Structured terminology for capsule endoscopy: results of retrospective testing and validation in 766 small-bowel investigations.

BACKGROUND AND STUDY AIMS: Capsule endoscopy (CE) is an effective means of investigating the small bowel in patients with gastrointestinal diseases. Computerized reports are frequently used in endoscopy, and the Minimal Standard Terminology (MST) has been promoted by endoscopy societies as the official vocabulary for endoscopy. The aims of this study were to design a lexicon for CE reports based on the principles of the MST and to validate lists of terms for describing findings and reasons for performing a CE by cross-matching them with the results of CE procedures collected during ongoing clinical studies. MATERIALS AND METHODS: A consensus-based Capsule Endoscopy Structured Terminology (CEST) was developed by experts involved in CE studies. Lists of terms suitable for CE were designed for the various sections of an endoscopic report. They were then correlated with the corresponding MST lists for duodenal and intestinal endoscopy. The results of 766 CE procedures, collected in an electronic case record form (eCRF), were analyzed to provide lists of reasons for performing the procedures and of the findings. The eCRF provided only a limited number of items for each data field, along with free-text facilities. Only descriptions pertaining to the small bowel were analyzed. Lists of terms were then reviewed by two experts to group obvious synonyms. The accuracy of the CEST was defined beforehand as the capability to describe 90 % of entries. RESULTS: A total of 766 CE procedures were analyzed. The eCRF included 824 entries as reasons for the examination in 655 CEs (1.3 per procedure). These represented 122 different expressions. After grouping of synonyms, 28 expressions remained. Among them, 10 were matched with terms from the list of reasons for performing CE offered in the CEST. These were the most frequently used, accounting for 768 entries in this field (93.2 %). All eCRFs contained at least one description of findings. A total of 109 CE procedures were classified as normal (14.3 %). A total of 2624 entries for abnormal findings were recorded for 657 procedures (4.0 per procedure). In all, 213 different expressions were used to describe abnormal findings. After grouping of synonyms, 52 expressions remained. Among these, 27 were matched with terms from the list of findings in the CEST, covering 2403 entries (91.6 %). CONCLUSIONS: In this study, CEST terms were capable of describing more than 90 % of the reasons for performance and of the findings in an unselected set of CE procedures. CEST is therefore suitable for use as the standard lexicon for CE reports. Adopted as a standard, it could significantly improve the quality of the data collected and reported in CE studies.

Standardization in endoscopic reporting: implications for clinical practice and research.

The large number of endoscopies and endoscopic reports produced in the United States represents a large repository of clinical data. However, reports are highly variable in content and structure and therefore cannot be used to create clinical databases. The introduction of automated endoscopic reporting systems should permit database creation only if acceptable standards for the structure and content of the report are developed. The structure of an endoscopic report is the framework in which the specific details of the endoscopy can be recorded. The basic components can consist of the following: Patient, Visit, Study, Result, Diagnosis, and Recommendation. Precise definition of each of these components requires consensus on what the minimum included elements should be. Experience with the Minimal Standard Terminology indicates that it is possible to create a broadly acceptable lexicon of descriptive endoscopic terms which can be included as a Result. The systematic development of the structure and content of endoscopic reports is mandatory before it is possible to create large, clinically useful databases of endoscopic reports.

Structured reporting in gastrointestinal endoscopy: integration with DICOM and minimal standard terminology.

The interest of the international gastrointestinal endoscopy community in developing standards for endoscopic reporting resulted in a standard lexicon for describing endoscopic findings. It became clear that in order to facilitate the widespread use of this lexicon, a messaging standard which could link images to text had to be adopted. The DICOM 3.0 Standard (digital imaging and communication in medicine) was extended by the introduction of the Visible Light Supplement and the SNOMED-DICOM microglossary. These two standards should expand the ability of DICOM to accommodate endoscopic images and the clinical description of these images.

The minimal standard terminology for digestive endoscopy: introduction to structured reporting.

The wider use of computers for the management of endoscopic data and the use of electronic endoscopes for the production of high quality endoscopic images has made the standardization of terminology and images formats necessary in digestive endoscopy reports. The European Society for Gastrointestinal Endoscopy and the American Society for Gastrointestinal Endoscopy have combined their efforts to propose a Minimal Standard Terminology for Computerized Databases in Endoscopy. This terminology is based on the following principles: no term describing findings less frequent than 1%, of the daily practice, and no term based on subjective impressions. The Minimal Standard Terminology has been developed according to the natural process of constructing an endoscopic report in natural language and deals with the following: reasons for performing the examination, endoscopic findings, endoscopic diagnosis, additional therapeutic and diagnosis procedures (biopsies, etc.). It is subdivided according to the main organs examined with an endoscopy. Until now, the Minimal Standard Terminology was tested in many centers and was shown to accurately cover 95% of routine examinations for the upper gastrointestinal tract, colonoscopy and cholangio-pancreatography. It is currently being tested in an a prospective way in several centers in Europe (with a grant from the European Commission DGXIII-C4) and in the USA (with grant from the AHDHF).

Representation of the Gastrointestinal Endoscopy Minimal Standard Terminology in the SNOMED DICOM microglossary.

In Gastroenterology, endoscopic images and interpretation reports are essential elements of the patient record. The Digital Imaging and Communications in Medicine (DICOM) Visible Light and Structured Reporting Standards provide a standard representation of images and reports. However, the message standards are not sufficient in themselves. Controlled terminology is needed to enable interchange of patient records and to facilitate the pooling of multi-center data for large-scale outcomes studies and clinical research. The ASGE has joined with European and Japanese colleagues to develop and publish a lexicon of endoscopic terminology. The lexicon is being tested now in a multi-center trial. In addition, the ASGE is collaborating with the DICOM Standards Committee to transform the endoscopic lexicon into a database structure that is suitable for use with the DICOM Visible Light and Structured Reporting Standards. The combination of an internationally accepted, tested and non-proprietary lexical standard and a DICOM message standard supporting endoscopic images and reports represents a powerful tool for clinicians to improve communication, research and the quality of care.

Variety and evolution of American endoscopic image management and recording systems.

The rapid evolution of computing technology has and will continue to alter the practice of gastroenterology and gastrointestinal endoscopy. Development of communication standards for text, images, and security systems will be necessary for medicine to take advantage of high-speed computing and communications. Professional societies can have an important role in guiding the development process.

Insulin-like growth factor-I binding in injury-induced intimal hyperplasia of rabbit aorta.

PURPOSE: The proliferation of arterial-wall smooth muscle cells is an important step in the formation of intimal hyperplasia. Insulin-like growth factor-I (IGF-I) is a mitogen that exerts its effects through specific receptors located on the cell membrane. IGF-I has been found to promote the multiplication of vascular smooth muscle cells in culture. This study aimed to evaluate the status of IGF-I binding in injury-induced intimal hyperplasia in a rabbit model. METHODS: We used binding techniques to study IGF-I binding of control and hyperplastic aortas of adult White New Zealand rabbits. Hyperplasia was induced by balloon-catheter injury. At 2 weeks and 1, 2, 4, and 7 months after injury, segments of abdominal aortas were harvested from two control and six study rabbits, and 20-micrometer-thick frozen sections were obtained. Hematoxylin and eosin-stained sections confirmed the presence of intimal hyperplasia in the hyperplastic aortas. Adjacent sections were incubated in a buffer solution containing 125I-IGF-I in the presence and absence of an excess of unlabeled IGF-I. Autoradiograms were then obtained by apposing the treated sections to autoradiography film, which was developed at 3 days and analyzed by comparison with the hematoxylin and eosin-stained sections under light microscopy. A marked increase in IGF-I binding grain density was observed in the areas corresponding to the hyperplastic lesions. To characterize these binding sites, binding inhibition studies were performed and the dissociation constant (K d) and maximum binding capacity (B max) were obtained from Scatchard analysis. RESULTS: Six hyperplastic aortas for each time interval and a total of nine control aortas were evaluated. The K d of the hyperplastic aortas (1.5+/-0.2 nmol/L) was not significantly different from that of control aortas (1.3+/-0.2 nmol/L), which indicated similar high-affinity IGF-I binding sites in normal and hyperplastic arteries. The results of B max were 6.9+/-1.2, 8.5+/-2.1, 12.4+/-2.1, 20.4+/-5.9, 20.6+/-3.2, and 8.1+/-1.3 pmol/L for control, 2 weeks, 1 month, 2 months, 4 months, and 7 months, respectively. With analysis of variance (p<0.05), B max values at 1, 2, and 4 months were significantly higher than those of control aortas. B max values returned to levels not significantly different from those of control aortas at the 7-month interval. CONCLUSION: Increased IGF-I binding in the hyperplastic aortas suggests that IGF-I plays an important role in the proliferation of arterial wall cellular components during the hyperplastic process.

Increased specific binding of insulin-like growth factor-I in healing cutaneous wounds.

Insulin-like growth factor-I is a polypeptide hormone structurally related to insulin. It is a potent mitogen that promotes growth and differentiation in many tissues. A role for insulin-like growth factor-I in wound healing is suggested by its rapid rise in levels and increased insulin-like growth factor-I messenger RNA expression in tissue after wounding. We designed our study to characterize possible changes in insulin-like growth factor-I receptor binding during wound healing. Surgical wounds created on the abdominal skin of anesthetized New Zealand White rabbits were either left open or closed primarily. Size- and weight-matched specimens were harvested at wounding time (day 0), and at 1, 4, 7, 38, and 50 days after wounding. Preliminary experiments showed that the greatest difference in specific binding occurred between day 0 and day 7. (125)I-insulin-like growth factor-I binding studies were performed on frozen tissue specimens and autoradiography was performed and analyzed by computerized densitometry. Scatchard analysis of the binding data showed a single class of insulin-like growth factor-I binding sites whose affinity that is, binding constant (K(d) = 0.6 x 10(-9)) did not change significantly over time; in contrast there was a threefold increase in the number of receptors per milligram tissue in day 7 wound tissue versus normal skin harvested at day 0 (17.3 +/- 2.6 x 10(10) versus 4.7 +/- 2.5 x 10(10), respectively, p < 0.05). Binding inhibition experiments showed that (125)I-insulin-like growth factor-I binding was most specific to insulin-like growth factor-I with insulin-like growth factor-I > insulin-like growth factor-II > insulin. This increase in binding was due to upregulation of insulin-like growth factor-I receptors rather than increased levels of insulin-like growth factor-I binding protein as less than 20% of the threefold increase in binding at day 7 could be attributed to insulin-like growth factor-I binding protein in membrane-free extracts. The presence of specific, high-affinity insulin-like growth factor-I receptors in the skin and their upregulation at day 7 after wounding suggest that insulin-like growth factor-I plays an important role during wound healing.

Epidermal growth factor primes intestinal epithelial cells for proliferative effect of insulin-like growth factor I.

Insulin-like growth factor I (IGF-I) synergistically enhances epidermal growth factor (EGF)-stimulated proliferation of intestinal epithelial cells. A possible mechanism of this synergy is that EGF acts as a "competence" factor increasing the fraction of proliferating cells by promoting transition from G0 to G1, thus allowing IGF-I, a "progression" factor, to act as a proliferative agent on the cycling population. Consistent with this hypothesis would be temporally distinct actions wherein initial brief exposure to EGF would permit synergy, whereas pretreatment with IGF-I would not. Rat intestinal epithelial cells of the IEC-18 crypt cell line were serum-deprived, then treated with EGF (5 x 10(-9) M), IGF-I (5 x 10(-9) M), or insulin (2 x 10(-6) M) for a 30-min pulse and then media containing EGF, IGF-I, insulin, or no factor was substituted for 48 hr. IGF-I and EGF each stimulated enterocyte proliferation; together they synergistically promoted cell growth. A brief pulse of IGF-I neither induced cell proliferation nor enhanced the EGF effect. Initial brief exposure to EGF, however, was equally efficacious as continuous exposure and allowed full synergy with IGF-I. Insulin at supraphysiologic levels acted similarly to IGF-I. Thus, EGF acted as a competence factor priming the cells for subsequent action by IGF-I. The cell kinetic parameters of these growth factors may be important to both physiologic and pathologic enterocyte growth regulation.

Corticotropin-releasing factor stimulates cyclic AMP, arachidonic acid release, and growth of lung cancer cells.

The effects of corticotropin-releasing factor (CRF) on human lung cancer cell lines was investigated. Corticotropin-releasing factor increased the cAMP levels in a dose-dependent manner; CRF (100 nM) elevated the cAMP levels approximately eleven-fold using NCI-H345 cells and increased the gastrin-releasing peptide (GRP) secretion rate by approximately 70%. Similarly, sauvagine, a structural analogue of CRF, elevated the cAMP levels with a half-maximal effective dose (ED50) of 20 nM. The increase in cAMP caused by CRF and sauvagine was reversed by alpha-helical CRF(9-41). Corticotropin-releasing factor had no effect on cytosolic calcium but stimulated [3H]arachidonic acid release from NCI-H1299 cells with an ED50 of 30 nM. The increase in [3H]arachidonic acid release caused by 100 nM CRF was significantly reversed by 1 or 10 microM alpha-helical CRF(9-41). Also, CRF stimulated the clonal growth of NCI-H345 and H720 cells and the growth increase caused by CRF was reversed by alpha-helical CRF(9-41). These data suggest that CRF may be a regulatory peptide in lung cancer.

Autoradiographic mapping and characterization of insulin-like growth factor-I receptor binding in human greater saphenous vein.

PURPOSE: The proliferation of vascular smooth muscle cells is an important step in the process of intimal hyperplasia. Veins exposed to arterial pressure develop intimal hyperplastic lesions that lead to failure of vein bypasses. Insulin-like growth factor-I is a polypeptide hormone structurally related to insulin with insulin-like metabolic effects. Insulin-like growth factor-I has been found to work in concert with other growth factors, including platelet-derived growth factor, to promote the growth of vascular smooth muscle cells in culture. Insulin-like growth factor-I exerts its effects via specific receptors located on the cell surface. We studied the in situ distribution of insulin-like growth factor-I receptor binding using autoradiography and examined insulin-like growth factor-I binding characteristics in normal human greater saphenous vein. METHODS: Frozen sections 20 microns thick were prepared from the greater saphenous vein specimens. The sections were incubated in a buffer containing 125I-insulin-like growth factor-I in the presence of increasing concentrations of the unlabeled peptide. Autoradiograms were obtained by apposing the treated sections to autoradiography film. RESULTS: Analysis of the autoradiographs showed that insulin-like growth factor-I binding was consistently present in the wall of human greater saphenous vein. To characterize these binding sites binding inhibition studies were performed. High-affinity insulin-like growth factor-I receptor binding was found with dissociation constant of 1.0 +/- 0.32 nmol/L and maximum binding capacity of 0.46 +/- 0.23 pmol/mg protein. These values are consistent with a physiologic role for insulin-like growth factor-I in the tissue examined. CONCLUSIONS: The presence of high-affinity (dissociation constant = 1.0 +/- 0.32) insulin-like growth factor-I binding sites in the wall of saphenous vein suggests that insulin-like growth factor-I plays an important role in regulating the proliferation of venous wall cellular components, an essential step in the process of venous intimal hyperplasia.

Extracellular matrix composition influences insulinlike growth factor I receptor expression in rat IEC-18 cells.

BACKGROUND: The composition of the extracellular matrix (ECM) as well as insulinlike growth factor I (IGF-I) receptor density vary along the crypt-villus axis. We determined whether components of the ECM influence IGF-I receptor expression in IEC-18 rat small intestine crypt cells. METHODS: IEC-18 cells were cultured on plastic, collagen type IV, Matrigel, and laminin at the plateau and proliferative growth phases. Receptor affinity (Kd) and number (Bmax) were determined by competitive binding of 125I-IGF-I in the presence of increasing concentrations of unlabeled IGF-I. Receptor isolation was performed by affinity cross linking. Messenger RNA (mRNA) for IGF-I receptor was quantified by Northern analysis. RESULTS: Specific binding of IGF-I > IGF-II > insulin was observed. A 130,000-molecular weight protein was identified by cross-linking, consistent with the alpha subunit of the IGF-I receptor. Scatchard analysis revealed no effect of ECM on IGF-I binding affinity. In contrast, the Bmax was 18% lower for plateau-phase cells cultured on Matrigel vs. plastic and was 42% lower for cells cultured on laminin vs. collagen type IV. The Bmax for proliferative growth phase cells was decreased when cultured on Matrigel vs. plastic and was 10-fold less than for cells cultured at the plateau growth phase. Northern analysis revealed that IEC-18 cells cultured on Matrigel had less mRNA for IGF-I receptor than cells cultured on plastic. CONCLUSIONS: The rate of cell proliferation and the composition of the ECM influence IGF-I receptor expression in IEC-18 cells.

Insulin-like growth factor I receptors in the arteries of the rabbit: autoradiographic mapping and receptor characterization.

Insulin-like growth factor I (IGF-I) is a polypeptide hormone structurally related to insulin with insulin-like metabolic effects. It is a potent mitogen, eliciting cell multiplication in tissue culture by increasing deoxyribonucleic acid and protein synthesis. IGF-I was found to promote the growth of cultured arterial smooth muscle cells. We studied the in situ distribution of IGF-I receptors in different arteries of the rabbit by autoradiography and examined their binding characteristics in the wall of the thoracic aorta. The thoracic and abdominal aortas and carotid, superior mesenteric, renal, and iliac arteries of three adult New Zealand rabbits were harvested and stored at -70 degrees C. Autoradiographic analysis of 125I-labeled IGF-I binding to frozen arterial sections showed that silver-grain density was consistently located in the arterial wall. Binding studies in the thoracic aorta demonstrated high-affinity IGF-I receptors with a dissociation constant of 2 nmol/L and maximum IGF-I binding capacity of 4.17 pmol/mg protein. Inhibition studies with insulin, IGF-I, and IGF-II showed that these binding sites were more specific for IGF-I than for IGF-II or insulin, with a concentration of peptide that inhibits 50% of maximum binding of 1.75 nmol/L, 5 nmol/L, and greater than 100 mumol/L, respectively. The presence of high-affinity, specific IGF-I receptor binding in rabbit arteries suggests that IGF-I plays an important role in regulating the multiplication of arterial smooth muscle cells; a role that may prove important in different pathologic processes.

Insulinlike growth factor I receptors in rabbit gastrointestinal tract. Characterization and autoradiographic localization.

Insulinlike growth factor I is a potent mitogen with insulinlike metabolic effects. Insulinlike growth factor I is synthesized in the liver, intestine, and other organs. Insulinlike growth factor I receptors are widely distributed and structurally similar to insulin receptors. Frozen sections of rabbit gastrointestinal tract were incubated in buffer containing 40 pmol/L [125I]insulinlike growth factor I. Binding was saturable, temperature- and time-dependent, and reversible. Saturation binding experiments showed a single class of high-affinity receptors (Kd = 0.9 nmol/L, Bmax = 0.36 pmol/mg protein). The IC50s for insulinlike growth factor I and insulinlike growth factor II were 3 nmol/L and 90 nmol/L, respectively; whereas insulin at 1-3 mumol/L displaced 50% of specific binding. Autoradiography of insulinlike growth factor I binding demonstrated significant differences in receptor density in gastrointestinal smooth muscle, epithelium of the esophagus, stomach, small intestine, and colon. These results indicate that a single class of specific, high-affinity insulinlike growth factor I receptors were distributed in muscular and mucosal layers of the entire rabbit gastrointestinal tract. Insulinlike growth factor I is likely to be an important local mediator of intestinal growth and metabolism.

Distribution of vasoactive intestinal peptide and its receptors in the arteries of the rabbit.

Vasoactive intestinal peptide (VIP) is a widely distributed neurotransmitter whose dilatory effects on vascular smooth muscle are believed to be mediated via specific receptors. To determine the possible role of VIP in regulating specific vascular beds, we examined the relationship between arterial wall VIP content as determined by radioimmunoassay and VIP receptors mapped by autoradiography. Analysis of arteries from 12 adult New Zealand rabbits showed that VIP receptors were consistently located in the wall of all muscular arteries, and that the 125I-VIP grain density correlated with VIP content. 125I-VIP binding in the mesenteric, renal, and iliac arteries was abundant and their VIP content was 192 +/- 56, 51 +/- 5, and 74 +/- 23 fmole/mg protein, respectively. 125I-VIP binding to the thoracic aorta was indistinguishable from nonspecific binding, its VIP content being 15 +/- 2 fmole/mg protein. The abundance of VIP receptors and the high VIP levels associated with the mesenteric, renal, and iliac arteries suggest that VIP is a potential regulator of flow to the vascular beds supplied by these arteries. In contrast, the much lower density of receptors in the extracranial carotid, which is also a muscular artery, suggests that, in rabbits, control of carotid vasomotion may be less dependent on VIP innervation. Furthermore, these results suggest that VIP receptors and VIP-containing neurons are not uniformly distributed in the arterial vasculature and that VIP may have selective vasodilatory effects.

Distribution of vasoactive intestinal polypeptide and substance P receptors in human colon and small intestine.

Vasoactive intestinal polypeptide (VIP) and substance P are found in neurons in the lamina propria and submucosa and muscularis propria of human small intestine and colon. VIP receptors coupled to adenylate cyclase are present on epithelial, smooth muscle, and mononuclear cells. This study analyzes the distribution of [125I]VIP binding and [125I]substance P in human colon and small intestine using autoradiographic techniques. [125I]VIP binding was present in high density in the mucosal layer of colon and small intestine. [125I]VIP binding was not significantly greater than nonspecific binding in smooth muscle layers or the lymphoid follicles. In contrast, [125I]substance P binding was present in high density over the colonic muscle but was not present over the mucosal layer. In human colon cancer, [125I]VIP grain density over the malignant tissue was only slightly higher than background. These autoradiographic studies of [125I]VIP binding indicate that the highest density of VIP receptors was found in the small intestine and superficial colonic mucosa, whereas the density of substance P receptors was highest over the smooth muscle layers. These findings suggest a mismatch between immunochemical content of the peptide and autoradiographic density of the receptor.

VIP receptors and content after bowel transplantation.

Advances in immunosuppressive therapy have renewed interest in small bowel transplantation. Little is known, however, about the functional capacity of transplanted intestine. To clarify the potential for normal function, we investigated whether elements of the enteric nervous system are preserved after denervation in our rat model of intestinal transplantation. We investigated whether VIP, a major peptide neurotransmitter of the enteric nervous system, and its receptors are preserved in the bowel after transplantation. In our model of transplantation, avascular fetal jejunum from term Fisher rats is transplanted to the subcutaneous tissues of host syngeneic rats. This "neogut" becomes vascularized and develops characteristics of native small bowel. VIP content was measured by RIA and the in situ distribution of VIP receptors was determined by the technique of receptor autoradiography. Neogut was studied 1 and 3 weeks after transplantation and compared with age-matched rat pup jejunum. Autoradiographs showed high silver grain density, representing VIP binding sites, in the mucosal layers of all tissues studied. VIP content in the transplanted bowel was comparable to that of native gut and showed a rise with developmental age similar to that of native gut. VIP levels (pmole/mg protein, x +/- SEM) were neogut 1 week, 0.26 +/- 0.14; jejunum 1 week, 0.25 +/- 0.07; neogut 3 weeks, 0.60 +/- 0.21; and jejunum 3 weeks, 0.69 +/- 0.16. These results show that VIP receptors and content are preserved in this model of transplantation. This suggests that the enteric nervous system and receptors for peptide neurotransmitters remain intact after transplantation and may retain the potential for regulatory function.