Tadaharu Okazaki

Enhanced expression of vascular endothelial growth factor in lungs of newborn infants with congenital diaphragmatic hernia and pulmonary hypertension

BACKGROUND Pulmonary hypoplasia accompanied by pulmonary hypertension resistant to treatment is an important feature of congenital diaphragmatic hernia (CDH). The pathogenesis of the pulmonary vascular abnormalities in CDH remains to be elucidated at the molecular level. Vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, is known to play a role in pulmonary angiogenesis and vascular remodelling but there are no data on VEGF expression in patients with CDH. METHODS Necroscopic lung specimens from 21 patients with CDH with lung hypoplasia and from seven age matched control newborn infants without lung hypoplasia were processed for immunohistochemical analysis using affinity purified anti-human VEGF antibodies. All the cases of CDH had pulmonary hypoplasia, indicated by a lung/body weight index of ⩽0.012, and pulmonary hypertension indicated by repeated cardiac ultrasonography. Cellular localisation of VEGF was semiquantitatively analysed using a staining score ranging from 0 (no staining) to 4 (very strong staining). RESULTS Significantly raised levels of VEGF immunoreactivity were observed in lung specimens from cases of CDH compared with controls. VEGF was detected mainly in the bronchial epithelium and the medial smooth muscle cells of large (>200 μm) and small (<200 μm) pulmonary arteries, the most intense staining being in the medial smooth muscle cells of the small pulmonary arteries. Endothelial cells were positive for VEGF staining in patients with CDH but not in controls. CONCLUSIONS This is the first study of VEGF expression in newborn infants with CDH. Increased levels of VEGF, especially in the small, pressure regulating pulmonary arteries, point to a potential role in vascular remodelling. This may reflect an unsuccessful attempt by the developing fetus to increase the pulmonary vascular bed in the hypoplastic lungs to alleviate the associated pulmonary hypertension.

Long-term postsurgical outcome of biliary atresia

BACKGROUND/PURPOSE A successful Kasai procedure is effective in creating biliary drainage and radically altering the natural history of infants with biliary atresia (BA). Since its introduction in the 1950s, long-term follow-up would appear to show that only 30% to 50% of patients have a good long-term prognosis despite initially good surgical outcome. The authors reviewed their experience in treating BA from 1968 to 1997 to assess long-term outcome. MATERIALS AND METHODS The records of 163 patients treated surgically for BA from 1968 to 1997 were reviewed. Forty-eight (29%) were alive at the end of 1997, of whom, 14 had received liver transplants (LT). Surviving patients who had not undergone transplantation were divided into two groups according to clinical condition: group A, normal liver function without cholangitis (CG) and portal hypertension (PH) and group B, liver dysfunction with CG or PH. The study period was divided arbitrarily into three periods, 1968 to 1975 (period I, n = 34); 1976 to 1985 (period II, n = 81); 1986 to 1997 (period III, n = 48). RESULTS Thirty-four patients were alive without LT at the end of 1997. There were eight patients (mean age, 16.3+/-4.8 years) in group A, and 26 patients (mean age, 14.3+/-7.6 years) in group B. Recently, four group A patients (mean age, 19.3+/-1.9 years) shifted to group B because of sudden deterioration in condition involving severe CG with multiple bile lakes (n = 2), uncontrollable intestinal bleeding (n = 1), and liver atrophy (n = 1). Survival deteriorated with length of follow-up. There were three survivors from 34 patients treated in period I, 16 survivors from 81 patients treated in period II (three had LT), and 29 survivors from 48 patients treated in period III (11 had LT). CONCLUSIONS Although satisfactory bile drainage can be obtained with portoenterostomy, our data suggest that liver function can deteriorate progressively, with a possible turning point in late adolescence, indicating that as the length of follow-up increases, clinical assessment should be regular and comprehensive. The timing of LT in postoperative BA patients with deteriorating liver function is a vital management issue.

Lack of intestinal pacemaker (C-KIT-positive) cells in infantile hypertrophic pyloric stenosis☆

The pathogenesis of infantile hypertrophic pyloric stenosis (IHPS) is not well understood. Recent studies have shown that the protonocogene c-kit is essential for the development or maintenance of autonomic gut motility, and also show that the c-kit gene protein product (C-KIT) positive cells in the mammalian gut are responsible for intestinal pacemaker activity. This study examines cells in the pyloric muscles of 23 patients (16 with IHPS, 7 controls) for the presence of the C-KIT (C-KIT+), using immunohistochemical techniques with antihuman C-KIT sera. In the controls, many C-KIT immunoreactive (IR+) cells were observed in the muscle layers. The myenteric plexuses were demarcated by a moderate number of C-KIT-IR+ cells. However, in the IHPS patients, C-KIT-IR were either absent or significantly reduced. No C-KIT-IR+ cells were found around the myenteric plexuses. These findings suggest that a lack of c-kit expression (as an indicator of intestinal pacemaker activity) in the hypertrophic pyloric smooth muscles may be an important factor in the pathogenesis of IHPS.

Abnormal distribution of nerve terminals in infantile hypertrophic pyloric stenosis

Smooth muscle biopsy specimens obtained from nine infants with infantile hypertrophic pyloric stenosis (IHPS) and from three controls were studied immunohistochemically with respect to the distribution of nerve terminals and neurofilaments. To label nerve terminals and neurofilaments, monoclonal antibodies (MAb) 171B5 and 2F11 were used, respectively. In all specimens of the control group, nerve terminals were numerous in both the myenteric plexus and the muscle layer. There were abundant neurofilaments in the myenteric plexus and a moderate number in the muscle layer. In all specimens of the IHPS group, the density of nerve terminals and neurofilaments was reduced in the muscle layer. In the myenteric plexus, there was no such reduction. The results indicate poor neuronal innervation of the muscle layer in the pylorus of infants with IHPS. This poor innervation may be related to the pathogenesis of pyloric stenosis and hypertrophy.

Hyaluronic acid: A specific prognostic indicator of hepatic damage in biliary atresia

BACKGROUND/PURPOSE Hepatic fibrosis can progress in biliary atresia (BA) and is associated with capillarization of hepatic sinusoids. The significance of serum hyaluronic acid (HA) as a noninvasive indicator of histological sinusoidal endothelial cell (SEC) damage and hepatic fibrosis in BA, is investigated. METHODS A total of 28 postoperative BA patients (mean age, 11.0+/-3.7 years) and 20 normal controls (mean age, 10.5+/-2.8 years) were studied. BA patients were divided into group I, good liver function (n = 8); group II, moderate liver dysfunction (n = 10); and group III, severe liver dysfunction (n = 10). Serum HA was determined using a one-step sandwich enzyme immunoassay, and liver histological damage was confirmed immunohistochemically using an antibody against factor VIII-related antigen (FVIIIRAg), which is specific for detecting damaged SEC. RESULTS Serum HA was significantly higher (P < .0001) in group III (84.6+/-36.5 ng/mL) than in group I (15.9+/-6.9 ng/mL) or group 11 (28.7+/-10.7 ng/mL). Although immunoreactive products of FVIIIRAg were abundant in group III, they were not detected in SEC from group II. CONCLUSION Serum HA may be of value for monitoring postoperative BA patients as a noninvasive indicator of SEC damage and progressive hepatic fibrosis.

Intraoperative measurement of rectourethral fistula: prevention of incomplete excision in male patients with high-/intermediate-type imperforate anus

INTRODUCTION We report a novel technique to measure the length of the rectourethral fistula (RUF) in male patients with high-/intermediate-type imperforate anus during laparoscopically assisted anorectal pull-through (LAARP) to prevent incomplete excision. METHOD During LAARP for RUF in 5 male patients (mean age, 4.6 months; prostatic in 3, bulbar in 2), the RUF was dissected carefully close to the urethra and opened; and a fine catheter with 10-mm calibrations was inserted by the laparoscopic surgeon until it was seen to emerge at or near the verumontanum by another surgeon performing cystoscopy. The laparoscopic surgeon then measured the distance from the point where dissection was ceased at the rectal end to the urethral orifice. The RUF was dissected free from the prostate for exactly this length, tied, and excised; and colon pull-through was performed to finish LAARP. RESULT Rectourethral fistulae ranged from 5 to 15 mm and were much longer than expected. All dissections were uncomplicated without any injury to the urethra, and postoperative courses were unremarkable. At mean follow-up of 11 months, urination is normal in all without evidence of residual fistula. CONCLUSION Knowing the exact length of the RUF facilitates safe and complete excision in an otherwise blind situation.

Comparison of anorectal angle and continence after Georgeson and Peña procedures for high/intermediate imperforate anus

AIM The anorectal angle (AA) influences defecation after pull-through (PT) for imperforate anus (IA). We compared postoperative AA and continence after Georgesons laparoscopy-assisted colon PT (GPT) and Peñas posterior sagittal anorectoplasty (PSARP) for high/intermediate-type IA. METHODS We reviewed 33 high/intermediate-type IA cases (20 GPTs and 13 PSARPs) prospectively. All had colostomy initially as neonates. Anorectal angle was measured as the angle between the rectum and the anal canal on barium enema. A fecal continence evaluation questionnaire (FCEQ) consisting of 5 parameters (frequency of defecation, staining/soiling, perianal erosion, anal shape, and requirement for medication; maximum score = 10) was evaluated in 28 cases (15 GPTs and 13 PSARPs) followed up for more than 3 years. RESULTS Mean age at PT was similar (6.6 months for GPT and 6.3 months for PSARP; P = not significant). There was no significant difference in mean AA. The FCEQ scores for GPT were generally higher throughout the study and significantly better from 3 years postoperatively (P < .05). CONCLUSIONS We are the first to confirm that effective AA similar to PSARP can be achieved after GPT, although FCEQ would suggest that GPT has less detrimental functional impact.

Laparoscopic splenopexy and gastropexy for wandering spleen associated with gastric volvulus.

Wandering spleen is not a common condition in childhood and has been described only rarely in association with gastric volvulus. The authors report the successful management of wandering spleen associated with gastric volvulus using laparoscopic splenopexy and gastropexy in a 4-year-old girl.

Open Versus Laparoscopic Treatment for Pan-Peritonitis Secondary to Perforated Appendicitis in Children: A Prospective Analysis

PURPOSE Reports on laparoscopic treatment (LT) of peritonitis secondary to perforated appendicitis (PA) in children often include localized peritonitis/appendiceal mass, without specifically referring to pan-peritonitis (PP). This study compared LT with open treatment (OT) in only those patients with PP secondary to PA. METHODS PP was defined as generalized abdominal rigidity on presentation with purulent material intraoperatively found throughout the entire abdominal cavity. Based on this definition, we identified 23 cases of PP secondary to PA from all our cases of appendicitis from 2004 to 2008 and prospectively collected data. RESULTS Surgical intervention was LT in 12 cases and OT in 11 cases. Appendectomy was successful in all cases without intraoperative complications. Mean age at surgery, sex ratio, preoperative mean white blood cell count, and C-reactive protein were similar. Mean operative time was 119 minutes for LT and 107 minutes for OT (P = NS). Mean volume of saline used for peritoneal lavage was 2730 mL for LT and 2950 mL for OT (P = NS). Duration of analgesic usage was significantly shorter in LT (P = 0.01). Postoperative wound infections were significantly less in LT (P = 0.04: LT 0, OT 4/11). Adhesive bowel obstruction occurred in one LT case and three OT cases (P = NS); none required surgery. There were two cases of intraabdominal abscess in each group, all were conservatively treated. Time taken to become afebrile, for white blood cell count and C-reactive protein to normalize, for intravenous antibiotics to be ceased, and for oral feeding to be commenced were not significantly different. Mean hospitalization was significantly shorter for LT (P = 0.04). CONCLUSIONS LT would appear to be superior for the treatment of PP secondary to appendicitis in children and would even seriously consider it as the procedure of choice.

A Prospective Analysis of Endoloops and Endostaples for Closing the Stump of the Appendix in Children

AIM The aim of this study was to compare endoloops and endostaples for closing the stump of the appendix during laparoscopic appendectomy (LA) for uncomplicated appendicitis in children. METHODS All LA performed for appendicitis from 2005 to 2009 were analyzed prospectively. Cases of complicated appendicitis such as perforated appendicitis or intra-abdominal abscess were excluded, leaving 75 cases closed with loops and 81 cases closed with staples. Choice of technique was determined by the attending surgeons preference. All patients were managed according to the same pre-, intra-, and postoperative protocols. RESULTS There were no significant differences between mean age at surgery, gender ratio, preoperative mean white blood cell count and mean C-reactive protein, histopathologic findings, mean duration of surgery, and mean hospitalization. There were no intra-operative complications in either group, but one loop case required conversion to open surgery (P = NS). There were no significant differences in the incidences of intra-abdominal abscess, transient ileus, small bowel obstruction, and wound infection. The postoperative readmission rate for management of complications was 4.0% for loop cases and 2.5% for staple cases (P = NS). Overall, using staples for a standard LA (anesthesia and stump closure) was U.S.