Fetal lung growth in laryngeal atresia and tracheal agenesis

Abstract Three cases of airway obstruction in fetuses born at 21, 32 and 40 weeks gestation are reported. The first had laryngeal atresia, cystic dysplastic kidneys, oligohydramnios and immense fluid-filled lungs. The second had upper tracheal agenesis, a tracheo-oesophageal fistula, a cystic dysplastic horseshoe kidney, oligohydramnios and normal-sized lungs. The third had a pin-hole mucosal tract through an otherwise atretic larynx, normal kidneys, no oligohydramnios and normal-sized lungs. Lung weight:body weight ratios, radial alveolar or radial canalicular counts and point-counting of sections of lungs in cases 1 and 2 show that laryngeal or tracheal obstruction may prevent or reduce the pulmonary hypoplasia associated with renal dysplasia, and in cases 2 and 3, that grossly enlarged, hyperplastic lungs may not be seen unless obstruction is complete.     

Cloacal Dysgenesis Sequence: Observations in Four Patients Including Three Fetuses of Second Trimester Gestation

Cloacal dysgenesis is a rare malformation sequence. We studied cloacal dysgenesis in four fetuses, including three at 18–22 weeks of gestation. All four fetuses showed a smooth perineum with absence of anal, urethral, and/or vaginal openings. The urinary bladder was dilated in 3 cases. The labia majora and minora were absent in the two female fetuses; the scrotum and penis were absent in one male fetus and hypoplastic in the second. The kidneys were either absent (1 case), dysplastic (1 case), or hydronephrotic (1 case). Normal kidneys were seen in a fetus of 20–22 weeks gestation in whom the urinary obstruction was alleviated by a vesicocolonic fistula. This fetus did not have pulmonary hypoplasia. Severe renal anomaly and pulmonary hypoplasia are the limiting factors for the survival of infants born with cloacal dysgenesis. The unique observation of normal kidneys and lungs in one of our fetuses, despite anhydramnios, suggests that the effect of oligohydramnios on lung development may be limited early in gestation, at least up to 20–22 weeks. It may also indirectly support the theory that there are factors other than oligohydramnios that interfere with early lung development, such as reduced production of a pulmonary growth factor by the kidney or reduced proline production by malformed kidneys, that may cause decreased collagen formation and result in hypoplastic lung mesenchyme. Received December 12, 1996; accepted September 15, 1997.     

Fetal Obstructive Uropathy: Patterns of Renal Pathology

Fetal obstructive uropathy (FOU) is characterized by obstruction of the urethra, renal anomalies, ureterovesical dilatation, oligohydramnios, cryptorchidism, and abdominal muscle wall changes. The main objective of the present study was to better understand the relationship between FOU and renal pathology using a series of 15 male autopsy cases. A total of 11 cases with patent anus and 4 with imperforate anus were analyzed. Of the first group, most cases showed obstruction at the level of prostatic urethra. Seven cases showed obstruction at the level of the prostatic urethra and histologic study revealed scarring and partial or complete absence of the prostate, while in the remaining four cases the prostate was present. Of the cases with imperforate anus, two showed obstruction at the level of prostatic urethra, one showed posterior urethral valves, and one was obstructed at the proximal urethra. In all cases the kidneys showed mixed (dysplastic and cystic) changes with no significant differences between the two groups. An inverse correlation was observed between degree of renal dysplasia and gestational age, whereas the opposite was true for cystic changes. Distal and collecting tubules were more intensely immunoreactive to the anti-cytokeratin antibody when compared to proximal tubules. Moreover, anti-cytokeratin immunoreactivity was more prominent in tubules displaying cystic dilatation. DNA fragmentation analysis of renal tissue revealed a higher apoptosis of mesenchymal and tubular cells in the FOU cases, compared to gestational aged–matched controls. These results suggest that renal anomalies in FOU might be related to the gestational age at which the injury occurred and to the duration of the obstruction. Received February 12, 1999; accepted August 17, 1999.     

电子支气管镜在儿童上气道梗阻性疾病中的诊断价值

目的 评价电子支气管镜在儿童上气道梗阻性疾病中的诊断价值及安全性.方法 对91例上气道梗阻患儿行电子支气管镜检查,总结分析病因.结果 (1) 儿童上气道梗阻病因依次为先天性喉气管软化合并感染(45例)、声门下异物(13例)、喉气管占位性病变(9例)、声门区水肿(6例)、气管狭窄(5例)、喉咽腔病变(咽后脓肿3例、肿物2例)、声门区增生(3例)、声门下狭窄(2例)、声带麻痹(2例)、喉蹼(1例);(2) 不同年龄段病因不同:新生儿期依次为声带麻痹、喉气管软化;~6个月依次为先天性喉气管软化、会厌囊肿,其他少见病因如气管狭窄、咽后脓肿、喉蹼等疾病;~1岁依次为喉气管软化、气管狭窄、声门下异物等;~3岁依次为声门下异物、声门区水肿、喉气管软化等;>3岁儿童1例为喉乳头状瘤.(3) 疾病好发的年龄段不同:先天性喉气管软化好发于6个月以下婴儿,气管异物好发于1~3岁幼儿,先天性会厌囊肿多见于3个月以下婴儿.(4) 并发症:16例有一过性血氧饱和度下降,11例出现气管支气管痉挛,术后8例有一过性发热,6例有短期喉鸣加重.结论 电子支气管镜在儿童上气道梗阻性疾病的诊断中起重要作用,可迅速、直观地判断病变部位和性质,避免误诊,有助于指导治疗.

Abstract：

Objective To investigate the diagnostic value and safety of bronchovideoscope in the pediatric upper airway obstruction.Methods Bronchovideoscope was performed in 91 pediatric patients with upper airway obstruction.The etiology was analyzed and summarized.Results (1) Our study showed that the etiology of pediatric upper airway obstruction were as follow in turn:congenital laryngo-trachemalacia (45 cases),subglottic foreign body (13 cases),laryngotracheal occupying lesion (9 cases),vocal area edema (6 cases),tracheal stenosis (5 cases),laryngopharyngeal lesion (3 cases of retropharyngeal abscess,2 cases of tumor),vocal area hyperplasia (3 cases),subglottic stenosis (2 cases),glottic paralysis (2 cases),laryngeal web (1 case).(2) The common etiology of pediatric upper airway obstruction was different with age.Neonatal period:glottic paralysis,laryngomalacia in turn;1~6 month:laryngo-trachemalacia,tracheal stenosis,subglottic foreign body in turn;1~3 year:subglottic foreign body,vocal area edema,laryngo-trachemalacia in turn,>3 year:laryngeal papilloma.(3) Specific disease had predominant age:laryngo-trachemalacia predominated in infants less than 6 month;tracheal foreign body was most common in child aged 1~3 years old;epiglottic cyst was most common in infant less than 3 month.(4) Complication:during procedure,16 patients had transient decrease of saturation of blood oxygen and 11 patients had tracheobronchial spasm.After procedure,8 patients had transient fever and 6 patients had transient aggravation of laryngeal stridor.Conclusion Bronchovideoscope plays an important role in the diagnosis of pediatric upper airway obstruction.It can directly identify position and nature of disease,and then guide treatment.     

Doppler sonography in congenital ureteropelvic junction obstruction and multicystic dysplastic kidneys

The accurate diagnosis of severe congenital ureteropelvic junction obstruction (UPJO) and the indications for surgical intervention are a matter of debate. Differential diagnosis from, for example, congenital cystic kidney malformations is important. In the present study we analysed the value of Doppler sonography (DS) for assessment of obstruction in congenital UPJO and its usefulness for differential diagnosis. A total of 138 infants and children were examined. Forty-three healthy infants and 24 children who had had a pyeloplasty at least 1 year previously served as control groups. Seventy-one children with UPJO and cystic kidney malformations underwent DS in addition to the usual examinations of intravenous urography and scintigraphy. Resistive Index (RI) was measured in both kidneys. Twenty infants showed decompensated UPJO and had needed an operation. Preoperatively all showed significantly increased RI (RI=74%), which returned to normal after operation (RI=68.3%). Thirty-nine children with UPJO could be managed conservatively, showing compensated obstruction on diuretic renography. On DS they had normal and symmetrical RI values (RI=67%). Eleven children had multicystic dysplastic kidneys; 4 underwent nephrectomy. On DS all showed either absence of perfusion signals or very low flow velocities with very high RI values (RI=90–100%) in the renal vessels. One child was found to be suffering from a cystic nephroma. DS was able to reveal quite normal vessel distribution in renal parenchyma with slightly elevated RI values (RI=80%). Our results indicate that DS a non-invasive, non-ionising method of investigation, may serve as an additional functional parameter for defining accurately the degree of obstruction in UPJO. DS can influence the indication for surgical treatment and improves the differential diagnosis of congenital cystic kidney malformations. It provides an adequate method for frequent monitoring in conservative treatment.     

小儿先天性发育不良肾的临床特点和治疗

目的 探讨小儿先天性发育不良肾的临床特点、诊断和治疗.方法 总结分析1988年至2009年我科收治的83例单侧先天发育不良肾的临床资料.所有患儿术前均行多普勒超声、静脉肾盂照影和99mTc-DTPA肾脏扫描.35例患儿行增强CT检查,39例行IVP后延迟CT检查三维重建.所有病例均行发育不良肾切除,肾切除的指征包括无功能发育不良肾脏合并临床症状55例,无临床症状的无功能多囊发育不良肾,随访不消退或增大27例,无功能发育不良肾合并肾输尿管积水1例.结果 各项术前检查中IVP后延迟CT三维重建技术阳性诊断率最高,达100%.术后病理均提示为发育不良肾脏.4例因高血压行发育不良肾切除的患儿,术后2例仍然有高血压,其他患儿术后临床症状消失,没有恶变者.结论 儿童先天发育不良肾脏发育不良程度不一,合并畸形不同,临床表现各异.IVP后延迟CT检查三维重建技术诊断发育不良肾脏阳性率高.合并临床症状的无功能发育不良肾、多囊发育不良肾长期随访不消退者可手术治疗,随访过程中有明显消退的多囊发育不良可定期观察,有功能的非多囊发育不良肾可以保留.近19%发育不良肾脏可合并对侧肾脏畸形,应密切监测对侧肾脏功能及血压.     

小儿先天性发育不良肾的临床特点和治疗

目的 探讨小儿先天性发育不良肾的临床特点、诊断和治疗.方法 总结分析1988年至2009年我科收治的83例单侧先天发育不良肾的临床资料.所有患儿术前均行多普勒超声、静脉肾盂照影和99mTc-DTPA肾脏扫描.35例患儿行增强CT检查,39例行IVP后延迟CT检查三维重建.所有病例均行发育不良肾切除,肾切除的指征包括无功能发育不良肾脏合并临床症状55例,无临床症状的无功能多囊发育不良肾,随访不消退或增大27例,无功能发育不良肾合并肾输尿管积水1例.结果 各项术前检查中IVP后延迟CT三维重建技术阳性诊断率最高,达100%.术后病理均提示为发育不良肾脏.4例因高血压行发育不良肾切除的患儿,术后2例仍然有高血压,其他患儿术后临床症状消失,没有恶变者.结论 儿童先天发育不良肾脏发育不良程度不一,合并畸形不同,临床表现各异.IVP后延迟CT检查三维重建技术诊断发育不良肾脏阳性率高.合并临床症状的无功能发育不良肾、多囊发育不良肾长期随访不消退者可手术治疗,随访过程中有明显消退的多囊发育不良可定期观察,有功能的非多囊发育不良肾可以保留.近19%发育不良肾脏可合并对侧肾脏畸形,应密切监测对侧肾脏功能及血压.     

Biochemical and Morphometric Analyses in Hypoplastic Lungs

We report the results of biochemical and morphometric studies on lungs of infants with bilateral lung hypoplasia either with or without oligohydramnios (OH or NOH) in comparison with findings in normally grown lungs. The OH and NOH lungs were equally hypoplastic in terms of DNA content but OH lungs had a significantly lower disaturated phosphatidylcholine (DSPC) concentration than NOH or normal lungs, apart from a subgroup with gastrointestinal or airway obstruction. Hydroxyproline concentration in OH lungs was higher than that in NOH or normal lungs. Desmosine concentrations did not differ significantly between groups despite the obvious lack of elastin in the septal crests of the OH group on histology. Morphometry revealed low lung volume, low radial alveolar counts, low alveolar numbers, and low alveolar surface area in both OH and NOH groups. Alveoli and alveolar ducts constituted a higher proportion of lung volume in NOH than in OH lungs. The similarity of most morphometric indices in the two groups implies that maturation does not depend on quantitative elaboration of airways and alveoli. The finding of impaired epithelial maturation despite the high hydroxyproline concentration in the OH lungs suggests an abnormality in epithelial-mesenchymal interaction that is not present in the equally small lungs of the NOH group.     

Biochemical and morphometric analyses in hypoplastic lungs

We report the results of biochemical and morphometric studies on lungs of infants with bilateral lung hypoplasia either with or without oligohydramnios (OH or NOH) in comparison with findings in normally grown lungs. The OH and NOH lungs were equally hypoplastic in terms of DNA content but OH lungs had a significantly lower disaturated phosphatidylcholine (DSPC) concentration than NOH or normal lungs, apart from a subgroup with gastrointestinal or airway obstruction. Hydroxyproline concentration in OH lungs was higher than that in NOH or normal lungs. Desmosine concentrations did not differ significantly between groups despite the obvious lack of elastin in the septal crests of the OH group on histology. Morphometry revealed low lung volume, low radial alveolar counts, low alveolar numbers, and low alveolar surface area in both OH and NOH groups. Alveoli and alveolar ducts constituted a higher proportion of lung volume in NOH than in OH lungs. The similarity of most morphometric indices in the two groups implies that maturation does not depend on quantitative elaboration of airways and alveoli. The finding of impaired epithelial maturation despite the high hydroxyproline concentration in the OH lungs suggests an abnormality in epithelial-mesenchymal interaction that is not present in the equally small lungs of the NOH group.     

Nondysplastic Fetal Renal Hypoplasia Associated with Severe Oligohydramnios: Clinical, Pathologic, and Morphometric Findings

Two fetuses with severe bilateral renal hypoplasia are described; both diagnoses were made following elective abortion for oligohydramnios andsuspected renal dysplasia. A 20-week female fetus (46,XX) had pulmonary hypoplasia and very small kidneys (7% of expected weight) the' were normally shaped and nondysplastic, with well-formed medullae and metanephric blastema and markedly diminished cortices with only rare glomeruli. A 23-week male fetus (46, XY) had small kidneys (13 % of expected weight) that were nondysplastic, normally shaped, and histologically well organized with moderately decreased numbers of glomeruli. Isolated bilateral renal hypoplasia has not previously been well characterized in fetuses; the presence of oligohydramnios (both cases) and pulmonary hypoplasia (one case) suggests that this finding is associated with impaired fetal renal function and may adversely influence neonatal survival.     

新生鼠输尿管不全梗阻后肾盂压力和肾脏形态变化的观察

目的 了解新生鼠输尿管不全梗阻后肾盂压力和肾脏形态的变化。方法 65只新生鼠用腰大肌包埋不同长度的左侧输尿管，制成轻（n=31)、重（n=34)度输尿管不全梗阻。对照组仅进行剖腹探查。术后8周和24周分别用核磁共振检查肾脏形态变化，术后分别于24周和30周进行肾盂测压和组织学检查。结果 梗阻肾脏均有不同程度积水。严重梗阻组除积水较严重外，发现4例肾脏肾发育不全，其平均肾实质重量仅是对照组的35％。轻度梗阻组和对照组未见发育不良的肾脏。严重梗阻组的肾脏灌注压明显高于轻度梗阻组和正常对照组。结论 新生鼠输尿管不全梗阻后均产生明显肾积水。严重梗阻组可产生肾脏发育不良，可能与严重梗阻组肾盏灌注压明显增加有关。     

Early detection of prune belly syndrome in utero by ultrasonography

A report is presented of a male infant with prune belly syndrome (PBS) in whom bladder enlargement was detected by ultrasound (US) as early as 13 weeks of gestation. Subsequent fetal US identified progressive urinary tract dilatation, ascites and oligohydramnios. At 22 weeks, the fetal bladder was drained under US guidance. A gradual resolution of oligohydramnios was detected on US performed after 26 weeks of gestation. Delivery by cesarean section was performed at 34 weeks of gestation. The newborn had typical features of PBS with a vesico-cutaneous fistula but did not show respiratory distress. Imaging studies showed hypoplastic left kidney, slightly dysplastic but functioning right kidney, megaureter, megacystis, vesicoureteral reflux and dilated prostatic urethra. The early detection of genitourinary system abnormalities and serial US suggest that a distal urethral obstruction may be the underlying mechanism of PBS. Spontaneous (or therapeutic) intra-uterine decompression of the bladder might ameliorate obstructive nephropathy and oligohydramnios, allowing adequate lung development.     

Multicystic dysplastic kidney and pelviureteric junction obstruction

Two infants with nonfunctioning antenatally detected multicystic dysplastic kidneys developed acute renal failure in conjunction with pelviureteric obstruction of the contralateral kidney at 9 and 14 months of age, respectively. The initial postnatal ultrasounds had shown mild pelvic dilatation in both cases. Clinicians need to be aware of the possibility of late obstruction. We suggest that it is good practice to review patients with antenatally detected urinary tract abnormalities and equivocal investigations at joint nephrouroradiology meetings.     

The management of renal conditions in the perinatal period

Most urogenital abnormalities are now diagnosed antenatally on high resolution ultrasound scans. This has enabled recognition of those that are not compatible with survival and these are managed with termination of pregnancy. Renal anomalies that require surgical intervention continue to pose challenges. Conditions such as multicystic dysplastic kidney can be easily recognised and managed based on the experience gained with long-term studies of its natural history. Polycystic kidney on the other hand while not posing a diagnostic problem remains beyond the reach of therapeutic intervention and postnatal supportive measures are the only available means of dealing with this entity at present. The major difficulty is with the management of antenatally diagnosed pelvicalyceal dilatation. The goal of intervention is to preserve renal function when dilatation is the consequence of obstruction. Unfortunately, by the time ultrasound evidence of significant obstruction is apparent renal damage is already established. Fetal intervention should be considered in those cases where severe oligohydramnios is associated with hydronephrosis, especially in the presence of a solitary kidney or in bilateral disease. Postnatally, all neonates with renal tract dilatation should be managed according to a protocol which mandates serial measurements of renal pelvis diameter and correlates this with data from radionuclide scans. This will enable recognition of kidneys that are at risk of losing function while at the same time avoiding unnecessary surgical intervention in those which remain dilated but are functionally stable.     

Subglottic Ductal Cysts Associated with Complete Tracheal Ring Deformity: Coexistence of Two Rare Airway Abnormalities with Fatal Outcome

Subglottic cysts are rare and may cause airway obstruction. Most cases are acquired secondary to endotracheal intubation, even short-term, particularly in the premature neonate. Complete tracheal rings are rare anomalies associated with tracheal stenosis. To our knowledge, the two have not been reported coexisting. A 16-month-old ex-premature boy was found unresponsive, with his tracheostomy tube dislodged. Tracheomalacia, subglottic stenosis, and a laryngeal cyst had been diagnosed shortly after birth, and the cyst was surgically treated at that time. At autopsy, a complete tracheal ring was noted in the subglottic region, above the tracheostomy site, and the tracheal diameter was markedly decreased in this area. In addition, multiloculated cysts were present at that level, arising from both anterolateral tracheal walls. These completely occluded the airway. To our knowledge, this is the first case of a combination of tracheal ring anomaly and subglottic cysts. Pediatric pathologists must be aware of iatrogenic lesions associated with care of the premature neonate, particularly as the age of viability continues to decrease.     

Neonatal Pulmonary Hypoplasia: An Autopsy Study of 25 Cases

Pulmonary hypoplasia (PH) is defined as defective or incomplete development of lungs that are immature for gestational age. A prospective study was done to establish practical criteria for the diagnosis of pulmonary hypoplasia and to determine the relative frequency of pulmonary hypoplasia and its associated congenital malformations. Postmortem, formalin-inflated, routinely processed lungs were examined for fresh lung weight, fixed lung volume, radial alveolar count, and tissue maturity. Of these, lung volume was found to be the least useful. However, no single parameter was adequate for diagnosis in every case. Using the remaining three in conjunction, reliable diagnostic criteria were established. In this series of 113 cases, 22% had pulmonary hypoplasia as the primary cause of death, of which one-third had no associated congenital malformations to account for the development of pulmonary hypoplasia. It was found that premature rupture of membranes (PROM) for as short as 5 days could lead to fatal PH. It is concluded that PH is a common problem in neonatal autopsies and can be diagnosed in the average laboratory. Recognizing PH is important because once it has developed, intrauterine intervention in cases of oligohydramnios and postnatal treatment with surfactant inhalation cannot influence the outcome. It remains to be seen whether early fluid replacement in PROM will prevent development of PH.     

MR imaging appearance of laryngeal atresia (congenital high airway obstruction syndrome): unique course in a fetus

Congenital high airway obstruction syndrome (CHAOS) is a rare life-threatening syndrome. Most cases are diagnosed prenatally by US. We report a fetus with this syndrome that showed a unique course revealed on MRI. Ultrasonography at 22 weeks demonstrated that the fetus had ascites and bilaterally enlarged hyperechoic lungs. Congenital infection, congenital cystic adenomatoid malformation or CHAOS was suspected. Subsequent MRI performed at 24 weeks demonstrated bilaterally enlarged high-signal lungs, dilated bronchi, massive ascites, subcutaneous oedema and polyhydramnios. MRI confirmed the diagnosis of CHAOS. A second MRI at 35 weeks showed that the bilateral lung enlargement, ascites, oedema and polyhydramnios had resolved, but that the appearance of the airway was unchanged. The infant was delivered by caesarean section at 38 weeks of gestation and immediate tracheostomy was performed. This spontaneous regression was explained by a tracheo-oesophageal fistula that may have decreased the intrathoracic pressure.     

Asynchronous Pulmonary Hyperplasia Associated with Tracheal Atresia: Pathologic and Prenatal Sonographic Findings

We describe a case of pulmonary hyperplasia associated with tracheal atresia and a complete obstruction to the egress of pulmonary secretions. In classical pulmonary hyperplasia associated with cartilagenous laryngeal atresia and a persistent pharyngotracheal duct, the histologic appearance of the lungs is normal but exhibits “synchronous” hypermaturity. The histologic pattern in our case is much less mature, resembles CAM type III, and exhibits “asynchronous” development. We suggest that these histologic patterns be distinguished and that pulmonary hyperplasia is probably underrecognized and not nearly as rare as previously thought.     

Laryngeal foreign bodies in children: first stop before the right main bronchus

Laryngeal foreign bodies may produce either complete or incomplete airways obstruction. In complete airways obstruction the presentation is with calamitous respiratory difficulty. However incomplete laryngeal obstruction may present with less severe symptoms, resulting in possible misdiagnosis and confusion with other causes of upper airway obstruction such as infectious croup. This report describes three cases of incomplete laryngeal obstruction secondary to inhaled foreign bodies. In each case, the diagnosis of an inhaled foreign body was initially missed, resulting in delay in diagnosis and in one case prolonged recovery. The importance of considering laryngeal foreign bodies, both in cases of suspected foreign body inhalation and clinical cases of incomplete laryngeal obstruction are discussed.