Leopoldo Martinez

Colonic interposition for esophageal replacement in children remains a good choice: 33-year median follow-up of 65 patients

INTRODUCTION Gastric pull-up has become the predominant technique for esophageal replacement because of allegedly deficient results of colon grafts. This retrospective study examines the long-term results in a large series of colonic interpositions. PATIENTS AND METHOD One hundred six children (median, 2.9 years; range, 0.32-15 years) had their esophagus replaced between 1965 and 2008, of which 96 had colon grafts. Those survivors who were 18 years and older were contacted and, if willing, interviewed, examined, and had their functional ability rated using the Karnofsky index. RESULTS Ninety-six children had undergone a colon graft, and of these, 9 (9.3%) died. There were 65 long-term survivors whose indications for surgery included caustic injury (n = 32), failed tracheoesophageal fistula repair (n = 16), pure esophageal atresia (n = 14), and others (n = 3). The graft was either retrosternal (n = 49) or mediastinal (n = 16 patients). Twelve patients were unavailable for long-term assessment. After a median follow-up of 33.3 (11-41) years, 23 (43%) of 53 individuals experienced mild symptoms of reflux; scoliosis, 12 (22%) of 53, and/or other complications, 15 (27%) of 53 required further surgery. Thirty-two patients (60%) with Karnofsky indexes of 80% or higher felt healthy, 19 (36%) had mild life-style limitations (index, 40%-80%), and 2 had indexes less than 40%. Most patients live normal lives. CONCLUSIONS Colon conduits restored gastrointestinal continuity with limited mortality and considerable morbidity but good functional outcome and health perception in the long-term. Our study suggests that colon grafts are no worse than gastric pull-ups in the long-term.

Architecture and function of the gastroesophageal barrier in the piglet.

We describe the anatomy and function of the gastroesophageal barrier in the piglet, Male piglets underwent dissection (N = 6) and gastroesophageal muscle layer histometry (N = 6). Sedated, nonintubated animals (N = 13) underwent four-probe perfusion esophageal manometry and the pressure profiles were related to the muscular thickness in the four quadrants. Hiatal and gastroesophageal anatomy are similar to our own. The muscle is thicker at the point where the clasp (on the right side) and sling fibers (on the left) concentrate. The pressure profiles were axially and radially asymmetric in coincidence with the thickness variations of the corresponding muscle layers. Sphincteric pressure was recorded as a plateau, whereas diaphragmatic crural pressure appeared as phasic oscillations in synchrony with respiration. The sphincter relaxed upon deglutition. In conclusion, the gastroesophageal structure and physiology are so similar in men and piglets that piglets are excellent models for research in this area.

Bacterial translocation in acute rejection after small bowel transplantation in rats

Acute rejection after small bowel transplantation (SBTx) may facilitate bacterial translocation (BT) and subsequent changes in the liver, spleen, and lungs. This study investigated whether BT occurs after acute rejection and whether this is followed by changes in the structure of the intestine and the phagocytic organs interposed between the gut and the general circulation. Orthotopic SBTx was performed in allogeneic (ALLO) rat-strain combinations (BN–Wistar, n=5). For comparison we used syngeneic SBTx (SYN) (BN–BN, n=6) controls. Animals were sacrificed on postoperative day 7. Mesenteric lymph nodes and portal and caval blood were cultured for aerobes and anaerobes. Escherichia coli β-galactosidase DNA was assessed by polymerase chain reaction in the blood samples. Intestine, liver, spleen, and lung protein and DNA contents were measured. Histologic changes were graded according to standard criteria of acute rejection. For comparisons we used chi2 and nonparametric Mann–Whitney test with a threshold of significance of p<0.05. ALLO rats lost more weight after SBTx than SYN rats (−13.02±4.39% vs. −8.04±5.08% of preoperative weight), although the difference was not significant (ns). A variable degree of graft rejection was histologically demonstrated in all ALLO rats, and DNA/protein content in the graft was significantly higher in this group (0.245±0.85 vs. 0.134±0.21, p<0.05). Gram-negative enteric bacteria were found in 4/5 ALLO and 4/6 SYN rats (ns), and aerobic Gram-positive bacteria in 2/5 and 3/6 (ns), respectively. Anaerobic growth occurred in mesenteric lymph nodes in one ALLO rat and in the bloodstream in another one. E. coli DNA was isolated in none of the ALLO but in two SYN rats (ns). BT was frequent after SBTx in both syngeneic and allogeneic strain combinations. Contrary to our expectations, BT after SBTx was not higher in ALLO group rats. However, anaerobic germs were isolated only in this group.

Effects of Nitrofen and Vitamins A, C and E on Maturation of Cultured Human H441 Pneumocytes

Background/Aim: Nitrofen (2,4-dichloro-4´-nitrodiphenyl ether), a teratogen with oxidant properties, induces congenital diaphragmatic hernia (CDH) with lung hypoplasia and delayed lung development and maturation in rat embryos. Several phenotypic features of the alveolar epithelium including surfactant proteins A and B synthesis and its regulation by transcription factors are reproduced in cultured human H441 pneumocytes. The aim of the present study was to test whether vitamins A, E and C with anti-oxidant properties were able to recover the expression of such regulators in an in vitro setting. Materials and Methods: Cultured human H441 pneumocytes were treated with nitrofen with or without additional exposure to vitamins A, E and C. Thyroid transcription factor 1 (TTF-1), hepatocyte nuclear factor 3-β (HNF-3β) and hepatocyte nuclear factor 3-β surfactant protein B (SP-B) mRNAs were measured by real-time polymerase chain reaction (RT-PCR). The cells were also immunohistochemically stained for assessment of proliferation (PCNA) and apoptosis (bis-benzimide) status and SP-B and TTF-1 protein expressions. Results were compared by ANOVA with a significant threshold of 5%. Results: Nitrofen severely decreased TTF-1, HNF-3β and SP-B mRNA expression by H441 pneumocytes in culture. Addition of vitamin E normalized the levels of the three transcripts, while vitamin A normalized only those of TTF-1 and SP-B mRNA. Vitamin C was significantly beneficial only for SP-B transcript. Nitrofen decreased proliferation and TTF-1 and SP-B protein expressions with no apparent effect on apoptosis. Additional exposure to vitamins A, C or E rescued near normal values. Conclusions: The changes induced by nitrofen in cultured H441 human pneumocytes are reverted in part by anti-oxidant vitamins by upregulating TTF-1, HNF-3β and SP-B and stimulating proliferation and maturity in nitrofen-treated cells. These effects of anti-oxidant vitamins could be of some interest for developing new transplacental therapeutic strategies aimed at improving lung development and maturation in fetuses with CDH.

Impact of preoperative diagnosis of congenital heart disease on the treatment of esophageal atresia

Congenital heart disease (CHD) has a major impact on the survival of babies with esophageal atresia (EA). The present study assesses whether early diagnosis influences the management strategies in a large series of EA. Cases of EA treated between 1982 and 2002 were retrospectively divided into groups according to the presence or absence of CHD and to whether this was diagnosed or not prior to tracheo-esophageal fistula repair. Patients were also staged according to Spitz’s classification in which major congenital heart disease (MCHD) are those associated with cyanosis and/or heart failure requiring surgery. Comparisons between groups of patients were made by standard statistical tests. Among 195 babies with EA (99 boys and 96 girls), 82 (42%) had CHD (31 boys, 39% and 51 girls, 61%, χ2P<0.05) and 43 out of these 82 (52%) had MCHD. Six children died without treatment. CHD was diagnosed prenatally in six cases and before EA repair in 26 cases. The diagnoses were missed in 12 instances (in five it was a MCHD). Regardless of preoperative diagnosis of right aortic arch in 3/6 cases, the oesophagus was approached from the right thorax in all cases and only in one of them the operation was not completed due to hemodynamic instability. There were 145/195 (75%) Spitz group I patients; 44/195 (22%) were group II and 6/195 (3%) group III. The mortality was respectively 9.5, 59 and 83%. We lost 15/113 (13%) babies with EA without CHD, 4/39 (10.2%) with EA and CHD and 26/43 (60%) with EA and MCHD. In children with CHD diagnosed prior to the esophageal operation 8/26 (30.7%) died and among those without diagnoses 3/12 (25%) died, (χ2P>0.1). 1.CHD was diagnosed after EA repair in one-third of cases.2.Preoperative diagnosis of CHD changed the operative indication only in one case.3.Survival after treatment for EA was not influenced by the moment or the accuracy of the diagnosis of CHD in this series.4.With only a few exceptions, associated CHD should not change the strategies of EA repair.

Failed Nissen Fundoplication in Children: Causes and Management

INTRODUCTION Nissen fundoplication (NF) is the gold standard procedure for the treatment of gastroesophageal reflux (GER) in children. However, it fails in a significant proportion of patients. The purpose of this study was to identify preoperative predictors of failure and to examine the results of reoperations. PATIENTS AND METHODS The charts of patients who underwent NF at our institution between 1992 and 2011 were retrospectively reviewed. Surgery was indicated in patients with symptomatic GER in whom medical treatment failed, particularly, in cases of esophageal atresia (EA), congenital diaphragmatic hernia (CDH), and neurologic impairment (NI). Chi-square comparisons and logistic regression were used to test comorbidities, previous abdominal surgery, surgical technique, gastrostomy, pyloromyotomy or pyloroplasty, age, weight, and surgical complications as possible predictors of NF failure. RESULTS A total of 360 children (217 male and 143 female) underwent NF. Comorbidities were NI (n = 100, 27.8%), EA (n = 50, 13.9%), CDH (n = 22, 6.1%), and abdominal wall defects (AWD) (n = 6, 1.7%). A total of 35 patients (9.7%) had esophageal stenosis. Age at surgery was 3.06 years (0.04-20.7 years) and weight was 12 kg (2-77 kg). NF was open in 196 patients (54.4%) and laparoscopic in 164 patients (45.6%) (with 9 conversions). Follow-up was 6.7 years (0.01-18.7 years). A total of 42 patients (11, 7%) had postoperative complications (10 wound infection, 9 dumping syndrome, 8 gastrostomy related complications, 7 intestinal obstruction, 5 evisceration, 2 chylothorax, and 1 pneumothorax). Reflux recurred in 42 patients (11.7%) and 35 patients (9.7%) underwent redo NF 1.01 years (0.02-8.4 years) after the initial surgery. A total of nine patients (2.5%) required further interventions (five another redo NF, three esophageal replacements, and one esophago-gastric disconnection). A total of 29 patients (8.1%) died during the follow-up (25 because of their baseline disease, 3 in the postoperative period, and 1 because of pulmonary aspiration 3 years after surgery). EA (31.6% failure) and CDH (46.7% failure) were the only comorbidities predictive of NF failure (p < 0.05). CONCLUSIONS Failure of NF is particularly frequent in patients previously operated upon for EA or CDH and can be predicted preoperatively. However, the benefits of the operation may outweigh this risk. Redo NF is indicated if symptoms of GER recur, but the proportion of failure is even higher. In subsequent failures, other options like esophageal replacement or esophagogastric dissociation should also be considered.

The vagus and recurrent laryngeal nerves in experimental congenital diaphragmatic hernia

BackgroundThe etiology of the anatomic and functional abnormalities of the esophagus in infants surviving congenital diaphragmatic hernia (CDH) remains unclear. We showed previously that fetal rats with CDH have malformations of neural crest-derived structures. The aim of this study was to examine the anatomy of the vagus and the recurrent laryngeal nerves, both of neural crest origin, in rats with CDH.MethodsWe used the nitrofen-induced CDH fetal rat model. Nine control fetuses from four dams and nine fetuses with CDH from seven dams were included in this study. Embryos were fixed in formalin and a thoracic block from the larynx to tracheal bifurcation was serially sectioned in the horizontal plane. One in every ten sections was stained with hematoxylin and eosin. The image was digitalized using biological software (TDR-3dbase). Vagus and recurrent laryngeal nerves, trachea, esophagus and the great vessels were examined. In order to obtain the three-dimensional reconstructions, 90–120 consecutive images were used.ResultsIn comparison with controls there were striking abnormalities of the vagus and the recurrent laryngeal nerves in fetuses with CDH: (1) absence of the left (2/9) or right (2/9) vagus nerves; (2) absence of the left (3/9) or right (3/9) recurrent laryngeal nerves; (3) marked hypoplasia of the trunk of the vagus (2/9); (4) deviations of their normal course and change of normal anatomical relationships into the mediastinum (2/9); and (5) abnormal branching of the lower portion of the vagus (1/9).ConclusionsRat fetuses with CDH have anomalies of the vagus and recurrent laryngeal nerves that support the concept of a neural crest involvement in the origin of this malformation. 3-D reconstructions allow a detailed analysis and provide a precise insight into the real anatomy. These observations may explain esophageal motility disorders in CDH.

Long-term results of the treatment of total colonic aganglionosis with two different techniques.

AIM Aim of this study was to assess the long-term results of the treatment of total colonic aganglionosis (TCA) with 2 different techniques in terms of growth, continence and quality of life (QOL). PATIENTS AND METHODS Forty-one patients treated for TCA between 1972 and 2007 were reviewed retrospectively with special attention paid to the length of aganglionosis, complications, growth, continence and QOL. Until 1992, patients underwent subtotal colonic resection and side-to-side ileosigmoid anastomosis (modified Martin). Since 1992, straight ileo-anal pull-through was preferred. At the end of follow-up (median 18 years, range 1-35), the height and weight, continence and QOL (scoring feeding habits, school/work performance, family life and professional development) were assessed by clinical visit or phone interview. RESULTS Twenty-eight patients were male and 13 female. Six had total intestinal aganglionosis and were excluded from this review together with the 2 who died before definitive treatment. The 33/41 persons in whom aganglionosis had involved less than 50 cm above the ileocecal valve and who had been considered suitable for the reestablishment of transanal fecal flow were included. Eighteen children underwent a modified Martin and 15 straight ileo-anal pull-through. Postoperative intestinal obstruction occurred in 4 cases, prolapse and prolonged TPN requirement in 2, and wound disruption and fistula in 1. Thirteen patients (39 %) had postoperative enterocolitis. Two children died after operation (1 wound disruption with sepsis and 1 pneumonia). Out of 31 survivors, 57 % and 53 % were > p50 with regard to height and weight whereas only 15 % and 19 % were <p3 respectively. Only half the patients had more than 3 bowel movements per day and the median Wildhaber continence score (normal = 14) was 11 (range 6-14). Both types of operations resulted in comparable defecation and continence patterns. QOL was rated as good in all cases but one. All patients but 2 attended high school, 8 attend university, 4 are employed and 1 is married and has 2 daughters. Social life is normal except for 1 patient who perceives his disease as a burden. CONCLUSIONS Patients with TCA amenable to reestablishment of the transanal fecal flow can have adequate growth, normal feeding, reasonably good continence and satisfactory QOL. However, complications and enterocolitis are frequent. A modified Martins procedure was performed as well as straight ileo-anal pull-through with little influence on the long-term outcome.

Abnormal intrinsic esophageal innervation in congenital diaphragmatic hernia: a likely cause of motor dysfunction

PURPOSE Patients with congenital diaphragmatic hernia (CDH) often have dilated esophagus and gastroesophageal reflux. Sparse intrinsic esophageal innervation has been described in rats with CDH, but this issue has not been investigated in patients with CDH. The present study tests the hypothesis that innervatory anomalies could account for motor dysfunction in human CDH. METHODS The esophagi of CDH (n = 6) and control babies dead of other causes (n = 6) were included in paraffin, transversally sectioned, and immunostained with antineurofilament and anti-S-100 antibodies. The proportion of the section surface occupied by neural structures, the ganglionar surface, and the number of neurons per ganglion were measured in 2 to 5 low-power fields from the proximal and distal esophagus with the assistance of image analysis software. Mann-Whitney tests were used for comparing the results using a threshold of significance of P < .05. RESULTS The percentage of neural/muscle surface was similar in the upper esophagus in both groups, but it was significantly decreased in the lower esophagus of patients with CDH in comparison with controls. There was a relative scarcity of neural tissue in the intermuscular plexus of the lower esophagus. On the other hand, the ganglionar surface and the number of neurons per ganglion were identical in both groups. These results were similar with both immunostainings. CONCLUSION Intrinsic innervation of the lower esophagus in CDH is abnormal in terms of decreased density of neural structures in the intermuscular plexus. These neural crest-derived anomalies could explain in part the esophageal dysfunction in survivors of CDH.

Ganglioneuroma: To Operate or Not to Operate

INTRODUCTION Ganglioneuroma (GN) is a benign, differentiated variety of neurogenic tumor. It is often asymptomatic and may be diagnosed by serendipity. Surgical removal is the treatment of choice. However, it has been suggested that postoperative complications and sequelae might outweigh the benefits of this approach. The purpose of the present study was to examine these issues in a large experience of neural tumors. METHODS Patients treated between 1992 and 2012 were retrospectively reviewed. Modern imaging, measurement of catecholamine metabolite excretion and metaiodobenzylguanidine were used for workup. Surgical treatment aimed at complete resection. Complications and sequelae were recorded. Literature was searched for regrowth or malignant transformation of GN. RESULTS Of 227 patients with neural tumors, 24 were GN patients (12 abdominal, 11 thoracic and 1 cervical with 8 dumbbell extensions). Six children were symptomatic (three with abdominal pain and mass, one with stridor or dysphonia, and one each with anisocoria and opsomyoclonus). However, 18 (75%) were asymptomatic and the diagnosis was incidental. Several tumors were large and involved more than one body space. There were no neurologic symptoms in eight cases with dumbbell extension. Complete resection was achieved in 20 children (83%) whereas gross residual was left in four. Postoperative complications were: Horner syndrome (3 patients), mild scoliosis (1 patient), adhesive bowel obstruction (1 patient) and acute urinary retention (1 patient). There was no evidence of either regrowth or malignant behavior in residual masses left in place after follow-up of 84 (1-194) months. CONCLUSIONS There were a limited number of general minor complications in this series that did not include cases of regrowth or malignant transformation. However, these unfavorable events were occasionally reported in the literature. Since diagnosis of GN cannot be ascertained before removal of the mass, this should remain the aim of the treatment, although limiting the chances of complications to a minimum even if incomplete resection is the price to pay. Nonoperative attitudes should not be recommended in all cases, but they are certainly justified in some.