Chronic intestinal pseudo-obstruction and delayed myenteric ganglion cell maturation]

BACKGROUND. Enteric nerve cells begin to mature during the last trimester of pregnancy and become mature only after birth. The degree of maturation seems to be related to bowel motility. CASE REPORT. A girl was born from a pregnancy complicated by hydramnios, and did not pass meconium before the 64th hr of life. Barium enema on day 4 showed a left microcolon with no distension of the transverse colon. Tests for cystic fibrosis were negative. On day 12, the patient presented with septicemia due to Pseudomonas maltophylia. Parenteral alimentation by central catheter was instituted. Surgical rectal biopsy showed that the number of ganglion cells was normal but the cells were immature. Progressive feeding was possible for the 3rd month of life. A second rectal biopsy at 3 1/2 months showed some remaining immature ganglion cells. CONCLUSION. Immature ganglion cells can account for neonatal functional intestinal obstruction, as has been established for the small left colon syndrome. The progressive loss of symptoms seems to be correlated with histological maturation of the neurological apparatus of the large bowel. Severe complications, such as occlusion, sepsis, nutritional disorders can occur during this long period of functional intestinal obstruction.     

Suitability of selected markers for identification of elements of the Intestinal Nervous System (INS).

The possibility of identifying and characterising elements of the enteric nervous system based on their contents of cathepsin D, chromogranin A, neuronal specific enolase and S-100 protein was studied in colorectal specimens (operative full-thickness, seromuscular and mucosomuscular biopsies) obtained from 15 children, aged 2 days to 10 years. Nine patients suffered from Hirschsprung's disease, and two from chronic constipation. Four neonates with imperforate anus or meconium ileus composed the control group. All markers were identified immunohistochemically by antibodies against human antigens with appropriate detection methods. Chromogranin A staining was not always adequate to identify all neuronal cell bodies and other nervous elements. However, it proved superior to the other methods in the depiction of neuroendocrine cells in the intestinal mucosa. Cathepsin D antibodies stained normal and abnormal neural cells with different intensity; nerve fibres were not stained. This marker did not allow an unequivocal differentiation of ganglion cells from macrophages within the submucosa; the latter exhibited exceptionally strong marking and in some cases represented the predominant elements in this area. Neuronal specific enolase was distinctly expressed in nerve cells and fibres of the intestinal wall. Atrophic and hypoplastic features could be identified, suggesting that this method may give some insight into functional aspects. Continuous connections between ganglions were also observed. S-100 protein antibodies resulted in a negative image of unstained ganglion cells surrounded by extensively marked Schwann cells and neural fibres. With respect to clinical application, all these markers may provide supplementary information for the differential diagnosis of intestinal motility disorders.     

Meconium‐related ileus in extremely low‐birthweight neonates: Etiological considerations from histology and radiology

Background: A nationwide survey on neonatal surgery conducted by the Japanese Society of Pediatric Surgeons has demonstrated that the mortality of neonatal intestinal perforation has risen over the past 15 years. The incidence of intestinal perforation in extremely low‐birthweight (ELBW) neonates has been increasing as more ELBW neonates survive and as the live‐birth rate of ELBW has increased. In contrast to necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP), the pathogenesis of meconium‐related ileus, defined as functional bowel obstruction characterized by delayed meconium excretion and microcolon, remains unclarified. Methods: The histology of 13 ELBW neonates with intestinal perforation secondary to meconium‐related ileus was reviewed, and the radiology of 33 cases of meconium‐related ileus diagnosed on contrast enema was reviewed. Specimens obtained from 16 ELBW neonates without gastrointestinal disease served as age‐matched controls for histological assessment. Results: The size of the ganglion cell nucleus in meconium‐related ileus and in control subjects was 47.3 ± 22.0 µm² and 37.8 ± 11.6 µm², respectively, which was not significantly different. In all cases of meconium‐related ileus, contrast enema demonstrated a microcolon or small‐sized colon, with a gradual caliber change in the ileum and filling defects due to meconium in the ileum or colon, showing not‐identical locations of caliber changes and filling defects. Conclusion: Morphological immaturity of ganglia was not suggested to be the pathogenesis of meconium‐related ileus. Impaction of inspissated meconium is not the cause of obstruction, but the result of excessive water absorption in the hypoperistaltic bowel before birth, although the underlying mechanism responsible for the fetal hypoperistalsis remains unclear.     

新生儿巨结肠类缘病

目的探讨新生儿期先天性巨结肠类缘病(HAD)的临床和病理特征及恰当的处理方式。方法回顾性总结1990～2004年间手术治疗的HD患儿315例，重新复习术后病理切片(HE染色)。发现新生儿HAD17例。其中14例表现为腹胀、便秘、呕吐；3例表现为肠穿孔的症状。病理分型混合型11例：HD IND3例、HD 节细胞减少症1例、HD 节细胞未成熟7例；单纯型6例：IND3例、肠神经元发育异常3例。经历的手术方式：单纯肠造瘘；小肠部分切除 肠吻合或造瘘；右半结肠切除；巨结肠根治术；造瘘口关闭术；肠粘连松解术等。6例行过2次手术；10例曾行3次(包括3次)以上手术；1例行回肠造瘘。13例已行巨结肠根治术。结果2例死于多次手术导致的肠功能异常、营养不良、感染等；2例需经常回流洗肠协助排便；1例回肠造瘘后4月在观察中；2例失访；其余随年龄增长肠道功能逐渐恢复正常。结论HAD的存在应引起临床医生足够的重视，疑似HD的患儿术前应尽量做到诊断明确，以便施以正确的术式，避免多次手术。按HD根治术后效果不满意者，应再复习病理切片，防止遗漏HAD的诊断。     

新生儿坏死性小肠结肠炎经回肠造瘘术后远端肠闭锁7例

目的探讨新生儿坏死性小肠结肠炎(NEC)行回肠造瘘术后,造瘘远端肠闭锁的临床特点和诊治经验。方法对本院自2010年7月至2015年2月收治的7例NEC行回肠造瘘术后,远端继发肠闭锁的临床资料进行回顾性分析。7例均无明显临床表现,结肠造影提示结肠梗阻。术中发现闭锁部位:2例为两处闭锁,1例为回肠末端、结肠肝区闭锁,1例为结肠脾区、乙状结肠闭锁;其余5例为单处闭锁,3例为乙状结肠闭锁,1例为降结肠闭锁,1例为横结肠闭锁。结果 7例手术后均痊愈出院,7例随访过程中,1例间断出现肉眼或镜下血便,经结肠造影发现有结肠狭窄,其余无明显排便异常表现,疗效满意。结论临床上NEC保守治疗后反复喂养不耐受、腹胀,应警惕肠狭窄;行回肠造瘘术后,远端肠管发生继发性闭锁应予以重视,炎症反应可能是其主要原因之一。一期造瘘术后应定期对远端肠管给予盐水灌肠,以避免肠管炎性闭锁发生。     

Neonatal functional intestinal obstruction and the presence of severely immature ganglion cells on rectal biopsy: 6 year experience

Purpose  

We report our experience of managing eight babies who presented with neonatal intestinal obstruction and whose rectal biopsies showed severely immature ganglion cells.     

胎粪性肠梗阻的临床研究

目的 探讨胎粪性肠梗阻的临床特点与治疗.方法 对4例胎粪性肠梗阻患儿的发病病因、临床症状、诊断及治疗进行回顾性分析.结果 4例胎粪性肠梗阻患儿以肠梗阻就诊3例,术前均怀疑为全结肠型无神经节细胞症,以消化道穿孔为首诊症状者1例,术前怀疑为新生儿坏死性小肠结肠炎.3例为新生儿期就诊,1例生后4个月就诊.4例患儿均进行手术治疗,其中2例行肠腔冲洗、末端回肠造瘘术,1例行回盲部狭窄肠管切除肠吻合术,1例行穿孔肠管修补术及腹腔冲洗引流术.3例新生儿患者术中均发现胎类极度黏稠、阻塞回盲部远端肠腔,4例患儿均在术中取病理证实肠壁存在神经节细胞.随访中1例患儿出院1个月后反复发生呼吸道感染、重症肺炎、呼吸衰竭而死亡:1例患儿X线胸片持续存在肺部阴影,但呼吸正常;其他2例患儿生长发育正常.结论 新生儿期便秘患儿在怀疑全结肠型无神经节细胞症的同时,应考虑到本病的可能,术中病理活检对诊断该病十分重要,术后随访应密切注意肺等其他器官系统的相应合并症.     

An unusual cause of meconium peritonitis in a foetus

Abstract:   Meconium peritonitis is a sterile chemical peritonitis resulting from intestinal perforation in-utero. We present a preterm male neonate weighing 1820 g in whom foetal meconium peritonitis was diagnosed by antenatal utrasonogram. Examination of the newborn in the immediate postnatal period revealed a firm lump of size 5 × 3 cm in the right lumbar and umbilical area. Rest of the abdomen was normal without any clinical evidence of intestinal obstruction. X-ray of abdomen done at 3 hours of life showed a cystic mass with calcified margin. Ultrasonography of abdomen ruled out any definite cause of intestinal obstruction and perforation. He was kept on conservative management. At 11 hours of life the neonate passed a small sticky white mucus plug per rectum followed by black colored meconium of normal consistency 2 hours later. The bowel habit remained regular thereafter. Screening for intrauterine infections and cystic fibrosis was negative. He is under regular follow-up and is now 6 months old with normal bowel habit. A lump of size 2 × 2 cm is still palpable and a small calcified mass is persistent in x-ray. Role of an intestinal mucus plug as the potential factor for intestinal obstruction and subsequent perforation has been highlighted in the present case.     

Calprotectin levels in meconium

AIM: To evaluate the effect of gender, gestational age, birthweight, mode of delivery, 5'-Apgar score and maternal conditions on calprotectin concentrations in meconium. METHODS: Calprotectin was measured in 131 neonates, in the first passed meconium. RESULTS: Calprotectin levels (mean +/- SD) resulted in 145.2 +/- 78.5 mg kg(-1) meconium, significantly correlated with birthweight (r = -0.333; p < 0.001), gestational age (r = -0.206; p = 0.018) and 5'-Apgar score (r = -0.243, p = 0.035). The estimated regression model was: calprotectin levels (mg kg(-1)) = 269.58-41.54 weight (kg): r = 0.383, p < 0.001. No differences were found in relation to gender, mode of delivery and maternal conditions. CONCLUSION: Calprotectin is already present in the first passed meconium, with higher levels in preterm and low birthweight neonates, as well as in neonates with some degree of perinatal asphyxia, as indicated by the negative correlation with 5'-Apgar score. These findings are probably secondary to both the immaturity of the intestinal mucosa and its hypoxic-ischaemic damage.     

Intestinal uptake and transmission of macromolecules into the blood in the young guinea pig.

The developmental changes in the ability of the small intestinal epithelium to take up and transfer into blood the macromolecules bovine serum albumin (BSA), bovine immunoglobulin G (BIgG), and fluorescein isothiocyanate-labeled dextran 70,000 (FITC-dextran) were studied in guinea pigs 0-14 days of age. In addition, in the same animals, the activities of the proteases cathepsin B and D within the intestinal mucosa were measured. Four hours after gavage feeding, 0-day-old guinea pigs showed an uptake of the markers into the enterocytes throughout the small intestine. In 2-day-old guinea pigs, the markers were only detected in the enterocytes in the distal part. All three macromolecules passed into the blood in these young animals. In 7-day-old guinea pigs, no epithelial marker uptake was observed, but low levels of BSA and FITC-dextran could still be detected in serum. Neither epithelial uptake nor transfer of the markers to the blood could be found in the animals that were 14 days of age. The activity of cathepsin B and D in the intestinal mucosa showed a tendency to increase with age, and for all ages the activity in the distal part was higher than in the proximal part. The results showed that the small intestine in guinea pigs at birth is capable of macromolecular uptake and transfer into the circulation. This ability decreased with age eventually leading to intestinal closure after 1 week. The histological findings implied that intestinal closure was a consequence of a replacement of fetal absorptive cells with adult cells lacking this ability.     

新生儿肠动力影响因素分析

目的从病理角度分析新生儿期非巨结肠性动力性肠梗阻的发病机制,以指导临床,避免不必要的手术。方法收集本院2005年1月至2010年1月新生儿期非巨结肠动力性肠梗阻病例32例,均经保守治疗无效后行手术探查,其中30例行回肠造瘘术,2例行横结肠造瘘术,取造瘘处肠管石蜡切片为实验第一组;以上32例患儿均于3个月后返回本院行封瘘术,取封瘘术中同段肠管石蜡切片为实验第二组;取10例同日龄同段正常肠管石蜡切片做对照组。三组石蜡切片分别行HE染色,分别对CD3、CD117行免疫组化检测及凋亡（Tunnel）检测。结果HE染色光镜下观察第二组较第一组黏膜及肌问神经节细胞数量增多,体积增大,光镜下观察肠壁肌纤维未见异常;CD3于实验组及对照组神经节周均未见表达;CD117第二组较第一组及对照组表达增多,实验组及对照组Tunnel凋亡实验见神经节周无表达。结论肠神经节周围炎症反应及肠神经节凋亡这两个影响年长儿肠动力的因素指标在新生儿动力性肠梗阻中并不常见;Cajal细胞发育异常及神经节细胞成熟度可能是新生儿肠动力异常的重要原因。     

Different expression of surfactant protein B mature peptide and proprotein at 21 weeks'' gestation in human fetal pulmonary epithelial cells

AIM: The aim of this study is to evaluate the maturation of pulmonary epithelial cells in human fetal lungs at 21 weeks' gestation. METHODS: Eight fetuses at 21 weeks' gestation were evaluated. The maturation of pulmonary epithelial cells was assessed by immunohistochemical examination for surfactant proteins and by electron microscopy. RESULTS: Surfactant protein B mature peptide was detected slightly in the epithelial lining of the bronchioles, but was totally absent in the terminal airways. Surfactant protein B proprotein was clearly detected in the epithelial lining of both bronchioles and terminal airways. Transmission electron microscopy of terminal airway cells showed abundant glycogen granules and few intracellular organelles. CONCLUSIONS: The production of mature surfactant protein B in terminal airways is scarce at 21 weeks' gestation, which is associated with the immature mechanism of proprotein processing in the cytoplasm.     

Neonatal necrotizing enterocolitis, a disease of the immature intestinal mucosal barrier

Necrotizing enterocolitis (NEC) is an enigmatic process in that one single etiologic factor has been sought and not found. Epidemiologic studies suggest that immaturity of the host plays a very important role. This article reviews the intestinal host defense system and its immature nature early in life in animal models and humans and suggests that it is this immaturity, along with other factors, which allows for the proliferation and invasion of antigens and organism, and the subsequent development of NEC. Data are presented which support the efficacy of pharmacologic maturation of the intestinal barrier with growth factors, either prenatally or postnatally, to decrease the incidence of NEC or, potentially, to provide a more benign course for the disease.     

Radiographic diagnosis of meconium peritonitis. A report of 200 cases including six fetal cases

The radiographic findings of 200 cases of meconium peritonitis were analyzed; 194 cases were discovered in newborn infants and six cases in fetuses. The radiographic features in the newborn group could be categorized as pneumoperitoneum with intestinal obstruction (adhesions) and calcification (35 cases), intestinal obstruction with calcification (143 cases), intestinal obstruction with no radiographically visible calcification (5 cases), and calcification alone (11 cases). All six cases of the fetal group were diagnosed when the mothers had been hospitalized for polyhydramnios and a plaque-like or ring-like calcification showed up in the fetal abdomen on the plain radiograph. Meconium peritonitis is one of the few conditions that can be diagnosed before birth and is almost the only condition around the time of birth to produce calcification in the abdomen. Therefore, if there is any sign of polyhydramnios, radiographs or ultrasonograms of the maternal abdomen should be obtained to detect any calcification within the peritoneal cavity of the fetus. A simple experiment carried out in rats showed that it takes at least eight days after the meconium escapes into the peritoneal cavity for calcification in the meconium to be radiographically demonstrable.     

新生儿胎粪性肠梗阻21例诊治分析

目的：探讨新生儿胎粪性肠梗阻的诊疗经验,提高新生儿外科医师对该病的认识。方法回顾性分析本院2002年至2012年收治的21例胎粪性肠梗阻患儿临床资料。结果21例中,17例为单纯型,4例为复杂型;20例行稀释泛影葡胺灌肠造影,依靠该检查明确诊断5例,其中3例经非手术治疗痊愈。18例手术患儿中,14例单纯型行急诊手术治疗,其中10例采用肠管切开灌洗＋肠造瘘术（7例采用回肠双腔造瘘术,3例采用回肠Bishop-Koop造瘘术）,4例采用阑尾切除、肠内灌洗术（3例留置阑尾造瘘管）。4例复杂型均行急诊手术,2例采用回肠双腔造瘘术,2例术中放弃治疗。18例手术患儿中,16例术后恢复良好,10例造瘘患儿术后7～16周行造瘘还纳术。结论稀释泛影葡胺灌肠造影既能有效协助诊断,又能使少部分患儿治愈;Bishop-Koop造瘘术为首选术式;胎粪较易排出的患儿可选用阑尾切除、肠内灌洗术。     

Colonic stricture secondary to torsion of an ovarian cyst

Intestinal obstruction in the newborn is a potentially life-threatening complication. The most common causes are meconium plug, meconium ileus, intestinal atresia, intestinal malrotation, and Hirschprung's disease. We present an unusual case of intestinal obstruction caused by torsion of an ovarian cyst. The left fimbria and ovary swirled around the sigmoid colon, causing colonic stricture.     

Problems of ileostomy in necrotizing enterocolitis

Exteriorization of the intestine and resection of the gangrenous bowel are major therapeutic regimens for necrotizing enterocolitis (NEC). Ileostomy associated complications are well known, therefore the time of ileostomy closure is a matter for discussion. Between 1975 and 1992, 84 patients with NEC were treated surgically. Ileostomies were performed in 37 children (44%). Of these 37 neonates, 9 (7M, 2F) died. In the remaining 28 patients (16M, 12F) with a mean gestational age of 35.8 weeks and a mean birth weight of 2412 g, ileostomies were performed between the 2nd and 11th days after birth. On average, the stomies were in function for 91 days, and within this period the average weekly weight gain was 153 g. Nineteen patients of this group did not show any problems attributable to the ileostomy. In 9 patients (32%) complications occurred, requiring a preplanned closure of the stoma. Postinflammatory strictures of bowel were diagnosed in 9 patients and resection of the stenotic intestine was performed at the same time as stoma closure. In conclusion, an appropriate weight gain can be achieved in patients with an ileostomy with an adequate feeding regimen. In otherwise uncomplicated cases, ileostomy closure can be delayed by up to 10 weeks when simultaneous surgical correction of additional intestinal strictures is possible. In one-third of patients with an ileostomy, however, complications may occur and urge a preplanned closure of the stoma.     

A male newborn with colonic atresia and total colonic aganglionosis

A case of colonic atresia (CA) and aganglionosis is presented, which is probably the tenth in the English literature. The boy presented on day 3 of life with delayed passage of meconium, milk intolerance, and progressive abdominal distension. A barium enema study was complicated by barium peritonitis. Emergency peritoneal lavage was done and the intestinal obstruction was relieved by a proximal defunctioning ileostomy; type III CA (Grosfeld classification) was identified. The proximal atretic end was the blind-ending caecum and the distal atretic end commenced in the splenic area as a microcolon extending to the pelvis and replacing the normal colon. Total colonic aganglionosis (TCA) was confirmed by biopsies. This is the first case in the literature of TCA with CA documented before any attempts at colonic resection and anastomosis were made. This association highlights the recommendation for biopsy of the micro-colon and rectum when Type III CA (Grosfeld classification) is encountered in a newborn. The infant underwent a cholecystectomy and Duhamel-Martin operation at 14 months that was complicated by abdominal wound dehiscence; the ileostomy was closed at 22 months of age. Accepted: 8 April 1998     

Endocytosis and processing of protein by isolated villus and crypt cells of the mouse small intestine

A small but antigenically significant amount of intact food proteins is absorbed at the intestinal level. These proteins are transported by an endocytotic mechanism mostly in degraded form via the lysosomal pathway of the enterocytes, but those that escape lysosomal degradation appear to be a small fraction of potential food antigens that enter the body. To establish whether protein uptake and processing are similar between mature and immature enterocytes, villus and crypts cells were isolated from the small intestine of adult mice. In each fraction, we measured lysosomal cathepsin activities and cell binding, uptake, and degradation of horseradish peroxidase (HRP). The following results were observed: (a) mice exhibited an increasing villus-to-crypt gradient of cathepsins B and D; (b) binding, internalization and degradation of HRP were twice as high in crypt cells as in villus cells, indicating that the rate of endocytosis in crypt cells doubled; and (c) the percentage of intracellular intact and degraded HRP remained similar in both cell types, suggesting that lysosomal degradation was not the limiting step of endocytosis. Chloroquine and ammonia increased intracellular intact HRP, but monensin did not. These results suggest that intestinal villus and crypt cells do not transfer proteins at the same rate. This may have important biological consequences in physiopathological states in which the crypt/villus ratio is greatly increased.