Feasibility and efficacy of argon plasma coagulation for early esophageal squamous cell neoplasia.

We present 19 cases in which argon plasma coagulation (APC) was used as curative initial treatment for 5 low-grade esophageal squamous intraepithelial neoplasias (ESINs), 12 high-grade ESINs, and 2 early esophageal squamous cell carcinomas (ESCCs). Complete response was defined as the absence of tumor from any biopsy taken from the ablated lesion. At follow-up endoscopy 2 - 4 months after APC, 94.7 % of patients had achieved complete response in a single treatment session. Only one patient with high-grade ESIN showed local recurrence. This patient underwent additional APC and showed complete response at 12 months after initial APC. At the 12-month follow-up endoscopy, again 94.7 % had a complete response. The exception was one patient with local recurrence, who underwent additional APC. After the 12-month follow-up endoscopy, no patient showed local recurrence during a median follow-up of 22 months. No stricture requiring endoscopic dilation occurred after the procedure. This study suggests that APC is a feasible and effective treatment modality for ESIN and early ESCC.

The association between coronary artery calcification and colorectal adenoma.

BACKGROUND/AIMS: Both colorectal neoplasm and coronary artery disease are prevalent diseases worldwide and share several risk factors. The aim of this study was to investigate the association between coronary artery calcification and prevalence of colorectal adenoma. METHODOLOGY: We retrospectively evaluated 3,092 subjects who underwent colonoscopy and coronary artery calcium computed tomography (CT) on the same day or within a 3-month interval, during routine check-ups between January 2006 and June 2009 at the Center for Health Promotion of the Samsung Medical Center. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs). RESULTS: Colorectal adenomas were detected in 1,067 (34.5%) of the 3,092 subjects, including 536 (41.0%) individuals with and 531 (29.7%) without coronary calcification (p<0.001). Multiple logistic regression analysis showed that the presence of coronary artery calcification (OR=1.346; 95% confidence interval [CI]=1.122-1.614), age ≥50 years (OR=1.516; 95% CI=1.256-1.829), waist circumference of 90-99cm (OR=1.364; 95% CI=1.008-1.844) and current smoker (OR=1.266; 95% CI=1.045-1.534) were associated with the prevalence of colorectal adenoma. CONCLUSIONS: The prevalence of colorectal adenoma is significantly higher in patients with coronary artery calcification. Our results support positive relationship between coronary artery disease and colorectal adenoma.

Gastric extremely well-differentiated intestinal-type adenocarcinoma: a challenging lesion to achieve complete endoscopic resection.

Extremely well-differentiated tubular adenocarcinomas (EWDAs) of the stomach are characterized by surface maturation and their mimicking of intestinal metaplasia. Endoscopically, intramucosal EWDAs are frequently ill defined with indistinct borders due to the pallor of the neoplastic mucosa and the lack of contrast against the background atrophic and metaplastic mucosa. We evaluated the effectiveness of endoscopic resection for EWDAs after endoscopic submucosal dissection (ESD). Among 872 patients with early gastric cancer, 17 EWDAs were identified (1.9 %). Endoscopically, the flat or depressed type was significantly more common among EWDAs (88.2 %) than among early gastric cancers of other histologies (37.8 %; P < 0.01). The discrepancy between endoscopically estimated tumor size and tumor size as confirmed in pathology reports was significantly greater among EWDAs (18.4 ±â€Š22.0  mm) than among others (5.8 ±â€Š7.5  mm). Involvement of the lateral resection margin was more common (29.4 % vs. 2.5 %; P < 0.05), and complete resection was achieved less often in EWDAs (47.1 % vs. 80.4 %; P = 0.01) compared to the others. EWDAs are associated with higher rates of incomplete resection after ESD, especially along the lateral margins. Pathologists should alert endoscopists when this diagnosis is made, with its associated risks; and endoscopists should pay particular attention to the extent of these tumors during resection.

Farnesoid X receptor, overexpressed in pancreatic cancer with lymph node metastasis promotes cell migration and invasion.

BACKGROUND: Lymph node metastasis is one of the most important adverse prognostic factors for pancreatic cancer. The aim of this study was to identify novel lymphatic metastasis-associated markers and therapeutic targets for pancreatic cancer. METHODS: DNA microarray study was carried out to identify genes differentially expressed between 17 pancreatic cancer tissues with lymph node metastasis and 17 pancreatic cancer tissues without lymph node metastasis. The microarray results were validated by real-time PCR. Immunohistochemistry and western blotting were used to examine the expression of farnesoid X receptor (FXR). The function of FXR was studied by small interfering RNA and treatment with FXR antagonist guggulsterone and FXR agonist GW4064. RESULTS: Farnesoid X receptor overexpression in pancreatic cancer tissues with lymph node metastasis is associated with poor patient survival. Small interfering RNA-mediated downregulation of FXR and guggulsterone-mediated FXR inhibition resulted in a marked reduction in cell migration and invasion. In addition, downregulation of FXR reduced NF-κB activation and conditioned medium from FXR siRNA-transfected cells showed reduced VEGF levels. Moreover, GW4064-mediated FXR activation increased cell migration and invasion. CONCLUSIONS: These findings indicated that FXR overexpression plays an important role in lymphatic metastasis of pancreatic cancer and that downregulation of FXR is an effective approach for inhibition of pancreatic tumour progression.

Comparison of a novel teeth-protecting mouthpiece with a traditional device in preventing endoscopy-related complications involving teeth or temporomandibular joint: a multicenter randomized trial.

BACKGROUND AND STUDY AIMS: After upper endoscopy, patients have complained of symptoms involving teeth or the temporomandibular joint; however, these endoscopy-related complications are usually ignored with few attempts to prevent them. The aim of this study was to identify the incidence of endoscopy-related complications involving teeth or temporomandibular joint, and to compare the effectiveness of a newly developed teeth-protecting mouthpiece (TPM) with a traditional mouthpiece (the MB-142) in preventing these complications. PATIENTS AND METHODS: 872 patients from 28 centers, who were undergoing their first upper endoscopy, were randomly assigned to TPM and MB-142 groups. At 3 - 4 days after the procedure, the occurrence of endoscopy-related complications involving the teeth or the temporomandibular joint was investigated using a structured questionnaire. Finally 865 patients (TPM group, n = 423; MB-142, n = 442) responded to this questionnaire and were included in the analysis. RESULTS: Overall, the incidence of complications was significantly lower in the TPM than in the MB-142 group (0.9% vs. 3.2%). With stratification according to sedation status, in nonsedated patients no significant difference was found between the two groups (0.7% vs. 0.9%). In sedated patients, however, the TPM group showed a significantly lower incidence of complication than the MB-142 group (1.7% vs. 11.6%). Clinically serious problems such as a tooth fracture or a loose tooth occurred only in sedated patients in the MB-142 group. CONCLUSIONS: The TPM showed an advantage over the MB-142 mouthpiece for preventing endoscopy-related complications involving teeth or the temporomandibular joint.

Primary NK-/T-cell lymphoma of the gastrointestinal tract: clinical characteristics and endoscopic findings.

BACKGROUND AND STUDY AIMS: Primary NK-/T-cell lymphoma of the gastrointestinal tract is a very rare disease with a poor prognosis. The aim of this study was to determine the clinical and endoscopic characteristics of patients with primary gastrointestinal NK-/T-cell lymphoma. PATIENTS AND METHODS: The clinical features of 14 patients with primary gastrointestinal NK-/T-cell lymphoma and the endoscopic findings in 11 of these patients were reviewed. Their median age was 42 years (range 23-78) at the time of diagnosis. RESULTS: The initial presenting symptoms of primary gastrointestinal NK-/T-cell lymphoma were gastrointestinal bleeding (n = 6, 42%), abdominal pain (n = 4, 29%), and epigastric soreness (n = 4, 29%). The disease was at an advanced stage at the time of diagnosis: stage II in 5 patients (36%); stage III in 4 (28%); and stage IV in 5 (36%). Initial treatment was with chemotherapy (n = 8, 57%) or surgical resection (n = 5, 36%). The median survival for all patients was 9 months. On endoscopy in 11 patients, the anatomic location of the primary lesion was found to be: stomach, n = 3 (27%); esophagus, n = 2 (18%); duodenum, n = 1 (9%); and the ileocolonic area, n = 5 (46%). These lesions were ulceroinfiltrative in 4 cases (36%), ulcerative in 3 cases (27%), superficial/erosive in 3 cases (27%), and infiltrative in 1 case (9%). No prominent fungating mass was seen in any patient. CONCLUSIONS: Primary gastrointestinal NK-/T-cell lymphoma was endoscopically characterized by superficial/erosive, ulcerative, or ulceroinfiltrative lesions without fungating mass. The most common presenting symptom was gastrointestinal bleeding. Despite aggressive treatments, the prognosis was very poor.

Enteroendocrine cell counts correlate with visceral hypersensitivity in patients with diarrhoea-predominant irritable bowel syndrome.

The objective of this study was to determine whether or not the number of enteroendocrine cells (ECs) in the gut is related to visceral hypersensitivity in patients with diarrhoea-predominant irritable bowel syndrome (D-IBS). Twenty-five subjects with D-IBS (mean, 43.1 years; 16 women, nine men) were recruited into our study, along with 13 healthy controls (mean, 40.7 years; nine women, four men). Maximally tolerable pressures were evaluated via barostat testing, and the levels of ECs were immunohistochemically identified and quantified via image analysis. The numbers of ECs between the D-IBS subjects and the controls were not significantly different in the terminal ileum, ascending colon and rectum. However, the maximally tolerable pressures determined in the D-IBS subjects were significantly lower than those of the control subjects (P < 0.01), and we detected a significant relationship between the maximally tolerable pressures and the numbers of ECs in the rectum (r = -0.37, P < 0.01). Rectal sensitivity was enhanced to a greater degree in D-IBS patients exhibiting an elevated level of rectal ECs. This study provides some evidence to suggest that ECs play an important role in visceral hypersensitivity.

Non-surgical management of microperforation induced by EMR of the stomach.

BACKGROUND: Perforation and bleeding are major complications associated with gastric endoscopic mucosal resection. Evident perforation during endoscopic mucosal resection can be managed by endoscopic clipping. However, management of microperforation is not well established. PATIENT AND METHOD: From January 2002 to June 2004, 109 early gastric cancers and 300 adenomas were treated with endoscopic mucosal resection. Iatrogenic perforations occurred in 4.16% (n=17) patients. Following exclusion of four evident perforations, microperforation was observed in 3.18% (n=13) patients. The clinical features of microperforation in patients were retrospectively reviewed. RESULTS: In a total of 13 microperforation cases, 2 patients were managed surgically. The remaining patients successfully recovered without surgical management. In the case of 11 patients without surgery, 7 experienced abdominal pain, which required analgesics, 2 patients experienced mild discomfort and 2 patients experienced no symptoms. A body temperature above 37.5 degrees C was observed in 9.1% (n=1) patients and leucocytosis above 9000 microL-1 was in 72.7% (n=8) patients. The mean duration of nasogastric tube drainage was 2.36+/-1.03 days, of fasting 4.18+/-1.17 days, of intravenous antibiotics 5.55+/-1.44 days and of hospitalisation 7.45+/-1.04 days. CONCLUSION: Microperforation induced by gastric endoscopic mucosal resection can be managed successfully using a non-surgical approach including fasting, nasogastric tube drainage and intravenous antibiotics.

Nonsurgical treatment of abdominal or pelvic abscess in consecutive patients with Crohn's disease.

BACKGROUND: There is little agreement about the efficacy of nonsurgical treatment for abscess associated with Crohn's disease. Furthermore, there is no study on characteristics of abscess or patient that nonsurgical treatment could be worth trying as initial treatment. AIMS: To evaluate the outcome of nonsurgical treatment in Crohn's disease-related abscess and identify factor leading to failure of nonsurgical treatment of this complication. PATIENTS: Twenty-four patients, who consecutively admitted for Crohn's disease-related abscess to our institution during a 7-year period, underwent nonsurgical treatment as initial therapy. METHODS: Outcome data such as recurrence and intractability, and clinical features were retrospectively analysed. Univariate analysis with patient-related factors and abscess-related factors was performed for risk factor identification. RESULTS: Median follow-up period was 47.5 months. Of the eligible patients, 19 patients were treated medically and 5 patients underwent percutaneous catheter drainage with medical treatment. Overall success rate of nonsurgical treatment in our centre was 66.7%. The cumulative recurrence rate at 7 months was 12.5%. All recurrences occurred within 7 months from complete resolution on follow-up imaging. Univariate analysis showed that the significant factors which lead to failure of nonsurgical treatment were presence of associated fistula and concurrent steroid use (P=0.019 and P=0.019, respectively). CONCLUSION: Nonsurgical treatment can be considered as initial treatment modality for the Crohn's disease-related abscess without concurrent steroid therapy or relevant fistula.

The role of follow-up endoscopy after total gastrectomy for gastric cancer.

BACKGROUND: Follow-up endoscopy after total gastrectomy for gastric cancer is commonly performed without there being any definite evidence of clinical relevance. Therefore, we investigated the role of the upper endoscopic examinations after total gastrectomy for gastric cancer. METHODS: The medical records of 212 early gastric cancer (EGC) patients and 622 advanced gastric cancer (AGC) patients who underwent follow-up endoscopic examination after total gastrectomy between 1994 and 2001 were reviewed. RESULTS: Two of 212 EGC patients and 233 of 622 AGC patients revealed tumour recurrence at all sites. All the endoscopically accessible local tumour recurrences (n=24) were found in the AGC group. Anastomosis site stenosis was detected in 72 of 834 patients. CONCLUSION: Follow-up endoscopy after total gastrectomy for gastric cancer is useful in detecting complications and tumour recurrence. However, this procedure has a limited role in the clinical management and overall survival for patients with recurrent gastric adenocarcinoma.

Does this patient have oesophageal motility abnormality or pathological acid reflux?

BACKGROUND AND AIMS: The diagnostic values of particular symptoms centred on oesophagus, among patients with suspected oesophageal motility abnormality or pathological acid exposure, are not yet fully understood. The aim of this study was to determine the predictive accuracy of these symptoms in diagnosis of oesophageal motility disorder or pathological acid exposure. PATIENTS AND METHODS.: A total of 462 patients who had undergone conventional oesophageal manometry and ambulatory 24-h pH monitoring to investigate a clinical suspicion of oesophageal motility disorder and pathological acid exposure were enrolled in this study. According to their principal complaints, the patients were divided into the dysphagia category, the non-cardiac chest pain category, the gastrooesophageal reflux disease-related symptom category and the extraoesophageal symptom category. RESULTS: Two hundred and two (44%) out of 462 patients yielded abnormal findings on manometry and/or pH monitoring. Dysphagia was associated with a likelihood ratio (LR) of 2.11 [95% confidence interval (CI), 1.02-4.00)] in patients exhibiting a combination of oesophageal motility abnormality and pathological acid exposure. During oesophageal manometry, the dysphagia substantially increased the likelihood of classic achalasia (LR, 6.24; 95% CI, 3.32-8.78) and diffuse oesophageal spasm (LR, 3.58; 95% CI, 1.03-7.12). When the patients with dysphagia were divided into two groups according to the severity of their symptoms, classic achalasia was significantly frequent in patients with severe dysphagia (P = 0.016). On the other hand, non-cardiac chest pain was the clinical factor that reduced the likelihood of classic achalasia (LR, 0.22; 95% CI, 0.04-0.93). The distribution of pathological acid exposure was significantly frequent between the groups of patients with and without gastrooesophageal reflux disease-related symptom (P = 0.011). CONCLUSION: A small number of oesophageal symptoms are helpful in predicting the likelihood of abnormal findings on oesophageal tests among patients with a clinical suspicion of oesophageal motility disorder and pathological acid exposure. The most useful finding is a severe dysphagia, which is likely to have classic achalasia.

Efficacy of low-dose clarithromycin triple therapy and tinidazole-containing triple therapy for Helicobacter pylori eradication.

BACKGROUND: Proton pump inhibitor-based triple therapies are recommended as the first-line treatment for Helicobacter pylori eradication. AIM: To evaluate the efficacies of low-dose clarithromycin triple therapy and tinidazole-containing triple therapy in a metronidazole resistance prevalent area and to compare the efficacies with standard triple therapy. METHODS: In a randomized, multicentre, prospective study, a total of 352 patients with duodenal ulcer or non-ulcer dyspepsia were randomly divided into three groups according to the administered regimen: OAC250 group (omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 250 mg), OAC500 group (omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg) and OTC group (omeprazole, 20 mg, tinidazole, 500 mg, and clarithromycin, 500 mg). The three groups received each regimen twice daily for 7 days. Upper gastrointestinal endoscopy was performed before and 4 weeks after treatment. H. pylori status was determined by rapid urease test and 13C urea breath test. RESULTS: The eradication rates in the OAC250, OAC500 and OTC groups were 76.2%, 65.7% and 64.8% (95% confidence interval: 67.9-84.4%, 56.7-74.8% and 55.7-73.9%), respectively, by intention-to-treat analysis (P=0.149) and 92.8%, 87.2% and 84.1% (95% confidence interval: 84.4-97.3%, 77.9-93.8% and 73.9-91.2%), respectively, by per protocol analysis (P=0.088). All regimens were well tolerated and compliance was excellent. CONCLUSIONS: Both low-dose clarithromycin triple therapy and tinidazole-containing triple therapy are effective and safe regimens for H. pylori eradication.

Intracellular Ca2+ oscillations in vascular smooth muscle cells.

We monitored caffeine- and histamine-induced [Ca2+]i oscillations by patch-clamp whole-cell recordings of K(Ca)-current in single smooth muscle cells of rabbit cerebral (basilar) artery. Superfusion of caffeine (1 mM) or histamine (1-3 microM) induced periodic oscillations of large whole-cell K-current with fairly uniform amplitudes and intervals. Repetitive activations of the large-conductance K(Ca)-channels were recorded in the cell-attached patch mode. Inclusion of heparin (3 mg/ml) in the pipette solution failed to inhibit the oscillations caused by caffeine treatment, but blocked histamine-evoked oscillations. Ryanodine (1-10 microM) abolished both caffeine- and histamine-induced oscillations. Removal of extracellular Ca2+, but not verapamil or Cd2+, abolished the caffeine-induced oscillations, and the changes in the oscillatory frequency closely reflected the altered Ca2+ influx rate. These results indicate that in smooth muscle cells of the rabbit cerebral artery, ryanodine-sensitive Ca(2+)-induced Ca2+ release (CICR) pools play key roles for the generation of the [Ca2+]i oscillations.

Colonoscopic manifestations of typhoid fever with lower gastrointestinal bleeding.

BACKGROUND: Intestinal bleeding in patients with typhoid fever usually occurs in the ileum. However, endoscopic findings in such patients are not well established. We examined the colonoscopic manifestations of intestinal lesions with bleeding in patients with typhoid fever. PATIENTS AND METHODS: The colonoscopic findings of seven patients who presented with haematochezia due to typhoid fever were reviewed retrospectively. Typhoid fever was diagnosed when the Salmonella typhi was isolated or when the Widal test showed strongly positive reactions. RESULTS: Clinical data and colonoscopic findings were reviewed in seven patients (four men and three women with an average age of 42 years). The most commonly involved area was the terminal ileum (100%), followed by the ileocecal valve (57%), the ascending colon (43%), and the transverse colon (29%). Left colon was intact in all cases. The most common colonoscopic finding was multiple variable-sized punched-out ulcers with slightly elevated margin, as found in five patients. In two patients, only several oedematous hyperaemic mucosal patches with haemorrhagic spots or shallow erosions were seen. Active bleeding was noticed only in one patient, who received endoscopic haemostasis twice. The remaining six patients were treated by conservative treatment including antibiotic therapy. There was no complication during or after the colonoscopic examination. CONCLUSIONS: Intestinal bleeding in typhoid fever usually occurs from the ulcers in the ileum or proximal colon, and the most common colonoscopic manifestations are multiple variable-sized punched-out ulcerations.

Role of autonomic dysfunction in patients with functional dyspepsia.

BACKGROUND: The role of autonomic dysfunction in patients with functional dyspepsia is not completely understood. AIMS: 1. to prospectively assess abnormalities of autonomic function in patients with functional dyspepsia, 2. to assess whether autonomic dysfunction in these patients is associated with a. visceral hypersensitivity or b. delayed gastric emptying or c. severity of dyspeptic symptoms. PATIENTS: A series of 28 patients with functional dyspepsia and 14 healthy volunteers without gastrointestinal symptoms were studied. METHODS: All patients and controls were submitted to a battery of five standard cardiovascular autonomic reflex tests, dyspeptic questionnaire, gastric barostat tests and gastric emptying tests. RESULTS: 1. Autonomic function tests showed that both sympathetic and parasympathetic scores of dyspeptic patients were significantly higher than in controls; 2. visceral hypersensitivity was confirmed in dyspeptics in response to proximal gastric distension, demonstrating lower pain threshold; 3. delayed gastric emptying occurred more frequently in patients with functional dyspepsia than in controls; 4. epigastric pain and epigastric burning were significantly more prevalent in patients with definite evidence of autonomic dysfunction; 5. No significant association was found between presence of autonomic dysfunction and presence of visceral hypersensitivity or presence of delayed gastric emptying in patients with functional dyspepsia. CONCLUSIONS: We concluded that a possible role of autonomic dysfunction in eliciting dyspeptic symptoms could not be determined from alterations in visceral hypersensitivity or delayed gastric emptying. Autonomic dysfunction might not be the major explanation for symptoms associated with functional dyspepsia.

Increased risk of peristomal wound infection after percutaneous endoscopic gastrostomy in patients with diabetes mellitus.

BACKGROUND: Results of prospective studies on the effect of prophylactic antibiotics before percutaneous endoscopic gastrostomy are conflicting. Factors for increased risk of peristomal wound infection have not been clearly identified. AIM: To evaluate the incidence of complications of percutaneous endoscopic gastrostomy and to determine the predictors of wound infection. PATIENTS AND METHODS: Percutaneous endoscopic gastrostomy was performed on 134 patients in different disease groups between January 1996 and June 2000. Medical records were carefully reviewed for demographic data, indications for percutaneous endoscopic gastrostomy, use of prophylactic antibiotics, complications and comorbid conditions predisposing to wound infection. RESULTS: Of 134 patients, 22 (16.4%) developed complications after percutaneous endoscopic gastrostomy Wound infection, the most common complication, occurred in 19 patients (14.2%) and Pseudomonas aeruginosa was the most frequently isolated microorganism. In univariate analysis, non-malignant disease and diabetes mellitus were significantly associated with peristomal wound infection after percutaneous endoscopic gastrostomy. In multivariate analysis, only diabetes mellitus was an independent risk factor for the development of peristomal wound infection after percutaneous endoscopic gastrostomy (p = 0.035) CONCLUSIONS: Patients with diabetes mellitus have a higher risk of peristomal wound infection after percutaneous endoscopic gastrostomy.

Outcomes in patients with hepatopulmonary syndrome undergoing liver transplantation.

Hepatopulmonary syndrome (HPS) is a condition of significant hypoxia due to intrapulmonary shunting (IPS) in patients with advanced liver disease. Reversibility of HPS after liver transplantation (LT) has been suggested, but the results of LT for HPS remain poorly defined. We studied 78 patients with decompensated liver disease who underwent LT after a preoperative evaluation including contrast echocardiography. We compared the baseline characteristics and outcomes after LT in patients with HPS (n = 13) with those of patients without HPS (n = 65, controls). Before LT, prolongation of prothrombin time was more severe and an advanced Child-Pugh class were more frequent among HPS, patients compared with controls (INR 2.5 +/- 0.8 vs 1.9 +/- 0.7, P = .01; Child-Pugh class A:B:C = 0%:31%:69% vs 14%:65%:21%, P < .01). After LT, no significant differences were observed between the two groups in: clinical outcomes, duration of endotracheal intubation (4.5 +/- 7.7 vs 4.4 +/- 15.0 days), duration of intensive care unit stay (12.0 +/- 8.7 vs 14.4 +/- 19.4 days), duration of total hospital stay (40.0 +/- 33.5 vs 39.8 +/- 23.0), rate of pulmonary complications (7.7% vs 9.2%), or 3-month survival rates (92.3% vs 86.1%). These findings suggest that the presence of HPS does not significantly affect LT outcomes in patients with decompensated liver disease.

Interpretation of overall colonic transit in defecation disorders in males and females.

BACKGROUND: There is little information regarding gender-specific measurements of colonic transit and anorectal function in patients with defecation disorders (DD). To compare overall colonic transit by gender in DD. METHODS: In 407 patients with constipation due to DD diagnosed by a single gastroenterologist (1994-2012), DD was characterized by anorectal manometry, balloon expulsion test, and colonic transit by scintigraphy. The primary endpoint was overall colonic transit (geometric center, GC) at 24 h (GC24). Effects of gender in DD on colonic transit, and comparison with transit in 208 healthy controls were assessed by Mann-Whitney rank sum test. Secondary endpoints were maximum anal resting (ARP) and squeeze (ASP) pressures. We also tested association of the physiological endpoints among DD females by pregnancy history and among DD patients by colectomy history. KEY RESULTS: The DD patients were 67 males (M) and 340 females (F). Significant differences by gender in DD patients were observed in GC24 (median: M: 2.2; F: 1.8; P = 0.01), ARP (median: M: 87.8 mmHg; F: 82.4 mmHg; P = 0.04), and ASP (median: M: 182.4 mmHg; F: 128.7 mmHg; P < 0.001). GC24 was slower in DD compared with same-gender healthy controls. GC24 did not differ among DD females by pregnancy history. Anorectal functions and upper GI transit did not differ among DD patients by colectomy history. CONCLUSIONS & INFERENCES: Patients with DD have slower colonic transit compared with gender-matched controls. Among DD patients, males have higher ARP and ASP, and females have slower colonic transit. Although the clinical significance of these differences may be unclear, findings suggest that interpretation of these tests in suspected DD should be based on same-gender control data.

Inhibition of cell proliferation and invasion in a human colon cancer cell line by 5-aminosalicylic acid.

BACKGROUND: 5-Aminosalicylic acid lacks the well-known side effects associated with the long-term use of non-steroidal anti-inflammatory drugs. We investigated anti-carcinogenic mechanisms of 5-aminosalicylic acid on a colon cancer cell line. METHODS: MTT analysis was performed for various colon cancer cell lines. The expression of NF-kappaB and metalloproteinases was examined in either HT-29 cells treated with IL-1beta and/or 5-aminosalicylic acid. Matrigel assay was used to evaluate invasive potential of HT-29 cells. Analysis of a cDNA microarray containing 8700 genes was performed to identify the alteration of gene expression in response to treatment to 5-aminosalicylic acid. RESULTS: The use of MTT analysis showed that 5-aminosalicylic acid suppressed the growth of HT-29 cells. The activity of NF-kappaB was also decreased by combined-treatment with IL-1beta and 5-aminosalicylic acid. The use of an ELISA and zymography demonstrated that MMP-2 and MMP-9 enzyme activity were decreased in HT-29 cells by treatment with various concentration of 5-aminosalicylic acid. A matrigel analysis demonstrated that 5-aminosalicylic acid treatment on HT-29 significantly inhibited the invasiveness of the cells. In cDNA microarray, 163 genes following 5-aminosalicylic acid exposure showed altered expression. CONCLUSIONS: This study indicated that 5-aminosalicylic acid suppresses the growth of human colon cancer cells and is able to inhibit MMPs expression via NF-kappaB mediated cell signals and invasiveness.