功能性便秘的临床研究进展

功能性便秘是一种常见消化道疾病,严重影响人们生活质量.功能性便秘的发病与精神心理因素、激素、排便动力学异常等多因素有关.影像学、肛门直肠测压等多种方法可诊断该病,药物、生物反馈、心理等多途径治疗有一定疗效.本文就功能性便秘的病因、诊断、治疗等临床研究新进展作一综述.     

不同型别的功能性便秘患儿肛门直肠测压对照研究

目的探讨功能性便秘（FC）患儿与健康儿童肛门直肠动力学差异,为其临床分型诊断及治疗提供依据。方法采用功能性胃肠病罗马Ⅲ诊断标准,收集2008年1月至2009年1月在第四军医大学唐都医院儿科门诊及住院的FC患儿为FC组。选取同期无消化系统症状,平日排便正常的健康儿童为正常对照组。采用不透光X线硫酸钡条测定结肠传输指数（TI）,依据TI将FC组分为出口梗阻型（OOC）亚组、慢传输型（STC）亚组和混合型（MIX）亚组。通过肛门直肠测压法分析FC各亚组与正常对照组肛门直肠动力学差异。结果研究期间FC组纳入25例,其中STC亚组10例,OOC亚组15例,未发现MIX患儿;正常对照组纳入10名。FC组与正常对照组肛门括约肌静息压差异无统计学意义（P〉0.05）。STC亚组肛门括约肌最大收缩压与正常对照组差异无统计学意义（P〉0.05）,OOC亚组肛门括约肌最大收缩压显著高于正常对照组及STC亚组（P〈0.05）。FC组直肠最低敏感量及最大耐受量均显著高于正常对照组（P均〈0.05）。STC亚组与OOC亚组直肠最低敏感量及最大耐受量差异均无统计学意义（P均〉0.05）。结论FC患儿存在明显的肛门直肠动力和感觉异常;OOC和STC患儿的肛门直肠动力学存在差异。肛门直肠测压检查对协助诊断FC有一定价值。     

Predictive Capability of Anorectal Physiologic Tests for Unfavorable Outcomes Following Biofeedback Therapy in Dyssynergic Defecation

The purpose of this study is to evaluate the predictive capability of anorectal physiologic tests for unfavorable outcomes prior to the initiation of biofeedback therapy in patients with dyssynergic defecation. We analyzed a total of 80 consecutive patients who received biofeedback therapy for chronic idiopathic functional constipation with dyssynergic defecation. After classifying the patients into two groups (responders and non-responders), univariate and multivariate analyses were performed to determine the predictors associated with the responsiveness to biofeedback therapy. Of the 80 patients, 63 (78.7%) responded to biofeedback therapy and 17 (21.3%) did not. On univariate analysis, the inability to evacuate an intrarectal balloon (P=0.028), higher rectal volume for first, urgent, and maximal sensation (P=0.023, P=0.008, P=0.007, respectively), and increased anorectal angle during squeeze (P=0.020) were associated with poor outcomes. On multivariate analysis, the inability to evacuate an intrarectal balloon (P=0.018) and increased anorectal angle during squeeze (P=0.029) were both found to be independently associated with a lack of response to biofeedback therapy. Our data show that the two anorectal physiologic test factors are associated with poor response to biofeedback therapy for patients with dyssynergic defecation. These findings may assist physicians in predicting the responsiveness to therapy for this patient population.     

Anorectal dysfunction in systemic sclerosis.

This study was aimed to evaluate the anorectal dysfunction in systemic sclerosis (SSc) and propose the clinical significance of anorectal manometry in patients with SSc. Seven patients with SSc were evaluated with manometry for anorectal function and an additional 11 normal subjects were collected as a control group. The study group underwent esophageal manometry as well and the correlation between the degree of anorectal and esophageal dysfunction was evaluated. Patients showed a lower tolerance for balloon distention of the rectum than controls (minimal sensory volume and urgency volume, P < 0.05). The resting and squeezing pressure of the anal sphincter and the functional length of the anal canal showed no significant difference in these two groups. Rectoanal inhibitory reflex was absent in one (14%) and diminished in two (29%) of seven patients with SSc. SSc patients also showed abnormal esophageal manometry findings, notably decreased LES pressure and body amplitude of distal 2/3 esophagus. The comparison between manometric profiles of anorectum and esophagus showed no significant correlation by statistical analysis. In conclusion, our data could suggest that anorectal function may be impaired in patients with SSc which could reflect the involvement of the anorectum by the disease, and that anorectal manometric studies can be useful to detect such dysfunction in patients with SSc, even before clinical symptoms.     

腹腔镜下改良Soave巨结肠根治术后排便功能评价

目的评价婴幼儿先天性巨结肠行腹腔镜下改良Soave巨结肠根治术后的排便控制功能。方法2003年2月￣2006年3月行腹腔镜下改良Soave巨结肠根治术25例,年龄为3.5个月～4岁,平均年龄13.1个月。术后定期随访,随访时间为1～4年,平均2.5年。对患儿的排便控制能力、便秘、小肠结肠炎的发生率进行评价,术后1年行钡剂灌肠及直肠肛管测压检查。结果获访21例,根据李氏评分标准,排便功能优者(6￣5分)14例,良者(4￣3分)7例,无"差"者病例,便秘1例,小肠结肠炎2例。钡剂灌肠检查发现结肠扩张段、痉挛段消失,肛管直肠角度正常。直肠肛管测压检查均未出现直肠肛管抑制性反射。结论应用腹腔镜下改良Soave巨结肠根治术治疗婴幼儿先天性巨结肠,术后可获得良好的排便控制功能。     

Malignant degeneration of presacral teratoma in the Currarino anomaly

The autosomal dominant Currarino anomaly (CA) comprises a presacral mass, partial sacral agenesis, and anorectal defects. Chronic constipation in childhood related to anorectal defects is the most common presenting symptom and hemisacrum the most frequent malformation. The presacral mass may be an anterior meningomyelocele, teratoma, hamartoma, dermoid cyst, neuroenteric cyst, or a combination of these. Sepsis and meningitis are frequent serious problems related to the anterior meningomyelocele, whilst malignant transformation of presacral teratoma is a rare, severe complication in CA. Here, we report on a three-generation family segregating the CA, presenting with anorectal defects, severe constipation, and sacral involvement in affected relatives. Teratoma was the most frequent component of the presacral mass. In this kindred a 22-year-old man died of a neuroendocrine tumor, probably related to malignant change in a presacral teratoma. A novel mutation in HLXB9 consisting of a 24-bp deletion and insertion of 2-bp into exon 1, was identified in all patients and in also three asymptomatic members of this family. Anterior meningomyelocele is the most frequently reported component of the presacral masses in CA; however, presacral teratomas carry an inherent risk for malignancy that must be considered in the counseling, surgical treatment options, and follow-up of CA patients.     

Currarino syndrome with pelvic neuroendocrine tumor diagnosed by post-mortem genetic analysis of tissue specimens

Currarino syndrome (CS) is an autosomal dominant disorder of embryonic development characterized by the triad of anorectal abnormalities, partial sacral agenesis, and presacral mass. Mutations of the HLXB9 gene have been identified in most CS cases, but a precise genotype-phenotype correlation has not been described so far. We report the clinical case of a 44-year-old Caucasian woman with malignant neuroendocrine transformation of a pre-sacrococcygeal mass combined with bicornuate uterus, dermoid cyst of the ovaries, and chronic constipation. After the patient died, a sacrococcygeal malformation and anterior meningocele were diagnosed in her 22-year-old son. CS diagnosis was then retrospectively confirmed by molecular analysis of normal and pathological tissue specimens of the mother, with identification of a HLXB9 mutation (c.727C>T; p.R243W). CS should be considered, and genetic counseling recommended, to all patients with presacral masses. Since malignant neuroendocrine transformation of presacral mass in CS is a possible complication, even thought rare, close follow up in these patients is advisable.     

Hirschsprung's disease: an appraisal of histochemically demonstrated acetylcholinesterase activity in suction rectal biopsy specimens as an aid to diagnosis

Suction rectal biopsy specimens, from a series of 168 infants and children with constipation and other gastrointestinal problems, were stained with a sensitive acetylcholinesterase method, and the results were compared with routine histology, radiology, anorectal manometry, and the final diagnosis. In all cases of Hirschsprung's disease, there was an increase in numbers and sizes of cholinergic nerves in the lamina propria and muscularis mucosae. No false-positive or false-negative results were found. The test was found to be more reliable and consistent than other methods available.     

Rearrangement of chromosome 15 in the region q11.2→q12 in an individual with obesity syndrome and her normal mother

Rearrangements of the proximal long arm of chromosome 15 have been found in most patients with the Prader-Willi syndrome (PWS) and in some with Angelman syndrome. We present an individual with syndromic obesity and her normal mother, who both have an abnormal chromosome 15. The proposita is a 26-year-old woman with marked obesity, acanthosis nigricans, short fingers, and severe cone degeneration of the retina. She has high plasma insulin levels, hypothyroidism, and an empty sella on CT scan. High-resolution chromosome banding demonstrated an increase in band 15q12. Further analysis showed the same abnormal 15 in her normal mother but not in her normal sister. This case and recent reports in the literature indicate that duplications of chromosome 15q in the PWS region may be associated with a syndrome of obesity, acanthosis nigricans, empty sella, and rodcore dystrophy as well as with a normal phenotype. Whether normal individuals with such a duplication carry increased risk of having offspring with an obesity syndrome is yet to be determined.     

Rearrangement of chromosome 15 in the region q11.2----q12 in an individual with obesity syndrome and her normal mother

Rearrangement of the proximal long arm of chromosome 15 have been found in most patients with the Prader-Willi syndrome (PWS) and in some with Angelman syndrome. We present an individual with syndromic obesity and her normal mother, who both have an abnormal chromosome 15. The proposita is a 26-year-old women with marked obesity, acanthosis, nigricans, short fingers, and severe cone degeneration of the retina. She has high plasma insulin levels, hypothyroidism, and an empty sella on CT scan. High-resolution chromosome banding demonstrated an increase in band 15q12. Further analysis showed the same abnormal 15 in her normal mother but not in her normal sister. This case and recent reports in the literature indicate that duplication of chromosome 15q in the PWS region may be associated with a syndrome of obesity, acanthosis nigricans, empty sella, and rodcore dystrophy as well as with a normal phenotype. Whether normal individuals with such a duplication carry increased risk of having offspring with an obesity syndrome is yet to be determined.     

Herpes simplex virus proctitis in homosexual men. Clinical, sigmoidoscopic, and histopathological features

Acute herpes simplex virus (HSV) infection was detected in 23 of 102 consecutively examined, sexually active male homosexuals who presented with anorectal pain, discharge, tenesmus, or hematochezia, as compared with 3 of 75 homosexual men without gastrointestinal symptoms (P less than 0.01). Findings that were significantly more frequent in men with HSV proctitis than in men with proctitis due to other infectious causes included fever (48 per cent), difficulty in urinating (48 per cent), sacral paresthesias (26 per cent), inguinal lymphadenopathy (57 per cent), severe anorectal pain (100 per cent), tenesmus (100 per cent), constipation (78 per cent), perianal ulcerations (70 per cent), and the presence of diffuse ulcerative or discrete vesicular or pustular lesions in the distal 5 cm of the rectum (50 per cent). Serologic evidence indicated that 85 per cent of the men with symptomatic HSV proctitis were having their first episode of HSV-2 infection. The diagnosis of HSV proctitis is suggested by the presence of severe anorectal pain, difficulty in urinating, sacral paresthesias or pain, and diffuse ulceration of the distal rectal mucosa.     

金梦贤-华佗消痔灵之方证分析

华佗消痔灵是天津市名老中医金梦贤教授根据多年临床经验,自拟的治疗多种中医肛肠疾病常用方剂之一。尤其对肛门肿痛,痔疮便血,大便秘结,脱肛不收等临床症状的治疗效果显著。本文就金梦贤-华佗消痔灵的组方、方解及临床效果进行逐一探讨。     

小麦纤维素治疗妊娠晚期妇女功能性便秘的30例疗效观察

目的观察小麦纤维素（商品名：非比麸）治疗妊娠晚期合并功能性便秘患者的疗效及安全性。方法采用自身前后对照的前瞻性研究方法,按标准入选30例妊娠晚期合并功能性便秘的患者,给予连续口服小麦纤维素治疗2周,记录服药前后便秘症状和大便性状的变化情况,并进行评分,比较疗效。结果受试患者口服小麦纤维素治疗后,排便困难、排便不尽感、粪便性状和排便的频率均有明显改善,与治疗前比较差异有统计学意义（P〈0.05）,总有效率为90%（27/30）,服药期间未发现明显的不良反应。结论小麦纤维素治疗妊娠晚期合并功能性便秘妇女疗效安全、有效。     

Enteric neuropathology of the terminal ileum in patients with intractable slow-transit constipation

Slow-transit constipation is usually considered a colonic motor disorder. However, there is some evidence that abnormalities may be present in locations other than the colon. In particular, several studies have reported abnormal motor activity of the small bowel in these patients. We evaluated the neuropathological aspects of the terminal ileum in patients with slow-transit constipation to see whether abnormalities are present that may explain an abnormal motility of the small intestine. Specimens of the terminal ileum were obtained from 16 female patients (age range, 42-76 years) with slow-transit constipation undergoing surgery for intractable symptoms. Fifteen age- and sex-matched controls were used for comparison. Histologic and immunohistochemical evaluation of the myenteric plexus and the smooth muscle of the proximal ileal resection margin was carried out by means of hematoxylin and eosin, trichrome and periodic acid-Schiff stain, neuron-specific enolase, S-100, CD117, CD34, anti-alpha-actin, desmin, and vimentin antibodies. The patient group displayed a significantly reduced number of glial cells, compared with controls, in both the submucosal and the myenteric plexus. Only 1 of the 3 populations of interstitial cells of Cajal (that associated with the deep muscular plexus) was decreased in patients. No differences were found between patients and controls concerning ganglia neurons, fibroblast-like cells, enteric neurons, apoptotic phenomena, and smooth muscle. Patients with slow-transit constipation display neuropathological abnormalities of the terminal ileum to a lesser extent than those we previously found in the colon, which might explain the abnormal motor aspects sometimes found in these patients.     

先天性巨结肠Ⅰ期经肛门术后肛肠功能评估

目的探讨先天性巨结肠I期经肛门术后患儿的排便功能、结肠和肛门括约肌功能。方法对I期经肛门术后5～9年的89例先天性巨结肠患儿进行排便功能问卷调查,同时对来院随访的58例患儿进行肛门直肠测压和钡灌肠检查,评价其术后肛肠功能。结果 89例先天性巨结肠术后患儿中,72例排便功能良好,排便次数1～2次/d,仅6例3～4次/d,7例稀便时污便,1例经常污便;3例便秘。89例患儿均有便意无便失禁。直肠肛门测压结果：2例患儿术后直肠肛管反射弱阳性;污便组肛管静息压较无症状组及对照组显著降低[（29.4±3.2）mmHg vs（40.2±5.1）mmHg vs（36.9±2.6）mmHg,P〈0.05,P〈0.05）],而直肠静息压显著增高[（65.9±7.2）mmHg vs（25.7±4.1）mmHg vs（11.0±1.3）mmHg,P〈0.05,P〈0.05）];污便组肛管收缩压明显低于无症状组及对照组[（183.5±15.6）mmHg vs（210.2±18.3）mmHg vs（200.6±13.8）mmHg,P〈0.01];而持续缩榨时间三组间差异无统计学意义。便秘组与其他三组间比较差异无统计学意义,且有1例出现括约肌反常运动。钡灌肠结果：先天性巨结肠术后所有患儿的结肠形态恢复良好,结肠框基本正常,未见到明显的痉挛段、移行段和扩张段,乙状结肠迂曲减少或消失,与术中切除肠管长度相符。先天性巨结肠术后所有病例的直肠肛管角比对照组明显增大（121.6°±14.2°vs 82.0°±11.4°,P〈0.01）,污便组又较便秘组及无症状组明显增大（138.4°±16.8°vs 106.3°±13.8°vs 110.6°±15.2°,P〈0.05）。结论先天性巨结肠I期经肛门术后患儿多数排便功能良好,结肠形态及肛门括约肌功能恢复良好,少数患儿污便可能与拖出结肠储便功能代偿不全、乙状结肠迂曲减少或消失、肛门括约肌损伤等有关。     

VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5

We have identified an ethylnitrosourea (ENU)-induced recessive mouse mutation (Vcc) with a pleiotropic phenotype that includes cardiac, tracheoesophageal, anorectal, anteroposterior patterning defects, exomphalos, hindlimb hypoplasia, a presacral mass, renal and palatal agenesis, and pulmonary hypoplasia. It results from a C470R mutation in the proprotein convertase PCSK5 (PC5/6). Compound mutants (Pcsk5(Vcc/null)) completely recapitulate the Pcsk5(Vcc/Vcc) phenotype, as does an epiblast-specific conditional deletion of Pcsk5. The C470R mutation ablates a disulfide bond in the P domain, and blocks export from the endoplasmic reticulum and proprotein convertase activity. We show that GDF11 is cleaved and activated by PCSK5A, but not by PCSK5A-C470R, and that Gdf11-deficient embryos, in addition to having anteroposterior patterning defects and renal and palatal agenesis, also have a presacral mass, anorectal malformation, and exomphalos. Pcsk5 mutation results in abnormal expression of several paralogous Hox genes (Hoxa, Hoxc, and Hoxd), and of Mnx1 (Hlxb9). These include known Gdf11 targets, and are necessary for caudal embryo development. We identified nonsynonymous mutations in PCSK5 in patients with VACTERL (vertebral, anorectal, cardiac, tracheoesophageal, renal, limb malformation OMIM 192350) and caudal regression syndrome, the phenotypic features of which resemble the mouse mutation. We propose that Pcsk5, at least in part via GDF11, coordinately regulates caudal Hox paralogs, to control anteroposterior patterning, nephrogenesis, skeletal, and anorectal development.     

Anorectal melanomas do not harbour the Kaposi sarcoma-associated human herpesvirus type 8 DNA

Anorectal melanomas are similar to cutaneous melanomas with regard to the mode of spread and to the immunophenotype. When compared with patients with cutaneous melanoma, those suffering from anorectal melanoma have a much worse outcome. The etiology of anorectal melanomas is as yet completely unknown. For anatomical reasons, ultra-violet (UV-B) radiation can not cause anorectal melanomas as in cutaneous tumours, that are associated with exposure of the skin to UV-B radiation. As the cytokine interleukin-6 (IL-6) is known to stimulate melanoma tumour cell proliferation and a functional homologue of human IL-6 has been identified recently in the HHV-8 genome, this tumorigenic virus might be involved in the pathogenesis of anorectal melanomas. Twelve formalin fixed and paraffin embedded primary anorectal melanomas from seven female and five male patients with a mean age at diagnosis of 71 years (range 38-88 years) were investigated for the presence of HHV-8 DNA. Using a specific and highly sensitive polymerase chain reaction protocol, this tumorigenic gamma-herpesvirus was not detectable in any tumour. This data indicates that HHV-8 is not involved in the development of anorectal melanomas.     

Autoimmunity in systemic lupus erythematosus: integrating genes and biology

Susceptibility to the autoimmune phenotype of systemic lupus erythematosus (SLE) is heritable. Linkage analysis and recent advances in the field of single nucleotide polymorphisms (SNPs) have resulted in the identification of several genetic loci and functional allelic variants of signaling proteins which have become the mainstay of understanding disease susceptibility and exploring the basis of autoimmunity in SLE. However, genetic heterogeneity and possible epistatic interactions among genetic elements have precluded replication of these findings in multiple population groups and thus complicated their interpretation. In this regard, the discovery that a plethora of normal signaling proteins are expressed in abnormal amounts in immune cells from patients with SLE has gained significance. Thus, the key to precise elucidation of the pathologic basis of autoimmunity in SLE lies in tying genetics and disease biology. This review highlights recent discoveries of important functional genetic variants and altered expression of normal signaling proteins that network together to disrupt peripheral tolerance and initiate the autoimmune process in SLE.