Algorithm for detection of small-bowel metastasis in malignant melanoma of the skin.

BACKGROUND AND STUDY AIM: The aim of this study was to develop an algorithm to detect small-bowel metastasis (SBM) of melanoma by sequential laboratory parameters and pan-intestinal endoscopy (PIE) including video capsule endoscopy (VCE). PATIENTS AND METHODS: A total of 390 melanoma patients (AJCC stage I/II/III/IV, 140/80/121/49) were screened for signs of intestinal blood loss (fecal occult blood test [FOBT] or overt bleeding) in an open, multicenter, prospective study, and those who were positive underwent PIE. Independent of the presence of intestinal bleeding, all stage IV patients were offered PIE. Follow-up was obtained in 357 patients (91.5 %) for a median of 16 months. We undertook to identify possible associations between SBM and clinical and laboratory data. Survival data were analyzed with regard to clinical and laboratory data and small-bowel findings. RESULTS: Intestinal blood loss was suspected in 49 of 390 patients (12.6 %), 38 of whom (77.6 %) agreed to undergo endoscopy. In 10 patients, SBM was detected by VCE (intention-to-diagnose, 20.4 %; AJCC III, n = 2; AJCC IV, n = 8). The SBM was resected in five patients. Total detection rates of SBM were 14 of 49 patients in stage IV (28.6 %, intention-to-diagnose), 2 of 121 in stage III (1.7 %), and 0 in stage I/II. In FOBT-positive patients, SBM detection rates were 72.7 %, 14.3 %, and 0 % in tumor stages IV, III, and I/II, respectively. Positive FOBT proved to be an independent negative prognostic factor for total survival in stage III and IV melanoma. CONCLUSIONS: SBMs are frequent in advanced melanoma. In stage III patients, screening for intestinal blood loss by PIE may help to identify SBMs. In stage IV, indication for PIE should depend on the individual consequences of detecting SBM, but not on bleeding symptoms alone.

Endoscopy in Barrett's oesophagus: adherence to standards and neoplasia detection in the community practice versus hospital setting.

OBJECTIVE: Potential process differences between hospital and community-based endoscopy for Barrett's oesophagus have not been examined. We aimed at comparing adherence to guidelines and neoplasia detection rates in medical centres (MC) and community practices (CP). DESIGN: Retrospective analysis. SETTING: All histologically confirmed Barrett cases seen over a 3-year period in six MC and 19 CP covering a third of all upper gastrointestinal endoscopies (n = 126,000) performed annually in Berlin, Germany. MAIN OUTCOME MEASURE: Rate of relevant neoplasia (high-grade intraepithelial neoplasia or more) in both settings in relation to adherence to standards. RESULTS: Of 1317 Barrett cases, 66% were seen in CP. CP patients had a shorter mean Barrett length (2.6 cm vs. 3.8 cm; P < 0.001) with fewer biopsies taken during an examination (2.5 vs. 4.1 for Barrett length

Esophageal capsule endoscopy in patients with suspected esophageal disease: double blinded comparison with esophagogastroduodenoscopy and assessment of interobserver variability.

BACKGROUND AND STUDY AIMS: The study aim was to compare the diagnostic yield of capsule endoscopy and esophagogastroduodenoscopy (EGD) in patients with suspected esophageal disease. Secondary aims were to assess interobserver variability of capsule endoscopy readings and safety. PATIENTS AND METHODS: In total, 98 patients (53 men, 53 +/- 13 years) with an indication for EGD were included. The patient population was artificially enriched to include two thirds of patients with abnormal esophageal findings at EGD, which was followed by capsule endoscopy. Capsule recordings were blindly read by three endoscopists, one from the center that recruited the patient and two from the other center. Study outcomes were the findings described on EGD and capsule endoscopy, agreement between EGD and capsule endoscopy for findings, quality of the capsule recording, and interobserver agreement for capsule endoscopy quality and findings. RESULTS: EGD was normal in 34 patients and showed esophageal findings in 62 (esophagitis 28, hiatus hernia 21, varices 21, Barrett's esophagus 11, others 7). Average esophageal transit time of the capsule was 361 +/- 393 seconds. Capsule endoscopy was normal in 36 patients but detected esophagitis in 23, hiatus hernia in 0, varices in 23, Barrett's esophagus in 18, and others in 4. The positive predictive value of capsule endoscopy was 80.0 % and the negative predictive value was 61.1 %. Overall agreement per patient was moderate between EGD and capsule endoscopy for the per-patient (kappa = 0.42) and per-findings (kappa = 0.40) analyses. Interobserver agreement between capsule endoscopy readings was moderate for findings (kappa = 0.39) and quality assessment (kappa = 0.24). No adverse event was observed after either EGD or capsule endoscopy. CONCLUSION: In this study, despite artificial prevalence enrichment, capsule endoscopy showed a moderate sensitivity and specificity in the detection of esophageal diseases.

Macroscopic appearance of intestinal angiodysplasias under antiangiogenic treatment with thalidomide.

BACKGROUND AND STUDY AIMS: Angiodysplasias are the main cause of bleeding from the small intestine. Single lesions may be treated by endoscopic coagulation or surgical resection. However, multiple disseminated angiodysplasias are frequently present, making local therapy an unfavorable choice or impossible. Currently there is no established medical treatment available for these patients. Thalidomide is a potent inhibitor of angiogenesis in experimental models. As angiodysplasias are a result of unregulated vessel growth, antiangiogenic treatment may inhibit growth of angiodysplasias. PATIENTS AND METHODS: We studied the effect of thalidomide on the macroscopic appearance of angiodysplasias in three patients with bleeding due to multiple angiodysplasias of the small intestine. During the previous 12 months patients had experienced 3 - 7 bleeding episodes and had received a mean of 16.7 blood units. RESULTS: After start of treatment with thalidomide at a dose of 100 mg daily, no further bleeding episodes occurred. Although thalidomide was stopped after 3 months, bleeding did not recur and hemoglobin reached and maintained normal levels without further transfusions for the whole observation period (mean follow-up 34 months). Repeat wireless capsule endoscopy after 3 months' thalidomide demonstrated substantial reductions in the number, size, and color intensity of angiodysplasias. CONCLUSION: Thalidomide seems to inhibit growth of intestinal angiodysplasias and may be useful for treatment of patients with bleeding related to angiodysplasias. Wireless capsule endoscopy allows monitoring of the macroscopic effects of antiangiogenic therapy.

Does passage of a patency capsule indicate small-bowel patency? A prospective clinical trial?

BACKGROUND AND STUDY AIMS: At many centers wireless capsule endoscopy (WCE) without prior radiographic examination to rule out relevant strictures is considered to be contraindicated in suspected obstructive small-bowel disease. However, the accuracy of radiography in this situation has often been questioned. The purpose of this prospective study was to investigate the feasibility and safety of the recently developed patency capsule, and its predictive value regarding the clinical relevance of radiographic small-bowel strictures. PATIENTS AND METHODS: 22 patients with suspected obstructive small-bowel disease and/or radiological evidence of small-bowel strictures underwent a patency capsule examination. Intact passage, patient experience of pain, and capsule disintegration were correlated with radiographic findings, clinical variables, and outcome. RESULTS: 13 patients passed an intact capsule without complaints, despite radiographically observed small-bowel stenosis; the subsequent video capsule examination was uneventful in all. In nine patients either intact passage was painful or the capsule disintegrated; in one of these, impaction of an intact capsule led to an ileus and emergency surgery. The type of capsule passage did not correlate with radiographic presence of a stricture, underlying diagnosis, or previous surgery. There was a statistically significant correlation between outcome (surgery performed or recommended) and occurrence of painful capsule passage and disintegration ( P < or = 0.05). CONCLUSIONS: Painless egestion of an intact patency capsule indicates safety of WCE. Patients without obstructive symptoms require neither small-bowel radiography nor a patency capsule study prior to WCE. Disintegration of the patency capsule or painful passage seems to be associated with a clinically relevant small-bowel stricture and with a high probability of surgery.

Small bowel involvement in Crohn's disease: a prospective comparison of wireless capsule endoscopy and computed tomography enteroclysis.

BACKGROUND: Wireless capsule endoscopy (WCE) offers endoscopic access to the small bowel and may therefore change diagnostic and therapeutic strategies in small bowel diseases. AIM: The aim of this prospective study was to validate the gain in information and therapeutic impact of WCE in patients with Crohn's disease. METHODS: Fifty six consecutive patients with Crohn's disease underwent computed tomography (CT) enteroclysis, and if stenoses <10 mm were excluded, WCE was carried out. RESULTS: In 15 patients (27%), WCE could not be performed due to strictures detected by CT enteroclysis. From the other 41 patients, jejunal or ileal lesions were found in 25 patients by WCE compared with 12 by CT enteroclysis (p=0.004). This gain in information was mainly due to detection of small mucosal lesions such as villous denudation, aphthoid ulcerations, or erosions. Both methods were not significantly different in the detection of lesions in the terminal/neoterminal ileum (WCE 24 patients, CT enteroclysis 20 patients). Therapy was changed due to WCE findings in 10 patients. Consecutively, all of them improved clinically. CONCLUSIONS: Capsule endoscopy improves the diagnosis of small bowel Crohn's disease. This may have significant therapeutic impact.

Diagnostic yield of wireless capsule enteroscopy in comparison with computed tomography enteroclysis.

BACKGROUND AND STUDY AIMS: It is still difficult to visualize changes in the small intestine. Wireless capsule enteroscopy is a new method that promises to provide new insights into the small intestine. In a prospective study, the diagnostic yield of wireless enteroscopy was therefore compared with computed tomography (CT) enteroclysis. PATIENTS AND METHODS: Twenty-two patients with suspected small-bowel pathology underwent CT enteroclysis and wireless capsule enteroscopy examinations, conducted by two independent blinded investigators. The results of the two investigations (diagnoses and the number, extent, and location of lesions detected) were compared by a third investigator. RESULTS: The patients included in the study had obscure gastrointestinal bleeding (n = 8), Crohn's disease (n = 8), unexplained diarrhea (n = 5), or suspected carcinoid tumor (n = 1). Pathological lesions were detected using capsule enteroscopy in 13 patients (59 %) and using CT enteroclysis in eight (36 %; P = 0.12). In seven patients (one case each of colonic Crohn's disease, diverticulitis, Meckel's diverticulum, carcinoid tumor, mesothelioma, colonic polyps, and irritable bowel syndrome), no pathological changes were found in the small intestine using either method. The diagnosis was established by wireless capsule enteroscopy in four patients with obscure bleeding, whereas CT enteroclysis was positive in only one patient ( P = 0.1). Crohn's disease was found in two patients with unexplained diarrhea. Small-bowel lesions were identified in six patients with known Crohn's disease using capsule enteroscopy or CT enteroclysis. The only side effect of wireless capsule enteroscopy observed was abdominal pain in one patient with Crohn's disease. There were no serious side effects with CT enteroclysis. CONCLUSIONS: Wireless capsule enteroscopy detects more small-bowel lesions than CT enteroclysis in patients with obscure gastrointestinal bleeding and Crohn's disease.

Gastric outlet obstruction and pulmonary infiltrate in a patient with Crohn's disease: successful treatment by Billroth-II-resection.

We present a 28-year-old women with a 3 yr history of duodenal ulcers. Following four treatment attempts to eradicate helicobacter pylori she was admitted because of gastric outlet obstruction and a weight loss of 20 kg within the last two years. Endoscopy and x-ray showed a circular inflammatory stenosis of the proximal duodenum extending over 8 cm. Additionally, chest x-ray showed a circumscript infiltrate in the third segment of the right lung. Mycobacterial infection could be excluded. Ileocolonoscopy and small intestinal follow-through beyond the duodenum were unremarkable, and Zollinger-Ellison-syndrome was ruled out. Bronchopulmonary histology showed intramucosal epithelioid-cell granulomas and bronchiolitis obliterans. Because the patient did not improve under conservative therapy a Billroth-II-resection was carried out. Histologically the resected specimen showed Crohn-like lesions. Postoperatively, severe peripheral arthritis was treated by steroids over 6 weeks. At follow-up the patient regained 20 kg and was free of symptoms without any medication. The pulmonary infiltrate had subsided almost completely. In summary, this extremely rare coincidence of isolated stenosing duodenal Crohn's disease and pulmonary involvement was successfully treated by Billroth-II-resection. This course of disease is compatible with the hypothesis that Crohn's disease may be maintained by antigens derived from ingested food.

Dysplasia of the submucous nerve plexus in slow-transit constipation of adults.

AIM: A clinicopathological entity, intestinal neuronal dysplasia type B (IND) has been described in children with severe constipation. The present study was designed to evaluate whether IND could be identified in adult patients with idiopathic slow-transit constipation. METHODS: Rectal biopsies were taken from 27 constipated patients with documented slow colonic transit and 23 controls and stained for S100 protein, acetylcholine esterase and lactate dehydrogenase. The mean and maximal number of ganglion cells per ganglion, mean number of ganglia and mean number of ganglion cells per mm2 of submucosal tissue, mean and maximal diameter of ganglion cells, maximal thickness of submucosal nerve fibres, and number of S100-positive cells per mm2 mucosal tissue were quantified. The density of submucosal ganglia, presence of heterotopic ganglion cells, intensity of staining of the adventitial layer of submucosal arteries, and density of nerve fibres in submucosa and lamina propria were evaluated qualitatively. In addition, subjective evaluation by an experienced pathologist was performed. RESULTS: There were no major differences between patients and controls, except that patients had slightly thicker submucosal nerves than controls (30.8 +/- 1.6 versus 25.5 +/- 2.0 microm, P < 0.05) and more frequent heterotopic ganglion cells (32 versus 6%, P < 0.05). Neither discriminant analysis of the morphometric data nor subjective evaluation was able to correctly classify the slides as originating from patients or controls. CONCLUSIONS: The existence of the clinicopathological entity IND in adults with slow-transit constipation is unlikely. For further classification of slow-transit constipation, rectal biopsies do not appear to be useful at present.

Paradoxical sphincter contraction is rarely indicative of anismus.

BACKGROUND: Anismus is thought to be a cause of chronic constipation by producing outlet obstruction. The underlying mechanism is paradoxical contraction of the anal sphincter or puborectalis muscle. However, paradoxical sphincter contraction (PSC) also occurs in healthy controls, so anismus may be diagnosed too often because it may be based on a non-specific finding related to untoward conditions during the anorectal examination. AIMS: To investigate the pathophysiological importance of PSC found at anorectal manometry in constipated patients and in patients with stool incontinence. METHODS: Digital rectal examination and anorectal manometry were performed in 102 chronically constipated patients, 102 patients with stool incontinence, and in 18 controls without anorectal disease. In 120 of the 222 subjects defaecography was also performed. Paradoxical sphincter contraction was defined as a sustained increase in sphincter pressure during straining. Anismus was assumed when PSC was present on anorectal manometry and digital rectal examination and the anorectal angle did not widen on defaecography. RESULTS: Manometric PSC occurred about twice as often in constipated patients as in incontinent patients (41.2% versus 25.5%, p < 0.017) and its prevalence was similar in incontinent patients and controls (25.5% versus 22.2%). Oroanal or rectosigmoid transit times in constipated patients with and without PSC did not differ significantly (total 64.6 (8.9) hours versus 54.2 (8.1) hours; rectosigmoid 14.9 (2.4) hours versus 13.8 (2.5) hours). CONCLUSIONS: Paradoxical sphincter contraction is a common finding in healthy controls as well as in patients with chronic constipation and stool incontinence. Hence, PSC is primarily a laboratory artefact and true anismus is rare.

Symptoms in chronic constipation.

OBJECTIVES: This study was designed to evaluate whether detailed symptom analysis would help to identify pathophysiologic subgroups in chronic constipation. METHODS: In 190 patients with chronic constipation (age, 53 (range, 18-88) years; 85 percent of whom were women), symptom evaluation, transit time measurement (radiopaque markers), and functional rectoanal evaluation (proctoscopy, anorectal manometry, defecography) were performed. Patients were classified on the basis of objective data from all tests in four different groups ("disordered defecation," "slow gastrointestinal transit," "disordered defecation combined with slow-transit stool," and "no pathologic finding"). RESULTS: In 59 percent of patients, disordered defecation was found, and 27 percent had slow-transit stool. In 6 percent of patients, a combination of both was found; in only 8 percent of patients, there were no pathologic findings. Straining was reported by the vast majority in all groups (82-94 percent). Infrequent bowel movements and abdominal bloating were more common in slow-transit stool (87 and 82 percent vs. 69 and 55 percent, respectively; both P < 0.01). Feeling of incomplete evacuation was more common in disordered defecation (84 vs. 46 percent; P < 0.0001). However, specificity of these symptoms was discouraging (for slow-transit stool: infrequent bowel movements had a sensitivity of 87 percent and a specificity of 32 percent and abdominal bloating had a sensitivity of 82 percent and specificity of 45 percent; for disordered defecation: feeling of incomplete evacuation had a sensitivity of 84 percent and a specificity of 54 percent). Only the sense of obstruction and digital maneuvers were acceptably specific (79 and 85 percent, respectively) for disordered defecation, but sensitivity was low. CONCLUSIONS: Definition of chronic constipation by infrequent bowel movements alone is of little value; the symptom "necessity to strain" is much better suited (94 percent sensitivity). Specificity of infrequent bowel movements for slow-transit stool was discouraging. Sense of obstruction and digital manipulation for evacuation are relatively specific for disordered defecation but insensitive. Therefore, symptoms of chronically constipated patients are not well suited to differentiate between the pathophysiologic subgroups suffering chronic constipation.

[Intra-individual comparison of gastric peristalsis after ingestion of a semiliquid and solid test meal]. / Intraindividueller Vergleich der Magenperistaltik nach Gabe von semiliquiden und festen Testmahlzeiten.

AIM: Patients with various disorders of gastric function were studied with radiolabeled test meals of different consistency to elaborate the effect of ingested media on gastric peristalsis and emptying. METHODS: In 12 patients parameters of gastric function were intraindividually compared after ingestion of a semiliquid and a solid test meal. In addition to the standard evaluation derived from time activity curves condensed images were established from two fixed time intervals (early and late period). These images were used to evaluate the amplitude and frequency of gastric contractions using Fourier analysis. RESULTS: As expected gastric emptying was influenced by the consistency of the test meal. Mean emptying rates for the solid meal were significant lower than those for the semiliquid one (p < 0.01). The amplitude and frequency of gastric contractions, however, did not depend on the consistency of the test meal. Within the course of the examination contraction amplitudes significantly increased (p < 0.05) from the early to the late period using both, solid as well as semiliquid test meals. The frequency of gastric contractions remained unchanged. CONCLUSION: As shown by an intraindividual data comparison amplitude and frequency of gastric contractions seem to be independent of the consistency of ingested test meals whereas gastric emptying is significantly influenced by the administered media. Semiliquid meals offer advantages with respect to the shorter examination time and simpler preparation and therefore may be preferred for routine use. Since amplitudes seem to vary within the observation period standardized acquisition protocols are recommended for the evaluation of this parameter.

Clinical response to dietary fiber treatment of chronic constipation.

OBJECTIVES: To determine the clinical outcome of dietary fiber therapy in patients with chronic constipation. METHODS: One hundred, forty-nine patients with chronic constipation (age 53 yr, range 18-81 yr, 84% women) at two gastroenterology departments in Munich, Germany, were treated with Plantago ovata seeds, 15-30 g/day, for a period of at least 6 wk. Repeated symptom evaluation, oroanal transit time measurement (radiopaque markers), and functional rectoanal evaluation (proctoscopy, manometry, defecography) were performed. Patients were classified on the basis of the result of dietary fiber treatment: no effect, n = 84; improved, n = 33; and symptom free, n = 32. RESULTS: Eighty percent of patients with slow transit and 63% of patients with a disorder of defecation did not respond to dietary fiber treatment, whereas 85% of patients without a pathological finding improved or became symptom free. CONCLUSION: Slow GI transit and/or a disorder of defecation may explain a poor outcome of dietary fiber therapy in patients with chronic constipation. A dietary fiber trial should be conducted before technical investigations, which are indicated only if the dietary fiber trial fails.

Decreased substance P levels in rectal biopsies from patients with slow transit constipation.

OBJECTIVE: Previous studies in patients with chronic constipation found abnormalities in the nervous tissue of the large intestine, predominantly in the muscularis externa. Since there is evidence that the nervous system of mucosa and submucosa is also involved in the control of colonic motility we investigated the contents of vasoactive intestinal polypeptide (VIP), somatostatin and substance P in rectal biopsies of patients with slow colonic transit constipation. DESIGN AND METHODS: Twenty-two patients (17 females, 5 males) with chronic slow transit constipation (oro-anal transit with radio-opaque markers on high fibre diet > 70 h) and long-term use of laxatives, and 20 controls (12 females, 8 males) with no history of constipation, were included in this study. Large rectal biopsy specimens including the submucosa were obtained from 5 cm above the dentate line and frozen in liquid nitrogen. After microdissection of the biopsies into mucosa and submucosa the neuropeptides were extracted by boiling and homogenizing the tissue in acetic acid and determined using validated radioimmunoassays. RESULTS: Patients with slow transit constipation showed, compared to healthy controls, significantly lower levels of the excitatory neurotransmitter substance P in the mucosa and submucosa of rectal biopsies. There was no difference between the two groups concerning the levels of the inhibitory neurotransmitters, VIP and somatostatin. CONCLUSION: Slow transit constipation is associated with abnormalities of the substance P content of the enteric nervous system of mucosa and submucosa. This seems not to be related to chronic laxative use, since anthranoids cause a reduction in the levels of inhibitory neurotransmitters (VIP, somatostatin), but not of substance P, in the rat colon.

Reappraisal of quantitative esophageal scintigraphy by optimizing results with ROC analyses.

UNLABELLED: This study investigates whether systematic analyses of methodological issues contribute to improve and renew the diagnostic role of quantitate esophageal scintigraphy. METHODS: Forty-seven patients with normal (n = 26) and pathologic (n = 21) esophageal function were studied with scintigraphy and manometry, using the latter findings as the gold standard. Scintigraphic data were analyzed by receiver operator characteristic (ROC) methods to: establish the optimal decision threshold for six different quantitative parameters, evaluate their inherent discrimination capacity and compare liquid compared with solid bolus data. RESULTS: Quantitative parameters have shown remarkable differences in their potential to discriminate between normal and pathologic findings (percentage of emptying at definite time points > mean time > transit time > mean transit time > Tmax). Sensitivity of 95% at a specificity of 96% was the optimum obtained. At comparable specificity levels, solid bolus studies generally demonstrated higher sensitivity than liquid bolus studies. CONCLUSION: The diagnostic performance of optimized esophageal scintigraphy is close to that of manometry. Our findings do not only renew the role of esophageal scintigraphy as an accurate screening test for esophageal motility disorders but also invalidate recent reservations about the diagnostic potential of this method.

Diagnostic value of histology in non-erosive gastro-oesophageal reflux disease.

BACKGROUND: In the absence of oesophageal erosions longterm pH monitoring is the present gold standard for diagnosing gastro-oesophageal reflux disease (GORD). This method, however, is invasive, time consuming, expensive, and not generally available. AIMS: As histological changes have been described in GORD, this study looked at the possibility of whether the diagnosis of non-erosive reflux disease could be made by histological examination routinely during endoscopy. SUBJECTS: A total of 24 prospectively selected patients with symptoms suggestive of GORD and seven healthy volunteers. METHODS: Oesophageal erosions and other peptic lesions were excluded by oesophago-gastroduodenoscopy. Oesophageal pinch biopsy specimens were taken 2 cm and 5 cm above the oesophagogastric junction and evaluated blindly for the histological parameters cellular infiltration, basal zone hyperplasia, and papillary length. Twenty four hour pH monitoring was used as gold standard for the definition of reflux disease. It was abnormal in 13 patients (reflux patients) and normal in 11 patients (symptomatic controls) and in seven healthy volunteers. RESULTS: Sparse infiltration of the epithelium with lymphocytes in at least one biopsy specimen was found in all patients and volunteers, with neutrophils in three reflux patients, and with eosinophils in two reflux patients and in two healthy volunteers. The basal zone thickness was increased in three reflux patients, in one symptomatic control, and in one healthy volunteer. The papillary length was greater than two thirds of total epithelium in six of 13 reflux patients in contrast with none in 11 symptomatic controls (p < 0.05) and to one healthy volunteer. The sensitivity of the parameter papillary length hence was only 46%. CONCLUSIONS: Although gastro-oesophageal reflux produces slight histological changes apart from oesophageal erosions in a few subjects, none of the established histological parameters can fulfil the for the diagnosis of GORD in patients without visible oesophageal erosions.