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DOI: 10.1055/s-2007-995347
© Georg Thieme Verlag KG Stuttgart · New York
Colon tumors and colonoscopy
T. Ponchon, MD
Department of Hepatogastroenterology
Hôpital Edouard Herriot
Place d’Arsonval
Lyon 69003
France
Fax: +33-4-72-11-01-47
Email: thierry.ponchon@chu-lyon.fr
Publication History
Publication Date:
16 November 2007 (online)
- Introduction
- Diagnostic colonoscopy
- Polyp prevalence and screening
- Therapeutic colonoscopy
- References
Introduction
Although already a well-established technique, colonoscopy has featured prominently at recent Digestive Disease Week (DDW) meetings. Efforts have been made to set standards of practice, to improve its diagnostic and therapeutic utility, and even to replace it. Colonoscopy remains a particularly attractive subject for clinical research and debate, and this was evidently still the case at this year’s DDW.
#Diagnostic colonoscopy
For some considerable time colonoscopy has been the “gold standard” diagnostic examination for neoplastic colorectal lesions and this still obtains. This said, however, colonoscopy is now being widely critically reappraised and its disadvantages are regularly propounded. The four main disadvantages of the technique are as follows:
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Colonoscopy does not detect all polyps. There are increasing numbers of studies being published on the rate of missed colorectal adenomas and on the detection of greater numbers of flat adenomas and small, depressed cancers by Japanese authors in comparison with their Western colleagues.
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Colonoscopy is painful and patients need expensive sedation.
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Colonoscopy has to be preceded by bowel preparation, which is often not acceptable to patients.
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Colonoscopy uses a device which cannot be sterilized, and a costly disinfection process is required which is difficult to manage within the endoscopy suite setting.
Several options have been studied from technological as well as practical points of view in a bid to minimize the disadvantages of colonoscopy or even to replace colonoscopy. These can be summarized as:
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Improvements in colonoscopic technique.
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Improvement of the imaging capability in order to facilitate or improve the diagnostic yield.
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Improvement or even radical modification of the mechanical structure of the endoscopes.
Improvements in colonoscopic technique
Quality control. Quality control has been the subject of several studies published recently. As a result of these studies, the American Society for Gastrointestinal Endoscopy (ASGE) has implemented two new quality criteria: (a) the colonoscopic withdrawal time should now be more than 6 minutes; and (b) adenomas should be detected in more than 25 % of men aged over 50 and in more than 15 % of women aged over 50. Several papers were presented on this subject this year. Simmons & Harewood [1] validated these two new criteria in a cohort of 9528 colonoscopies performed by 43 endoscopists. They confirmed that a withdrawal time of more than 6 minutes will allow the detection of adenomas in more than 25 % of men aged over 50 and in more than 15 % of women aged over 50.
Retroflexion. Retroflexion during colonoscopy is often considered to be a risky maneuver and so is not recommended. Saad & Rex [2] presented an impressive series of 1552 consecutive colonoscopies during which rectal retroflexion was systematically attempted. Retroflexion in the rectum was successful in 94 % of cases, and no complications were observed. However, only one 4-mm distal adenoma not seen by forward viewing was found in retroflexion and the authors concluded that retroflexion did not add clinically important information after a careful forward examination of the rectum to the dentate line. Visualization of the proximal aspect of haustral folds is more difficult, however, and, in an attempt to improve this, a retrograde-viewing auxiliary imaging device was evaluated in 12 patients [3]. This single-use device, called the “third eye retroscope,” is inserted through the operating channel of a colonoscope and when it is extended beyond the colonoscope’s tip it is automatically retroflexed to provide a retrograde view. The feasibility and safety of the system were demonstrated in this small series. Suction through the operating channel was not impeded. We are still hoping that the endoscope-manufacturing companies will soon be providing colonoscopes with integral retrograde or lateral-viewing facilities.
Other issues. As usual, a number of different aspects of the technique have been studied and were reported at DDW, including bowel cleansing, the risk of bleeding, sedation, and training. The authors of one abstract demonstrated that oral sodium phosphate, by increasing serum phosphate, releases a urinary enzyme which is an early marker of renal tubular injury [4]. Another randomized study evaluated a new type of bowel cleansing regime that combined a low volume of polyethylene glycol (1 liter in the evening, 1 liter in the morning) with ascorbic acid, and compared this with sodium phosphate [5]. This combination provided superior bowel cleansing to that achieved by sodium phosphate and was better tolerated. In one randomized study of 100 patients, Entonox was shown to be as effective as propofol in terms of both the cecal intubation rate and patient satisfaction [6]. One case-control study that looked at the risk of postpolypectomy bleeding found that the main factors associated with this complication were anticoagulation therapy following polypectomy and polyp diameter; arterial hypertension and aspirin, in contrast, were not associated with an increased risk of postpolypectomy bleeding [7]. A study on training in colonoscopy concluded that experience of 150 colonoscopies is the threshold for technical competence in colonoscopy, not only for cecal intubation per se but also in terms of the time taken to achieve cecal intubation [8].
#Improvement of the imaging capability
Imaging capability has recently undergone a number of technological improvements and quite a few studies were presented this year on this topic, including studies on autofluorescence, and narrow-band imaging (NBI). Essentially, the concept of “virtual chromoscopy” has been developed. Electronic coloration is achieved by one of two methods: by projecting light with a particular wavelength onto a tissue, so revealing structures within the tissue that are reactive to this wavelength (autofluorescence); or by preferential light absorption patterns of tissues (narrow-band imaging or NBI) or processing of the signal obtained in white light (the Fuji Intelligent Chromo Endoscopy or FICE system). NBI has been the most extensively evaluated and contradictory results have emerged.
NBI and patients with a very high risk of cancer (hereditary nonpolyposis colon cancer or HNPCC). Chromoscopy, mainly using indigo carmine, has been proved to be effective in increasing the rate of colorectal adenoma detection in patients with HNPCC and is presently recommended for this indication. However, will the detection rate be even higher with NBI? That was the question that one study of 61 patients aimed to address [9]. Patients were examined twice from cecum to sigmoid colon, first with white light, then with NBI: with white light alone, 28 % of patients had at least one adenoma detected; this figure rose to 43 % for examination with white light plus NBI (P = 0.003). NBI seemed to be more effective than chromoendoscopy, which was evaluated by the same team in a previous trial.
NBI and patients with a high cancer risk. East et al. [10] studied the NBI system in the cecum in 91 patients with a high risk of cancer (patients with a history of colorectal cancer; patients with a history of three or more adenomas or of an adenoma measuring > 1 cm diameter in a previous colonoscopy; or patients with a positive fecal occult blood test [FOBT]). The study randomized patients to NBI or to white-light, high-definition examination. NBI increased the adenoma detection rate by more than 40 %: a 30 % increase in patients with at least one adenoma (P = 0.12), a 45 % increase for all adenomas (P < 0.04), and increased detection of flat adenomas (P = 0.09). Only two endoscopists were involved in this analysis.
Another study from Berlin of 401 patients with a high cancer risk had less convincing results for the role of NBI, however [11]. This was a randomized study comparing NBI with conventional colonoscopy in different groups of patients. In the NBI group adenomas were detected in 22.7 % of patients, compared with an adenoma detection rate of 16.7 % in the control group, but this difference was not statistically significant, either for the group as a whole or for any of the various subgroups (grouped according to location, size, and pattern). However, a difference was observed in the first 100 cases (NBI, 26 % vs. control, 8 %; P = 0.015) though this was not observed in the last 100 cases (NBI, 27 % vs. control, 19 %; not statistically significant). The authors therefore postulated that the use of NBI has mainly a learning effect. Hyperplastic polyps were detected more frequently using NBI than by conventional colonoscopy (28 % vs. 11 %, P < 0.001).
NBI and patients with a medium cancer risk. NBI has not improved the adenoma detection rate in this population. Two pilot studies, one of 40 patients [12] and another of 100 patients [13], demonstrated that NBI detected up to 40 % and 14 % of adenomas missed by standard colonoscopy, respectively. Another, randomized study found that NBI facilitated the detection of small/flat lesions [14]. This was not confirmed by another well-constructed randomized study, however [15], in which patients were randomized to examination with standard white light (n = 121) or with NBI (n = 119) during the first withdrawal. The patients then had a second examination by the same endoscopist using white light. An overall miss rate of 11 % for neoplasms of any size was observed; the rate was 3 % for adenomas ≥ 6 mm in size. NBI did not significantly improve the miss rate in comparison with white light. The results of NBI are similar to those of chromoendoscopy examination in this population of patients, in whom chromoendoscopy has also been shown to be ineffective.
In conclusion, the efficacy of NBI approaches that of chromoendoscopy. Its efficacy improves with increasing levels of cancer risk: NBI seems to be effective in very-high-risk patients but is not effective in average-risk patients. The results for high-risk patients are contradictory. NBI could also have a role in the characterization of polyps, as suggested by Ikematsu et al. [16] and by van der Broek et al. [17].
Autofluorescence. Autofluorescence has been studied for a long time in the field of gastrointestinal endoscopy, but has not yet found its place in clinical practice. It works on the premise that when near-ultraviolet-wavelength light is projected onto a tissue, that tissue can emit light with a higher wavelength (called “fluorescent” light). Molecules in the tissue (known as “fluorophores”) are responsible for this effect. Tissues have a mixed content of fluorophores, each of which will emit a specific wavelength of light when excited with a particular wavelength of light. This emission varies according to the tissue architecture, the distribution of fluorophores in each tissue layer, the biochemical environment, and the metabolic status, and is also affected by the presence of hemoglobin within vessels. Emission is therefore tissue-specific and so it is theoretically possible to distinguish normal from pathological tissue. Obviously, the problem is finding the wavelength that will excite the fluorophores present in a specific tissue. As light is monochromatic, lasers are used instead of filters. Lasers are low-energy and emit in the ultraviolet spectrum (337 - 370 nm) for collagen and in slightly higher wavelengths for porphyrins (maximum 440 nm).
There are two techniques, single-dot spectroscopy and image spectroscopy. Single-dot spectroscopy uses an optic fiber connected to a spectrograph. This fiber is emitting and receiving at the same time. In a probe, the central fiber is emitting and the peripheral ones are receiving. Fluorescence intensities are shown by the spectrograph for each wavelength. In order to better differentiate normal from pathological tissue, different wavelengths are used in an algorithm that will combine results and will set the final diagnostic. The probe is positioned under direct view in white-light endoscopy, which is turned off when the fluorescence is being measured. The problem with single-dot spectroscopy, however, is that the area of tissue being analyzed at any one time is very small and this method is therefore only useful for examining lesions already identified as suspicious on white-light endoscopy. It is therefore of interest only for tissue characterization and does not allow the detection of pathological tissue within at-risk areas of mucosa.
Because of the limitations of single-dot spectroscopy, recent research has focused mainly on image spectroscopy, which allows real-time visualization of the mucosa. This method superimposes a classic video image onto an image obtained with the help of spectroscopy, allowing the visualization of neoplastic areas. The LIFE system (Xillix Technologies, Vancouver, Canada) uses this method. White light is emitted to obtain a video image and at the same time an ultraviolet light corresponding to the excitation wavelengths is also emitted intermittently; a mirror system separately receives the red light (wavelength 590 - 700 nm) and the green light (wavelength 490 - 530 nm). The video image is obtained using a video endoscope, and “red” and “green” images are regularly superimposed on this image. Normal tissue will therefore appear green and pathological tissue will appear red. This “autofluorescence endoscopy” (AFE) system has been proved useful in bronchoscopy but not in gastrointestinal endoscopy.
One back-to-back colonoscopy study compared the sensitivity of AFE and white-light endoscopy for diagnosing colorectal neoplasia in patients belonging to HNPCC or familial colorectal cancer families [18]. Thirty patients were included. White-light endoscopy was performed first and then a second endoscopist, unaware of the results of the previous white-light endoscopy, performed AFE. White-light endoscopy identified 16 adenomas in nine patients. AFE detected all these lesions except for one, and in addition identified another 15 adenomas (including four flat adenomas) in 13 patients. The sensitivity and specificity values were much higher for AFE than for white-light endoscopy. This study is interesting, but a randomized study is still needed (i. e. with randomization to AFE first or to white-light endoscopy first) to show whether AFE is superior to white-light endoscopy because the results obtained in other, similar studies have been less convincing.
The autofluorescence imaging (AFI) system currently being proposed by Olympus Company uses a very different method, one which is simpler and which is not tissue- or fluorophore-specific. The principle behind AFI is excitation of the fluorophores in the submucosal layer, with subsequent analysis of all the fluorescence emanating from this source. Because the submucosa is the source of the autofluorescence, if the mucosa overlying it is thickened by a pathological process it will act as a barrier to light transmission from the submucosa to the gastrointestinal lumen; the submucosa will receive less light because of light scattering and absorption and, inversely, less of the autofluorescent signal will be transmitted to the exterior. The final result is that there will be a normal amount of reflected white light but less autofluorescence in such pathological areas. The system shows this phenomenon electronically by demarcation of areas of magenta coloration on a green background. This appearance is therefore not specific and the system will only reveal mucosal thickening. If the mucosa is not thickened but only inflamed, the absorption of white light by hemoglobin will decrease the autofluorescent light as well as the reflected light and the electronic reduction results in the image remaining green.
A randomized crossover study was performed by van den Broek et al. [19] in 87 patients to assess AFI for the detection of colorectal adenomas. Colonoscopy was performed with AFI first in 46 patients. In these patients, 82 polyps (33 adenomas) were detected by AFI. Subsequent white-light imaging detected 32 additional polyps (12 adenomas). In the 41 patients assigned to white-light imaging first, a total of 60 polyps (32 adenomas) were found. Subsequent AFI revealed 22 additional polyps (14 adenomas). The sensitivity of AFI for the primary detection of adenomas was therefore 73 %, compared with 70 % for white-light imaging (not statistically significant). AFI was therefore not proved to be any better than the white-light endoscopy for this indication. Obviously, this negative result needs to be confirmed. However, a different result was obtained by a Japanese team [20] who performed a back-to-back colonoscopy study using a similar model to that used in the van den Broek et al. study. A total of 167 patients were randomized in their study: 71 % of the neoplastic lesions were detected when AFI was the first withdrawal technique, compared with only 53 % neoplastic lesions detected when white light was the first withdrawal technique (P < 0.018). They concluded that AFI was effective for the detection of flat and diminutive lesions. Nevertheless, considering the principles of how the technique works (see above), we suspect that AFI will reveal mainly elevated lesions, which are already easy to visualize using white-light endoscopy.
It might be possible to improve the polyp detection rate simply by changing patient position during colonoscopy. This has been shown to be the case by a team from St. Mark’s Hospital in London [21], who conducted a randomized, crossover trial in 64 patients. The proximal colon was examined in three segments: cecum to hepatic flexure; transverse colon; and splenic flexure to descending colon. Each segment was examined twice, either with the patient in the left-lateral position throughout or with the patient in a series of changing positions (left-lateral from the cecum to the hepatic flexure, supine for the transverse colon, and right-lateral from the splenic flexure to the descending colon). Patients were randomized before colonoscopy to either the left-lateral-only group or to the changing-positions group. A difference was observed between the two groups in the percentage of patients with at least one polyp detected at the level of the transverse colon, splenic flexure, or descending colon: this figure was 33 % for the left-lateral-only group vs. 47 % for the changing-positions group (P < 0.03). The authors highlighted how this simple maneuver could improve the effectiveness of colorectal cancer screening without any increase in costs.
#Mechanical modifications
Among the goals of any modification to the equipment used in colonoscopy are: procedures that are easier to perform, reduction or elimination of pain, elimination of the need for disinfection, and an increased success rate in “difficult” colonoscopies. This last goal was the aim of double-balloon colonoscopes, which work in a similar way to double-balloon enteroscopes. It has already been shown in two studies in 10 patients [22] and in 16 patients [23] that these enteroscopes will work in cases of incomplete colonoscopy. A double-balloon colonoscope has been developed and it allowed cecal intubation in 15/16 patients with a previous incomplete colonoscopy in another study [24]. The colonoscope was used with or without the overtube, depending on the reason for the failure of the previous colonoscopy.
This year, as in 2005 and 2006, new endoscopes (Aeroscope, Invendo, Stryker, Neoguide) and new overtubes (USGI ShapeLock, EndoEase) have been presented on the stands but few of these have been studied in large clinical trials. Perhaps difficulties have emerged with their use that need to be surmounted first. The Invendo endoscope has been evaluated among the most to date, and a poster presentation summarized initial results of this scope in asymptomatic volunteers [25]. The Invendo is single-use colonoscope with inverted sleeve technology and an operating channel. A total of 28 volunteers underwent colonoscopy with the new device: four were technical failures; and of the 24 remaining examinations, the cecum was reached in 19 volunteers (79 %). The mean time to reach the cecum was 26 minutes. Discomfort was reported as minimal and no sedation was required in any volunteer.
A study has been also performed using the Spirus EndoEase overtube in 168 patients [26]. The EndoEase is an overtube with a raised helix at its distal end, which, when rotated, has a natural tendency to follow the lumen of the colon. In 11 % of cases, the overtube was not successfully deployed due to patient discomfort, difficult anatomy, or reluctance on the part of the physician to use a new device. When it was used, cecal intubation was achieved in 97 % of cases without any adverse effects.
In this arena, however, the real star was the colon capsule. Pilot studies have shown colon capsule endoscopy to be feasible and to be able to detect colon polyps and cancers. An eight-center, prospective study with a target of 329 patients is being conducted in Europe. The first planned interim analysis was reported [27]. Patients went through a traditional polyethylene glycol colon preparation and ingested the capsule in the morning. The protocol included prokinetic agents and additional small doses of laxatives. Independent physicians performed capsule imaging analysis and traditional colonoscopy (the gold standard) after excretion. Significant findings were defined as at least one polyp ≥ 6 mm in size or three or more polyps of any size. A total of 84 patients were analyzed for this interim analysis. Capsules were expelled within 8 hours after ingestion in 91 % of patients and 9 % reached the rectosigmoid. The quality of colon preparation for the capsule endoscopy was evaluated as excellent to good (66 %), fair (29 %), or poor (6 %). The negative predictive value of capsule endoscopy compared with conventional colonoscopy was 58 % for any polyp and 82 % for significant findings. Six polyps were detected only by the capsule study. No adverse events related to the capsule endoscopy were reported. This interim analysis therefore showed encouraging negative predictive values for detection of significant findings compared with conventional colonoscopy.
Finally, a small number of abstracts were presented this year on virtual colonoscopy. Debate concerning this technique has focused on the risk of leaving adenomas measuring < 10 mm in situ. This risk is certainly not zero if we consider results presented at DDW 2006: a third of adenomas less than 10 mm in size have a villous component; 7 % are already dysplastic, according to our Japanese colleagues, and decisional analysis has shown an improved prognosis if these are resected. A new abstract on the subject was presented at this year’s DDW based on the CORI database [28]: the results of 13 714 colonoscopies were recorded - one or more 6 - 9-mm polyps were the largest polyps in 1137 patients. Advanced features (villous histology, high-grade dysplasia, or invasive cancer) were found in 60 patients (5.3 % of all patients, 7.9 % of patients with adenoma). Advanced features were observed more frequently in men, in the distal vs. the proximal colon, and in patients aged 60 years and older. These findings confirm the results of previous studies, and the authors recommended detection and resection of these polyps. An English team hypothesized that if virtual colonoscopy was to be embraced for screening, a large number of readers would be required [29]. These readers could be radiologists but could also be endoscopists or endoscopy nurses because they are already involved in screening. This study demonstrated that after a short period of training an experienced endoscopist or an experienced endoscopy nurse can read animated virtual colonoscopies to a similar standard as radiologists. This raises the possibility of performing immediate therapeutic colonoscopy on a bowel that has already been prepared for diagnostic colonoscopy.
#Polyp prevalence and screening
Several studies reported on the factors associated with the prevalence of polyps, such as female sex, ethnicity, age, obesity, and diabetes [30] [31] [32] [33] [34] [35]. Women have a lower risk than men, but this is not the case if they are obese or have diabetes. Screening campaigns are less effective for women in terms of lesions in the proximal colon and for African American men. Considerable research attention has been paid to screening people aged 80 and over, mainly in order to find out how to select people who can still benefit.
#Therapeutic colonoscopy
An interesting aspect of DDW meetings is the juxtaposition of experiences, for example those of traditional endoscopists and those of certain Japanese endoscopists with regard to endoscopic submucosal dissection (ESD). Although difficult, this method is undoubtedly justified in the stomach and the esophagus, but not in such a systematic way in the colon. For traditional endoscopists, even mucosectomy is difficult. One presentation, entitled “Treatment of large and giant colorectal polyps in the real world” dealt with colorectal polyp management in an FOBT-based mass colorectal screening program in a French region over a 3-year period [36]. A total of 325 large polyps (diameter > 2 cm) were detected, and 110 of these were classified as “giant” (diameter > 3 cm). Endoscopic resection was attempted in only 76 % of cases - en bloc in 67 % of cases, and by endoscopic mucosal resection in 8.6 % of cases. Referral to surgery was indicated on the basis of a sessile or flat appearance, proximal or rectal location, size, or the presence of malignant foci. Two major issues were emphasized by the authors: the limited use of endoscopic mucosal resection and the lack of referral to another endoscopist. Better training in mucosectomy and better adherence to national guidelines are needed before implementing new techniques such as ESD. The same authors [37] also underlined the poor interobserver agreement between pathologists when analyzing colorectal polyps in community practice and the frequent lack of adequate characterization of malignant polyps.
At the opposite end of the spectrum, Japanese authors presented impressive case series of ESD for large colorectal tumors. For example, Tamegai [38] reported 199 colorectal ESD procedures (including 14 in the cecum and 181 in the ascending colon). The average polyp size was 30 mm and the average operating time was 53 minutes. Remarkably, there was only one case of microperforation (0.8 %), which was successfully treated by clipping. Sixteen lesions were classified as Vienna type 5, two with submucosal cancer. All lesions were followed up for at least 3 months and, amazingly, no residual tumors or recurrences were seen. Another large series included 97 ESD procedures, comparing these with 154 mucosal resections: a higher en-bloc resection rate was achieved with ESD (82 % vs. 29 %) and a lower recurrence rate (0 % vs. 18 %), but also a higher perforation rate (6 % vs. 1 %) [39]. Will ESD also become standard care in Europe? This is the question.
Guidelines on the endoscopic management of malignant colorectal polyps are very precise. They are based on the incidence of metastatic lymph nodes assessed by histological analysis of surgical specimens. However, the outcomes of endoscopic treatment of malignant polyps, assessed in long-term follow-up studies, are not known. The US National Cancer Registry was used to construct a Cox proportional hazards model to assess the impact of different types of treatment on cancer-free survival [40]. A total of 8221 patients with colorectal malignant polyps were identified; 7.1 % were treated by endoscopy. There was no difference between endoscopic and surgical treatments in the relative hazard of colorectal cancer-specific mortality. This confirms the role of endoscopic treatment in these cases.
Competing interests: None
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- 38 Tamegai Y. Endoscopic submucosal dissection for large colorectal tumors comparing with endoscopic piecemeal mucosal resection. Gastrointest Endosc. 2007; 65 AB275
- 39 Saito Y, Mashimo Y, Kikuchi T. et al . Endoscopic submucosal dissection resulted in higher en-bloc resection rates and reduced lower recurrence for LST > 20 mm compared to conventional EMR. Gastrointest Endosc. 2007; 65 AB273
- 40 Das A, Chak A, Leighton J A. et al . Endoscopic resection is as effective as surgical resection in managing malignant colorectal polyps: analysis of data from a National Cancer Registry. Gastrointest Endosc. 2007; 65 AB112
T. Ponchon, MD
Department of Hepatogastroenterology
Hôpital Edouard Herriot
Place d’Arsonval
Lyon 69003
France
Fax: +33-4-72-11-01-47
Email: thierry.ponchon@chu-lyon.fr
References
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T. Ponchon, MD
Department of Hepatogastroenterology
Hôpital Edouard Herriot
Place d’Arsonval
Lyon 69003
France
Fax: +33-4-72-11-01-47
Email: thierry.ponchon@chu-lyon.fr