Colonoscopy: An Increased Detection Yield?

• The Emerging Concept of Nonpolypoid Colorectal Neoplasia
• The Impact of Technology
• High-Resolution Fiberscopes
• Chromoscopy
• Magnification
• The Impact of the Methodology
• Is There a Benefit in the Use of Chromoscopy Without Magnification?
• Is There a Benefit From Using Magnification?
• References

The Emerging Concept of Nonpolypoid Colorectal Neoplasia

The frequent occurrence of flat or nonpolypoid neoplastic colorectal lesions has been reported recently in the Japanese literature, and also now in Western countries. In the large series collected by S. Kudo [1] [2] [3] at the Akita Red Cross Hospital in Japan, 45 % of early neoplastic lesions detected at colonoscopy were found to have a nonpolypoid morphology. The figure was only slightly lower (32 %) in the revisited results of the National Polyp Study in the USA [4]. In Japan, nonpolypoid lesions (adenoma or cancer) are classified as variants of superficial lesions of types 0-II, i. e. superficially elevated (0-II a), completely flat and flush with the surrounding mucosa (0-II b) or superficially depressed without frank ulcer (0-II c). In mixed types, both depression and elevation are present (II a + II c or II c + II a). Depressed lesions represent less than 5 % of all early neoplastic colorectal lesions.

There is no doubt that the endoscopic detection of nonpolypoid lesions will increase the yield of colonoscopy. The question is whether nonpolypoid lesions are important precursors of advanced cancer. In fact, most of these lesions have a weak evolutive potential: false-negative results for nondepressed and nonpolypoid lesions have no serious consequences. In contrast, depressed nonpolypoid lesions are highly evolutive, even when their size is small. False-negative findings for depressed lesions have severe repercussions, because these lesions often progress to advanced cancer. It is now considered that up to 40 % of advanced cancer cases arise from depressed lesions.

The Impact of Technology

The recent interest in the endoscopic detection of nonpolypoid colorectal lesions (neoplastic and non-neoplastic) stems from the impact of cumulative progress in technology (e. g. availability of high-resolution video fiberscopes, and optical zoom for magnification) and the revival of chromoendoscopy [5] [6] [7] [8] [9] . In this issue of Endoscopy, Kiesslich et al. [5] confirm the frequent occurrence of nonpolypoid lesions in Western populations and stress the contribution of chromoendoscopy.

High-Resolution Fiberscopes

During the last decade, continuous progress in imaging, allied to the digital technology of electronic video colonoscopes, led to a new generation of instruments described as high-resolution video colonoscopes. The new generation have more pixels and an improved optic with a wider field of view and a greater depth of field. Considerable progress is being made in the development of the video processor, in color rendering, and coupling of the digital signal to the analogue monitor. The recent addition of a structural enhancement function to the video processor has improved the contrast of images obtained after chromoscopy and magnification, by selection of specific frequencies and specific enhancement of their amplitude. This function potentiates the benefit provided by chromoscopy (enhanced chromoendoscopy) or by magnification.

Chromoscopy

Chromoscopy is an old but not obsolete technique, and dyes have been used for years with first-generation fiberscopes. Chromoscopy in the early days of endoscopy was helpful in the study of the healing process of peptic ulcers, and later in the analysis of early digestive cancer. The technique has been revitalized because of its contribution to detailed analysis of the mucosal surface using high-resolution and magnifying fiberscopes. Chromoscopy tends to be used routinely for the interpretation of any superficial and often small abnormal surface in the digestive mucosa. A number of dyes are suitable for chromoscopy; some are not absorbed by cells, others are absorbed and stain specific cell constituents (in vivo histochemistry).

In the colon, the universally used dye is indigo carmine solution (0.4 to 1 %). The unabsorbed dye accumulates in the depressions of the mucosal surface and delineates the general architecture with a clear (and transient) blue outline; this proves helpful in assessing the limits of small and relatively flat areas, particularly in the evaluation of a depression. Diffuse dyeing prior to colonoscopy after ingestion of a solution or a capsule [10] has been proposed, but this is not recommended. Focal application, with or without a spray catheter, is preferred.

Absorbed dyes are also used in colonoscopy; either cresyl violet or crystal violet will stain the surface with a sharp violet contrast, less transiently than indigo carmine. These agents are used in histochemistry; fixed at the apical pole of the cells, they transcribe the surface pattern with greater accuracy. Indigo carmine, is used in the first step of detection for the macroscopic analysis of elevated or depressed morphology; the absorbed dyes may be used in a second step to study the pit pattern during magnification.

Magnification

The addition of an optical zoom to the tip of a fiberscope is not a new development. It has been proposed for two decades, and the first report on its use for the colonic mucosa was in 1980 [11]. However it was considered to be a gimmick by most endoscopists, and did not gain wide acceptance whilst it was still coupled to a standard fiberscope and a poor mechanism.

A new era began when the zoom was coupled with high-resolution colonoscopes and improved mechanisms. The initial objective was simply to obtain an enlarged view of the surface. In a short time this became the more ambitious one of achieving a reliable prediction of histological nature. This is virtual biopsy, aiming at a distinction between neoplastic and non-neoplastic lesions, between dysplasia and cancer. The pilot studies with magnifying video colonoscopes were conducted in Japan under the leadership of S. Kudo [1] [2] [3] , and many other reports, mostly from Japan, confirmed his results [12] [13] [14] [15] [16] [17] [18] [19] . Magnifying electronic video endoscopes incorporate an optical zoom with a power of up to ×150, and their mechanisms have been consistently improved over the past 2 years, as compared with the first prototypes. The zoom video colonoscope can now be used as efficiently as a standard colonoscope. A distinct magnified image is obtained, with the help of chromoscopy with indigo carmine, crystal violet or cresyl violet, when the tip of the scope is placed at a short distance from the mucosal surface. If the instrument has a structure enhancement function, it should be used during magnification.

With magnifying endoscopy, the surface openings of the crypts display distinct patterns (“pit patterns”) in normal and abnormal colonic mucosa [1] [2] [3] [12] [13] [14] [15] [16] [17] [18] [19] , which are similar to those observed ex vivo with a stereo microscope [20] [21] at the same magnification. The obvious connection between the surface architecture and the underlying histological changes justifies the prediction of histology from the surface pattern. Most Japanese authors adopt the classification into types I to V as proposed by Kudo [1] [2] [3] , where type I corresponds to normal mucosa, type II to hyperplastic polyps, and types III to V to neoplastic lesions with a scale from low-grade dysplasia to cancer. Some patterns are composed of large elements which are easily identified, even without magnification, such as the large hexagonal pits of type II, and the ridged cerebriform pattern of type III L and type IV. Other patterns are composed of very small elements, such as small round pits (regular in type I, irregular and scarce in type III s) or even absence of pits. The classification of the pit pattern has clinical relevance in the evaluation of nonpolypoid lesions: those recognized as hyperplastic polyps need not be biopsied, while those recognized as neoplastic are given appropriate treatment (mucosectomy or surgery).

The routine application of magnification is based upon a close collaboration between the endoscopist and the pathologist and leads to a completely new approach to endoscopic diagnosis. Using a magnifying colonoscope is slightly more time-consuming, but using the most recent instruments complete colonoscopy is performed with the same success rate. In this situation the progression of the colonoscope is ensured while the zoom is not in function and the zoom is only operated when a lesion has been detected. As a first step, the focal abnormal area is detected without magnification and without chromoscopy, the lesion is then analyzed with the help of chromoscopy. Finally, the histological prediction is based upon the magnified view. The indications for biopsy sampling, mucosectomy or surgery are based on the image obtained during magnification.

The first indications for magnification which had clinical relevance were found in colonoscopy. In the upper digestive tract, the technique is impaired by the amplitude of cardiorespiratory movements. A transparent hood at the end of the fiberscope helps to maintain the tube at a fixed distance from the mucosa, and the hood has also been used in the colon [22]. Promising results from use of the magnification technique in cases of Barrett’s esophagus have been recently published [23]. These involve the detection of areas with specialized epithelium (intestinal metaplasia), with magnification associated with spraying of an acetic acid solution in order to enhance the contrast.

The Impact of the Methodology

In Japan, for more than 30 years, priority has been given to the detection of digestive cancer at an early stage. This was justified by the high mortality toll from stomach cancer. Very particular attention has been given the methodology of gastroscopy. As a consequence, colonoscopy received the same attention to the quality of intestinal preparation and to the method of exploration. Endoscopists who are trained to detect small lesions will introduce the scope into the cecum promptly, with minimal insufflation. The exploration is conducted on withdrawal, alternating insufflation and aspiration. Chromoscopy is used when a focal abnormality is suspected. Japanese operators, liaising closely with the manufacturers, acquire the most recent high-resolution fiberscope models, and now magnification is employed by most teams performing colonoscopy.

Adoption of this standard in the West means that more time is devoted to each exploration, while using sophisticated and more costly equipment. The occurrence of nonpolypoid neoplastic lesions in the colon and their potential role as precursors of advanced cancer is now universally accepted, justifying an increased capacity for detection in colonoscopy and a renewal of interest in the routine use of chromoscopy to help in identification.

In the present issue of Endoscopy, Kiesslich et al. [5] highlight the increased yield of detection of colorectal lesions when chromoendoscopy is coupled with the use of high-resolution endoscopes. Chromoendoscopy with the indigocarmine solution was performed in 100 consecutive patients, using either a standard high-resolution video colonoscope (n = 81) or a magnifying video colonoscope (n = 19).

In 52 patients, colorectal lesions were detected prior to chromoscopy and were classified as polypoid (n = 89), or nonpolypoid (n = 16) out of which two were depressed. The lesions were then examined with focal chromoscopy. Histologically the lesions were classified as non-neoplastic (n = 45), adenomatous (n = 54) or cancerous (n = 6).

The remaining 48 patients had no visible colorectal lesion prior to chromoscopy. Diffuse chromoscopy was then performed in the 30-cm distal segment (sigmoid and rectum). With chromoscopy, 178 nonpolypoid lesions were detected; out of these, two were depressed, most of them were non-neoplastic (n = 165) and the others adenomatous (n = 3), and no cancer was found in this group.

These results deserve comment:

1. The authors compare chromoscopy in focal lesions and chromoscopy in apparently normal mucosa. One should remember that during colonoscopy the recommended sequence is: detection, without chromoscopy, of an abnormal area; chromoscopy, and only then, magnification.

2. They classify adenomas into three groups: no dysplasia, low-grade dysplasia and high-grade dysplasia. Only 26 out of the 67 adenomas found in the 100 patients had dysplasia. One may question the exact nature of the other 41 neoplastic lesions with no dysplasia: does this correspond to the group „indefinite for dysplasia” in the Vienna classification?

3. The authors detected four depressed lesions in 100 procedures; two were visible before chromoscopy, and two only after chromoscopy. Histologically, there was one cancer (visible before chromoscopy), one high-grade dysplasia (detected at chromoscopy) and two non-neoplastic lesions.

4. They attempted to classify the 283 lesions detected, according to the five groups of pit pattern described by Kudo, without the help of magnification; comparison was made with the histology classified in four groups (non-neoplastic, adenomatous without dysplasia, adenomatous with dysplasia, cancer). Most of the detected lesions were non-neoplastic and were classified accordingly as types I or II. Neoplastic lesions with high-grade dysplasia or cancer were classified in higher proportions as types IV to V. Some confusion persists concerning the interpretation of the so-called adenoma without dysplasia, found more frequently in group III.

5. In conclusion, the authors produce a convincing demonstration that the detection of nonpolypoid lesions is improved by chromoscopy, and that they are often present in patients with apparently negative findings. They attempt to classify the pit pattern as seen without magnification, and observe some correlation with the histology. However there is a major bias because most of the 283 lesions detected were either non-neoplastic or of unclear histology (adenoma without dysplasia). The non-neoplastic pit pattern types (I and II) were together the easiest to identify and the most frequently found (199/283).

Is There a Benefit in the Use of Chromoscopy Without Magnification?

The routine use of chromoendoscopy with indigo carmine in colonoscopy with a high-resolution instrument, increases considerably the proportion of persons found to have colorectal lesions. There is no doubt that the additional lesions detected are nonpolypoid, and that a large proportion of them are non-neoplastic. One may question the clinical relevance of this increased yield of detection. Hyperplastic, non- neoplastic polyps should not be removed. The generalized practice of chromoendoscopy may increase the number of procedures which are not useful (of biopsy sampling, or mucosectomies), with accompanying consequences for complications and cost. In the absence of specific risk factors, the systematic chromoscopy of a large segment of an apparently normal colonic mucosa is not a routine and helpful practice: most lesions detected are small hyperplastic polyps. Chromoscopy is helpful in the analysis of limited segments of the colon with an area of suspicion, or in patients at high risk of cancer (e. g. on account of familial syndromes).

If a small colorectal lesion is detected, the selection of a further procedure is guided by a reliable prediction of its histological nature. In fact, the tentative classification of the pit pattern without magnification [5] is not comparable to the rigorous approach of the studies with magnification. However the authors show that the common non-neoplastic types I - II can be identified with sufficient confidence. Neither adenoma with dysplasia nor cancer were misclassified into this group. Finally, chromoendoscopy contributes to the detection of nonpolypoid and nondepressed lesions: one depressed lesion with high-grade dysplasia was detected by chromoendoscopy in this study.

Is There a Benefit From Using Magnification?

The predictive value of magnification with regard to histology, by pit pattern classification, is much higher than that of chromoscopy, and reaches the level of a virtual biopsy. A few years ago Tanaka et al. [15] compared the relative efficacy of both methods when using a high-resolution video colonoscope. They concluded that chromoscopy without magnification is partially helpful in the diagnosis of relatively large pit patterns: this concerns the non-neoplastic type II (hyperplastic polyps) and the large types III L and IV (dysplasia). They also stated that the analysis of small and irregular pit patterns is not reliable without magnification.

The exploration of the colon by chromoscopy and magnification combined is increasingly practiced in Japan, and is linked to treatment decisions. The frequently found, small, non-neoplastic lesions are neither biopsied nor resected. At the limit of its capability, investigation using magnification can detect atypical crypt foci [24] [25] . When found, such minute defects, concerning one to five crypt openings, may be registered but require no treatment because their potential for evolution is too uncertain. Magnification provides rational support to indications for endoscopic mucosectomy, and proves particularly helpful in the analysis of small and depressed lesions because of their high potential for malignancy. As an example, magnification has predictive value for extension in depth: when a nonstructural pit pattern occurs at the periphery of the lesion, there is a high risk for extended submucosal invasion, and direct surgery is recommended.

When a high-resolution fiberscope combined with chromoscopy and magnification is used, colonoscopy is unrivalled in the early detection of colorectal cancer. Virtual colonoscopy with magnetic resonance imaging (MRI) or computed tomography (CT) scan, may only be capable of detecting polypoid neoplasia of at least 1 cm in diameter. The future of colonoscopy depends on the routine use of high-resolution instruments equipped with an optical zoom and with recent mechanical improvements, such as variable stiffness.

References

• 1 Kudo S, Hirota S, Nakajima T, et al. Colorectal tumours and pit pattern.  J Clin Pathol. 1994;  47 880-885
  CrossrefPubMedSearch in Google Scholar
• 2 Kudo S, Tamura S, Nakajima T, et al. Diagnosis of colorectal tumorous lesions by magnifying endoscopy.  Gastrointest Endosc. 1996;  44 8-14
  CrossrefPubMedSearch in Google Scholar
• 3 Kudo S, Rubio C A, Teixeira C R, et al. Pit pattern in colorectal neoplasia: Endoscopic magnifying view.  Endoscopy. 2001;  33 367-373
  Thieme ConnectPubMedSearch in Google Scholar
• 4 O’Brien M J, Winawer S J, Zauber A G, et al. Blinded assessment of the flat adenoma in the National Polyp Study does not demonstrate an excess risk for high grade dysplasia initially or for advanced adenomas at surveillance.  Gastroenterology. 2001;  120 (5 Suppl 1) A96
  PubMedSearch in Google Scholar
• 5 Kiesslich R, van Bergh M, Hahn M, et al. Chromoendoscopy with indigo carmine improves the detection of adenomatous and non-adenomatous lesions in the colon.  Endoscopy. 2001;  33 1001-1006
  Thieme ConnectPubMedSearch in Google Scholar
• 6 Axelrad A M, Fleischer D E, Geller A J, et al. High-resolution chromoendoscopy for the diagnosis of diminutive colon polyps: implications for colon cancer screening.  Gastroenterology. 1996;  110 1253-1258
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  CrossrefPubMedSearch in Google Scholar
• 8 Jaramillo E, Watanabe M, Befrits R, et al. Small, flat colorectal neoplasias in long-standing ulcerative colitis detected by high-resolution electronic video endoscopy.  Gastrointest Endosc. 1996;  44 15-22
  CrossrefPubMedSearch in Google Scholar
• 9 Kim C Y, Fleischer D E. Colonic chromoscopy. A new perspective on polyps and flat adenomas.  Gastrointest Endosc Clin N Am. 1997;  7 423-437
  PubMedSearch in Google Scholar
• 10 Mitooka H, Fujimori T, Maeda S, et al. Minute flat depressed neoplastic lesions of the colon detected by contrast chromoscopy using an indigo carmine capsule.  Gastrointest Endosc. 1995;  41 453-459
  CrossrefPubMedSearch in Google Scholar
• 11 Nishizawa M, Kariya A, Kobayashi S, et al. Clinical application of an improved magnifying fiber-colonoscope (FCS-ML II), with special reference to the remission features of ulcerative colitis.  Endoscopy. 1980;  12 76-80
  PubMedSearch in Google Scholar
• 12 Mizuno M, Matsumoto T, Iida M, et al. Magnifying colonoscopic features in non-neoplastic polyps of the colorectum.  Gastrointest Endosc. 1997;  46 537-541
  PubMedSearch in Google Scholar
• 13 Nagata S, Tanaka S, Haruma K, et al. Pit pattern diagnosis of early colorectal carcinoma by magnifying colonoscopy: clinical and histological implications.  Int J Oncol. 2000;  16 927-934
  PubMedSearch in Google Scholar
• 14 Makiyama K, Bennett M K, Jewell D P. Endoscopic appearances of the rectal mucosa of patients with Crohn's disease visualised with a magnifying colonoscope.  Gut. 1984;  25 337-340
  PubMedSearch in Google Scholar
• 15 Tanaka S, Haruma K, Hirota Y, et al. Clinical significance of detailed observation for colorectal neoplasia using the high resolution or magnifying video colonoscope (abstract).  Endoscopy. 1999;  31 E52
  PubMedSearch in Google Scholar
• 16 Tanaka S, Haruma K, Ito M, et al. Detailed colonoscopy for detecting early superficial carcinoma: recent developments.  J Gastroenterol. 2000;  35 (Suppl 12) 121-125
  PubMedSearch in Google Scholar
• 17 Tarta C, Teixeira C R, Burger M B, et al. Magnifying colonoscopy in the diagnosis of colorectal carcinoma invading the submucosa in familial adenomatous polyposis (In Portuguese).  Arq Gastroenterol. 2000;  37 125-128
  PubMedSearch in Google Scholar
• 18 Togashi K, Konishi F, Ishizuka T, et al. Efficacy of magnifying endoscopy in the differential diagnosis of neoplastic and non-neoplastic polyps of the large bowel.  Dis Colon Rectum. 1999;  42 1602-1608
  CrossrefPubMedSearch in Google Scholar
• 19 Kato S, Fujii T, Koba I, Sano Y, et al. Assessment of colorectal lesions using magnifying colonoscopy and mucosal dye spraying: can significant lesions be distinguished?.  Endoscopy. 2001;  33 306-310
  Thieme ConnectPubMedSearch in Google Scholar
• 20 Nishizawa M, Okada T, Sato F, et al. A clinicopathological study of minute polypoid lesions of the colon based on magnifying fiber-colonoscopy and dissecting microscopy.  Endoscopy. 1980;  12 124-129
  PubMedSearch in Google Scholar
• 21 Kawano H, Tsura O, Ikeda H, et al. Diagnosis of the level of depth in superficial depressed type colorectal tumors in terms of stereomicroscopic pit patterns.  Int J Oncol. 1998;  12 769-775
  PubMedSearch in Google Scholar
• 22 Urita Y, Nishino M, Ariki H, et al. A transparent hood simplifies magnifying observation of the colonic mucosa by colonoscopy.  Gastrointest Endosc. 1997;  46 170-172
  PubMedSearch in Google Scholar
• 23 Guelrud M, Herrera I, Essenfeld H, et al. Enhanced magnification endoscopy: a new technique to identify specialized metaplasia in Barrett’s esophagus.  Gastrointest Endosc. 2001;  53 559-565
  CrossrefPubMedSearch in Google Scholar
• 24 Takayama T, Katsuki S, Takahashi Y, et al. Aberrant crypt foci of the colon as precursors of adenoma and cancer.  N Engl J Med. 1998;  339 1277-1284
  CrossrefPubMedSearch in Google Scholar
• 25 Yokota T, Sugano K, Kondo H, et al. Detection of aberrant crypt foci by magnifying colonoscopy.  Gastrointest Endosc. 1997;  46 61-65
  PubMedSearch in Google Scholar

R. Lambert,M.D. 

International Agency for Research on Cancer

150 Cours Albert Thomas
Lyon 69, cedex 08
France


Fax: + 33-4-72738650

Email: lambert@iarc.fr

References

• 1 Kudo S, Hirota S, Nakajima T, et al. Colorectal tumours and pit pattern.  J Clin Pathol. 1994;  47 880-885
  CrossrefPubMedSearch in Google Scholar
• 2 Kudo S, Tamura S, Nakajima T, et al. Diagnosis of colorectal tumorous lesions by magnifying endoscopy.  Gastrointest Endosc. 1996;  44 8-14
  CrossrefPubMedSearch in Google Scholar
• 3 Kudo S, Rubio C A, Teixeira C R, et al. Pit pattern in colorectal neoplasia: Endoscopic magnifying view.  Endoscopy. 2001;  33 367-373
  Thieme ConnectPubMedSearch in Google Scholar
• 4 O’Brien M J, Winawer S J, Zauber A G, et al. Blinded assessment of the flat adenoma in the National Polyp Study does not demonstrate an excess risk for high grade dysplasia initially or for advanced adenomas at surveillance.  Gastroenterology. 2001;  120 (5 Suppl 1) A96
  PubMedSearch in Google Scholar
• 5 Kiesslich R, van Bergh M, Hahn M, et al. Chromoendoscopy with indigo carmine improves the detection of adenomatous and non-adenomatous lesions in the colon.  Endoscopy. 2001;  33 1001-1006
  Thieme ConnectPubMedSearch in Google Scholar
• 6 Axelrad A M, Fleischer D E, Geller A J, et al. High-resolution chromoendoscopy for the diagnosis of diminutive colon polyps: implications for colon cancer screening.  Gastroenterology. 1996;  110 1253-1258
  CrossrefPubMedSearch in Google Scholar
• 7 Jaramillo E, Watanabe M, Slezak P, Rubio C. Flat neoplastic lesions of the colon and rectum detected by high-resolution video endoscopy and chromoscopy.  Gastrointest Endosc. 1995;  42 114-122
  CrossrefPubMedSearch in Google Scholar
• 8 Jaramillo E, Watanabe M, Befrits R, et al. Small, flat colorectal neoplasias in long-standing ulcerative colitis detected by high-resolution electronic video endoscopy.  Gastrointest Endosc. 1996;  44 15-22
  CrossrefPubMedSearch in Google Scholar
• 9 Kim C Y, Fleischer D E. Colonic chromoscopy. A new perspective on polyps and flat adenomas.  Gastrointest Endosc Clin N Am. 1997;  7 423-437
  PubMedSearch in Google Scholar
• 10 Mitooka H, Fujimori T, Maeda S, et al. Minute flat depressed neoplastic lesions of the colon detected by contrast chromoscopy using an indigo carmine capsule.  Gastrointest Endosc. 1995;  41 453-459
  CrossrefPubMedSearch in Google Scholar
• 11 Nishizawa M, Kariya A, Kobayashi S, et al. Clinical application of an improved magnifying fiber-colonoscope (FCS-ML II), with special reference to the remission features of ulcerative colitis.  Endoscopy. 1980;  12 76-80
  PubMedSearch in Google Scholar
• 12 Mizuno M, Matsumoto T, Iida M, et al. Magnifying colonoscopic features in non-neoplastic polyps of the colorectum.  Gastrointest Endosc. 1997;  46 537-541
  PubMedSearch in Google Scholar
• 13 Nagata S, Tanaka S, Haruma K, et al. Pit pattern diagnosis of early colorectal carcinoma by magnifying colonoscopy: clinical and histological implications.  Int J Oncol. 2000;  16 927-934
  PubMedSearch in Google Scholar
• 14 Makiyama K, Bennett M K, Jewell D P. Endoscopic appearances of the rectal mucosa of patients with Crohn's disease visualised with a magnifying colonoscope.  Gut. 1984;  25 337-340
  PubMedSearch in Google Scholar
• 15 Tanaka S, Haruma K, Hirota Y, et al. Clinical significance of detailed observation for colorectal neoplasia using the high resolution or magnifying video colonoscope (abstract).  Endoscopy. 1999;  31 E52
  PubMedSearch in Google Scholar
• 16 Tanaka S, Haruma K, Ito M, et al. Detailed colonoscopy for detecting early superficial carcinoma: recent developments.  J Gastroenterol. 2000;  35 (Suppl 12) 121-125
  PubMedSearch in Google Scholar
• 17 Tarta C, Teixeira C R, Burger M B, et al. Magnifying colonoscopy in the diagnosis of colorectal carcinoma invading the submucosa in familial adenomatous polyposis (In Portuguese).  Arq Gastroenterol. 2000;  37 125-128
  PubMedSearch in Google Scholar
• 18 Togashi K, Konishi F, Ishizuka T, et al. Efficacy of magnifying endoscopy in the differential diagnosis of neoplastic and non-neoplastic polyps of the large bowel.  Dis Colon Rectum. 1999;  42 1602-1608
  CrossrefPubMedSearch in Google Scholar
• 19 Kato S, Fujii T, Koba I, Sano Y, et al. Assessment of colorectal lesions using magnifying colonoscopy and mucosal dye spraying: can significant lesions be distinguished?.  Endoscopy. 2001;  33 306-310
  Thieme ConnectPubMedSearch in Google Scholar
• 20 Nishizawa M, Okada T, Sato F, et al. A clinicopathological study of minute polypoid lesions of the colon based on magnifying fiber-colonoscopy and dissecting microscopy.  Endoscopy. 1980;  12 124-129
  PubMedSearch in Google Scholar
• 21 Kawano H, Tsura O, Ikeda H, et al. Diagnosis of the level of depth in superficial depressed type colorectal tumors in terms of stereomicroscopic pit patterns.  Int J Oncol. 1998;  12 769-775
  PubMedSearch in Google Scholar
• 22 Urita Y, Nishino M, Ariki H, et al. A transparent hood simplifies magnifying observation of the colonic mucosa by colonoscopy.  Gastrointest Endosc. 1997;  46 170-172
  PubMedSearch in Google Scholar
• 23 Guelrud M, Herrera I, Essenfeld H, et al. Enhanced magnification endoscopy: a new technique to identify specialized metaplasia in Barrett’s esophagus.  Gastrointest Endosc. 2001;  53 559-565
  CrossrefPubMedSearch in Google Scholar
• 24 Takayama T, Katsuki S, Takahashi Y, et al. Aberrant crypt foci of the colon as precursors of adenoma and cancer.  N Engl J Med. 1998;  339 1277-1284
  CrossrefPubMedSearch in Google Scholar
• 25 Yokota T, Sugano K, Kondo H, et al. Detection of aberrant crypt foci by magnifying colonoscopy.  Gastrointest Endosc. 1997;  46 61-65
  PubMedSearch in Google Scholar

R. Lambert,M.D. 

International Agency for Research on Cancer

150 Cours Albert Thomas
Lyon 69, cedex 08
France


Fax: + 33-4-72738650

Email: lambert@iarc.fr