A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) are frequently used in the treatment of irritable bowel syndrome (IBS) although evidence of their efficacy is scarce. AIM: Twenty three non-depressed IBS patients were recruited from a tertiary care centre and included in a crossover trial comparing six weeks of treatment with the SSRI citalopram (20 mg for three weeks, 40 mg for three weeks) with placebo. IBS symptom severity was the primary outcome measure, and depression and anxiety scores were also measured. The effect of acute administration of citalopram on colonic sensitivity and on colonic response to feeding was investigated as a putative predictor of symptomatic response to the drug. RESULTS: After three and six weeks of treatment, citalopram significantly improved abdominal pain, bloating, impact of symptoms on daily life, and overall well being compared with placebo. There was only a modest effect on stool pattern. Changes in depression or anxiety scores were not related to symptom improvement. The effect of acute administration of citalopram during a colonic barostat study did not predict clinical outcome. Analysis of the first treatment period as a double blind parallel arm study confirmed the benefit of citalopram over placebo. CONCLUSIONS: The SSRI citalopram significantly improves IBS symptoms, including abdominal pain, compared with placebo. The therapeutic effect is independent of effects on anxiety, depression, and colonic sensorimotor function.

The role of tension receptors in colonic mechanosensitivity in humans.

BACKGROUND: Perception of colonic distension, which is enhanced in a subset of patients with irritable bowel syndrome, requires activation of mechanoreceptors. In animal studies, distension activates both in series ("tension") and in parallel ("elongation") mechanoreceptors. During active contractions against a fixed volume balloon, tension receptors are activated without elongation of receptor activation. AIM: To evaluate the role of tension receptors in the perception of mechanical stimuli from the colon in healthy subjects. METHODS: A 700 ml balloon connected to a barostat-manometer assembly was placed in the descending colon of 10 healthy subjects. After volume controlled distension (50 ml/2 minutes) to assess the first perception threshold, fixed volume subthreshold distension (122 (16) ml) was maintained for a 30 minute period before and after administration of neostigmine 0.5 mg intravenously. Mean intraballoon pressure, number, amplitude, and duration of contractions, and frequency of sensations were analysed. The period after neostigmine was divided into 10 second intervals and evaluated for the occurrence of contractions and onset of sensations. Fisher's exact test was applied to calculate the sensation-contraction association probability (SAP) as (1.0-p)x100%. RESULTS: Neostigmine increased intraballoon pressure (p<0.01), number of contractions (p<0.01), and number of sensations (p<0.01) per minute in all subjects. In seven of 10 subjects a significant association (SAP >95%) was found between sensations and contractions. In the remaining subjects, contractions were not associated with sensations and had lower amplitude (p<0.05) and duration (p<0.01) compared with contractions in the other seven subjects. CONCLUSION: In humans, tension receptors are involved in mediating colonic mechanosensitivity.

Endoscopic laser therapy for palliation of patients with distal colorectal carcinoma: analysis of factors influencing long-term outcome.

BACKGROUND: Incurable rectal cancer often reduces the quality of life because of obstruction, bleeding, pain and tenesmus. For such symptoms palliative therapy is often carried out. METHODS: From 1986 to 1995, 219 patients, 118 men and 101 women, mean age 67 years, with distal colorectal adenocarcinoma were referred for palliative endoscopic laser therapy. In this retrospective analysis of outcome, patients were allocated to 3 subgroups according to their dominant symptom: obstruction, bleeding and others (soiling, diarrhea, tenesmus). After initial successful treatment, maintenance therapy was carried out in cases of obstruction at intervals of 2 to 4 months; patients with bleeding, tenesmus or diarrhea were retreated if there was recurrence of symptoms. RESULTS: Initial successful palliation was obtained in 198 patients (92%), with similar results in the 3 subgroups. Long-term, effective palliation was achieved in 160 patients (75%) of the total study population. Seventy-six patients (65.0%) with obstruction, 63 (82.9%) with bleeding and 21 (80.8%) with other symptoms remained symptom free until death or this analysis of results. There was a significantly negative relation between long-term successful outcome and local spread of the tumor in the obstruction (p = 0.040) and bleeding groups (p = 0.014). The total number of treatments was significantly higher if obstruction was present at presentation (p< 0.05) and if tumors were circumferential (p = 0.05). Major complications were perforation (4.1%), fistula (3.2%), abscess (1.7%) and bleeding (4.1%). There were 5 (possibly) procedure-related deaths. The survival rate was 44.4% at 1 year and 20.4% at 2 years. CONCLUSIONS: Laser therapy is effective for initial palliation but careful patient selection is necessary. Long-term palliation is less feasible in patients with obstruction.

Upper and lower gastrointestinal evaluation of elderly inpatients who are iron deficient.

PURPOSE: Iron deficiency anemia is commonly caused by chronic gastrointestinal blood loss, and a thorough examination of the gastrointestinal tract has become standard practice. In contrast, iron deficiency without anemia has hardly been studied, and its causes are less certain. The aim of the present study was to determine the diagnostic value of upper and lower gastrointestinal evaluation in elderly hospitalized patients with iron deficiency, irrespective of the hemoglobin level. PATIENTS AND METHODS: In a prospective study, 151 consecutive elderly patients with iron deficiency (serum ferritin level < 50 microg/L at two separate occasions) were investigated using esophagogastroduodenoscopy with colonoscopy (n = 90) or barium enema (n = 61). RESULTS: A potential upper gastrointestinal tract lesion was found in 47 (49%) of the 96 anemic patients and in 31 (56%) of the 55 nonanemic patients (P = 0.38). Nonanemic patients had a greater prevalence of erosive gastritis or duodenitis. Anemic patients (72%) were more frequently investigated with a colonoscopy than nonanemic patients (38%, P = 0.001), and a lower gastrointestinal lesion was found in 32% of the anemic patients and 16% of the nonanemic patients (P = 0.03). Cancer was the most common lesion in the colon; 11 of the 18 patients were asymptomatic. Site-specific symptoms, fecal occult blood loss, and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) were not associated with the detection of gastrointestinal lesions. In 9.5% of the patients with a benign upper gastrointestinal lesion, a synchronous colonic tumor was found. CONCLUSION: Elderly patients with iron deficiency should undergo endoscopic examination, irrespective of the hemoglobin level. The presence of gastrointestinal symptoms, a positive fecal occult blood test, and the use of NSAIDs are of limited value in guiding the diagnostic procedure.

A comparison of laser therapy, plastic stents, and expandable metal stents for palliation of malignant dysphagia in patients without a fistula.

BACKGROUND: Many options are available for palliation of inoperable malignant stenoses of the esophagus. We report our experience with different modalities of endoscopic therapy. METHODS: From 1986 to 1996, we treated 125 patients with dysphagia caused by unresectable malignant tumors with endoscopic therapy. Seventy patients were treated with laser therapy, 34 with a plastic endoprosthesis, and 21 with an expandable prosthesis. Therapeutic outcome and complication rates were analyzed for the three groups. RESULTS: Mean dysphagia score decreased in the same manner in all three groups. Major and minor complications were significantly more common in the plastic endoprosthesis group and in the metallic stent group compared with the laser therapy group. Therapy and patient survival were not significantly different among the three groups. CONCLUSIONS: Plastic and metal stents carry a high complication rate for a short period of palliation. Endoscopic laser therapy, in contrast, has a low complication rate. Laser therapy should be the first choice for palliation in malignant dysphagia in patients with a short life expectancy. Stents might be used when laser therapy fails, in the presence of fistulas, or in patients with a reasonable life expectancy.

Self-expandable metallic stents in the palliation of rectosigmoidal carcinoma: a follow-up study.

BACKGROUND: Currently applied endoscopic palliative treatment of advanced rectosigmoidal carcinoma is hampered by the cost of the equipment, the need for repeated, often painful treatment sessions, and the occurrence of complications. Metallic expandable stents are effective in the palliation of malignant esophageal and biliary stenoses. We evaluated the use of a new type of self-expandable nitinol stent in the palliation of rectosigmoidal carcinoma. METHODS: In 10 patients with advanced obstructing rectosigmoidal carcinoma, initial Nd:YAG laser treatment was performed if necessary to allow passage of a gastroscope. Subsequently, a self-expanding nitinol stent with flanged ends was inserted under combined fluoroscopic and endoscopic control. Endoscopic and clinical follow-up was carried out at regular intervals. RESULTS: After 2+/-0.4 sessions of initial laser therapy, minimal lumen diameter was 9+/-1 mm. Stent insertion was successful in 9 patients, increasing minimal lumen diameter to 14+/-1.2 mm (p < 0.005). In one patient, stent deployment was complicated by a sigmoid perforation, requiring surgery. After insertion, colorectal stents remained adequately positioned and free of obstruction for 103+/-31 days. Patient survival after stent placement was 204 +/-43 days. Stent migration occurred in 3 patients, after 38+/-10 days. Obstruction of the stent because of tumor ingrowth was observed in only one patient, after 268 days. CONCLUSION: Insertion of self-expandable nitinol stents in patients with rectosigmoidal carcinoma is technically feasible. Metallic stents are effective in the palliation of malignant rectosigmoid obstruction; they provide an alternative to repeated palliative laser therapy or palliative surgery.

Midazolam versus diazepam in lipid emulsion as conscious sedation for colonoscopy with or without reversal of sedation with flumazenil.

BACKGROUND: The efficacy and tolerance of midazolam (Dormicum R) versus diazepam in lipid emulsion (Diazemuls R, Dumex) was evaluated in a randomized, controlled, double-blind trial in 200 patients undergoing total colonoscopy. METHODS: Diazepam in a dosage of 11.2+/-2.3 mg and midazolam in a dosage of 5.3+/-1.1 mg were given over 2 minutes. Flumazenil in a dosage of 0.2 mg within 15 seconds was administered to 50% of patients after procedure. RESULTS: Diazepam and midazolam were equivalent as judged by sedation, recovery time, patient tolerance, and ease of examination. The effect of flumazenil (Anexate R, Roche) on the recovery time was not significant as most patients were fully awake by the end of the procedure. Midazolam induced significantly more amnesia, and the score for recall of the pain score was significantly less after 14 days in the midazolam group. There were only minor complications in both groups. CONCLUSIONS: We conclude that midazolam can be used safely in relatively fit patients between 17 and 65 years old and that it is the drug of choice if amnesia is desirable. As sole premedication this drug was insufficient in 42% of the patients (pain score was greater than 3), especially in young women.

Relation between endoscopic ultrasound findings and outcome of patients with tumors of the esophagus or esophagogastric junction.

BACKGROUND: Endoscopic ultrasound (EUS) is considered to be the best staging technique for cancer of the esophagus or the esophagogastric junction. This study evaluates the relation between preoperative EUS staging results of these tumors and survival. It also examines how EUS staging predicts resectability. METHODS: Survival data of 86 patients who underwent EUS for staging of tumors of the esophagus or esophagogastric junction were analyzed. Most patients (78 of 86) were treated surgically (73 resections, 5 bypasses). Eight patients did not undergo surgery. RESULTS: Survival of patients was significantly related to EUS T staging (log rank test: p = 0.05), EUS N staging (p = 0.02), detection of celiac lymph node metastasis (p = 0.0027), and the presence of stenosis (p = 0.02). Also, the endosonographic AJCC classification was significantly related to survival (p = 0.0012). Total accuracy for T staging amounted to 59%. Accuracy for recognition of transmural growth was 82%. There was a good association between endosonographic findings (EUS stage II, absence of lymph nodes) and the possibility of complete resection. Incomplete resection was less well predicted. CONCLUSION: Survival of patients with tumors of the esophagus or esophagogastric junction is strongly related to EUS TNM staging results. Tumor resectability is related to endosonographic findings. However, more advanced EUS findings do not necessarily predict unresectability.

Efficacy and safety of hydrostatic balloon dilatation of ileocolonic Crohn's strictures: a prospective longterm analysis.

Preliminary reports have suggested that dilatation using hydrostatic through the scope balloons may be useful for the treatment of Crohn's strictures, A prospective longterm follow up (mean (SD) 33.6 (11.2) months) was carried out in 55 Crohn's patients with 59 ileocolonic strictures submitted to 78 dilatation procedures. Hydrostatic balloons were used (Rigiflator, Microvasive) with a diameter of 18 mm on inflation. As soon as the balloons became available dilatation up to a diameter of 20 and 25 mm was attempted. The dilatations were performed under general anaesthesia using propofol (Diprivan). The patients were kept for one night in the hospital after dilatation. Seventy (90%) procedures were technically successful and passage of the stricture with a 13.6 mm diameter colonoscope was possible after 73% of the dilatations. Complications occurred in six patients (11%; 8% of procedures), including sealed perforations (n = 2), retroperitoneal perforations (n = 2), and intraperitoneal perforations (n = 2). Two of the patients were treated surgically with a one stage resection of the stricture and recovered uneventfully. Four patients were treated conservatively with intravenous fluids and antibiotics. There was no mortality. Dilatation completely relieved obstructive symptoms in 20 patients after one procedure, in another 14 patients after two (n = 13) or three (n = 1) dilatations. Total longterm success rate was 34 of 55 patients (62%). Nineteen patients (38%) were operated on because of persistent obstructive symptoms. The data show that endoscopic dilatation using the through the scope hydrostatic balloon system relieves obstructive symptoms resulting from ileocolonic Crohn's strictures. The procedure, however, carries a definite risk of perforation.

Efficacy and safety of hydrostatic balloon dilation of ileocolonic Crohn's strictures. A prospective long-term analysis.

Gastro-intestinal stricture frequently is a complication in Crohn's disease and often recurs after surgical resection. Stenosis with acute inflammation can be treated by anti-inflammatory medication. A conservative approach of sclerotic strictures has been possible since the introduction of Gruentzig balloon catheters for dilating stenosis in different parts of the gastro-intestinal tract. We present a prospective follow-up study in 55 patients, on the long-term results and safety of hydrostatic balloon dilations of ileo-colonic Crohn's strictures.

Endoscopic injection therapy to prevent rebleeding from peptic ulcers with a protruding vessel: a controlled comparative trial.

Seventy five patients with severely bleeding peptic ulcer were included in a controlled comparative trial to assess the efficacy and safety of endoscopic injection therapy in preventing rebleeding from peptic ulcers that presented at endoscopy with a protruding vessel. Twenty five patients were treated with injection of epinephrine followed by polidocanol, 25 were treated with injection of absolute alcohol, and 25 with sham injection. Rebleeding occurred in 44% of patients in the sham group, 40% of those treated with epinephrine and polidocanol, and in 20% of those treated with absolute ethanol. The difference in the haemostasis rate between the control and ethanol treated subjects nearly reached significance (p = 0.07). A second therapy session resulted in haemostasis rates of 68% in the epinephrine-polidocanol group and of 88% in the absolute ethanol group. These rates after two treatments as well as the emergency surgery rates (32% in the epinephrine-polidocanol group and 8% in the absolute ethanol group; p = 0.07) were not significantly different. In eight of the 11 patients with rebleeding in the sham treatment group, definitive haemostasis was achieved by elective injection therapy. Overall transfusion requirements were mean (SD) 6.0 (0.7) units in the sham group, 6.0 (0.9) in the epinephrine-polidocanol group, and 3.9 (0.5) in the absolute ethanol group. Only the difference between ethanol and sham was significant (p = 0.02). This study shows that injection with absolute ethanol reduces rebleeding in these patients and significantly lowers transfusion requirements. Absolute ethanol was superior to epinephrine-polidocanol, which was not significantly better than sham therapy.