João Gilberto Maksoud

Prophylactic sclerotherapy in children with esophageal varices: Long-term results of a controlled prospective randomized trial ☆

BACKGROUND/PURPOSE Experience using endoscopic prophylactic sclerotherapy (PS) is restricted to adult patients and has led to conflicting results. There has not been a randomized, controlled study on the use of PS in children. The purpose of this study is to evaluate prospectively the value of PS to prevent the first hemorrhage from esophageal varices in children with portal hypertension and to assess the effect of PS on survival rate. METHODS In a controlled, prospective, computer-based randomized trial, the effectiveness of PS was analyzed in 100 consecutive children allocated to a group receiving sclerotherapy (n = 50) or to a control group (n = 50) subjected only to regular clinical and endoscopic examinations. Clinical characteristics in both groups were similar. The minimum follow-up period was at least 18 months after the cessation of the sessions of sclerotherapy. RESULTS After a median follow-up of 4.5 years, PS eliminated the esophageal varices in 47 of 50 (94%) patients but only 38 (76%) of them do not present upper digestive hemorrhage. Before complete obliteration of the varices, upper gastrointestinal bleeding occurred in 12 patients (24%). Six children (12%) had gastric varices, 3 of 6 of whom (50%) bled. Congestive hypertensive gastropathy was observed to occur in 8 (16%) patients, 4 of 8 of which (50%) had hemorrhagic episodes. Two patients bled from undetermined cause. In the control group, only 29 (58%) children remained free from esophageal variceal bleeding and 26 (52%) from any upper gastrointestinal bleeding (P<.05). During the follow-up period, the development of gastric varices was observed in 5 (10%) patients (P>.05) and of congestive hypertensive gastropathy in only 3 (6%) patients (P<.05), but none of them bled. PS does not improve survival rate. CONCLUSIONS In children with cirrhotic and noncirrhotic portal hypertension, PS reduces the overall incidence of bleeding from esophageal varices that were eradicated in 94% of cases. The source of bleeding has been different in each group, being predominantly from esophageal varices in the control group and from the stomach in the prophylaxis group. When applied with appropriate technique, PS is a safe procedure with a low incidence of minor complications. PS does not change the incidence of gastric varices but increases the development of congestive hypertensive gastropathy. PS increases the risk of bleeding from the naturally formed gastric varices and from congestive hypertensive gastropathy. PS does not affect survival rate.

Prognostic factors associated with congenital cystic adenomatoid malformation of the lung

This study presents 18 cases of prenatally diagnosed congenital cystic adenomatoid malformation (CCAM) to identify potential factors that could predict prognosis. Comparisons of prenatal parameters were made between fetuses that survived and those that died perinatally. It was found that microcystic lesion, bilateral lung involvement and hydrops were each highly correlated with poor prognosis, while neither polyhydramnios nor mediastinal shift was significantly associated with had outcome. Fetal interventions were indicated only in two of the surviving cases: a thoracocentesis and a cysto‐amniotic shunt. A therapeutic amniocentesis was performed in one case of polyhydramnios. The diagnosis of CCAM was histologically confirmed in all cases by necropsy or by postnatal lobectomy. Copyright

The Endoscopic and Surgical Management of Portal Hypertension in Children: Analysis of 123 Cases

Since 1973, 178 children with portal hypertension (PH) have been seen at Instituto da Criança of the University of São Paulo Medical School. Fifty-five of these children were excluded from this analysis for various reasons, including no treatment required, death before treatment, or incomplete data. From the remaining 123 children with esophageal varices, only 96 (76.1%) of them had at least one episode of upper gastrointestinal hemorrhage. Eighty-eight children were submitted to injection sclerotherapy; 26 treated prophylactically, and 62 for treatment of previous bleeding. Eleven (42.3%) children from the prophylactic group bled from esophageal varices during the treatment. They were all successfully managed thereafter. Satisfactory results were achieved in 53 (85.4%) children in the therapeutic group. Twenty-eight (45.1%) children had at least one episode of bleeding after beginning of sclerotherapy, 19 of whom eventually had successful control of the variceal bleeding. From 1973 to 1984, distal splenorenal shunt (DSS) was the procedure of choice for the treatment of bleeding esophageal varices. Forty-two children have undergone DSS during this period. Only one child was shunted prophylactically. Since 1985, injection sclerotherapy has been the first choice for the treatment and only seven children with sclerotherapy failure have since been treated by DSS. Characteristically these children had very similar splenoportographic pattern with huge esophageal and gastric varices and deviation of portal vein blood flow toward the left gastric vein.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgically produced congenital diaphragmatic hernia in fetal rabbits.

Animal models of congenital diaphragmatic hernia (CDH) still are indispensable for the evolution of knowledge related to this disease and to fetal surgery in general. The lamb has provided the most reliable experimental design thus far. Considering the possible advantages of using rabbits (rather than lambs) namely lower costs, no need of special veterinary facilities, smaller body size, year-round availability, higher number of fetuses per pregnancy, and shorter gestational period, a successful model of CDH was developed in fetal rabbits. Sixteen pregnant New Zealand rabbits underwent hysterotomy and fetal operation. Group 1 (6 does) underwent surgery on gestational day 20 and group 2 (10 does) on gestational day 24 or 25. The normal full gestation time is 31 to 33 days. In group 1, the CDH was created by transabdominal puncture and dilatation of the fetal diaphragm. In group 2, the CDH was created through open thoracotomy, either left or right. The fetuses were delivered by cesarean section on gestational day 30. The overall fetal survival rate was 0 for group 1 and 70% for group 2. All operated fetuses in group 2 that were born alive had CDH. The histological morphometric examinations (radial alveolar count after sustained lung expansion) of the normal and operated fetuses in group 2 showed pulmonary hypoplasia in all the lungs on the same side as the CDH (statistical analysis was performed using the Neuman-Keuls test and analysis of variance; the significance level was set at .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic venous reconstruction in pediatric living‐related donor liver transplantation – Experience of a single center

Abstract:  In pediatric patients submitted to living related liver transplantation, hepatic venous reconstruction is critical because of the diameter of the hepatic veins and the potential risk of twisting of the graft over the line of the anastomosis. The aim of the present study is to present our experience in hepatic venous reconstruction performed in pediatric living related donor liver transplantation. Fifty‐four consecutive transplants were performed and two methods were utilized for the reconstruction of the hepatic vein: direct anastomosis of the orifice of the donor left or left and middle hepatic veins and the common orifice of the recipient left and middle hepatic veins (group 1–26 cases), and wide triangular anastomosis after creating a wide triangular orifice in the recipient inferior vena cava at the confluence of all the hepatic veins with an additional longitudinal incision in the inferior angle of the orifice (group 2–28 cases). In group 1, eight patients were excluded because of graft problems in the early postoperative period and five among the remaining 18 patients (27.7%) presented stricture at the site of the hepatic vein anastomosis. All these patients had to be submitted to two or three sessions of balloon dilatations of the anastomoses and in four of them a metal stent had to be placed. The liver histopathological changes were completely reversed by the placement of the stent. Among the 28 patients of the group 2, none of them presented hepatic vein stenosis (p = 0.01). The results of the present series lead to the conclusion that hepatic venous reconstruction in pediatric living donor liver transplantation must be preferentially performed by using a wide triangulation on the recipient inferior vena cava, including the orifices of the three hepatic veins. In cases of stenosis, the endovascular dilatation is the treatment of choice followed by stent placement in cases of recurrence.

The outcome of newborns with abdominal wall defects according to the method of abdominal closure: the experience of a single center

Recent reports suggest that the technique of abdominal closure in neonates with anterior abdominal wall defects (AWD) correlates with the outcome. The aim of this study is to analyze factors related to mortality and morbidity, according to the technique of abdominal closure of these neonates. Retrospective analysis of charts from 76 consecutive neonates with AWD treated in a single institution. They were divided according to the type of abdominal wall closure: group I: primary closure, group II: silo followed by primary closure and group III: silo followed by polypropylene mesh. Outcome was analyzed separately for neonates with gastroschisis and omphalocele. There were 13 deaths (17.1%). Mortality for neonates with isolated defects was 9.6%. Mortality rate was similar in all groups for either neonates with gastroschisis or omphalocele. Postoperative complications were not significantly different among groups except for a prolonged time of hospitalization in group III. Mortality rate is not correlated with the type of abdominal closure. Neonates with primary closure or with other methods of abdominal wall closure had similar rate of postoperative complications. Neonates with mesh closure of the abdomen have prolonged hospitalization. The use of a polypropylene mesh is a good alternative for neonates whose primary closure or closure after silo placement is not possible.

Total gastric transposition: An alternative to esophageal replacement in children

Total gastric transposition was performed in 21 children as an alternative procedure for esophageal replacement. The age at the operation ranged from 15 months to 11 years. Half of the children were less than 2 years old. Fifteen patients had esophageal atresia. The stomach was passed toward the neck either through the esophageal bed (6 cases, with concomitant blunt esophagectomy without thoracotomy) or the retrosternal route (15 cases). There was one death in the early postoperative period secondary to an anastomotic leak and acute mediastinitis in a case of pharyngogastric anastomosis. Three other patients developed cervical leak with spontaneous closure but this ultimately led to a late anastomotic stricture (more than 6 months) requiring endoscopic dilatation. Only one child needed more than three attempts of endoscopic dilatation. None of these patients required surgical revision. The mean follow-up was 60 months (range, 10 to 122 months). Despite bulky atonic intrathoracic stomach occurring in some children, only two patients developed regurgitation and symptoms of poor gastric emptying. There were neither early nor late respiratory problems. Excellent and good functional outcome were achieved in 85% and 15% of the patients, respectively. Two patients have not undergone a weight catch-up phase. The majority of the children have been between the 20th and 80th percentile for weight. Five children remain below the 20th and two below the 5th percentile. The remarkably low morbidity and mortality combined with satisfactory functional results indicate that the total gastric transposition is a safe and easy alternative surgical procedure for esophageal replacement in children.

Mycophenolate mofetil promotes prolonged improvement of renal dysfunction after pediatric liver transplantation: experience of a single center.

Abstract:  Few studies have evaluated the long‐term use of MMF in liver transplanted children with renal dysfunction. The aim of this study is to report the experience of a pediatric transplantation center on the efficacy and security of long‐term use of a MMF immunosuppressant protocol with reduced doses of CNIs in stable liver transplanted children with renal dysfunction secondary to prolonged use of CsA or Tac. Between 1988 and 2003, 191 children underwent OLT and 11 patients developed renal dysfunction secondary to CNIs toxicity as evaluated by biochemical renal function parameters. The interval between liver transplantation and the introduction of the protocol varied from one to 12 yr. Renal function was evaluated by biochemical parameters in five phases: immediately prior to MMF administration; 3, 6, 12 and 24 months after the introduction of MMF. Among the patients, nine of them (82%) showed improvement of renal function parameters in comparison with the pretreatment values. The two patients that did not show any improvement were patients in whom the interval of time between OLT and the introduction of MMF was longer. All parameters of liver function remained unchanged. No episodes of acute or chronic rejection or increases in infection rates during the period were detected. Two patients developed transitory diarrhea and leukopenia that were reverted with reduction of MMF dosage. In conclusion, in liver transplanted pediatric patients with CNI‐induced chronic renal dysfunction, the administration of MMF in addition to reduced doses of CNIs promotes long‐term improvement in renal function parameters with no additional risks.

Evolution with age of the acetylcholinesterase activity in rectal suction biopsy in Hirschsprung's disease

The acetylcholinesterase (AChE) activity in Hirschsprungs disease was analyzed for histochemical patterns according to age. Its evolutional nature was also assessed. Two hundred thirty children (0 to 16 years of age) with acute or chronic obstipation were submitted to rectal suction biopsy for AChE histochemical staining. One hundred nineteen of them showed abnormal AChE activity. Retrospective analysis of those cases permitted us to establish three histochemical patterns: Pattern I, thick nerve trunks present only in the submucosa and, characteristically, absence of AChE activity in the lamina propria. This pattern was predominant in newborn up to 3 months of age and was designated the newborn pattern. Pattern II, thin nerve fibers in the muscularis mucosae and submucosa with a clear infiltration in the lamina propria. This pattern was mainly seen in children older than 1 year of age and was called classical pattern. Pattern III, an intermediate pattern showing morphologic characteristics of the two previous patterns with predominance of one or another, according to the age. A prospective study was also made in 15 children with Hirschsprungs disease who were submitted to suction rectal biopsies at different ages. In this study, a clear evolutional character of the AChE activity was observed from the newborn pattern to the intermediate and finally to the classical pattern.

Alterations of enteric nerve plexus in experimental gastroschisis: is there a delay in the maturation?

BACKGROUND/PURPOSE After surgical correction of gastroschisis, intestinal transitory hypoperistalsis usually occurs. Long-term parenteral nutrition often is necessary leading to a higher morbidity associated with this malformation. The etiology of this transitory intestinal hypomotility is unknown. It may be caused by a reversible inflammatory process in the intestinal wall or other causes, including an alteration of the maturation of intestinal neural plexus, because the disturbance disappears spontaneously after a variable period. The aim of this work was to study the neuronal cells of the myenteric plexus of the fetal intestine in experimental gastroschisis. The main hypothesis was that the transitory intestinal dismotility seen in gastroschisis could be secondary to alteration in the maturation of the enteric nervous plexus. METHODS Twenty-seven time-mated rabbits, on gestational day 25, were submitted to a midline laparotomy; the gravid bicornuate uterus was exposed and opened, and the more distal fetuses relative to the vaginal opening had the abdominal wall opened by a small incision to produce gastroschisis (n = 29). The fetuses not submitted to gastroschisis were used as controls (n = 12). The amniotic fluid was carefully aspirated from the opened uterus and saved for later repositions. On gestational day 30, the does were again submitted to general anesthesia, and the fetuses were delivered by cesarean section. The fetal intestine was removed, the adjacent mesentery excised, and intestinal specimens were harvested for histologic studies. The specimens were stained for acetyl-cholinesterase activity (AChE) to assess the maturity of the nervous enteric cells and for lactate dehydrogenase (LDH) that identify specifically immature nervous cells. The histologic sections stained by LDH were submitted to histomorphometric analysis of the nervous cells through an image system analysis (Kontron 300). The results were submitted to statistical analyses (P <.05). RESULTS Macroscopic alterations of the fetal gastroschisis intestine are similar to the human findings: shortening of the intestine, intestinal wall thickening, and a hypertrophied muscular layer. In the gastroschisis group, histologic AChE activity was decreased in comparison with control intestines. The histomorphometric assessment in slices stained with LDH, which identify immature nervous cells, showed that the neuronal intestinal cells of the gastroschisis group were significantly smaller and more numerous relative to the control group. CONCLUSIONS There were significant differences in the nervous plexus of the intestine of fetuses with gastroschisis relative to the controls. The observed morphologic changes may be caused by alteration in the maturation of the intestinal neuronal in gastroschisis. This alteration may explain the transitory intestinal hypomotility observed in infants after surgical correction of gastroschisis.