Cell proliferation in the process of oviducal tissue remodeling during induced molting in hens

BACKGROUND: After surgical correction of their esophageal atresia and tracheoesophageal fistula (EA-TEF), many patients exhibit evidence of esophageal dysmotility. Controversy exists as to whether the esophageal motility disorders result from denervation caused by surgery or from an inherent abnormal innervation of the esophagus. METHODS: The present study used an Adriamycin-induced EA-TEF fetal rat model to trace the course and branching of both the vagus and recurrent laryngeal nerves. Abnormalities observed in EA-TEF rat fetuses include: (1) fewer branches from both recurrent laryngeal nerves; (2) deviation of the left vagus from its normal course below the aorta, passing behind the fistula to approach and join with the right vagus to form a single nerve trunk on the right side of the esophagus; (3) relatively few branches from the single vagal nerve trunk (composed of fibers of the left and the right vagus) on the surface of the lower esophagus. CONCLUSIONS: Fetuses affected by EA-TEF have inherent abnormalities in the course and branching pattern of the vagus nerves as they descend through the thorax, culminating in a deficient extrinsic nerve fiber plexus in the lower esophagus. These observations may account for the esophageal motility disorders seen in patients who have EA-TEF even before surgical intervention.     

The involvement of two or more systems and the severity of associated anomalies significantly influence mortality in esophageal atresia

PURPOSE: The aim of this study was to examine the influence of associated anomalies in babies born with esophageal atresia (EA). METHODS: A retrospective review of the records of 41 consecutive cases of esophageal atresia managed over an 11-year period was undertaken. RESULTS: A higher incidence of associated anomalies was seen in those babies with lower birth weights. Although all five (100%) babies with EA who weighed less than 1,800 g had associated anomalies, those who weighed 1,800 to 2,500 g and more than 2,500 g were associated with 67% (10 of 15) and 43% (9 of 21) anomalies, respectively. The most common system in which anomalies occurred was the cardiovascular system (37%) followed by gastrointestinal (24%), musculoskeletal (17%), genitourinary (7%), chromosomal (5%), and others (12%). All 17 (41%) babies with no associated anomalies survived. Four of the 10 babies who had two or more systems involvement died, whereas only one of 31 babies with less than two systems involvement died; the difference between these two groups was highly significant (Fisher's Exact test, P = .009). The overall mortality rate was 12%. Three of the deaths were associated with severe anomalies that were incompatible with life such as bilateral renal agenesis, trisomy 18, and complex cardiac anomalies. CONCLUSION: The association of two or more system anomalies and the severity of associated anomalies influence mortality in esophageal atresia.     

An unusual case of esophageal atresia and double distal tracheoesophageal fistula

This report describes a neonate with a very rare and an unusual variety of esophageal atresia and tracheoesophageal fistula. The anomaly consisted of esophageal atresia and double distal tracheoesophageal fistula. The two fistulae as well as part of the distal esophagus were made up of tracheobronchial tissues. The embryology of the anomaly is also discussed.     

Oral motor patterns during feeding in severely physically disabled children

Surface electrogastrography was performed in 18 patients with esophageal atresia (EA) and 10 normal controls to investigate the possible role of a congenital enteric nerve defect as a cause of gastroesophageal reflux (GER), which is common after repair of EA. The means of the dominant frequencies and ranges of the frequency distribution were compared. The dominant frequencies (0.047+/-0.007 Hz) in the EA group did not differ significantly from those of the controls (0.050+/-0.007 Hz, P >0.1), although 2 patients had bradygastria and 2 had tachygastria in the EA group. The range of the frequency distribution was significantly wider in the EA group compared with normal children (P = 0.002). The wide frequency distribution in children with EA suggests disturbed electrical activity of the stomach, which could be associated with poor electromechanical coupling and, hence abnormal gastric contraction.     

Concurrent right diaphragmatic hernia and esophageal atresia

The occurrence of a coexisting congenital diaphragmatic hernia (CDH) and esophageal atresia (EA) with distal tracheoesophageal fistula is extremely rare and is considered highly lethal. Only 19 cases of CDH with EA have been reported in the world literature to date. This is a very challenging clinical problem, and the neonate is likely to deteriorate rapidly. Such a case is reported with a successful outcome, probably the first survivor with a right CDH and EA. Management guidelines for such a case are discussed.     

Proliferation of human non-small-cell lung cancer cell lines: role of interleukin-6

PURPOSE: The aim of this study was to describe the dysmorphogenetic process leading to esophageal atresia and tracheoesophageal fistula (EA + TEF) in the recently developed Adriamycin model of the malformation. METHODS:Time-mated pregnant rats were given either Adriamycin (1.75 mg/kg intraperitoneally) or saline on days 6 to 9 of gestation, and their embryos recovered on days 12, 12.5, and 13 were serially sectioned in the transversal plane and studied microscopically after H&E and PAS staining. The findings were compared with those of age-matched untreated embryos. RESULTS: All untreated and saline embryos were normal, whereas 49% of Adriamycin embryos had foregut malformations. Tracheoesophageal separation was complete on day 12 in control embryos, whereas 9 of 10 Adriamycin-exposed embryos had a common esophagotrachea with low emergence of the bronchi at that stage. This pattern had evolved into that of a regular EA + TEF in all nine malformed embryos by day 13. On day 12.5, esophagotrachea was found in 6 of 13 and EA + TEF in 5 of 13 embryos. Two had less well-defined malformations. CONCLUSIONS: Esophagotrachea equivalent to complete tracheoesophageal cleft is the first step leading to EA + TEF in this model. The full-blown malformation is finally acquired by partial loss of the posterior wall of the foregut, which tapers-off in the mediastinal mesenchyme and respiratory differentiation of the anterior wall down to the level of bronchial bifurcation, where it constitutes the fistula and the distal esophagus.     

A new variant of esophageal atresia with tracheoesophageal fistula and duodenal atresia: a diagnostic dilemma

A new variant of esophageal atresia (EA) with tracheoesophageal fistula (TEF) associated with duodenal atresia is reported. The TEF was between the lower pouch and the trachea, with a cystic dilatation in the midportion. The tracheal end of the fistula was obstructed by a membranous septum at both ends of a cystic dilatation, leading to a diagnosis of pure EA (gasless abdomen). After the lower pouch was opened beyond the cystic dilatation, 100 ml nonbilious fluid was obtained. A laparotomy revealed a type III atresia of the first part of the duodenum.     

Expression of smooth-muscle actin in cultured cells from human plasmacytoid myoepithelioma

BACKGROUND: Endoscopic sclerotherapy (ST), widely used as treatment of bleeding esophageal varices, might cause motility disturbances of the esophagus as well as mucosal damage. We performed this study to evaluate the long-term effects of repeated sclerotherapy on esophageal motility and mucosa. METHODS: Ten patients with liver cirrhosis and bleeding esophageal varices treated with repeated ST were evaluated after the last ST, median 52 months, by esophageal manometry and gastroscopy where forceps biopsies were taken. RESULTS: We found a significant difference in the distal esophageal sphincter intraabdominal length. The distal esophageal sphincter pressure was somewhat lower in the ST group although the difference did not reach statistical significance. There was infiltration of neutrophil leukocytes in biopsies from four patients and normal findings in the rest. CONCLUSIONS: Long-term follow-up evaluation showed statistically longer distal esophageal intraabdominal length in the ST group. No mucosal alterations were found at the histopathological investigation.     

Blood supply of esophageal stumps

BACKGROUND/AIMS: The purpose of the study was to determine the blood supply of stumps of mobilized esophagus. METHODOLOGY: Esophageal stumps of five groups of rabbits were studied. The esophageal stumps were dyed via intravenous injection of trypan blue, and were analyzed by color image processing. RESULTS: The dyed length of the esophageal stump was 7.15+/-0.5 cm in the stomach-connecting group; 4.6+/-0.69 cm in the stomach-connecting with myotomy group; 6.1+/-0.88 cm in the distal stomach-connecting group; 3.0+/-0.47 cm in the neck-connecting group; and, 2.1+/-0.2 cm in the neck-connecting with myotomy group. There was a significant difference in the dyed length between the stomach-connecting and neck-connecting groups (p=0.000), and between the stomach-connecting and stomach-connecting with myotomy groups (p=0.026), but there was no significant difference between the neck-connecting and neck-connecting with myotomy (p=0.094), or the stomach-connecting and distal stomach-connecting groups (p=0.053). CONCLUSIONS: Stumps of the mobilized esophagus in rabbits, with or without myotomy, exhibit differences in dyed length, depending on the diameter, wall thickness and location of the blood supply in the esophagus.     

Evaluation of long-term results and donor site defects following transposition of connective tissue flaps

Tracheoesophageal fistula, with or without esophageal atresia (TEF/EA) appears to be a defect of blastogenesis, as is the oculoauriculovertebral (Goldenhar) spectrum (OAVS), with which it has occasionally been associated. We reviewed the records of all OAVS patients evaluated through the University of South Florida Regional Genetics Program between 1985 and 1993. Of 60 OAVS patients, three had TEF/EA. These results suggest that TEF/EA in association with OAVS is underreported. The occurrence of TEF/EA should prompt a thorough search for other known anomalies of OAVS.     

MPK38 expression is upregulated in immature T cells activated by concanavalin A

Between 1974 and 1994, 25 colonic interposition procedures were performed for esophageal replacement in 23 cases of esophageal atresia (EA) and 2 corrosive strictures. Nine patients had one-stage and 16 had two-stage reconstructions. The transthoracic route was used in 16 cases (64%) and the retrosternal route in 9 (36%). Average age at the time of operation in EA patients was 17 months (range 12-33), and the children with corrosive injuries were 3 and 6 years old. Mean age at follow-up was 11.8 years (2.3-20.5 years). There was no mortality in the series. One patient developed full-graft necrosis and had a gastric pull-up procedure later. One child had partial graft necrosis (3 cm at the cervical end), however, enough colon was available for reconstruction. Ten patients developed a leak from the cervical anastomosis (40%) and 7 developed a stricture at the cervical esophago-colonic anastomosis (28%). The strictures were treated by repeated esophageal dilatation, and 3 patients required revision of the anastomosis (12%). Other complications included acid reflux in 2 cases (8%), small-intestinal obstruction in 1 (4%), redundancy of the colon in 1 (4%), and chest infections in 2 (8%). Follow-up included assessment of the patient's symptoms, serial growth measurements (height and weight), and where relevant, endoscopy and a contrast swallow or meal. There was a 52% improvement in weight and height percentiles post-operatively. Each of the 19 patients who had barium swallows showed rapid transit and emptying without any significant delay or hold-up. Overall long-term results were excellent in 13 patients (52%), good in 7 (28%), and fair in 5 (20%). The colon conduit thus provides an excellent substitute esophagus in pediatric patients.     

Velocity of peristaltic propagation in distal esophageal segments

Recent studies of the peristaltic pressure wave have suggested the presence of two sequential but overlapping contraction segments in the distal esophageal body. In this report, propagation velocity of esophageal peristalsis was determined in these segments in normal subjects (N = 35) and in patients with high-amplitude peristalsis (nutcracker esophagus, N = 25) to see if intersegment differences were present in the normal or abnormal setting. Velocity measurements were made from conventional manometric tracings in two 4-cm regions representing the distal smooth-muscle segments. A novel method of velocity measurement was employed that used regression lines established from contraction onset times. In normal subjects, propagation velocity decreased significantly from the proximal to distal segment (4.9 +/- 0.5 cm/sec, vs 3.2 +/- 0.2 cm/sec, P < 0.01). Velocity also decreased across segments in nutcracker-esophagus patients (5.3 +/- 0.6 cm/sec, vs 3.6 +/- 0.7 cm/sec, P = 0.06), but the difference reached statistical significance only when the subset with highest amplitudes (> or = 180 mm Hg) was analyzed separately. Greater variance in velocity in the distal smooth-muscle segment of nutcracker-esophagus patients (P < 0.01) was, in part, responsible for this statistical observation. We conclude that normal propagation velocity decreases across regions corresponding to the smooth-muscle contraction segments defined by recent studies of peristalsis, supporting the assumption that they represent separate neuromuscular units. The mechanisms responsible for contraction wave abnormalities in the nutcracker esophagus have a minimal effect on propagation velocity, an effect that is restricted to the distal smooth-muscle segment of the esophageal body.     

Expression of androgen receptors and steroidogenic enzymes in relation to follicular growth and atresia following ovulation in pigs

Among the new antral follicles that develop after ovulation in pigs, the incidence of atresia, based on granulosa cell apoptosis, increases between Days 5 and 7 of the estrous cycle. The purpose of this study was to determine how follicular growth and atresia affected the expression of some key enzymes regulating follicular steroidogenesis and androgen receptor on Days 3, 5, and 7 after the onset of estrus. Ovaries were frozen in liquid propane for subsequent sectioning and immunohistochemical analysis. Ninety-six follicles were classified according to size as small (< 3 mm), medium (3-5 mm), or large (> 5 mm). Follicles in the active stages of the cell cycle were identified by the presence of the cell proliferation-associated nuclear antigen Ki-67 in granulosa cells. Follicles with apoptotic cells were identified by in situ 3'-end labeling of DNA. Staining intensity of antigens on sections was assigned a numeric value (0-3). Follicles assigned a value > 1 for 3'-end labeling in their granulosa cells were classified atretic. The percentage of atretic follicles increased (p < or = 0.05) from 5% on Days 3 and 5 to 41% on Day 7. Expression of Ki-67 in granulosa cells was more strongly (p < or = 0.05) associated with nonatretic follicles (98% expressing) than with atretic follicles (41% expressing). Aromatase cytochrome P450 (P450arom) was localized predominantly in granulosa cells of nonatretic follicles and was undetectable in atretic follicles. Androgen receptor in granulosa cells and expression of P450 17 alpha-hydroxylase/C17-20 lyase (P450c17) in theca interna were lower (p < or = 0.001) in atretic follicles than in nonatretic follicles. The expression of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) was localized to the theca interna and was unaffected by follicle atresia. In nonatretic small follicles, the expression of P450arom and P450c17 decreased (p < 0.01) between Days 3 and 7 while expression of Ki-67 was unchanged. In nonatretic follicles, increased follicle size was associated with a decrease (p < 0.01) in androgen receptor expression and increases (p < 0.01) in P450arom, P450c17, and 3 beta HSD expression. In conclusion, increased expression of steroidogenic enzymes was associated with follicular growth. Loss of P450arom expression in vivo is an early event in atresia and is followed by decreased cell proliferation, and decreased expression of androgen receptor and P450c17.     

Esophageal anastomosis: an experimental model to study anastomotic healing and the use of lyophilized collagen

This experimental study assessed the use of lyophilized collagen to reinforce cervical esophageal anastomosis in rabbits. Twenty New Zealand White rabbits weighing 2.3-3.2 kg were used. In group I (n = 10) a 1-cm-long segment of the esophagus was excised and the two free edges anastomosed, to mimic the conditions found in newborn esophageal atresia. Group II (n = 10) had a segmental esophageal resection and end-to-end anastomosis as in group I but the anastomotic site was circumferentially covered with lyophilized type I collagen film. The resected segments were processed immediately and served as controls for the postoperative tissue in each animal. The animals were starved for the first 24 h and water was given on the 2nd postoperative day; on the 3rd postoperative day the animals were allowed a normal diet. Two rabbits in group II died on the 7th and 8th postoperative days because of a fistula. All the rabbits were killed on the 10th postoperative day and 4-cm segments of esophagus with the anastomosis at the centre were removed. At this time gross leakage was detected in four animals (one in group I and three in group II). Each anastomosis was evaluated for bursting pressure, collagen content, and histologic appearance. Bursting pressure was higher in group I. Collagen (measured as hydroxyproline) levels in anastomotic and adjoining 1-cm segments were compared with concentrations in control segments resected during operation. In group II animals there was a significant reduction in the lowering of hydroxyproline concentrations around the anastomosis. Microscopic evaluation revealed no significant differences between the two groups. This experiment showed no demonstrable benefit from the use of lyophilized collagen in preventing the esophageal anastomotic leakage that occurs in repaired esophageal atresia.     

Microleakage of cervical restorations using two resin bonding systems

OBJECTIVES: To determine whether coins located in different portions of the esophagus differ in their likelihood of spontaneous clearance, and to determine the frequency of asymptomaticity among children with esophageal coins. DESIGN: Retrospective case review. SETTING: Pediatric academic tertiary care center. PATIENTS: All 73 children presenting in an 18-month period to a pediatric emergency department for coin ingestion whose roentgenographic evaluation revealed an esophageal coin. INTERVENTIONS: None. OUTCOME MEASURES: Hospital records of all children were reviewed for demographic information, coin denominations, esophageal locations of ingested coins based on roentgenographic reports, performance of invasive removal procedures, and the presence or absence of signs and/or symptoms. RESULTS: All of the 58 children with proximal or middle esophageal coins underwent invasive removal procedures, while nine (60%) of 15 distal esophageal coins passed into the stomach spontaneously (P < .001). Five children (7%) were asymptomatic. CONCLUSIONS: Proximal and middle esophageal coins should be promptly removed, as per present practice. Children with distal esophageal coins should be observed up to 24 hours before an invasive removal procedure, since many will spontaneously clear their coins. Since esophageal coins may be asymptomatic, all children who have swallowed coins should undergo roentgenographic evaluation.     

Severe dysphagia, dysmotility, and unusual saccular dilation (diverticulum) of the esophagus following excision of an asymptomatic congenital cyst

Iatrogenic dysmotility syndromes, particularly achalasia-like conditions, occasionally complicate esophageal and paraesophageal surgery. We describe a patient who developed a very unusual (and as far as we know unreported) syndrome characterized by severe dysphagia, esophageal dysmotility (segmental simultaneous contractions of the distal esophagus), and very large saccular outpouching (diverticulum) involving the right wall of the distal half of the esophagus as a consequence of excision of an asymptomatic congenital cyst. The cyst had been discovered as an incidental finding on a preemployment chest x-ray. Our patient's dysphagia did not improve with nonsurgical treatments that are usually successful for idiopathic and iatrogenic achalasia.     

Potential application of p53 as an intermediate biomarker in Barrett's esophagus

Diagnosis of the neoplastic progression in Barrett's esophagus using the histologic classification of dysplasia is frequently difficult. The tumor suppressor protein p53, when mutated, confers a promoter effect on cell growth. The purpose of this study was to evaluate the applicability of p53 as an intermediate biomarker of malignancy in Barrett's esophagus. Archival analysis of 100 biopsy specimens of Barrett's esophagus and 10 esophageal adenocarcinomas were compared with 35 chronic esophagitis biopsy specimens. Immunocytochemistry using an anti-p53 monoclonal antibody was performed and elevated immunoreactivity quantitated microscopically. Data were analyzed using a logistic regression model. Significant p53 immunoreactivity occurred as follows: chronic esophagitis (0%), Barrett's esophagus without dysplasia (10%), with low-grade dysplasia (60%), with high-grade dysplasia (100%), and adenocarcinoma (70%). All cases of Barrett's esophagus were significantly immunoreactive when compared with the chronic esophagitis cases (p = 0.001). There was an increase in p53 immunoreactivity as the histologic classification progressed toward adenocarcinoma (p = 0.001). Progression to high-grade dysplasia may be predicted based on p53 immunoreactivity. These findings suggest a role for p53 as an intermediate biomarker in Barrett's esophagus.     

Tracheomalacia with esophageal atresia and tracheoesophageal fistula in fetal rats

BACKGROUND: Many patients who have esophageal atresia and tracheoesophageal fistula (EA-TEF) have associated tracheomalacia, which is thought to be one of the reasons for respiratory complications after surgical correction of the abnormality. METHODS: In this study, tracheas from Adriamycin-induced EA-TEF fetal rats were examined histologically and relevant cross-sectional parameters of the tracheas were measured. RESULTS: The tracheal lumen in tracheomalacia was small and irregular, losing its normal "D" shape. In most rats, the cartilaginous ring was broken into two to four segments, making the trachea lose its rigid support. The submucosa was thickened with prominent bulging of its membranous part into the tracheal lumen. The ratio of the inner luminal cross-sectional area to the outer tracheal cross-sectional area in EA-TEF rats was 15.7%, compared with a control ratio of 47.2%. In EA-TEF rats, the length of the cartilaginous ring was significantly shortened (P < .001), but not the length of membranous trachea, thus resulting in a cartilaginous/membranous (C/M) ratio of 1.55:1, markedly lower than that of normal rats (4.34:1, P < .001). The reduction of anterior-posterior diameter of the tracheal lumen was more marked than that of the transverse diameter. CONCLUSIONS: These observations suggest that the trachea in EA-TEF rats has a smaller lumen and is more flaccid than normal, making it prone to airway obstruction. The fact that tracheomalacia developed only in fetuses who had EA-TEF indicates that the factors that result in EA-TEF also cause tracheomalacia.     

Intraesophageal balloon distension test in Chagas' disease patients with noncardiac chest pain

Patients with Chagas' disease often have chest pain as a prominent symptom. The objective of this study was to compare the results of intraesophageal balloon distension in chagasic and nonchagasic patients with chest pain not caused by coronary obstruction. We studied 40 patients with chest pain and angiographically normal coronary arteries, 25 with a positive serologic test for Chagas' disease (Chagas group, 16 women, mean age 53+/-10 years), and 15 with a negative serologic test (control group, 11 women, mean age 46+/-10 years). All patients had radiologic and endoscopic examinations of esophagus, stomach, and duodenum, esophageal manometry with the acid infusion test in the distal esophagus, and intraesophageal balloon distension. None of them had esophageal dilation or any signs of cardiovascular disease. A 25-mm-long latex balloon located 10 cm above the lower esophageal sphincter was inflated and deflated over a period of 10 sec at 1-ml increments of air until the subjects reported chest pain or to a maximum volume of 20 mi. The test caused chest pain in 14 subjects in the control group (93%) and in 12 in the Chagas' disease group (48%, P < 0.05). The mean volume of air that caused chest pain was 10+/-3 ml in the control group and 15+/-4 ml in the Chagas' disease group (mean+/-SD, P < 0.05). The maximum intraesophageal pressure during the examination was higher in Chagas' disease patients with chest pain during balloon distension (60 +/- 21 mm Hg) than in patients who did not have chest pain (37 +/-18 mm Hg, P < 0.05) and did not differ from the control group (48+/-16 mm Hg, P > 0.05). With the other examinations there was no difference between groups or between patients with or without chest pain during the balloon distension test. Although esophagitis was observed in 47% of patients in the control group and in 40% of the Chagas' disease group, the acid infusion test was positive in 27% of patients in the control group and in 4% of patients in the Chagas' disease group. We conclude that, as compared to a group of patients with similar chest pain, chagasic patients are less sensitive to esophageal distension. Thus, it is unlikely that their chest pain is related to esophageal mechanisms.     

Manometric study of the effects of experimental fundoplication in rats

BACKGROUND: The manometric effects of surgical repair of gastroesophageal reflux remain largely unknown, making the interpretation of the changes in the esophagogastric high pressure zone after fundoplication difficult. AIM: To measure in a murine model the transdiaphragmatic pressure gradients, intraabdominal esophageal length, and lower esophageal sphincter pressure and length after Nissen fundoplication. MATERIAL AND METHODS: Adult Wistar rats were divided into two groups Control group (n = 10): in which measurements were made after laparotomy and intraabdominal esophageal dissection. Nissen Group (n = 15): in which measurements were made at baseline, after fundoplication and 1 week after surgery. We considered the following variables: end-inspiratory and end-expiratory transdiaphragmatic gradient (TDIG and TDEG respectively), lower esophageal sphincter pressure (LESP) length (LESL), and length of the intraabdominal segment of the esophagus (LIAS). RESULTS: The LIAS increased significantly after esophagogastric dissection in the control group (11.38 +/- 3.22 mm vs 16.02 +/- mm, p < 0.05). No differences between pre- and postoperative status were found in TDIG, TDEG, LESP and LESL in the control group. However, LESP increased significantly after fundoplication (14.22 +/- 13.3 vs 32.96 +/- 7.8 mmHg, p < 0.05) and these differences were still present one week later (30.72 +/- 6.73 mmHg, p < 0.05). LESL was also increased (1.91 +/- 1.76 mm vs 7.68 +/- 1.83 mm) after fundoplication (p < 0.05), and reached 7.02 +/- 2.18 mm (p < 0.05) 1 week later. No differences were found in pre- and postoperative TDIG, TDEG and LIAS in the Nissen Group. CONCLUSION: In this murine experimental model, intraabdominal esophageal dissection increased the length of the intraabdominal esophagus without modifying the esophagogastric high pressure zone, while Nissen fundoplication increased lower esophageal sphincter pressure and length, without modifying the length of the intraabdominal esophagus or the transdiaphragmatic pressure gradients.