Digestive and Liver Disease 46 (2014) 146–151
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Digestive Endoscopy
Endoscopic resection for superficial colorectal neoplasia in Italy: A prospective multicentre study Livio Cipolletta a , Gianluca Rotondano a,∗ , Maria A. Bianco a , Federico Buffoli b , Giuseppe Gizzi c , Francesco Tessari d , for the Italian Colorectal Endoscopic Resection (ICER) Study Group1 a
Gastroenterology, Hospital Maresca, Torre del Greco, Italy Gastroenterology, Azienda Ospedaliera di Cremona, Italy c Department of Internal Medicine and Gastroenterology, University of Bologna, Italy d “Idea 99”, Padua, Italy b
a r t i c l e
i n f o
Article history: Received 9 May 2013 Accepted 20 September 2013 Available online 1 November 2013 Keywords: Adverse events Colorectal neoplasia Endoscopic resection Mucosectomy Outcomes
a b s t r a c t Background: Since there are few prospective studies on colorectal endoscopic resection to date, we aimed to prospectively assess safety and efficacy of endoscopic resection in a cohort of Italian patients. Methods: Prospective multicentre assessment of resection of sessile polyps or non-polypoid lesions ≥ 10 mm in size or smaller (if depressed). Outcome measures included complete excision, morbidity, mortality, and residual/recurrence at 12 months. Results: Overall, 1012 resections in 928 patients were analysed (62.4% sessile polyps, 28.8% laterally spreading tumours, 8.7% depressed non-polypoid lesions). Lesions were prevalent in the proximal colon. Enbloc resection was possible in 715/1012 cases (70.7%), whereas piecemeal resection was required in 297 (29.3%). Endoscopically complete excision was achieved in 866 cases (85.6%). Adverse events occurred in 83 (8.2%), and no deaths occurred. Independent predictors of 12-month residual/recurrence were the location of the lesion in the proximal colon (OR 2.22 [95% CI 1.16–4.26]; p = 0.015) and piecemeal endoscopic resection (OR 2.76 [95% CI 1.56–4.87]; p = 0.0005). Limitations of the study were: potential expertise bias, no data on eligible and potentially resectable excluded lesions, high percentage of lesions < 20 mm, follow-up limited to 1 year. Conclusion: In this registry study the endoscopic resection of colorectal lesions was safe and achieved high rates of long-term endoscopic clearance. © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
1. Introduction Colorectal cancer is one of the leading causes of cancer death in Europe and the United States [1,2]. Endoscopic resection (ER) is a minimally invasive alternative to surgery for the removal of superficial neoplastic lesions in the colorectum, i.e. those lesions confined to the mucosa or to the upper third of the submucosa. These lesions have a negligible risk of lymph node metastases and are therefore amenable to curative ER [3,4]. Unlike pedunculated polyps, larger sessile or non-polypoid lesions (NPL) can be challenging to remove endoscopically. Most of the data regarding outcomes of ER in the colon come from Japanese series [5–11], though a number of Western studies have recently been published [12–15]. Unfortunately, only scant data are available for the Italian population [16–20].
Peculiar to the present study is the use of a simplified terminology (i.e. endoscopic resection) to describe different technical variants of a single procedure, which is the deliberate attempt of removing mucosa and submucosa down to the level of the muscularis propria [21]. This unifying term incorporates all means of previous different terminologies, from polypectomy to mucosectomy to submucosal dissection, since all these merely represent diverse technical modalities of performance of the same procedure necessary to remove large, sessile, or other high-risk lesions [22]. Objective of the study was to provide a real-life picture of ER for superficial colorectal neoplasia, assessing safety and efficacy in a large prospective cohort of patients in Italy. Secondary aim was to collect data to create a National Registry on colorectal ER. 2. Methods
∗ Corresponding author at: Via Cappella Vecchia 8, I-80121 Naples, Italy. Tel.: +39 3391923522. E-mail address:
[email protected] (G. Rotondano). 1 See Appendix A for the list of members.
2.1. Study design, setting, and patients The Italian Colorectal Endoscopic Resection (ICER) study group is a collaborative initiative developed under the auspices of the
1590-8658/$36.00 © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.dld.2013.09.019
L. Cipolletta et al. / Digestive and Liver Disease 46 (2014) 146–151 Table 1 Clinical and endoscopic characteristics of the ICER study population.
Table 2 Technical details of colorectal endoscopic resection (N = 1012). N. (%)
Total n. of patients Males Mean age (SD) years
928 544 (58.6) 66.0 (10.6)
Use of antiplatelet medications Use of anticoagulants
161 (17.3) 29 (3.1)
Total n. of lesions resected
1012
Sessile polyps Granular-type laterally spreading tumour Non granular-type laterally spreading tumour Depressed non polypoid lesions (0-IIc or 0-IIa + 0-IIc)
632 (62.5) 221 (21.8) 71 (7.0) 88 (8.7)
Location of lesions (proximal colon/distal colon/rectum) Non polypoid lesions Sessile polyps Laterally spreading tumours
57/22/9 308/205/119 203/49/40
Size of lesions Depressed non polypoid lesions (N = 88) 30 mm Laterally spreading tumours (N = 292) 10–20 mm 21–30 mm >30 mm
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88 (100) 391 (61.8) 126 (19.9) 115 (18.2) 145 (49.6) 83 (28.4) 64 (21.9)
Non polypoid lesions were by definition less than 10 mm in diameter, otherwise they would have been categorized as laterally spreading tumour. 67 patients (7.2%) had multiple lesions: 58 patients had 2 lesions, 7 patients had 3 lesions, 1 patient had 6 lesions and 1 patient had 7 lesions.
Italian Society for Digestive Endoscopy to prospectively collect data on colorectal ER performed in 46 Italian academic or communitybased endoscopy units. Minimal standards required for participating units were set a priori and included high-volume endoscopic activity (≥1200 colonoscopies/year) and adequate local expertise in colorectal ER (≥130 resections/year). Lesions were assessed by white-light colonoscopy without cap attachment. Lesions were classified according to the Paris Classification of lesion morphology [23]. All NPLs that were larger than 10 mm in width were more appropriately termed “laterally spreading tumours” (LST), and sub-classified as either granular or non-granular [24]. Consecutive or referred patients were enrolled during a 3month run-in period from May 2010 to July 2010. Patients were included if they had colonoscopic evidence of a sessile polyp >10 mm and/or a laterally spreading tumour and/or a depressed NPL of any size (Paris classification types 0-IIc or 0-IIa + 0-IIc). Patients who refused to provide informed consent and those with pedunculated polyps or sessile polyps < 10 mm or flat-elevated NPL (Paris classification types 0-IIa and 0-IIb) were excluded. For details of procedures, outcome measures and definitions, follow-up schedule and data management and analysis, see Appendix B (Supplementary Material [25,26]). 3. Results A total of 928 patients (58.6% males; mean age, 66.0 ± 10.6 years; range, 32–87) with 1012 lesions were enrolled. Clinical features of patients and endoscopic characteristics of the resected lesions are outlined in Table 1. Mean age of males was significantly higher than that of females (66.8 ± 10.2 vs. 64.9 ± 10.8, p = 0.01). Use of antiplatelet agents was recorded in 161 patients (17.3%) and was withheld prior to ER in 138 cases (85.7%). Use of oral anticoagulants
N. (%) Chromoendoscopy prior to ER Dyes (indigo carmine/methylene blue) Opto-electronic (NBI, FICE, I-scan) Magnification endoscopy prior to ER Peripheral marking of lesion Submucosal lifting prior to ER Standard injector needle Hydro-jet device Substance used for submucosal lifting Saline Saline plus epinephrine 50% dextrose Glycerol Hyaluronic acid Succynilated gelatine Technique of resection Inject and cut Lift and cut Suck and cut ESD Type of snare Standard Crescent Single wire Semi-rigid Type of high-frequency current delivery programme Endocut Free Adjunctive procedures APC treatment of resection margins Magnified inspection of the resected margins Tattooing Clip closure of resection margins
393 (38.8) 161 (132/29) 232 (127/19/86) 89 (8.8) 129 (12.7) 1006 (99.4) 971 (96.5) 35 (3.5) 365 (34.1) 504 (47.1) 77 (7.6) 48 (4.7) 10 (0.9) 67 (6.2) 969 (95.8) 20 (2.0) 6 (0.6) 17 (1.7) 478 (47.2) 443 (43.7) 76 (7.1) 69 (6.5) 899 (88.8) 113 (11.2) 186 (18.4) 51 (5.0) 45 (4.4) 325 (32.1)
ESD: endoscopic submucosal dissection; APC: argon plasma coagulation; ER: endoscopic resection.
was recorded in 29 patients (3.1%) and was systematically switched to low-molecular-weight heparin or fractioned heparin 3–5 days before ER in all cases. Sessile polyps and granular-type LSTs were most prevalent. A depressed NPL was recorded in 8.7% of cases. The majority of the lesions (568/1012, 56.1%) were located proximally to the splenic flexure. Overall, 624 lesions (61.6%) were less than 20 mm in size. Lesions larger than 30 mm were recorded in 18% of sessile polyps and 22% of LSTs. Median size of depressed NPLs was 7 mm [IQR 6–9 mm], while that of sessile polyps was 18 mm [IQR 12–28 mm], and that of LSTs was 21 mm [IQR 15–29 mm]. A previous attempt of resection by the referring endoscopist had occurred in 42 cases (4.1%). Technical aspects of the resection are detailed in Table 2. Prior to ER, a subgroup of 393 lesions (292 LST, 88 depressed NPL and 13 sessile polyps) was assessed by means of image-enhanced endoscopy. A non-neoplastic pattern (Kudo type II) was reported in 5 cases, whereas a neoplastic non-invasive pattern (Kudo types IIIs, IIIL or IV) was reported in all other cases. Magnified inspection was reported in 89 of these lesions (71 depressed NPLs and 18 non granular LSTs). A neoplastic invasive pattern (Kudo type Vi/Vn) was recorded in 9/71 depressed lesions (6/9 showed submucosal cancer on histology), and in 9/18 non-granular LSTs (6/9 had submucosal cancer on histology). The standard “inject and cut” technique was by far the most widely accomplished variant of ER (95.8%). Only 17 lesions were resected using endoscopic submucosal dissection (ESD). This accounts for 1.7% of all ER and 4.4% of ER performed for lesions > 20 mm. In particular, a typical ESD was performed only in 8 patients and exclusively for rectal lesions (6 LSTs and 2 sessile polyps), while a simplified ESD was employed to remove the other 9 lesions (1 LST in the transverse colon, 3 sessile polyps in the sigmoid colon and 5 LSTs in the rectum).
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Table 3 Outcomes of colorectal endoscopic resection in the ICER cohort. N. (%) Complete excision at endoscopy All lesions Lesions larger than 20 mm En-bloc/piecemeal resection Radical resection (R0) Overall adverse events Immediate or delayed bleeding Transmural burn Perforation Residual or recurrence at 12-months
866 (85.6) 333 (85.8) 715/297 624 (87.4) 83 (8.2) 77 2 4 60 (6.5)
R0: disease-free lateral and vertical margins at histology.
Table 4 Univariate analysis: risk factors for residual or recurrent disease at 12 months (N = 60 vs. 863 controls). Risk factor
N. patients %
Odds ratio [95% CI]
p value
Proximal colon location
44/60 vs. 492/863 73.3% vs. 57.0% 20/60 vs. 161/863 33.3% vs. 18.6% 22/60 vs. 138/863 36.6% vs. 16% 32/60 vs. 232/863 53.3% vs. 26.9%
2.04 [1.1–3.7] 2.18 [1.2–3.8] 3.01 [1.7–5.3] 3.11 [1.8–5.2]
0.015
APC on margins at index ER Size ≥ 30 mm Piecemeal resection
0.0068 0.00009 0.00002
Incomplete resection at index ER, non lifting sign or the occurrence of adverse events during or after index ER were not significantly different between patients with residual or recurrence at 12 months and controls; ER: endoscopic resection.
3.1. Efficacy Submucosal lifting prior to ER was attempted in nearly all cases (1006/1012) and reported as successful in 984 cases (97.8%). An inadequate lifting or non-lifting sign occurred in 22 cases (5 previous biopsies of the lesion, 7 previous attempts of ER elsewhere, 1 depressed NPL, 3 non-granular and 1 granular LST, and 5 sessile polyps all larger than 20 mm). In such cases ER was not attempted: 18 patients were sent for surgical excision of the lesion and 4 were referred to other GI units for further evaluation. Outcomes of colorectal ER in the cohort are reported in Table 3. An en bloc resection was possible in 715/1012 cases (70.7%), whereas a piecemeal resection was required in the remaining 297 lesions (29.3%), with no difference between proximally or distally located lesions for either technique. Overall, an endoscopically complete excision was achieved in 866 cases (85.6%). A similar rate was recorded in the subgroup of 388 lesions larger than 20 mm (333/388, 85.8%). A radical resection (R0 on histology) was confirmed in 624/715 en bloc ER (87.4%). Incomplete resection was significantly higher for piecemeal than en bloc ER (18.9% vs. 12.6%, OR 1.61 [95% CI 1.02–2.62], p = 0.01). Histology findings included 61 hyperplastic and 951 neoplastic lesions. Of these, 602 were low-grade adenomas and 313 were high-grade adenomas or intramucosal carcinomas. Lesion size > 20 mm was a risk factor for the presence of a high-grade adenoma or intramucosal carcinoma compared to lesions < 20 mm in size in both sessile polyps (105/241 (43.6%) vs. 101/391 (25.8%), OR 2.21 [1.57–3.11], p = 0.0001) and in LST (58/147 (39.5%) vs. 26/145 (17.9%), OR 2.98 [1.74–5.10], p = 0.0005). Thirty-six lesions (3.5%) showed submucosal invasive carcinoma proven histologically (Fig. 1). Of the 30 invasive cancers found in endoscopic specimens, 5 were depressed NPLs (1 rectum, 2 left colon and 2 proximal colon), 16 were sessile polyps (1 rectum, 9 left colon and 6 proximal colon; 3 with size < 20 mm and 13 with size > 20 mm), and 9 were LSTs (3 rectum, 2 left colon and 4 proximal colon; 5 nodule mixed and 4 non-granular). Segmental colectomy was offered to 23 patients, while 7 patients underwent close endoscopic surveillance because of poor surgical risk or favourable histology (invasion limited to sm1 without vascular or lymphatic involvement), or both. One patient with submucosal cancer in the ER specimen with clear deep margins declined surgical referral. A significantly increased incidence of submucosal carcinoma was found only in sessile polyps larger than 20 mm (20/241 (8.3%) vs. 7/391 (1.8%), OR 4.96 [2.06–11.93], p = 0.0003), but not in LSTs (4/147 (2.7%) vs. 3/145 (2.1%), OR 1.32 [0.29–6.02], p = 0.716). Non-granular surface morphology was not a risk factor for submucosal cancer in LST. Complete 12 months follow-up data were available for 923/1012 lesions (91.2%). The flow diagram of the lesions during the follow-up period is illustrated in Fig. 2. Confident identification of the scar in the site of the previous ER was reported in 664/974 cases (68.1%) at 6 months and still in 615/923 cases (66.6%)
at 12 months. In the remaining cases no abnormality could be detected. Residual or recurrent neoplasia was recorded in 60 cases (6.5%). In 12 of them the residual adenoma was already present at the 6-month follow-up examination (4 underwent surgery, and 8 retreated endoscopically). At univariate analysis, location of the lesion in the proximal colon, size ≥ 30 mm, piecemeal ER, and the use of argon plasma coagulator on the resection margins at index ER were significant risk factors for recurrence/residual disease at 12 months (Table 4). At the per-patient multivariate analysis the independent predictors of 12-month residual/recurrence were the location of the lesion in the proximal colon (OR 2.22 [95% CI 1.16–4.26]; p = 0.015) and piecemeal ER (OR 2.76 [95% CI 1.56–4.87]; p = 0.0005). None of the patients with intramucosal or submucosal carcinoma at basal histology developed invasive or metastatic cancer during follow-up, independently of the reason for not undergoing surgery. 3.2. Safety Overall, adverse events were recorded in 83 cases (8.2%). Bleeding was immediate or intraprocedural in 60 cases and delayed in 17. Successful endoscopic management by means of clip application or thermal coagulation was reported in 75/77 haemorrhages, and only 2 patients (one with immediate and one delayed haemorrhage) required surgical haemostasis with uneventful recovery. The risk of bleeding was significantly higher for lesions larger than 20 mm vs. those of smaller size (15.3% vs. 3.6%, OR 4.22 [2.40–7.23], p < 0.0001), as well as for piecemeal vs. en bloc ER (14.8% vs. 5.4%, OR 3.41 [1.95–4.81], p < 0.0001). Transmural burns were recorded in 2 patients, both after ER of lesions located in the proximal colon. In the first case, after resection of a 20 mm sessile polyp in the ascending colon performed with blended coagulation current, the patient was observed for 2 days in the hospital and then discharged. The second patient was a 72-year old male who had undergone resection of 2 lesions (one 25 mm granular LST in the cecum and one 15 mm sessile polyp in the hepatic flexure). Older age, presence of fever and abdominal pain with localized tenderness prompted a longer hospital stay (5 days) together with supportive medical therapy (i.v. fluids, nil by mouth, and broad spectrum antibiotic coverage). A colonic perforation occurred in 4 resections (4.4%), with either en bloc (2 sessile polyps sized 20–25 mm) or piecemeal ER (1 nodule mixed LST and one 35-mm sized sessile polyp); three of them occurred with the standard “inject and cut” technique and 1 after “lift and cut” ER. One perforation was successfully managed by endoscopic clip closure, while a laparoscopic surgical repair was required in the other 3 instances. All patients recovered well and were discharged on day 6, 8, and 11, respectively. No clinical,
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Fig. 1. Details of the 36 histologically proven submucosal carcinomas.
Fig. 2. Flow diagram of lesions during the follow-up period.
endoscopic, or technical variable was predictive of the risk of perforation. There was no specific procedure-related mortality. 4. Discussion This is the first cooperative study reporting the outcomes of colorectal ER in Italy, and represents the largest cohort of patients reported in a Western country. The ICER registry aims at gathering data on ER for superficial colorectal neoplasia, ideally continuing and completing the previous experience of the Flat Lesions Italian Network [27,28]. The size of the lesion is considered the guiding criterion on which to select the type of ER (en bloc vs. piecemeal vs. ESD). The high en bloc and R0 resection rates reported herein reflect the fact that the study is primarily assessing a mix of lesions less than 20 mm in size. ESD enables en bloc resection and pathologically complete resection of larger colorectal tumours [8–11]. The substantial difference in study cohort precludes sound comparison of our results with those of most Japanese ESD studies. In fact, the majority of lesions were below the 20 mm size threshold, but the ICER database nonetheless comprises 388 lesions over 20 mm, thus theoretically
amenable to en bloc ESD. Only 4.4% of such lesions were approached by ESD, and were primarily located in the rectum. The overwhelming preference for the piecemeal technique recorded herein is in agreement with previous data showing a low adherence of Western endoscopists to ESD in the colorectum [3,11,29]. Although associated with a higher risk of incomplete resection compared to ESD, Italian endoscopists feel more confident with multi-step piecemeal resection, an established procedure that has demonstrated to be safe and effective, also in the long-term [13–15,30–32]. If the dimensional criterion guides the decision as to what type of resection, the suspicion of deep submucosal infiltration should determine the treatment strategy. The macroscopic appearance of the lesion with evident ulceration of the surface [33], a failure to lift the lesion [34], or the presence of mucosal invasive (disrupted) crypt pattern on magnified inspection [35] are specific markers of invasive neoplasia and should prompt the endoscopist to desist from any attempt of ER. The success rate of ER dramatically decreases for a previously attempted lesion, primarily owing to submucosal fibrosis, which increases both the risk of no-lift sign and the risk of perforation [30]. Patients with a prior attempt of ER should have probably been excluded, as their risk of complete
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resection or overall risk of resection may have been altered by the prior attempt, which was recorded in only 7 patients in the present cohort. In our experience, a previous biopsy also prevented adequate lifting of the lesion, thus precluding ER in 5 patients. In such cases, one may choose to proceed cautiously with resection or refer for surgery. The decision depends on multiple factors including lesion characteristics (site, size, and appearance), technical accessibility to the lesion, and clinical data, such as age of the patient, fitness for surgery, and type of surgery required. In terms of long-term disease clearance, the ICER data show favourable outcomes with an overall 12-month residual/recurrence rate of 6.5%. Location of the lesion in the proximal colon was the only independent predictor of residual/recurrent disease, possibly linked to larger size of these lesions and inherent complexity in their complete removal. The piecemeal method is confirmed to be associated with a higher rate of residual/recurrent neoplasia, as previously pointed out [36,37]. When adjusted for lesions’ size and piecemeal resection, the residual/recurrent rate in the ICER cohort rises to 14.2%, a figure similar to the 20.4% rate reported in the multicentre Australian study [32]. Additional procedures are needed to complete resection in more than 1 of 10 colonic piecemeal ERs [37] for the presence of residual neoplasia at first follow-up endoscopy. An earlier follow-up inspection, for example at 4–6 weeks [38], with the intent of retreating any residual adenoma “left behind”, may possibly detect the residual disease earlier and reduce the rate of recurrent adenoma (or inappropriately labelled as such). Additional use of argon plasma coagulation did not affect the recurrence rates after piecemeal resection. The present study confirms that, globally, colonic ER is performed with satisfactory safety. The overall 8.0% complication rate (7.6% bleeding and 0.4% perforation) may seem high, but it is indeed comparable to most series of advanced resection for larger colorectal lesions [10,11,32]. Bleeding could be controlled endoscopically in almost all instances and required surgery in only 2 cases. Delayed bleeding occurred in 1.7% of cases, a lower rate compared to the 4–7% reported in other series [9,11,32], possibly due to the smaller number of larger lesions in our database. Right colon location, use of aspirin, and age have been reported as independent risk factors for ER-related bleeding [39]. In our study, factors associated with increased risk of bleeding were larger lesion size and multiple excision rather than en bloc resection. Standardized ER technique and cessation of anticoagulant and antiplatelet therapy according to guidelines [40] would help to further decrease bleeding risk. The low perforation rate of 0.4% compares favourably with the 1.3% perforation rate reported in the Saito’s colorectal endoscopic mucosal resection study [10]. All the perforations were detected during the procedure and closed endoscopically with good clinical outcomes in 1 case. However, laparoscopic surgery for perforation was ultimately required in 3 out of 4 cases. Adequate submucosal lifting using long-lasting substances are preferred for piecemeal or ESD resection. In the present study, crystalloids as succynilated gelatin were employed in only 6.2% of the cases, while the inexpensive option of saline injection (with or without epinephrine) was chosen in over 80% of cases, despite the likely increased need for repeated injections during the procedure. The study has some inherent limitations. First and foremost, although a selection effort was made to include only “expert” centres according to predefined criteria, an individual expertise bias cannot be completely ruled out, since it is conceivable that not all operators had the same level of skill in performing these procedures, potentially affecting the investigated outcomes. Therefore, as for all prospective studies, ICER provides an overall informative content, a sort of “macro” picture, i.e. identifying the gross elements that concur to a determined outcome, but not single or specific risk factors. In fact, like in any endoscopic interventional study, different expertise of operators did not allow to standardize the
procedures completely. That is, the fundamental steps were agreed upon (lifting, dissecting or snaring, and retrieving), but every endoscopist was necessarily free to adjust his or her technique to the single case, tailoring the intervention to the specific characteristics of the lesion and to the available devices. Nonetheless, since the primary aim of the study was to provide a real life picture and the vast majority of resections were performed using the standardized “inject and cut” technique, such variability would only have limited impact. The number of cases provided was different between the 3 top-enrolling centres (163 total procedures) and all the others, which provided data on a mean of 19.7 resections per centre (range 10–28). Nonetheless, there was no overall significant difference in terms of positive or negative outcomes among the 46 centres as a whole, nor when stratified for the number of cases provided. Second, each patient was included in the study only when the lesion met the inclusion criteria of size and morphology, and was deemed amenable to ER. Therefore, the total number of eligible and potentially resectable lesions that were excluded are unknown, as are the reasons for exclusion (endoscopic appearance, patient’s or operator’s choice, or else). Third, 5-m thick serial sections were the standard for histological examination of resected specimens in this study, wider than the 3-m sections often adopted in Japanese studies, so the radical resection rate could possibly be overestimated. Fourth, as most resections were performed for lesions < 20 mm with the Endocut, the scar could not be confidently identified in almost 32% of the patients at 6 months. Fifth, the clinical research agency made great efforts to solve the queries for missing information from incomplete reports. Unfortunately, there was no way to assess whether any unsuccessful or aborted procedure had been “forgotten”. Last but not least, the end-point observation was censored at 12 months as in most studies of similar design. This time limit was considered adequate by the investigators to assess local recurrence or, more appropriately, the rate of residual disease. Clearly, a longer follow-up would have been desirable, however the high risk of patients’ drop out over time would have likely jeopardised the consistency of the results. In conclusion, the ICER registry shows that ER of colorectal lesions is accomplished with satisfactory safety and long-term outcomes in Italy. For the subgroup of lesions larger than 25 mm, piecemeal resection is by far the preferred approach. Conflict of interest statement None of the authors had any potential competing interests. Acknowledgments We thank SOFAR S.p.A., Italy, for the unrestricted educational grant given to the study. We acknowledge the great deal of work performed by medical and nursing staff in each of the participating units. Appendix A. COLLABORATORS – The ICER Study Group M. Gentile, F. Spirito (San Giovanni Rotondo) – L. De Luca, D. Baroncini (Pesaro) – R. Sassatelli, V. Iori (Reggio Emilia) – O. Tarantino, M. Biagini (Empoli) – G. Manes, S. Pallotta (Milano) – R. Briglia, F. Praianò (La Spezia) – F. Buffoli, E. Iiritano (Cremona) – L. Buri, F. Tonello (Trieste) – R. Cestari, G. Lancini (Brescia) – S. Sansone, F. Cipolletta (Torre del Greco) – O. Ignomirelli, M. Ciuffi (Rionero in Vulture) – G. Coccia, A. Allegretti (Genova) – L. Petruzziello, P. Cesaro, G. Costamagna (Roma) – L.M. Montalbano, M. Giunta (Palermo) – L. Corazza, G. De Maio (Matera) – M. Del Piano, M. Orsello (Novara) – P. Di Giorgio, F. Giannattasio (Napoli) – E. Di Giulio, S. Angeletti (Roma) – A. Pisani, A. Di Leo (Bari) – G. Di Matteo, P. Giorgio (Castellana Grotte) – R. Frego, M. Dinelli (Monza)
L. Cipolletta et al. / Digestive and Liver Disease 46 (2014) 146–151
– L. Familiari, S. Pallio (Messina) – L. Ficano, D. Ligresti (Palermo) – P. Parisi, S. Astretto (Caserta) – B. Germanà, L.G. Cavallaro (Belluno) – S. Rodinò, N. Saccà (Catanzaro) – G. Gizzi, V. Villani (Bologna) – M. Ingrosso, S. Marangi (Campobasso) – M. Delle Cave, G. Sarrantonio (Casoria) – P. Loriga (Cagliari), G. Asnaghi, A. Manca (Cuneo) – E. Masci, P. Viaggi (Milano) – O. Labianca (M. San Severino) – S. Morini, R. Lorenzetti (Roma) – A. Milano, F. Laterza (Chieti) – G. Del Vecchio Blanco, M. Coppola (Roma) – F. Parente, S. Bargiggia (Lecco) – P. Cesari, C. Petruzzellis (Brescia) – C. Widmeyer (Carrara) – E. Cavargini, E. Ricci (Forlì) – M. Giovanardi, F. Santilli (Rimini) – G. Scaglione, I. Sorrentini (Benevento) – M. Silla, A. Spadaccini (Vasto) – M. De Bellis, G.B. Rossi (Napoli) – A. Amato, V. Terlizzi (Como) – M. Silvestrelli, L.M. Tomarelli (Osimo) – G. Feliciangeli (Macerata) – A. Zambelli, G. Manfredi (Crema) – R. Marmo (Polla). Appendix B. Supplementary data Supplementary material related to this article can be found, in the online version, at http://dx.doi.org/10.1016/j.dld.2013.09.019. References [1] Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. European Journal of Cancer 2010;46:765–81. [2] Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA: A Cancer Journal for Clinicians 2008;58:71–96. [3] Lambert R, Kudo SE, Vieth M, et al. Pragmatic classification of superficial neoplastic colorectal lesions. Gastrointestinal Endoscopy 2009;70:1182–99. [4] Watanabe T, Itabashi M, Shimada Y, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer. International Journal of Clinical Oncology 2012;17:1–29. [5] Saito Y, Fujii T, Kondo H, et al. Endoscopic treatment for laterally spreading tumors in the colon. Endoscopy 2001;33:682–6. [6] Tamura S, Nakajo K, Yokoyama Y, et al. Evaluation of endoscopic mucosal resection for laterally spreading rectal tumors. Endoscopy 2004;36:306–12. [7] Uraoka T, Saito Y, Matsuda T, et al. Endoscopic indications for endoscopic mucosal resection of laterally spreading tumours in the colorectum. Gut 2006;55:1592–7. [8] Tamegai Y, Saito Y, Masaki N, et al. Endoscopic submucosal dissection: a safe technique for colorectal tumors. Endoscopy 2007;39:418–22. [9] Saito Y, Uraoka T, Yamaguchi Y, et al. A prospective, multicenter study of 1111 colorectal endoscopic submucosal dissections. Gastrointestinal Endoscopy 2010;72:1217–25. [10] Saito Y, Fukuzawa M, Matsuda T, et al. Clinical outcome of endoscopic submucosal dissection versus endoscopic mucosal resection of large colorectal tumors as determined by curative resection. Surgical Endoscopy 2010;24:343–52. [11] Repici A, Hassan C, De Paula Pessoa D, et al. Efficacy and safety of endoscopic submucosal dissection for colorectal neoplasia: a systematic review. Endoscopy 2012;44:137–50. [12] Ahamad NA, Kochman ML, Long WB, et al. Efficacy, safety, and clinical outcomes of endoscopic mucosal resection: a study of 101 cases. Gastrointestinal Endoscopy 2002;55:390–6. [13] Kaltenbach T, Friedland S, Maheshwari A, et al. Short- and long-term outcomes of standardized EMR of nonpolypoid (flat and depressed) colorectal lesions > or = 1 cm. Gastrointestinal Endoscopy 2007;65:857–65. [14] Mahadeva S, Rembacken BJ. Standard inject and cut endoscopic mucosal resection technique is practical and effective in the management of superficial colorectal neoplasms. Surgical Endoscopy 2009;23:417–22. [15] Ah Soune P, Ménard C, Salah E, et al. Large endoscopic mucosal resection for colorectal tumors exceeding 4 cm. World Journal of Gastroenterology 2010;16:588–95. [16] Conio M, Repici A, Demarquay JF, et al. EMR of large sessile colorectal polyps. Gastrointestinal Endoscopy 2004;60:234–41.
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