Single-stage operation without temporary colostomy for persistent cloaca with a short common channel.

Colorectal decompression with a catheter was performed for evacuation of stool before definitive surgery in two patients with a persistent cloaca. Two newborn female infants with persistent cloaca received placement of a silicone balloon-tipped catheter in the rectum via the cloacal orifice under fluoroscopic guidance at the time of diagnosis. The length of the cloaca was 2 and 1.5 cm, respectively. The diameter of the catheter was matched to the patients' rectal size and the open end was wrapped in a diaper to allow continuous drainage of stool. The infants underwent bowel irrigation with warm saline thrice a day, at home. Total urogenital mobilization was carried out in the infants at the age of 7 and 8 months, respectively. Both infants had no abdominal distension, colorectal dilatation, or urinary tract infection while the catheter was in situ. The postoperative course was uneventful, except for minimal wound dehiscence in one patient. At present, both infants can void spontaneously without any urological problems. In infants with a persistent cloaca less than 3 cm long and normal urinary tract function, adequate evacuation of stool may be achieved by colorectal decompression with a catheter, thus avoiding the need for a colostomy.

Successful surgical treatment of two cases of congenital chylous ascites.

The authors report on 2 patients with congenital chylous ascites who underwent successful lymphatic duct ligation after a laparoscopic lymphoid dye test. Fetal ascites had been detected in both cases, and both babies were born with marked abdominal swelling. Given that conservative treatment by medium-chain triglyceride (MCT) milk and total parenteral nutrition (TPN) was ineffective, the authors elected to perform lymphatic duct ligation on the 95th postnatal day in the former case and on the 27th postnatal day in the latter case. Lipophilic dye was administered preoperatively both through oral and subcutaneous routes, and the peritoneal cavity was explored using laparoscopy. This laparoscopic lymphoid dye test precisely identified the area of chylous leakage, and the authors were able to repair the malformed lymphatic duct directly at laparotomy. Both postoperative courses have been favorable with no recurrence of symptoms. The lymphatic duct ligation should be considered in cases resistant to conservative treatment for over a month. The present laparoscopic lymphoid dye test is a novel and useful procedure that allows surgeons to identify the exact location of chylous leakage, and thus successfully ligate the lymphatic duct.

Strangulated umbilical hernia in a child: report of a case.

Most umbilical hernias in children close spontaneously. Complications associated with umbilical hernias are rarely observed during follow-up. We report herein a 5-month-old girl with a strangulated umbilical hernia. Her umbilicus was hard, reddish, and irreducible. Plain radiography of the abdomen showed signs of mechanical ileus. The patient was thus diagnosed to have a strangulated umbilical hernia. A 5-cm section of the ascending colon and a 5-cm section of the terminal ileum, as well as the cecum and appendix, were congested, edematous, and erythematous, and together were enclosed by a firm hernial ring. A closure of the fascial defect and umbilicoplasty were performed. The postoperative course was uneventful. In patients with infantile umbilical hernias, strangulation may occur as the fascial defect decreases in size.

Pulsed Doppler sonography of the hilar renal artery: differentiation of obstructive from nonobstructive hydronephrosis in children.

BACKGROUND/PURPOSE: It is difficult to detect the arcuate or cortical renal arteries when performing pulsed Doppler sonography (PDS) for congenital hydronephrosis. This study was undergone to assess the usefulness of PDS of the hilar renal artery to differentiate obstructive from nonobstructive hydronephrosis. METHODS: The authors performed PDS of the hilar renal artery in 80 normal children: 20 aged 0 to 1 months (group I), 20 aged 1 to 12 months (group II), 20 aged 1 to 6 years (group III), and 20 aged 7 to 15 years (group IV). Based on diuretic renography findings, 22 kidneys from 19 children with a ureteropelvic junction (UPJ) stricture were divided into 7 dilated obstructed and 15 dilated nonobstructed kidneys. The peak-systolic velocity (PSV), end-diastolic velocity (EDV), mean average velocity (Vm) and the resistive index (RI = [PSV - EDV]/PSV) were measured at the hilar renal artery. RESULTS: There was a significant difference in the RI of the hilar renal artery between obstructive and nonobstructive hydronephrosis. CONCLUSION: A pulsed Doppler evaluation of the hilar renal artery is useful for detecting an obstructive UPJ stricture compared with assessing arcuate or cortical renal arteries.

Pulsed Doppler sonography for the diagnosis of strangulation in small bowel obstruction.

BACKGROUND/PURPOSE: This study was undertaken to assess the usefulness of pulsed Doppler sonography (PDS) for the detection of strangulation in small bowel obstruction by evaluating the hemodynamics in the superior mesenteric artery (SMA). METHODS: The authors performed PDS in 117 normal children: 22 children aged 0 to 1 months (group I), 27 children aged 1 to 12 months (group II), 36 children aged 1 to 6 years (group III), and 32 children aged 7 to 15 years (group IV). Patients included 25 with simple obstruction: 1 in group II, 10 in group III, and 14 in group IV; and 9 with strangulating obstruction: 2 in group I, 2 in group II, 3 in group III, and 2 in group IV. The authors measured the peak-systolic velocity, end-diastolic velocity (EDV), and mean average velocity and calculated the resistive index (RI). RESULTS: The authors observed both a significant decrease in the EDV and increase in the RI for the SMA in strangulating obstruction compared with simple obstruction. CONCLUSION: Analysis of the hemodynamics in the SMA using PDS is useful to differentiate strangulating obstruction from simple obstruction.

Doppler flow patterns through the ductus arteriosus in patients with congenital diaphragmatic hernia.

We investigated Doppler flow patterns through the ductus arteriosus (DA) of 13 newborn infants with congenital diaphragmatic hernia (CDH) using color Doppler ultrasonography (CDUS). Patterns were classified into 3 types: left-to-right (L-R), bidirectional (BD) and right-to-left (R-L) shunting. Among the 13 patients examined, 3 showed L-R shunting, 5 BD shunting and 5 R-L shunting. Patients with L-R shunting showed significantly better levels of PaO2 and AaDO2 than those with other Doppler flow patterns. However, there were no differences in clinical findings between patients with BD and R-L shunting. All patients with L-R shunting survived after CDH repair without pre-operative stabilization including Lipo-PGE1 (LPE) administration. Four of the 5 patients with BD shunting survived, but only one of the 5 patients with R-L shunting survived after CDH repair following administration of LPE. It was suggested that Doppler flow patterns through the DA may be useful for predicting prognoses and selecting suitable treatment for CDH.

Nonoperative management of blunt pancreatic injury in childhood.

PURPOSE: Nonoperative management for blunt pancreatic injury in children was performed between 1977 and 1998. The efficiency and safety of nonoperative management was examined. METHODS: Pancreatic injury was diagnosed in 20 children. The surgical indication was determined by hemodynamic instability and the management of associated injuries. Children without surgical indications were treated initially by nonoperative management. RESULTS: Nineteen of 20 children were treated initially nonoperatively, and 18 of the 19 survived. Surgical exploration was performed in only 1 child with perforation of the duodenum and bile duct. One child died of complications of total parenteral nutrition. Ultrasound scan and computed tomography scan showed pancreatic contusion in 9, laceration in 6, and injury of the main pancreatic duct (MPD) in 5. Pseudocysts were detected in 10 (5 laceration and 5 MPD injury). Pseudocysts smaller than 10 cm disappeared after nonoperative management, and those larger than 10 cm required operative management. Rupture of pseudocysts occurred in 2 children by rotating the upper torso. CONCLUSIONS: Nonoperative management of pancreatic injuries is effective in children, although careful management is required to avoid complications. Pseudocysts smaller than 10 cm were treated successfully by nonoperative management, and those larger than 10 cm required surgical management.

Boron neutron capture therapy for glioblastoma multiforme: interim results from the phase I/II dose-escalation studies

OBJECTIVE: The primary objective of these Phase I/II dose-escalation studies is to evaluate the safety of boronophenylalanine (BPA)-fructose-mediated boron neutron capture therapy (BNCT) for patients with glioblastoma multiforme (GBM). A secondary purpose is to assess the palliation of GBM by BNCT, if possible. METHODS: Thirty-eight patients with GBM have been treated. Subtotal or gross total resection of GBM was performed for 38 patients (median age, 56 yr) before BNCT. BPA-fructose (250 or 290 mg BPA/kg body weight) was infused intravenously, in 2 hours, approximately 3 to 5 weeks after surgery. Neutron irradiation was begun between 34 and 82 minutes after the end of the BPA infusion and lasted 38 to 65 minutes. RESULTS: Toxicity related to BPA-fructose was not observed. The maximal radiation dose to normal brain varied from 8.9 to 14.8 Gy-Eq. The volume-weighted average radiation dose to normal brain tissues ranged from 1.9 to 6.0 Gy-Eq. No BNCT-related Grade 3 or 4 toxicity was observed, although milder toxicities were seen. Twenty-five of 37 assessable patients are dead, all as a result of progressive GBM. No radiation-induced damage to normal brain tissue was observed in postmortem examinations of seven brains. The minimal tumor volume doses ranged from 18 to 55 Gy-Eq. The median time to tumor progression and the median survival time from diagnosis (from Kaplan-Meier curves) were 31.6 weeks and 13.0 months, respectively. CONCLUSION: The BNCT procedure used has been safe for all patients treated to date. Our limited clinical evaluation suggests that the palliation offered by a single session of BNCT is comparable to that provided by fractionated photon therapy. Additional studies with further escalation of radiation doses are in progress.

Effective endless-loop bougienage through the oral cavity and esophagus to the gastrostomy in corrosive esophageal strictures in children.

The authors present a safe, conservative method of endless-loop bougienage (ELB) through the oral cavity and esophagus to a gastrostomy without general anesthesia in three children with corrosive esophageal burns treated since 1966. Esophagogastroscopy was performed to evaluate for esophagitis at an early phase after ingestion of the caustic substance. When esophageal stricture formation was recognized after subsequent conservative treatment, a feeding gastrostomy was made. A continuous string loop with plummets of progressively larger size was positioned to pass through the patient's oral cavity and esophagus to the gastrostomy. Strictures were found in the upper esophagus in two patients and in the middle and lower esophagus in one. The gastrostomy was performed 15 months, 20 days, and 2 months after the injury, respectively, and the periods of ELB were 3, 5, and 2(1/2) years, respectively. The patients were able to start eating at 26, 42, and 29 months after injury, respectively. They are now 30, 18, and 17 years old, and slight dysphagia remains in patients 1 and 2. No patient developed esophageal carcinoma at the site of the corrosive stricture. Our method of ELB through the patient's oral cavity and esophagus to the gastrostomy appears to be safe, reliable, and useful. We believe that most caustic esophageal strictures in children can be treated by this conservative measure.

Long-term survival in a patient with congenital laryngeal atresia and multiple malformations.

Laryngeal atresia (LA) is an uncommon congenital anomaly, and only a few cases with long-term survival are reported in the literature. The authors describe a 2-year-old boy with LA and esophageal (EA), intestinal, and urethral atresia (UA). Immediately after birth, severe respiratory distress and mild abdominal distension became evident. Endotracheal intubation was unsuccessful and emergency tracheal puncture was performed, after which a tracheostomy was constructed. Direct laryngoscopy revealed LA at the vocal cord level. A cystostomy and gastrostomy were constructed immediately because of UA and EA. A cystocutaneostomy, ileocolic anastomosis, and resection of a tracheoesophageal fistula (TEF) were simultaneously performed 1 day after birth. The EA was proximal with a distal TEF. The gap between the ends of the upper and lower esophagus was 4 cm in length. It was thought impossible to perform a primary anastomosis, and therefore, a gastrostomy and resection of the TEF using multiple-stage surgery was undertaken. Intestinal resection and anastomosis were performed due to intestinal stenosis from necrotizing enterocolitis at the age of 3 months. Hypoxic encephalopathy developed due to accidental obstruction of the tracheostomy tube at the age of 10 months, and physical therapy was begun. He required a cutaneous nephrostomy due to a right hydromegaureter with vesicoureteric reflux and a left non-functioning kidney at the age of 23 months. He has been hospitalized for partial ventilatory assistance for 2 years at our institution. The course of this patient seems noteworthy in relation to the genesis of the multiple malformations.

Neuronal src and trk a protooncogene expression in neuroblastomas and patient prognosis.

Neuroblastomas present a wide variety of clinical and biological behaviors, which are reflected by the heterogeneous expressions of protooncogenes related to the neuronal differentiation and amplification of the N-myc gene. High expression of trk A and Ha-ras in neuroblastomas has been shown to be associated with an excellent patient outcome. We have previously reported that neuron-specific src mRNA was increased in chemically differentiated neuroblastoma cell lines and in clinically observed neuroblastomas without N-myc amplification. In the present study, to clarify both the value of neuronal c-srcN2 expression as a prognostic indicator and the significance of the coexpression of these protooncogenes, we examined the expression of 3 alternatively spliced src, trk A and Ha-ras in neuroblastoma tissues from 60 patients by competitive RNA-polymerase chain reaction (PCR). The results indicate that protooncogene expression in neuroblastomas correlated with a favorable outcome for c-srcN2 and trk A. N-myc gene was amplified exclusively in tumors with low levels of trk A. Low expression of c-srcN2 and trk A might thus characterize different aggressive phenotypes due to different signal transduction pathways of neural differentiation in neuroblastoma. The combined analyses for c-srcN2 and trk A expression by RNA-PCR should provide information about the biological phenotype of a neuroblastoma within a short period of time after obtaining tumor material.

Novel mutations of the endothelin B receptor gene in patients with Hirschsprung's disease and their characterization.

Hirschsprung's disease (HSCR) is a congenital intestinal disease, characterized by the absence of ganglion cells in the distal portion of the intestinal tract. Recently, three susceptibility genes have been identified in HSCR, namely the RET protooncogene, the endothelin B (ETB) receptor gene (EDNRB), and the endothelin-3 (ET-3) gene (EDN3). To investigate whether mutations in EDNRB could be related with HSCR in non-inbred populations in Japan, we examined alterations of the gene in 31 isolated patients. Three novel mutations were detected as follows: two transversions, A to T and C to A at nucleotides 311 (N104I) and 1170 (S390R), respectively, and a transition, T to C at nucleotide 325 (C109R). To analyze functions of these mutant receptors, they were expressed in Chinese hamster ovary cells. S390R mutation did not change the binding affinities but caused the decreases in the ligand-induced increment of intracellular calcium and in the inhibition of adenylyl cyclase activity, showing the impairment of the intracellular signaling. C109R receptors were proved to be localized near the nuclei as an unusual 44-kDa protein with the extremely low affinity to endothelin-1 (ET-1) and not to be translocated into the plasma membrane. On the other hand, N104I receptors showed almost the same binding affinities and functional properties as those of the wild type. Therefore, we conclude that S390R and C109R mutations could cause HSCR but that N104I mutation might be polymorphous.

Boron neutron-capture therapy (BNCT) for glioblastoma multiforme (GBM) using the epithermal neutron beam at the Brookhaven National Laboratory.

OBJECTIVE: Boron neutron-capture therapy (BNCT) is a binary form of radiation therapy based on the nuclear reactions that occur when boron (10B) is exposed to thermal neutrons. Preclinical studies have demonstrated the therapeutic efficacy of p-boronophenylalanine (BPA)-based BNCT. The objectives of the Phase I/II trial were to study the feasibility and safety of single-fraction BNCT in patients with GBM. MATERIALS AND METHODS: The trial design required (a) a BPA biodistribution study performed at the time of craniotomy; and (b) BNCT within approximately 4 weeks of the biodistribution study. From September 1994 to July 1995, 10 patients were treated. For biodistribution, patients received a 2-hour intravenous (i.v.) infusion of BPA-fructose complex (BPA-F). Blood samples, taken during and after infusion, and multiple tissue samples collected during surgical debulking were analyzed for 10B concentration. For BNCT, all patients received a dose of 250 mg BPA/kg administered by a 2-hour i.v. infusion of BPA-F, followed by neutron beam irradiation at the Brookhaven Medical Research Reactor (BMRR). The average blood 10B concentrations measured before and during treatment were used to calculate the time of reactor irradiation that would deliver the prescribed dose. RESULTS: 10B concentrations in specimens of scalp and tumor were higher than in blood by factors of approximately 1.5 and approximately 3.5, respectively. The 10B concentration in the normal brain was < or = that in the blood; however, for purposes of estimating radiation doses to normal brain endothelium, it was always assumed to be equal to blood. BNCT doses are expressed as gray-equivalent (Gy-Eq), which is the sum of the various physical dose components multiplied to appropriate biologic effectiveness factors. The dose to a 1-cm3 volume where the thermal flux reached a maximum was 10.6 +/- 0.3 Gy-Eq in 9 patients and 13.8 Gy-Eq in 1 patient. The minimum dose in tumor ranged from 20 to 32.3 Gy-Eq. The minimum dose in the target volume (tumor plus 2 cm margin) ranged from 7.8 to 16.2 Gy-Eq. Dose to scalp ranged from 10 to 16 Gy-Eq. All patients experienced in-field alopecia. No CNS toxicity attributed to BNCT was observed. The median time to local disease progression following BNCT was 6 months (range 2.7 to 9.0). The median time to local disease progression was longer in patients who received a higher tumor dose. The median survival time from diagnosis was 13.5 months. CONCLUSION: It is feasible to safely deliver a single fraction of BPA-based BNCT. At the dose prescribed, the patients did not experience any morbidity. To further evaluate the therapeutic efficacy of BNCT, a dose-escalation study delivering a minimum target volume dose of 17 Gy-Eq is in progress.

Expression of MRP and cMOAT in childhood neuroblastomas and malignant liver tumors and its relevance to clinical behavior.

Advanced neuroblastoma and malignant liver tumor are representative childhood cancers for which combined chemotherapy including cisplatin and doxorubicin is routinely performed. The prognosis of patients with tumors which develop multiple drug resistance (MDR) is unfavorable. To elucidate the role of multidrug resistance-associated protein (MRP) and canalicular multispecific organic anion transporter (cMOAT) in the clinical behavior of the tumors, we examined 42 neuroblastomas and 10 malignant liver tumors for the expressions of MRP and cMOAT by quantitative RNA-polymerase chain reaction (PCR). The amplification and expression of N-myc oncogene in the neuroblastomas were also investigated. We found a close association between MRP and N-myc expression in each neuroblastoma sample but no significant relationship between MRP expression and the patients' outcome. The forced expression of N-myc failed to enhance the expression of MRP in N-myc transfected neuroblastoma cell lines. cMOAT was rarely expressed in the neuroblastomas, but was frequently expressed in the malignant liver tumors. The expression of MRP and cMOAT in the childhood liver tumors was more common and higher, especially in advanced cases with a poor outcome, than that observed in normal liver or in 9 hepatocellular carcinomas from adult patients. The enhanced expression of these genes might be characteristic of childhood malignant liver tumors and related to their clinical chemoresistance.

The role of ERCP in biliary atresia.

BACKGROUND: It is not easy to discriminate between infantile hepatitis and biliary atresia in spite of several diagnostic tests including laboratory analyses, ultrasound, and hepatobiliary scans. ERCP is the most useful procedure for visualization of the extrahepatic biliary system, but ERCP is still an uncommon procedure in children. METHODS: ERCP examination was performed in 52 infants with biliary atresia (10 with infantile hepatitis, 5 with congenital biliary dilatation, 3 with paucity of intrahepatic bile duct, 2 with duodenal atresia, and 1 with postoperative jaundice of hepatoblastoma) aged from 8 days to 300 days (mean, 71 days). RESULTS: ERCP was successful in 47 with biliary atresia, in 9 with infantile hepatitis, and 10 with another disease. Liver biopsy was performed in 1 infant with hepatitis in whom the cannulation failed; in 9 with hepatitis in whom the cannulation was successful, exploratory laparotomy could be avoided. The ERCP findings in 46 patients with biliary atresia (excluding 1 in whom evaluation could not be performed because of poor x-ray quality) were classified into four patterns. CONCLUSIONS: A success rate of ERCP examinations in infants was 88%, so ERCP is recommended to make a correct decision regarding the need for surgery in cholestatic disorders.

Endoscopic variceal ligation using a clipping apparatus in children with portal hypertension.

BACKGROUND AND STUDY AIMS: Endoscopic variceal sclerotherapy (EVS) is a procedure frequently used to control bleeding from esophageal varices in adults. The use of EVS has been restricted in children due to the associated risks. The present paper describes the safety and efficacy of a new apparatus for endoscopic variceal ligation with clipping (EVLC). PATIENTS AND METHODS: Endoscopic variceal ligation using a clipping apparatus (HX-3 L, Olympus, Tokyo, Japan), was carried out in 12 children with portal hypertension (four with extrahepatic portal vein obstruction and eight with congenital biliary atresia; four boys and eight girls, age range 2-14 years). A total of 417 variceal clipping procedures were carried out in 56 separate EVLC sessions; 118 esophageal varices and 65 gastric fundic varices were ligated using 417 clips. Initially, the EVLC sessions were repeated at approximately monthly intervals until the varices were eradicated, but the interval was gradually extended to twice a year or once a year. RESULTS: Varices were successfully ligated at the first attempt in 414 (99.3%) of the 417 clipping procedures. The esophageal varices were initially eradicated in all patients. The follow-up period ranged from nine to 48 months, and complete variceal eradication or reduction of the grade of the varices was obtained in 11 of the 12 patients after initial eradication during this period. CONCLUSIONS: These data indicate that EVLC offers advantages in the treatment of patients with esophageal varices combined with gastric fundic varices.