Pseudopolyps in inflammatory bowel diseases: Have we learned enough?

Pseudopolyps are a well described entity in the literature and even though the exact pathogenesis of their formation is not completely understood, they are considered non-neoplastic lesions originating from the mucosa after repeated periods of inflammation and ulceration associated with excessive healing processes. Their occurrence is less common in Crohn's disease than in ulcerative colitis, and their overall prevalence ranges from 4% to 74%; moreover, they are found more often in colon but have been detected in other parts of the gastrointestinal tract as well. When their size exceeds the arbitrary point of 1.5 cm, they are classified as giant pseudopolyps. Clinical evaluation should differentiate the pseudopolyps from other polypoid lesions, such as the dysplasiaassociated mass or lesion, but this situation represents an ongoing clinical challenge. Pseudopolyps can provoke complications such as bleeding or obstruction, and their management includes medical therapy, endoscopy and surgery; however, no consensus exists about the optimal treatment approach. Patients with pseudopolyps are considered at intermediate risk for colorectal cancer and regular endoscopic monitoring is recommended. Through a review of the literature, we provide here a proposed classification of the characteristics of pseudopolyps.     

Favorable response to parenteral nutrition and medical therapy in Crohn's colitis. A report of 38 patients comparing severe Crohn's and ulcerative colitis

The courses of 38 patients with severe, uncomplicated acute colitis (16 with Crohn's colitis and 22 with ulcerative colitis) were analyzed retrospectively. The patients were placed on total parenteral nutrition and treated concomitantly with corticosteroids, antibiotics (often metronidazole), sulfasalazine, and/or azathioprine. Fifteen of the 16 Crohn's colitis patients were initially managed without surgery. Four patients subsequently relapsed, two responded to reinstituted medical therapy, and two underwent colon resection 2 and 4 years later. Of 22 ulcerative colitis patients, 16 required surgery during the initial hospitalization, one patient subsequently had surgery, and one died after refusing surgery. Three of the other four continue in remission on medical therapy. Thus, there were significant differences in this series between the clinical courses of severe ulcerative colitis and severe Crohn's colitis. While most of the ulcerative colitis patients with severe disease underwent colectomy, most of the patients with severe but uncomplicated Crohn's colitis responded to aggressive medical therapy, of which total parenteral nutrition and perhaps bowel rest seemed to be an important part. Afterwards, the majority remained in remission on long-term medical therapy.     

The Morphologic Relationship of Sinus and Fistula Formation to Intestinal Stenoses in Children with Crohn's Disease

Sinus and fistula (SF) formation in adults with Crohn's disease has been ascribed to increased intraluminal pressure from stenotic lesions or to inflammation. We retrospectively evaluated 55 surgically resected specimens from 30 children with Crohn's disease for stenotic lesions, sinuses, fistulas, and inflammation. Eighteen of 30 children had one operation, and there were 12 multiple surgeries. Thirty-one of 55 specimens (56%) contained stenoses. SF formation was seen in 16 of 31 specimens with stenosis; it developed proximal to the stenosis in seven patients, distal in five, and both proximal and distal in four. SF formation was also noted in 12/24 specimens without stenosis. In 93% of the cases, the SF was associated with moderate to severe inflammation. Although 56% of the patients had stenoses, SF frequently developed independent of stenosis. All SF were associated with inflammation. Therefore, inflammation rather than increased intraluminal pressure appears to be the primary factor in SF formation in children with Crohn's disease.     

Current treatment for prevention of relapse and recurrence in Crohn's disease

Maintenance of remission induced by medical therapy and prevention of recurrence after intestinal resection are two of the major goals in Crohn's disease treatment. Two main groups of drugs are employed in prevention of relapse and recurrence: sulfasalazine and 5-aminosalicylic derivatives and the group of azathioprine/6-mercaptopurine. Although most clinical trials on the efficacy of sulfasalazine as maintenance therapy of Crohn's disease have given negative results, it could probably be favourably used in remission maintenance of Crohn's colitis. Controlled studies and two reviews have shown that 5-aminosalicylic derivatives are effective in reducing the risk of relapse. Ileitis and ileocolitis respond better than colitis. These drugs are also able to reduce the severity of lesions and of symptoms after surgery. 6-mercaptopurine and azathioprine can be used in more aggressive forms of the disease. The efficacy of this immuno-suppressive therapy is reported in over 70% of patients and the incidence of associated side effects is acceptable, but 6-mercaptopurine and azathioprine act slowly and the long latency period limits the usefulness of these drugs in some patients.     

Myositis Associated with Crohn''s Colitis

A patient with myositis associated with Crohn's colitis is reported. Myositis preceded the clinical manifestations of colitis. Both symptoms responded promptly and rapidly to sulfasalazine. Serum creatine phosphokinase was markedly elevated and returned to normal after treatment. Muscle biopsy and electromyography were nondiagnostic. Myositis may be more common than reported in patients with inflammatory bowel disease. Careful attention to muscle pain and serum level of creatine phosphokinase in patients with inflammatory bowel disease is suggested.     

A case of diffuse inflammatory colonic pseudopolyposis caused by Crohn's disease

Inflammatory pseudopolyposis of the colon is an uncommon anatomoclinical entity. It is generally associated with ulcerative colitis, Crohn's disease or schistosomiasis. We report a case of a pseudopolyposis in Crohn's disease involving the entire colon. This case was characterized by three particular facts: a) the pseudopolyps were composed of granulation tissues only, b) severe exudative enteropathy was the most important symptom, c) the endoscopic ablation of the polyps, performed for the first time in Crohn's disease pseudopolyposis, resulted in clinical and biological improvement.     

Intestinal Mucosa Diamine Oxidase Activity Reflects Intestinal Involvement in Crohn''s Disease

The activity of diamine oxidase (DAO), an enzyme found in the apical villous cells of the small intestine mucosa, should reflect the status of the intestinal mucosa. Our purpose was to determine whether DAO activity in the intestinal mucosa is diminished in patients with Crohn's disease and correlates with the severity of histological changes. Mucosal DAO activity was determined in 42 tissue specimens from patients with Crohn's enteritis (n = 15), Crohn's colitis (n = 9), and ulcerative colitis (n = 11), and from patients with no intestinal disease (n = 7). DAO activity was estimated by the metabolism of [14C]putrescine. Histologic changes were graded on a scale of 0-4. Normal histology was graded as zero, mild edema, and inflammation in the lamina propria as one, crypt abscess formation and inflammation as two, more severe inflammation plus or minus granulomata as three, and most severe inflammation with active ulceration as four. Tissue DAO activity was significantly less in patients with ileitis (4.8 +/- 3.6) compared with those with Crohn's colitis (15.0 +/- 11.6), ulcerative colitis (16.8 +/- 19.7), and normal intestine (17.6 +/- 14.3 U/mg protein/h, p less than 0.05). Intestinal DAO activity showed a positive correlation with the histologic scores. Recurrence of Crohn's disease developed postoperatively in two patients with low tissue DAO activity (1.4 and 2.9 U/mg protein/h). Intestinal DAO activity is diminished in patients with Crohn's ileitis and correlates with the severity of histologic changes. Tissue DAO activity might prove useful in predicting the risk of recurrence or anastomotic complications after resection for Crohn's disease.     

Perioperative endoscopy of the whole small bowel in Crohn's disease.

The aim of this study was to search for small bowel lesions by means of a perioperative endoscopy in 20 patients operated on for Crohn's disease. Seven women and 13 men (mean age 29 years) had a total retrograde exploration to the angle of Treitz during an ileocolectomy (16 of 20 patients) or a colonic or ileal resection (four of 20 patients). Endoscopic exploration was completed, through an enterotomy, from the surgical area to the angle of Treitz. Periendoscopic biopsy samples were taken on macroscopic lesions and every 20 cm systematically. In 13 of 20 cases, various lesions scattered over the whole small intestine were found. These were aphthoid ulcerations (10 patients), superficial ulcerations (seven patients), mucosal oedema (three patients), non-ulcerative stenosis (three patients), erythema (two patients), pseudopolyps (two patients), deep ulcerations (two patients), and ulcerative stenosis (one patient). In seven patients none of the lesions detected at perioperative endoscopy had been recognised by preoperative evaluation or surgical inspection of the serosal surface. A typical granuloma was found at biopsy of lesions identified by endoscopy in three cases and at biopsy of an apparently healthy area in one case. Thus 65% of patients operated on for Crohn's disease had lesions of the small intestine detected by endoscopy, which were unrecognised before surgery in more than half of the cases.     

Concomitant colitis associated with primary sclerosing cholangitis

Between 1985 and 2001, seven Japanese patients (four males and three females) were diagnosed as having primary sclerosing cholangitis (PSC) in our hospital. All seven patients received total colonoscopy with distal ileoscopy. All four male patients were diagnosed as having colitis by colonoscopy, while none of the three female patients had colitis. The four patients with colitis did not have any symptoms attributable to colitis, such as diarrhea or hematochezia. In three of the four patients, unclassified colitis was the most suitable diagnosis, because there were no typical findings of ulcerative colitis or Crohn's disease. The remaining patient was diagnosed as having eosinophilic colitis. By colonoscopic visualization, the right-sided colon, including the terminal ileum, was mainly involved, but the lesions were not severe. The main findings were redness, erosion, stenosis, and insufficiency of haustral formation. Histologically, these lesions were nonspecific inflammatory changes in the three patients with unclassified colitis. In the patient with eosinophilic colitis, remarkable infiltration of eosinophils was observed. Thus, unclassified colitis appeared to be the main complication in these patients with PSC. Males predominated in regard to concomitant colitis, and they had no symptoms of the colitis. Colonoscopic examination revealed that the lesions were not severe. The main lesions were found in the right-sided colon, with nonspecific inflammatory changes. These results suggest that colonoscopic surveillance of patients with PSC should be performed even if they do not have any colitis symptoms.     

Filiform polyposis in Crohn's colitis mimicking toxic megacolon

Summary A patient with filiform polyposis in Crohn's colitis is reported. Unlike previous reports of filiform polyposis, this patient's colitis was of rapid onset and antedated development of pseudopolyps by a short duration. Additionally, unlike previous reports, the disease process was quite aggressive. The extensive degree of fissuring found throughout the bowel wall may have produced the unusually shaped polyps and caused the toxic colonic atony.     

The prognosis of inflammatory bowel disease

The complications of ulcerative colitis generally develop during the first two years of disease. The mortality is higher than expected and the highest likelihood of colectomy also occurs early in the disease. Mortality in Crohn's disease is greater than expected, especially in males. For both conditions, the overall mortality has decreased steadily, and currently is less than 5%. Ulcerative colitis is curable with proctocolectomy and ileostomy. In Crohn's disease, intestinal resection and reanastomosis is followed by recurrence in the majority of patients. The recurrence rate after proctocolectomy and ileostomy for Crohn's disease of the colon also is considerable, ranging from 20% to 35%. In ulcerative colitis, the more colon involved, the more frequent and more serious are the complications. In Crohn's disease, the anatomic pattern of disease tends to predict the type and extent of complications. Both ulcerative colitis and Crohn's disease appear to follow a more severe course in children and adolescents with "inflammatory bowel disease." Patients with either ulcerative colitis or Crohn's disease are at increased risk for the later development of cancer. In ulcerative colitis, the excess risk is limited to colorectal cancer. Patients with Crohn's disease have increased cancer rates for both the small and large bowel. Finally, most patients with these diseases are able to maintain normal occupations and enjoy reasonably stable social and economic situations. The successful adaptation of patients with inflammatory bowel disease is influenced by a hopeful, optimistic personality and by an encouraging, supportive physician.     

Serum lysozyme levels in Crohn's disease and ulcerative colitis.

Serum lysozyme levels were determined in healthy volunteers, patients with Crohn's disease, and patients with ulcerative colitis. The mean concentration in Crohn's disease was significantly greater than in the other groups. In patients with Crohn's disease, as well as in patients with ulcerative colitis, the lysozyme levels correlated with the severity of the disease process and with the extent of the lesions: the more severe the disease and the more extensive the involvement, the higher the lysozyme levels. However, the lysozyme values of the different groups overlapped considerably. Our results indicate that lysozyme determinations have only limited discriminative value for the diagnosis of Crohn's disease and for determining the severity and the extent of the disease process in the individual patient.     

Therapeutic efficacy of 5-ASA molecules in idiopathic intestinal inflammatory diseases: critical review]

Sulfasalazine has been the most widely prescribed drug for patients with inflammatory bowel disease. Clinical trials have established its usefulness in treating patients with active ulcerative colitis and Crohn colitis and its important role in maintaining remissions in patients with ulcerative colitis. Despite its widespread acceptance, the usefulness of sulfasalazine has been limited by the occurrence of adverse reactions in about 10 to 20% of the patients. Now the aminosalicylates are emerging as a treatment for both ulcerative colitis and Crohn disease. We have critically reviewed the clinical trials assessing the efficacy of 5-ASA molecules. Therapeutic efficacy of 5-ASA appears to be as good as sulfasalazine but causing less adverse effects. In mild to moderate ulcerative colitis relapse, 2g 5-ASA is active while 1 g 5-ASA seems equivalent to 2g sulfasalazine for maintaining remission. 5-ASA enema in the treatment of distal ulcerative colitis is helpful and can replace topical cortisone administration. Administration of 1g 5-ASA enema a day seems to be the best regimen. In case of Crohn's disease, preliminary studies are encouraging but more date are required to define the indications as well as the regimen.     

Incidence of severe local complications in ulcerative colitis and Crohn disease

At the example of the severe and foudroyant courses of the ulcerous colitis in patients who died or underwent a resection (n = 93) the severe local complications are demonstrated. 70 patients with resection of the intestine, 21 patients with diagnostic laparotomy as well as 32 deceased patients with Crohn's disease were compared with them. Transmigration peritonitides (3.3% of 458 patients with ulcerous colitis except haemorrhagic proctitis), perforation peritonitides (2.0%) as well as the toxic megacolon (3.3%) alone or in combination are the most frequent severe complications. Therapy-resistant intestinal haemorrhages (1.1%) are infrequent. In 0.9% of the cases colorectal carcinomata appear. The acute or chronic mechanical ileus is the most frequent complication in Crohn's disease (21.1% of 171 patients altogether). Intraabdominal abscesses are found in 11.7%. In participation of the colon fistulae are nearly twice as frequent as in localisation of the small intestine. Free perforations of the small intestine (3.8%) are more frequently observed than perforations of the colon (2.2%).     

Risk of relapse in new cases of ulcerative colitis and indeterminate colitis

PURPOSE: Changes in morbidity pattern of ulcerative colitis have created a need to update understanding of the course of the disease. METHOD: A follow-up study was done of relapse rates and progression of inflammation in 571 nonselected patients with ulcerative and indeterminate colitis. RESULTS: Relapse rate ten years after diagnosis was 70 percent in definite ulcerative colitis, 22 percent in probable ulcerative colitis, and 77 percent in indeterminate colitis. During the study period, there was no change in the relapse rate. In relapsing proctitis, 52 percent developed more extensive inflammation. Fifty-four percent of patients with only one attack of colitis had persistent signs of inflammatory bowel disease. CONCLUSIONS: Shift in morbidity pattern to a greater proportion of patients with proctitis at diagnosis and a shorter time from onset of symptoms to diagnosis had no influence on the relapse rate. Indeterminate colitis has a worse prognosis than definite ulcerative colitis. Considering the documented efficacy of sulfasalazine, the high relapse rate calls for studies of the effectiveness of such treatment in everyday practice.     

Clinical significance of erosive and/or small ulcerative lesions in the colon and terminal ileum--short-term follow-up study]

BACKGROUND/AIMS: Various etiologies and diseases may be related to erosions and/or small ulcers without gross inflammatory changes in the surrounding mucosa found in the colon and terminal ileum during colonoscopy. However, studies on follow-up of these lesions are rare. Thus, we investigated the clinical significance of these lesions and their characteristics helpful for differential diagnosis. METHODS: We reviewed the data of 183 patients with colonoscopically observed erosive or small ulcerative lesions (<2 cm), and analyzed them according to the location, number, and size of lesions, histopathologic findings, chief complaints, laboratory findings, changes of symptoms, and changes in lesions during 4-12 week follow-up period. RESULTS: Histopathologic findings of these lesions included acute nonspecific inflammation, chronic nonspecific inflammation, Crohn's disease, tuberculous colitis, ischemic colitis, Behcet's disease, cytomegalovirus infection, eosinophilic colitis, ulcerative colitis or pseudomembranous colitis, but most of them were nonspecific (84%). In patients with nonspecific inflammation, histopathologic findings, symptoms, location and multiplicity of the lesions were not prognostic factors for the persistency of symptoms and lesions during follow-up period. Two patients with acute inflammation, who showed no improvement in symptoms and lesions, were later diagnosed as Crohn's disease. CONCLUSIONS: Erosive or small ulcerative lesions without macroscopic inflammatory changes in the surrounding mucosa during colonoscopy, are mainly nonspecific. However, careful follow-up is required when the symptoms and/or lesions are not improved.     

溃疡性结肠炎360例临床特征分析

近年溃疡性结肠炎（UC）的发病率明显升高,明确临床特征有助于其诊断。目的：探讨UC的临床特征。方法：收集2008年7月-2011年7月西京医院收治并确诊的活动期UC患者的临床资料,回顾性分析其临床特征。结果：共收治活动期UC患者360例,男女之比1．25：1;平均就诊年龄40．5岁。疾病严重程度以轻中度UC多见（84．4％）。病变累及以左半结肠和直肠、乙状结肠多见;18例病变呈节段性分布,其余均为连续分布。本组患者以腹泻、黏液脓血便、腹痛为主要临床表现,内镜下黏膜弥漫性充血、水肿、糜烂和溃疡,44例伴有肠外表现。多数患者的白细胞、ESR和CRP水平增高。52例患者合并并发症。349例患者接受内科治疗,病情明显缓解。结论：UC患者以中青年男性多见,内镜下病变以左半结肠和直肠、乙状结肠多见,常见并发症为结肠假性息肉。UC确诊主要根据临床表现、结肠镜检查、病理学检查,其中结肠镜检查可明确病变部位、范围、程度以及肠腔有无狭窄或癌变,有助于临床病情分期,对指导临床治疗方案的选择具有重要意义。     

In vivo profiles of eicosanoids in ulcerative colitis, Crohn's colitis, and Clostridium difficile colitis

To compare the local release of arachidonic acid metabolites in inflammatory diarrheal disease, in vivo equilibrium dialysis of the rectum was done in consecutive untreated patients with ulcerative colitis (n = 20), Crohn's colitis (n = 10), and Clostridium difficile colitis (n = 7). All patients had endoscopically proven rectal inflammation. Eicosanoid profiles were determined in rectal dialysates by radioimmunoassay after preliminary purification. Concentrations of prostaglandin E2, prostaglandin F2 alpha, and thromboxane B2, but not 6-keto-prostaglandin F1 alpha, were raised in all groups and compared with healthy controls. The highest levels within each group were obtained in patients with widespread epithelial damage, as judged by endoscopy. In patients with ulcerative colitis, an extreme rise in prostaglandin E2 and thromboxane B2 were observed. Similarly, concentrations of leukotriene B4 were substantially increased in ulcerative colitis, but in Crohn's colitis and Clostridium difficile colitis only those patients with rectal ulcerations showed elevations. These findings probably reflect more severe tissue damages in ulcerative colitis, but differences between disease groups in cell-to-cell interaction may also contribute. The data suggest, therefore, that therapeutic inhibition of lipoxygenase pathways may prove more effective in ulcerative colitis than in Crohn's disease.     

Obliterative arteritis with nitric oxide synthase and HLA-DR expression in Crohn's colitis

BACKGROUND/AIMS: To cast light on whether inflammatory vascular injury is a possible pathogenic mechanism in Crohn's disease, the histological characteristics of vascular lesions were investigated. METHODOLOGY: Affected vessels in surgically resected colons from 23 patients with Crohn's disease, 20 with ulcerative colitis, 7 with ischemic colitis, and 9 normal controls were analyzed by Victoria blue and hematoxylin and eosin staining as well as immunohistochemistry for HLA-DR, nitric oxid synthase, vascular endothelial growth factor and E-cadherin. RESULTS: Inflammatory-cell infiltrates affecting arteries, accompanied by obliterative intimal thickening, were more frequent in Crohn's disease cases than in the other groups (P < 0.05-0.0001). Crohn's disease activity was positively correlated with the degree of obliterative arteritis. Granulomatous vasculitis was found exclusively in Crohn's disease (10 cases; 43.5%). In addition, focally enhanced endothelial staining of HLA-DR, with expression in granulomas adjacent to vessels was occasionally observed. In the endothelium of affected vessels, strong expression of HLA-DR was more prevalent in Crohn's disease and/or ulcerative colitis as compared with the ischemic colitis and controls (P < 0.05-0.01). In the involved arteries, enhanced endothelial nitric oxide synthase expression was most common in Crohn's disease among the groups (P < 0.05). A few cases of Crohn's disease, ulcerative colitis and ischemic colitis were positive for inducible nitric oxide synthase, vascular endothelial growth factor or E-cadherin in the vessel walls. CONCLUSIONS: The presence of characteristic obliterative arteritis and granulomatous vasculitis, a possible cause of ischemic injury, supports, in part, a vascular hypothesis for the pathogenesis of Crohn's disease. Enhanced expression of endothelial nitric oxide synthase and HLA-DR possibly reflects compensatory endothelium-mediated vasodilation and amplification of the immune response, respectively.