Prokinetic agents for lower gastrointestinal motility disorders

Prokinetic agents are currently being investigated as potential therapies for motility disorders of the lower gastrointestinal tract. Cholinergic agonists such as bethanechol are known to improve postoperative ileus but are limited because of side effects. Dopamine antagonists such as domperidone appear to have maximal prokinetic effect in the proximal gastrointestinal tract and are effective for such conditions as gastroparesis and gastroesophageal reflux, but they appear to have little physiologic effect in the colon or in colonic motility disorders. Naloxone, an opioid antagonist, appears to hold promise in patients with irritable bowel syndrome, small intestinal pseudo-obstruction, and constipation. Erythromycin exerts its prokinetic effect by acting as a motilin agonist; it has been used in the treatment of diabetic gastroparesis and appears to improve symptoms of colonic pseudoobstruction and postoperative ileus. Metoclopramide, a combined cholinergic agonist and dopamine antagonist, is currently used exclusively for proximal motility dysfunction. Cisapride appears to hold the most promise for patients with colonie motility disorders. In patients with postoperative ileus, cisapride is associated with an increased return of bowel function compared with placebo. In patients with chronic constipation, cisapride increases stool frequency and decreases laxative abuse in both adults and children. Hopefully, as an understanding of gastrointestinal motility increases, effective prokinetic agents will be developed that will improve symptoms of patients with large bowel motility disorders and may also help to predict those patients who benefit from surgical management for constipation.     

Surgery for constipation

PURPOSE: Constipation is related to intestinal motility disorders (colonic inertia (CI)), pelvic floor disturbances (pelvic outlet obstruction), or a combination of both problems. This review summarizes the physiologic and pathophysiologic changes in patients with intractable constipation and gives an overview of surgical treatment options. RESULTS: Although subtotal colectomy with ileorectal anastomosis is the best surgery for CI, there are still approximately 10 percent of patients who will complain of pain and constipation. A completion proctectomy and an ileoanal pouch procedure may be a viable option in a highly select group of patients. In patients with megabowel, reported results are mixed. Subtotal colectomy, partial colectomy for megacolon, and the Duhamel procedure for megarectum have all been reported with variable results. In patients with an isolated distended sigmoid colon, sigmoid colectomy has achieved good results. Anorectal myectomy has not been proven to be successful in the long term. However, in patients with adult short segment Hirschsprung's disease, myectomy can be successful. Patients with pelvic outlet obstruction can be successfully treated with biofeedback. In a small group of patients with a rectocele or a third degree sigmoidocele, surgical intervention yields a high success rate. Division or resection of the puborectalis muscle is not recommended. In patients with a mixed pattern of CI and pelvic outlet obstruction, surgical intervention alone is often not successful. These patients achieve better results by conservative treatment of pelvic outlet obstruction, followed by a colectomy. CONCLUSION: Surgical intervention for patients with intractable constipation is rarely necessary. However, thorough preoperative physiologic testing is mandatory for a successful outcome.     

慢性便秘外科手术治疗原则

重点阐述慢性便秘外科手术治疗原则。慢传输型便秘的外科治疗指证是确诊结肠传输减慢,病程在3年以上并经内科治疗无效,患者强烈要求手术,无精神障碍,了解有无合并出口梗阻型便秘和先天性巨结肠。手术方式多采用全结肠切除术或者次全结肠切除术。直肠内脱垂的外科治疗指证是有严重直肠内脱垂症状,严格内科治疗无效。手术方式首先采用经肛门手术。直肠前突手术指证是有明显临床症状,前突超过3cm,局部有造影剂存留,需要手助排便。单纯直肠前突无论经肛门、经阴道入路的手术,疗效均较好。对于耻骨直肠肌痉挛,目前多采用扩肛术或生物反馈治疗。     

Classification and treatment of constipation]

Constipation is a common symptom affecting 2-27% of general population in Western countries. According to a population-based study on bowel habits in a Korean community, the prevalence was 16.5% for self-reported constipation and 9.2% for functional constipation. There is a broad range of causes for constipation. There are three subtypes in functional constipation, although overlap is not uncommon. Physiologic studies such as colonic transit test, anorectal manometry, balloon expulsion test, and defecography can be helpful in further evaluating and classifying functional constipation. Slow transit constipation is characterized by prolongation of transit time through- out the colon, caused by either myopathy or neuropathy. Functional defecation disorder is characterized as an inability to initiate defecation following the urge to do so, a feeling of incomplete evacuation, tenesmus, excessive straining or manual evacuation. Normal transit constipation is the most common subtype and characterized by constipation occurring in the presence of normal colonic transit time and normal defecatory function. It is important for clinicians to choose appropriate treatment for constipation which are most efficacious for the individual patient. Most patients with functional constipation respond to laxatives, but a small proportion may be resistant to this treatment. In patients with functional defecation disorder, biofeedback is helpful. Sacral nerve stimulation may be helpful in some patients with slow transit constipation. Patients who are resistant to all the conservative modalities may require surgical intervention. Extensive clinical and physiological preoperative assessment of patients with slow colonic transit time is essential before considering surgery, including an assessment of small bowel motility and identification of coexistent defecatory disorder.     

Partial colectomy and coloanal anastomosis for idiopathic megarectum and megacolon

Adult patients with an idiopathic megarectum or megacolon can experience severe constipation requiring surgical treatment. Some of these patients have a proximal colon of normal diameter, with dilatation involving only the left or distal colon and rectum. The results of partial colonic and rectal resection with coloanal anastomosis in such patients have been reviewed. Seven patients (two female and five male) underwent a coloanal anastomosis over a seven-year period. The median age at operation was 19 years, the mean age at onset of symptoms was five years, and the mean follow-up period was one year. Five patients experienced a return to normal bowel frequency with the loss of most symptoms. One patient has an ileostomy because of persistent constipation after the procedure. One subject died because of postoperative bleeding from the anastomosis and subsequent cardiac and respiratory complications. This operation may have a place in the treatment of severe constipation caused by idiopathic megarectum and megacolon, but careful preoperative motility studies and meticulous attention to operative technique are required for a good outcome.G.S. is supported by the British Council.M.A.K. is supported by the St. Mark's Research Foundation.No reprints are available.     

Radionuclide colon transit study in patients with idiopathic constipation

BACKGROUND/AIMS: Constipation is the most common digestive complaint. Radionuclide colon transit study is a useful tool for assessing the motility of the colon. In this study, we evaluate patients with idiopathic constipation using the radionuclide colon transit study. METHODOLOGY: We studied radionuclide colon transit in 23 patients with idiopathic constipation. Thirty healthy volunteers were included as a control. RESULTS: Overall, patients with idiopathic constipation usually had slow or normal colon transit. CONCLUSIONS: Our study suggested that the radionuclide colon transit study may be clinically useful in evaluating and assessing the efficacy of therapy in patients with idiopathic constipation.     

Melanosis coli

Melanosis coli was diagnosed histologically in colon biopsies of 45 patients with prolonged administration of anthraquinone laxatives. Colonoscopies performed for increased constipation, abdominal pains, or distention disclosed discoloration of the mucosa in only 14 patients. Radiographic studies revealed motility disorders of the colon. In several cases, a circular stenosis occurred at the junction of the colon and the sigmoid, simulating a tumor. Electron microscopy showed abnormalities of the absorptive epithelial cells. The lamina propria contained pigment-laden macrophages, plasma cells, and several nerve fibers in different stages of degeneration. The most striking changes of autonomic nerve elements occurred in patients with the most serious motility disorders.     

Intact colonic motor response to sudden awakening from sleep in patients with chronic idiopathic (slow-transit) constipation

PURPOSE: There are few data about the relationships between colonic motor behavior and higher brain functions, such as sleep. Previous studies were done in healthy subjects, and it is unknown whether patients with functional motor disorders of the colon behave differently. This study was designed to characterize colonic motor activity in patients with constipation, both during sleep and after sudden awakening, and to compare it with that of healthy subjects. Our working hypothesis was that patients with constipation would have an impaired response to sudden awakening. PATIENTS AND METHODS: Twelve chronically constipated women, 22 to 49 years old, were recruited for the study, and their data were compared with those obtained from 12 healthy female volunteers, 21 to 38 years old. Manometric studies were performed in the descending and sigmoid colon for 30 minutes during sleep (immediately before awakening) and 30 minutes after being awakened suddenly. A motility index was calculated before and after the stimulus. RESULTS: In both groups motility in the descending and the sigmoid colon was almost absent during sleep and significantly increased after sudden awakening. No difference in postawakening values was found between patients with constipation and controls. CONCLUSIONS: In patients with chronic constipation, the brain-gut control of some fundamental mechanisms governing colonic motility is preserved. These data suggest that the alterations of colonic motility described in chronic constipation may be caused by an intrinsic dysfunction of the viscus.     

Colorectal manifestations of endocrine disease

PURPOSE: The aim of this review is to alert the colon and rectal surgeon to the colorectal manifestations of endocrine disease. METHODS: This report was obtained by a review of the medical literature. Endocrine disease may initially present as a symptom felt to be referable to colorectal disease. Furthermore symptoms of well-established endocrine disorders may have refractory colorectal symptoms. RESULTS: Constipation is the most common gastrointestinal symptom of diabetics; however, in patients with brittle diabetes, diarrhea may be chronic and intermittent. Unexplained diarrhea, despite an exhaustive work-up for an etiology, should alert the clinician to the possibility of a pancreatic endocrine tumor. Thyroid disorders, depending on activity of the gland, may have refractory constipation, diarrhea, or steatorrhea as the only presenting symptoms. Constipation is a common symptom of hypercalcemia, secondary to hyperparathyroidism. Primary hyperparathyroidism has been associated with increased incidence of malignancies, specifically of colonic origin. In patients with acromegaly a threefold to eightfold increased risk of colon carcinoma or adenomatous polyps is seen. Chronic adrenal insufficiency may present initially as diarrhea and malabsorption. The adrenal gland is a frequent site of metastases from colorectal cancer. Pheochromocytomas may be a cause of occult gastrointestinal bleeding or ischemic colitis. CONCLUSION: Unexplained symptoms referable to the colon and rectum should alert the clinician to the possibility of an underlying endocrine disorder.     

Gas Volume Analysis and Postoperative Bowel Functional Disorders in Patients Who Received Anterior Resection for Rectal Cancer

PURPOSE: Colon gas analysis using abdominal radiography has been reported as a reliable method for assessing functional bowel disorders. The aim of this study was to clarify the relevance of colon gas distribution in postoperative disorders such as constipation and feelings of incomplete evacuation following rectal cancer operation. METHODS: Colon gas volume score was calculated using plain abdominal radiographs and evaluated in 50 patients who had received low anterior resections. Twenty-one constipated patients who required laxatives and 29 patients who did not were compared in terms of colon gas distribution. In addition, 32 patients with postoperative feelings of incomplete evacuation and 18 patients without such feelings were assessed in similar fashion. RESULTS: Left colon gas scores in patients who required laxatives were significantly higher (2.82 ± 3.23 percent) than in nonusers (1.21 ± 0.96 percent; P < 0.01). Patients with feelings of incomplete evacuation displayed significantly higher left side colon gas scores (2.51 ± 2.66 percent) than those without such feelings (0.77 ± 0.81 percent; P < 0.0001). CONCLUSION: Patients with postoperative functional bowel disorders such as constipation or feelings of incomplete evacuation may experience relatively high volumes of gas in the left colon.     

Consensus statement AIGO/SICCR diagnosis and treatment of chronic constipation and obstructed defecation(Part Ⅱ:Treatment)

The second part of the Consensus Statement of the Italian Association of Hospital Gastroenterologists and Italian Society of Colo-Rectal Surgery reports on the treatment of chronic constipation and obstructed defecation.There is no evidence that increasing fluid intake and physical activity can relieve the symptoms of chronic constipation.Patients with normal-transit constipation should increase their fibre intake through their diet or with commercial fibre.Osmotic laxatives may be effective in patients who do not respond to fibre supplements.Stimulant laxatives should be reserved for patients who do not respond to osmotic laxatives.Controlled trials have shown that serotoninergic enterokinetic agents,such as prucalopride,and prosecretory agents,such as lubiprostone,are effective in the treatment of patients with chronic constipation.Surgery is sometimes necessary.Total colectomy with ileorectostomy may be considered in patients with slow-transit constipation and inertia coli who are resistant to medical therapy and who do not have defecatory disorders,generalised motility disorders or psychological disorders.Randomised controlled trials have established the efficacy of rehabilitative treatment in dys-synergic defecation.Many surgical procedures may be used to treat obstructed defecation in patients with acquired anatomical defects,but none is considered to be the gold standard.Surgery should be reserved for selected patients with an impaired quality of life.Obstructed defecation is often associated with pelvic organ prolapse.Surgery with the placement of prostheses is replacing fascial surgery in the treatment of pelvic organ prolapse,but the efficacy and safety of such procedures have not yet been established.     

A retrospective study of histopathological findings in 894 cases of megacolon: what is the relationship between megacolon and colonic cancer?

Patients with megaesophagus (ME) have increased prevalence of cancer of the esophagus. In contrast, a higher incidence of colorectal cancer is not observed in patients with megacolon (MC). MC is very common in some regions of Brazil, where it is mainly associated with Chagas disease. We reviewed the pathology records of surgical specimens of all patients submitted for surgical resection of MC in the Hospital das Clínicas of the Faculty of Medicine of Ribeir?o Preto (HC-FMRP), from the University of S?o Paulo. We found that 894 patients were operated from 1952 until 2001 for MC resection. Mucosal ulcers, hyperplasia and chronic inflammation were frequently found, while polyps were uncommon. No patients with MC presented any type of colonic neoplasm. This observation reinforces the hypothesis that MC has a negative association with cancer of the colon. This seems to contradict the traditional concept of carcinogenesis in the colon, since patients with MC presents important chronic constipation that is thought to cause an increase in risk for colon cancer. MC is also associated with other risk factors for cancer of colon, such as hyperplasia, mucosal ulcers and chronic inflammation. In ME these factors lead to a remarkable increase in cancer risk. The study of mucosal cell proliferation in MC may provide new insights and useful information about the role of constipation in colonic carcinogenesis.     

Diagnosis and treatment of spontaneous colonic perforation： Analysis of 10 cases

AIM： To investigate the etiology, diagnosis and treatment of spontaneous perforation of the colon.
METHODS： The clinical data of 10 cases of spontaneous perforation of the colon, observed at Fuding hospital from January 2004 to December 2007, were analyzed retrospectively.
RESULTS： The mean age at onset was 65 years （range from 45 to 73）. Seven patients had a history of chronic constipation. All patients complained of sudden lower abdominal pain. The perforation occurred after coloclysis and administration of senna leaves in two patients. Nine patients had signs of peritoneal irritation. Seven cases underwent abdominal paracentesis, which was diagnostic in six. Only one case was definitely diagnosed prior to surgery. One patient underwent neoplasty of the colon, another a partial resection of colon, six a neoplasty of the colon plus sigmoid colostomy, and two underwent Hartmann surgery. All perforation sites were opposite to the mesenteric edge. The perforation sites were located on descending colon in one case, sigmoid colon in three cases, and rectosigmoid colon in six cases. In five patients, surgical pathological examination was consistent with the microscopical changes of colonic perforation caused by feces. Three patients died after surgery.
CONCLUSION： Spontaneous perforation of the colon most commonly occurs among the elderly with chronic constipation. Abdominal paracentesis is helpful for the diagnosis. The perforation site is located opposite to the mesenteric edge. Sigmoid colon and rectosigmoid colon are the most frequent locations. Neoplasty of the colon and sigmoid colostomy are the most frequent treatment. The prognosis is bad and the mortality rate after surgery is high.     

Myths and misconceptions about chronic constipation

There are many strongly held beliefs about constipation that are not evidence based. The purpose of this review is to address these beliefs concerning various aspects of constipation. There is no evidence to support the theory that diseases may arise via "autointoxication," whereby poisonous substances from stools within the colon are absorbed. Dolichocolon, defined as an elongated colon, should not be seen as a cause of constipation. The role of sex hormones altering gut function during the menstrual cycle appears to be minimal. During pregnancy they may play a role in slowing gut transit. Hypothyroidism can cause constipation, but among patients presenting with constipation, hypothyroidism is rare. A diet poor in fiber should not be assumed to be the cause of chronic constipation. Some patients may be helped by a fiber-rich diet but many patients with more severe constipation get worse symptoms when increasing dietary fiber intake. There is no evidence that constipation can successfully be treated by increasing fluid intake unless there is evidence of dehydration. In the elderly constipation may correlate with decreased physical activity, but many cofactors are likely to play a role. Intervention programs to increase physical activity as part of a broad rehabilitation program may help. It is unlikely that stimulant laxatives at recommended doses are harmful to the colon. A proportion of patients with chronic constipation is dependent of laxatives to achieve satisfactory bowel function, but this is not the result of prior laxative intake. Tolerance to stimulant laxatives is uncommon. There is no indication for the occurrence of "rebound constipation" after stopping laxative intake. While laxatives may be misused, there is no potential for addiction.     

功能性便秘患者情绪和睡眠状况调查

背景：我国一般人群功能性便秘（FC）患病率较高,便秘症状持续存在可影响患者的情绪和睡眠。目的：调查FC患者的情绪和睡眠状况,分析两者与便秘的关系。方法：连续纳入符合罗马Ⅲ标准和研究要求的FC患者行面对面问卷调查。问卷内容包括便秘症状、情绪和睡眠状况、便秘与情绪、睡眠的关系、便秘诊治情况以及患者对便秘不良影响的自我评价等。结果：有效问卷为228份。近3个月内,60.5%的患者感到情绪紧张,61.4%感到情绪沮丧,经常或绝大多数时间感到情绪紧张和（或）沮丧,即合并情绪异常者占39.9%;52.6%的患者合并睡眠障碍。在合并情绪异常和睡眠障碍者中,多数患者便秘先于情绪异常和睡眠障碍出现;合并情绪异常的重度便秘患者就诊次数较无情绪异常者显著增加（3.92对2.57,P=0.013）;情绪异常和睡眠障碍不影响患者对治疗的满意度（P=0.286）。重度便秘患者中认为便秘对日常生活、健康状况等产生明显影响者的比例较高。结论：FC患者常合并情绪异常和睡眠障碍,便秘严重程度是影响患者日常生活、健康状况的主要因素,合并情绪异常可增加重度便秘患者的就诊次数。     

A Novel Surgical Approach to Slow-Transit Constipation: Report of Two Cases

Introduction Slow-transit constipation after proper diagnosis and extensive medical therapy may have a surgical solution. Total abdominal colectomy and ileorectal anastomosis, at our institution, is the surgical procedure of choice. Nonetheless, patients may reject this alternative because of morbidity. Discussion We report two cases of slow-transit constipation diagnosed after a thorough investigation with two colonic transit tests showing slow-transit constipation, a normal anorectal manometry, balloon expulsion test, small-bowel follow-through, defecography, laboratory and psychologic tests. The patients rejected standard surgical treatment (total colectomy + ileorectal anastomosis). A colonic bypass with an ileorectal anastomosis, leaving the colon in situ, was offered and accepted by the two patients. This was performed laparoscopically liberating the cecum and terminal ileum, transecting the terminal ileum through a small suprapubic incision, and anastomosing the terminal ileum to the rectosigmoid junction intracorporeally. The total surgical time was 50 and 60 minutes, respectively. Summary Both patients made uneventful recoveries and were discharged on the fourth postoperative day. They have completed four and two months of close follow-up and at present have one to four bowel movements per day with mild abdominal distension and pain. To our knowledge this is the first report of colonic bypass for the treatment of slow-transit constipation. Reprints are not available.     

Assessments of anorectal myectomy for short segment hypoganglionosis in childhood

BACKGROUND/AIMS: To clarify the significance of anorectal myectomy (ARM) in childhood patients with short segment hypoganglionosis (Hypo), we analyzed the clinical features of these patients before and after ARM. METHODOLOGY: A consecutive series of twenty-nine patients with short segment Hypo were included in this study. These were sixteen males and thirteen females, aged between 6 and 15 years with a mean age of 9.8 years. We performed an analysis of the clinical findings and outcomes for patients with short segment Hypo before and after ARM. Stool frequencies were less than twice per week (0.5-2 per week, mean: 1.6 per week) despite the use of laxatives, suppositories, and enema before ARM. RESULTS: About 90% of patients had an onset of constipation before the age of 6 years. In addition, significant differences were noted between 0 months < or = to <1 year and 1 year < or = to < or =15 years (P < 0.0001). There were no sexual differences. Difficulty in defecation was the most common symptom, followed by abdominal fullness, abdominal pain and soiling. In abdominal fullness and pain, there were significant differences between positive and negative groups (P < 0.0001, P = 0.0038, respectively). No patients responded to use of laxatives, suppositories, and enema before ARM. In patients after ARM, the most common outcome was good (65.5%; bowel movement every day without laxatives and no other symptoms), followed by satisfactory (20.7%; bowel movement 2-3 times per week without laxatives and no other symptoms) and poor (13.8%; no improvement) in decreasing order. Significant differences of patient numbers were noted between good and the remaining outcomes (P = 0.0181). Spontaneous evacuation without the need for laxatives, suppositories, and enema was recorded in 100% patients of good outcome, and 42.9% those of satisfactory outcome after ARM. Patients with poor outcome still required for laxatives, suppositories, and enema. Central nervous, psychological, and psychiatric disorders were recognized in patients with satisfactory outcome, and constipation was maintained to these patients. However, the necessity for medication to them was lost. Moreover, clinical symptoms disappeared. Redundant colon was only found in patients with poor outcome. CONCLUSIONS: Patients with short segment Hypo, especially those with redundant colon, psychological, psychiatric, or central nervous disorders, may experience persistent constipation after ARM.     

Rectocele is associated with paradoxical anal sphincter reaction

Rectocele is a frequent finding in constipated patients. However, constipation is not always relieved by rectocele repair, which may be due to other overlooked reasons for constipation. The study was designed to investigate patients with rectocele, in order to elucidate concomitant colorectal disorders and their association with rectocele. One hundred and twelve female patients suffering from severe constipation and rectal emptying difficulties were investigated using defecography, electrophysiology, anorectal manometry and colon transit time. Fifty-six patients with rectocele demonstrated by defecography were compared with 56 patients without rectocele, but with other abnormal findings at defecography. The frequency of paradoxical anal sphincter reaction (PSR) was higher in patients with rectocele (60%) than in patients without rectocele (24%). The present study supports an association between rectocele and PSR. We suggest that constipated patients with a rectocele should be investigated thoroughly before rectocele repair is considered. Further studies on the effect of biofeedback training in patients with rectocele and PSR are indicated. Accepted: 15 August 1997     

排便的生理和便秘的病理生理

慢性便秘可以看作是不同病理生理过程的最终症状表现 ,其胃肠运动主要出现以下病理生理变化 :( 1)结肠运动功能异常 :表现为运动亢进、减弱、不协调。结肠非推进性收缩幅度、频率增加 ,肠传输时间延长 ,肠内容物水分吸收过多 ,粪便干燥 ;结肠推进性收缩的幅度频率减少、结肠蠕动无力 ,肠传输时间增加 ,粪便无法正常推送至直肠 ;不协调运动 ,结肠某一部分收缩增强、逆向蠕动 ,影响传输时间 ;( 2 )直肠运动异常 :直肠张力下降 ,顺应性增加 ,感觉功能下降 ;( 3 )肛门括约肌功能异常 ;( 4 )盆底肌群收缩功能下降 ,持续收缩、不协调收缩或松弛。本文对排便的生理和便秘的病理生理进行综述     

Mesenteric panniculitis of the colon

Eighteen cases of mesenteric panniculitis of the colon collected from the literature, together with two cases from the authors' source, were reviewed. The disease occurred most often in late adult life, with a male predominance. Symptoms were abdominal pain, diarrhea, constipation, and a lower abdominal mass in most patients. Barium enema disclosed narrowing, shortening, and poor extensibility of the colon, and ultrasonography and computed tomography showed thickening of the mesocolon and colonic wall with soft-tissue density. Exploratory laparotomy was done in all patients, and colectomy, colostomy, or other surgical treatments were performed in 17 (85 percent). Gross appearance at the time of surgery was characterized by a marked thickening or a firm mass of the mesocolon with a puckered surface involving the appendices epiploicae of the colon. Microscopically, degeneration of the adipose tissue, revealed by aggregates of lipid-laden macrophages, was diagnostic. Inflammatory infiltration and fibrosis also were present in many patients. Mesenteric panniculitis of the colon seems to be a lesion more advaced than the same condition of the small intestine, and colostomy or bypass surgery may be needed for alleviation of severe symptoms.