Are the long-term results of the transanal pull-through equal to those of the transabdominal pull-through? A comparison of the 2 approaches for Hirschsprung disease

Purpose

The transanal endorectal pull-through (TERPT) is becoming the most popular procedure in the treatment of Hirschsprung disease (HD), but overstretching of the anal sphincters remains a critical issue that may impact the continence. This study examined the long-term outcome of TERPT versus conventional transabdominal (ABD) pull-through for HD.

Methods

Records of 41 patients more than 3 years old who underwent a pull-through for HD (TERPT, n = 20; ABD, n = 21) were reviewed, and their families were thoroughly interviewed and scored via a 15-item post-pull-through long-term outcome questionnaire. Patients were operated on between the years 1995 and 2003. During this time, our group transitioned from the ABD to the TERPT technique. Total scoring ranged from 0 to 40: 0 to 10, excellent; 11 to 20 good; 21 to 30 fair; 31 to 40 poor. A 2-tailed Student t test, analysis of covariance, as well as logistic and linear regression were used to analyze the collected data with confidence interval higher than 95%.

Results

Overall scores were similar. However, continence score was significantly better in the ABD group, and the stool pattern score was better in the TERPT group. A significant difference in age at interview between the 2 groups was noted; we therefore reanalyzed the data controlling for age, and this showed that age did not significantly affect the long-term scoring outcome between groups.

Conclusion

Our long-term study showed significantly better (2-fold) results regarding the continence score for the abdominal approach compared with the transanal pull-through. The stool pattern and enterocolitis scores were somewhat better for the TERPT group. These findings raise an important issue about the current surgical management of HD; however, more cases will need to be studied before a definitive conclusion can be drawn.     

Mutational spectrum of PTS gene and in silico pathological assessment of a novel variant in Mexico

Background

Tetrahydrobiopterin (BH4) is the cofactor for 6-pyruvoyl-tetrahydropterin synthase (PTPS); it is involved in BH4 biosynthesis and is encoded by PTS gene. Its deficiency (PTPSD) is characterized by hyperphenylalaninemia (HPA) and deficit in central monoamine neurotransmitters. We describe the clinical and mutational spectrum of five patients with PTPSD, from four unrelated Mexican families. All patients had symptomatic diagnosis and presented severe early neurological manifestations and HPA.

隐源性多灶性溃疡狭窄性小肠炎临床特征分析

目的　分析隐源性多灶性溃疡狭窄性小肠炎（CMUSE）临床特征,为临床诊治提供参考。方法　结合首都医科大学附属北京世纪坛医院2012年2月收治的1例CMUSE病例,检索中英文数据库,收集确诊或疑诊为CMUSE的个案报道,并对病例的一般资料、临床表现、实验室检查、影像学检查、内镜检查、病理检查、治疗方法与转归进行总结分析。结果　共收集22例患者,确诊18例,疑诊4例;男10例,女12例;中位年龄为32岁,自发病至确诊的中位时间为3年。常见的临床表现有腹痛（20例）,腹胀（10例）,恶心、呕吐（8例）,便血、黑便（7例）等;实验室检查低清蛋白血症12例,便隐血试验阳性11例;11例行小肠镜检查,9例行胶囊内镜检查,8例行小肠气钡双重对比造影,均可见阳性改变;12例行手术治疗,7例术后复发;12例行糖皮质激素治疗,8例病情缓解,4例无效;1例英夫利昔单抗治疗有效。结论　CMUSE是一种罕见的、病因不明的疾病,小肠多发浅表溃疡和肠腔狭窄是其典型表现。胶囊内镜、双气囊小肠镜对该疾病的诊断有重要意义,激素为其一线治疗,内镜下球囊扩张术开始用于治疗,其他治疗有营养支持、外科手术等。     

肠三叶因子对新生鼠NEC模型PI3K和caspase-3/9的影响

目的 利用PI3K的特异性抑制剂Wortmannin阻断PI3K/Akt细胞信号转导通路,观察ITF对新生鼠NEC模型caspase-3及caspase-9水平的影响,探讨ITF对NEC的保护作用机制.方法 建立NEC模型,对新生一日龄Wistar大鼠予100%氮气,1 min后放4℃冷环境中持续10min,每日2次,随后放回自制的保温箱内人工喂养,第四天处死,取肠组织待检.新生鼠50只随机分为5组,每组10只,A组为NEC模型后予以腹腔注射生理盐水0.2 ml;B组NEC模型后予以腹腔注射ITF0.2 mg;C组为NEC模型后腹腔内注射wortmannin(0.1 mg/kg);D组为NEC模型后腹腔内注射ITF+wortmannin;E组为正常对照组.取近回盲部1～2 cm肠道组织固定包埋、切片、HE染色做病理学检查,其他肠道组织制备组织匀浆取上清液应用ELISA试剂盒检测PI3K的含量及用分光光度法检测caspase-3/9的活性.结果 病理切片显示A组HE染色见肠壁损伤轻重不一,可见全肠黏膜绒毛坏死,病理评分中位积分3分;B组病变明显减轻,肠上皮细胞少量脱落,顶端绒毛坏死,病理评分中位积分1分;C、D组病理评分中位积分3分.A组组织匀浆中PI3K的含量(pg/ml)较E组略升高(P<0.05),与D组差异无统计学意义(P>0.05);B组PI3K表达水平较其他组显著升高(P<0.01);C组与E组比较显著降低,差异有统计学意义(P<0.01).Caspase-3及caspase-9活性在A组较B、E组明显升高,差异有统计学意义(P<0.01),C组更加明显升高(P<0.01),A、D组及B、E组之间,差异无统计学意义(P>0.05).结论 通过腹腔注射ITF可以减轻NEC后的肠道炎症反应,ITF有可能为治疗NEC提供新的方法 ;PI3K/Akt细胞信号转导通路参与了NEC发病过程,并起着信号转导作用.而ITF可能是通过激活PI3K/Akt信号转导途径来下调caspase-3/9的水平,从而保护新生Wistar大鼠NEC模型肠道损伤.     

肠三叶因子对新生鼠NEC模型PI3K和caspase-3/9的影响

Objective To study the effects of ITF on PI3K (phosphatidylinositol 3-kinase) and caspases-3/9 (cysteinyl aspartate-specific protea-ses) in neonatal rat NEC model. Methods NEC model of neonatal rats was established. Asphyxia stress was accomplished by exposure to l00% nitrogen for 60s, followed by exposure to coldness (4 ℃ ) for 10 min twice daily. Neonatal rats were fed formula (200 kcal/kg/day) every 3 h via an gavage tube. The feeding volume began at 0. 1 cc every 3 h and was increased incrementally. This procedure is done once everyday and continued for 3 days. On the 4th day,all the subjects were sacrificed. Fifty neonatal rats were randomized into five groups: A) NEC + NS0. 2mi, (B) NEC + ITF 0. 2 mg, (C) NEC(Wortmannin (0. 1 mg/kg) (D) NEC + ITF 0. 2 mg + Wortmannin (0. 1 mg/kg), (E) control. The intestinal tissue located at the boundary of ileum and cecum was sampled for histology. The remaining intestinal tissue was homogenized. After the homogenate was centrifuged,supernatants were used to assay PI3K and Caspase-3 and caspase-9. Results The pathological lesions showed that intestinal necrosis was severe in group A、C and D, which was graded as 3points. They were significantly decreased in group B,which was graded 1 point. The level of PI3K(pg/ml)in Group A was higher than those in group E (P<0. 05), the latter had difference with those in group D(P>0. 05). The level of PI3K(pg/ml) were the strongest in group B and were lowest in group C. The activity of Caspase-3 and Caspase-9 were significantly increased in group A compared to those in group B and E (P<0. 01 ),and was significantly increased in Group C(P<0. 01 ). Caspase-3 and Caspase-9 levels of group A and D,group B and E showed no significant difference(P>0. 05). Conclusions Intestinal inflammation was ameliorated by intraperitoneal ITF. ITF may provide a new therapy for NEC; PI3K/Akt signal pathways might play important roles in signal transduction during NEC;ITF may protect the intestinal injury of neonatal Wistar rat by activation of PI3K/Akt signal transduction pathway, and down regulation of caspase-9.     

新生鼠坏死性小肠结肠炎肠组织一氧化氮和一氧化氮合酶变化

目的动态观察新生大鼠坏死性小肠结肠炎(NEC)发病过程中肠组织一氧化氮(NO)含量、一氧化氮合酶(NOS)活性变化及其与肠损伤关系,为进一步阐明NEC发病机制、寻找新的治疗方法提供实验依据。方法40只新生SD大鼠按简单随机法分成模型组(M)32只,对照组(C)8只。模型组大鼠出生48h开始鼠配方奶人工喂养,并予以3次缺氧和冷刺激建立NEC模型,缺氧冷刺激开始后24h(M24)、48h(M48)、72h(造模结束,M72)及最后一次缺氧和冷刺激后24h(M96)分别空腹断头处死8只;实验结束时处死对照组大鼠,分别留取肠管进行肠组织损伤评分、肠组织中NO含量和NOS活性检测。结果建模后,模型组出现腹泻、腹胀、萎靡、活动减少。M24、M48、M72、M96及对照组肠组织损伤评分分别为(1.25±0.56)、(1.46±0.31)、(2.79±0.40)、(3.33±0.59)和(0.08±0.15)分,肠组织NO含量分别为(2.07±0.38)、(2.88±0.32)、(3.09±0.40)、(3.98±1.15)和(0.94±0.44)μmol/gprot,总NOS活性分别为(2.21±0.42)、(2.77±0...     

Long-term clinical outcome in patients with Hirschsprung's disease and associated Down's syndrome

Background/Purpose

Down's syndrome (DS) is the most common chromosomal abnormality associated with Hirschsprung's disease (HD). The purpose of this study was to review the long-term clinical outcome in patients with HD and associated DS.

Methods

Between 1975 and 2003, 39 (15%) of the 259 patients with HD had been associated with DS. Follow-up was carried out by means of examination of patient's records and personal/telephone interviews with the patient's parents or guardians.

Results

Twenty-six (67%) patients presented in the newborn period and 13 (33%) after the neonatal period. Twenty-eight (72%) patients had rectosigmoid HD, 10 long segment, and 1 total colonic aganglionosis. Thirty-two patients had other associated anomalies, 24 of these having cardiac anomalies. Definitive pull-through operation was performed in 33 patients. Parents of 1 child refused surgical intervention and parents of 2 children decided against pull-through operation after colostomy. Three children died before pull through. Thirteen patients had one or more episodes of enterocolitis after pull-through operation. At the time of follow-up (6 months to 28 years), 3 patients were found to have reverted to stoma because of poor bowel control or recurrent enterocolitis. Of the remaining 30 patients, 3 were lost to follow-up and 4 were too young to be assessed for bowel control. Assessment of bowel function in 23 patients revealed normal control in 8 (4 of these soiled for 6-17 years after definitive surgery), soiling in 8, and constipation requiring enemas or laxatives in 7.

Conclusions

The vast majority of patients with HD associated with DS continue to have disturbances of bowel function after definitive pull-through operation.     

新生鼠坏死性小肠结肠炎动物模型建立及评价

目的 利用新生SD大鼠建立缺氧、冷刺激、鼠乳代用品人工喂养等多因素造成的新生鼠坏死性小肠结肠炎动物模型,并对其进行评价.方法 按析因设计,32只新生SD大鼠出生48 h开始随机分成4组,每组动物各8只.A组采用鼠乳代用品人工喂养,并给予100%氮气缺氧90 s,4 ℃冷刺激10 min,每天2次,连续3 d;B组为单纯采用鼠乳代用品人工喂养,未进行缺氧冷刺激;C组采用鼠乳喂养,给予同样的缺氧冷刺激;D组为正常对照组,采用鼠乳喂养,未进行缺氧冷刺激.HE染色后光镜下观察回盲部近端肠组织形态学改变,采用肠损伤病理评分进行评价,组织学评分≥2分确定为坏死性小肠结肠炎(NEC).结果 A、B、C组新生SD大鼠相继出现腹泻、腹胀、萎靡、活动减少,生长减慢,A组程度最为严重.A、B、C、D 4组肠损伤病理评分(±s)分别为(3.25±0.89)分、(2.63±0.92)分、(1.13±1.36)分、(0.25±0.46)分,各组间差异均有统计学意义(H=19.30,P＜0.01).NEC发病率分别为100%、87.5%、37.5%和0.喂养方式和缺氧冷刺激为肠组织损伤病理评分值影响因素,两因素间无明显交互作用.结论 新生鼠在剔除鼠乳喂养,改用鼠乳代用品人工喂养的前提下,经过连续多次的缺氧冷刺激后,诱导的新生鼠坏死性小肠结肠炎模型与人类新生儿NEC临床特征、病理改变相一致,是一种理想的新生儿坏死性小肠结肠炎动物模型.     

New insights into the pathogenesis of Hirschsprung’s associated enterocolitis

The management of Hirschsprung’s disease (HD) has made dramatic strides over the last 20 years. Research into the embryological development and migration of ganglion cell has enabled a greater understanding of the pathogenesis of the disease. Coupled with new techniques in surgery, such as laparoscopy-assisted pull-through and the transanal pull-through, this knowledge has led to improved outcomes for children with HD. However, although our appreciation of Hirschsprung’s associated enterocolitis and its aetiology has increased, there are continued references in the literature to a multitude of theories of pathogenesis. The purpose of this review is to delineate the theories and demonstrate the evidence supporting or otherwise contradicting each other. An erratum to this article can be found at     

35. Intestinale Perforationen im Neugeborenenalter

Zusammenfassung Von 1976 bis Matz 1985 wurden 16 Neugeborene mit gastrointestinalen Perforationen behandelt. Häufigster Perforationsort war der Ileocoecalbereich, häufigste Perforationsursachen die Obstruktion, nekrotisierende Enterocolitis und sog. spontane (ischamische) Perforationen. Das operative Vorgehen richtete sich nach Lokalisation und Ursache der Perforation sowie dem Allgemeinzustand des Kindes. Von den 16 Kindern verstarben 7 (44%) in der Sepsis und deren Folgekomplikationen.