotypes (Asim et al. 2015). We consider that the pathogenesis of the present case, especially the necrosis and defectiveness of the third and fourth parts of duodenum and proximal jejunum by strong ischemia in the SMA perfusion area as well as the presence of multiple jejunal atresia, was caused not only by vascular accidents of the pancreaticoduodenal arcade but also by failure of recanalization. Chromosomal disorders may lie behind these processes.