Hiromichi Ikawa

Impaired expression of neural cell adhesion molecule L1 in the extrinsic nerve fibers in Hirschsprung's disease

Immunohistochemical studies on the ganglionic and aganglionic segment in Hirschsprungs disease (HD) were carried out using antibodies against three neural membrane proteins, Thy-1, integrin alpha5, and L1. Enteric neural elements were immunostained with antibodies against neurofilament, which is the neuronal cytoskeletal protein. In ganglionic segments, neurofilament-immunoreactivity was detected in neuronal cell bodies and fine nerve fibers of the myenteric and submucosal plexuses. All of these neural elements were immunopositive for Thy-1, integrin alpha5, and L1. In aganglionic segments, no intrinsic neurons were detected, and instead, hypertrophied nerve bundles were observed in intermuscular space, in submucosa, and in circular muscle layer by immunochemistry for neurofilament. These hypertrophied nerve bundles were immunopositive with anti-Thy-1 and anti-integrin alpha5 antibodies. However, they were not immunostained with anti-L1 in all five cases. These findings indicate that the expression of L1 molecule, which plays an important role in cell adhesion, neural cell migration, and neurite outgrowth, is impaired in the extrinsic nerve fibers in aganglionic colon. And this may perturb neural crest migration and adequate neurite outgrowth, with resulting aganglionic segment and abnormal nerve bundles of extrinsic fibers in HD.

Long-term results of surgical treatment in infants with total colonic aganglionosis

The authors describe the long-term results of the surgical treatment of total colonic aganglionosis (TCA) in nine boys who have been treated since 1975. The principal operative procedure was endorectal pull-through of the ganglionic ileum, with the aganglionic colon as an onlay patch. The procedure was employed in five infants, using the right or left colon. Ileorectostomy with an onlay patch was used in two patients; ileoanostomy without the patch was used in two. The distal end of the pulled-through ileum was, on average, 39 cm from the ileocecal junction. The average follow-up period was 11.0 years. Diarrhea and distension were temporary after the pull-through, and all patients ultimately tolerated normal feeding. Considering the variation in operative techniques, we were unable to demonstrate any advantage of one procedure over another. Z scores for height and weight at the last follow-up examination correlated with the weight gain before the definitive surgery and inversely correlated with the length of resected distal ileum at the time of operation.

More than 10 years' follow-up of total colonic aganglionosis-severe iron deficiency anemia and growth retardation

Seven cases of total colonic aganglionosis were reviewed with a follow-up period of 10 to 26 years, focusing on the relationship between the length of aganglionic ileum and postoperative metabolic disorders. Pulled-through ileum ranged from 0 to 65 cm from the ileocecal valve, and suprapelvic side-to-side anastomosis was performed between the pulled-through ileum and 17 to 40 cm of aganglionic colon (left side and transverse colon, four; right side colon, one; no colonic patch, two). Hemoglobin level in three out of four patients with ileal involvement of more than 25 cm was below 11 g/dL (10.9, 7.7, 6.6 g/dL, respectively). Serum iron level was less than 30 micrograms/dL (27, 21, 20, 18 micrograms/dL, respectively) in four out of five patients with ileal involvement of more than 10 cm. Serum vitamin B12 level was below 100 (100, 46 pg/dL, respectively) in two patients whose pulled-through ileum was 45 cm and 65 cm, respectively from the ileocecal valve. One patient needs periodical parenteral iron therapy and one was treated as megaloblastic anemia. In the patients with ileal involvement of more than 25 cm, both weight and height for age are very low at less than the fifth percentile, except for one patient whose side patch was at the right colon. One patient still needs parenteral nutritional support. Severe iron deficiency anemia, low level of B12, and growth retardation are apparent in the patients with total colonic aganglionosis with ileal involvement. Colonic side-to-side anastomosis does not substitute for the loss of terminal ileum.

Calculation of biliary atresia prognostic index using a multivariate linear model

The purpose of this study was to determine the relative value of liver function markers in predicting the magnitude of morbidity and to develop a quantitative estimate of the prognostic risk using a multivariate regression model in patients who have been operated on for biliary atresia. The study sample consisted of 37 patients who had undergone a Kasai portoenterostomy; the jaundice disappeared in 32 and persisted in five. A computer-based stepwise regression procedure produced the linear predictive models by the equation: biliary atresia prognostic index (BAPI) = 9.2 Cu:Zn + 1.0 ZTT + 3.2 TB - 0.05 ChE + 9.9 for infants under 1 year of age, and BAPI = 10.3 Cu:Zn + 0.8 ZTT + 0.03 GGTP - 0.12 ChE + 25.6 for children over 1 year of age. In validation of these models, the indexes fluctuated from -17 to 122, and the degree of morbidity increased linearly with the increase in BAPI. Postoperatively the patients were classified into four categories according to the dynamics of their postoperative course: A (BAPI < 25), successful cases that should not require liver transplantation (40.5%); B (25 < or = BAPI < or = 50), improved cases that have extended survival with their native liver (29.7%); C (50 < BAPI < or = 75), cases that improved in terms of disappearance of jaundice but ultimately will require liver transplantation (8.1%); and D (BAPI > 75), cases that require early referral for transplantation (21.6%). (The percentages indicate the distribution rate of patients at the time of final follow-up evaluation.) These models allow quantification of the risk of morbidity from progressive liver cirrhosis in the individual patient, permitting the clinician to consider whether such patients should be considered for liver transplantation.

Outcomes of ileocolic conduit for biliary drainage in infants with biliary atresia; Comparison with Roux-en-Y type reconstruction

This study was undertaken to define the role of an ileocolic conduit that was devised as anti-reflux procedure in comparative study with Roux-en-Y type reconstruction in infants with biliary atresia treated at a single institution. The ileocolic conduit (IC) consisted of 30 cm of distal ileum anastomosed to the portahepatis and a 10-cm segment of ascending colon vented through the abdominal wall, which was later anastomosed to the second portion of the duodenum. In the Roux-en-Y type reconstruction (RY), 40 to 60 cm of jejunum was used for the hepatic limb. Twenty-three infants in group IC and 16 infants in group RY were entered in this study. Mean ages at definitive surgery were 65.3 +/- 23.1 days for group IC and 65.0 +/- 19.5 days for group RY. The two groups were compared for the postoperative outcomes in terms of bile excretion, incidence of cholangitis, esophageal varices, survival rate, and the effects on physical development. The follow-up ranged from 4 to 15 years. Bile excretion was obtained in all infants in both groups. Twenty infants (87.0%) in group IC and 10 infants (62.5%) in group RY became anicteric. Cholangitis occurred in 60.9% of group IC, compared with 83.3% for group RY, in which 6 infants required revision to complete diversion of Roux-en-Y limb (Suruga II). There was the same occurrence rate of esophageal varices for both groups. However, the varices tended to develop later in group IC (53.0 +/- 18.4 months) than in group RY (12.7 +/- 6.0 months) (P < .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of invaginating anastomosis in Kasai hepatic portoenterostomy on resolution of jaundice, and long-term outcome for patients with biliary atresia

BACKGROUND/PURPOSE This report describes a technique of hepatic portoenterostomy (HPE) to keep sustained bile drainage in biliary atresia patients. In conventional HPE, the medial posterior row of the anastomosis is placed behind the main portal vein. But around both lateral corners where the portal branches enter the liver parenchyma, the anastomosis is placed across and outside of the portal veins. Resultantly, the proximal part of the portal veins become included in anastomosis attaching directly to the dissected area where bile ducts are copious. In a devised procedure designated as invaginating anastomosis (IA), an anastomotic line was placed to invaginate the medial branch of the right portal vein and also placed behind the veins even at their roots. This technique puts all portal branches outside of the anastomosis, preventing cicatricial adhesion at the dissected area with the posterior wall of the veins. METHODS The effect of IA was evaluated in terms of resolution of jaundice and long-term outcome compared with conventional anastomosis (CA). Group IA consisted of 20 patients and group CA of 18 patients. RESULTS Patients in whom jaundice resolved included 19 (95%) in group IA and 11 (61%) in group CA (P < .05). Reoperation was needed in only one infant in group IA, and in six in CA (P < .05). In patients with reoperation in group CA, the portahepatis was found to be contracted with dense cicatricial tissues. The survival rates for patients with a native liver, calculated excluding those in whom the cause of death was not liver deterioration, was 87% for IA compared with 41% for CA (P < .05). Averaged biliary atresia prognostic index at the last follow-up evaluation was 20.2+/-24.5 for group IA and 62.6+/-29.8 for group CA (P < .001). CONCLUSION The invaginating anastomosis in portoenterostomy promised a sustained bile drainage and improved long-term outcome by preventing cicatricial contraction of the portahepatis.

Recto-vagino-vestibuloplasty using a vagino-colonic flap with double colonic implantation for rectocloacal fistula

This technique was devised to obtain a good cosmetic appearance of the perineum and a functional neovagina, without any need for a dilator, by using a vaginocolonic flap marsupialized to the perineum and by creating a vestibule with noncornifying squamous epithelium. The technique was used to treat a 2 year old girl who had a single small orifice in the upper part of a featureless perineum, with a high-confluence rectocloacal fistula between a short urethra and double vagina, which was separated by a septum. A long inverted U-shaped flap at the posterior wall of the vagina was reversed to become the anterior wall of the distal vagina. The urogenital sinus (UGS) was preserved to serve as the urethra. The colon distal to the colostomy was divided into two loops; a segment of the distal loop was opened and trimmed to form a flap, and served as the posterior wall of the distal vagina. The proximal segment was pulled down to become the rectum. To construct the vestibule, a vertical midline incision was made from the fused labia minora to the perineum, cutting back the UGS. The anterior wall of the vagina, which was pulled through just behind the UGS, was divided vertically and sutured around the opened UGS and the suitably prepared labia minora. The posterior wall, which consisted of the colonic flap, was sutured to the incised perineal skin, creating a posterior commissure. At present, 2 1/2 years after the repair, the patient is dry between completely continent urinations and has little vaginal discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Motor activity of refashioned colorectoanus in patients with total colonic aganglionosis.

An ano-recto-sigmoid colon pressure study was designed to evaluate the characteristics of the motor activity of refashioned colorectoanus in patients with total colonic aganglionosis (TCA) in comparison to patients with rectosigmoid Hirschsprungs disease (HD) and healthy children (HC), and to elucidate the pathophysiology of the pulled-through ileum, with aganglionic colon as an onlay patch, in coordination with the anal sphincter. The study group consisted of six patients with TCA, six with HD who underwent endorectal colonic pull-through, and six HC. Pressure studies were performed using a triple-lumen catheter; recording sites were 15 and 9 cm from the anal verge, and at the anal canal. The following were measured and compared: (1) anal canal pressure profile, (2) resting pattern of activity at the refashioned colorectum and anal canal, and (3) changes in motor activity after stimulation with cold water and glycerin. The motor activities of the refashioned colorectoanus of TCA and HD patients differed greatly from those of HC. All six HC had no isolated high-amplitude contraction (IHAC) in the colorectum during the 45-minute study period; they complained of a strong urge to defecate after glycerin enema and actually did so. In contrast, IHAC appeared 2.0 +/- 1.3 times per 10 minutes, with maximal amplitude of 60.3 +/- 24.9 cm H2O in TCA, and 5.6 +/- 3.7 per 10 minutes with maximal amplitude of 79.5 +/- 11.7 cm H2O in HD. After glycerin enema, IHAC increased to 0.5 +/- 0.2 per minute and 69.3 +/- 44.6 cm H2O in TCA and to 0.8 +/- 0.4 per minute and 93.0 +/- 12.8 cm H2O in HD. Defecation was postponed for more than 10 minutes in two HD and all TCA patients. The mean motility index per minute was least for TCA patients (76.9 +/- 98.2); it was 406.5 +/- 197.1 (P < .05) for HD patients and 159.2 +/- 84.2 (P < .01) for HC. TCA patients had the lowest amplitude of maximal resting anal pressure, and hypoactivity of the colorectum during rest and after stimulation; this suggests that motor dysfunction involves even the ganglionic ileum, concomitant with suppressed signals to the higher integrating center for defecation.