EMR-C VS EMR-S in Colonic Lateral Spreading Tumors Treatment (LST)

Endoscopic Mucosal Resection Clinical Trial

— LST  

Official title:

"Cap-assisted" Endoscopic Mucosal Resection vs Standard "Inject and Cut" Endoscopic Mucosal Resection for Large Colonic "Lateral Spreading Tumors" Treatment: a Randomized Multicentric Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03498664
• Other study ID #: 90/2014
• Status: Recruiting
• Phase: N/A
• Start date: March 15, 2018
• Est. completion date: September 15, 2019

Study information

• Verified date: January 2019
• Source: Azienda Ospedaliera Universitaria Senese
• Contact: Antonella De Ceglie, MD
• Phone: +393391332951
• Email: adeceglie[@]libero.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

"Lateral Spreading Tumors" (LSTs) are dysplastic lesions whose protrusion within the lumens the colon is not more than twice as compared to the surrounding non-dysplastic mucosa.

They can be divided into two groups:

Granular type (LST-G) and Non Granular type (LST-NG) Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are currently the most used techniques to resect this type of lesions. Compared to other methods of tissue ablation, EMR allows to carry out the histological evaluation of the resected fragments and ESD of the lesion in toto ("en bloc") EMR is currently the most used technique for removal of LST, but for lesions of ≥ 30 mm the resection is performed "piecemeal", i.e. fragmentary. This can compromise an adequate histological evaluation of the lateral and deep margins of the lesion.

Colonic EMR (EMR-S) is usually performed using a polypectomy snare, after lifting the lesion from the underlying layers with a submucosal injection of liquid (EMR standard or "inject-and-cut"). The aspiration of the lesion inside a plastic cap preloaded on the tip of the colonoscope ("cap-assisted EMR" - EMR-C) is almost exclusively used for the treatment of gastric and esophageal lesions. Its use for lesions of the colon and duodenum has been reported in limited experiences The principal aim of this study is to evaluate the efficacy and the safety of the EMR-C for the removal of large colonic LST-G and LST-NG, comparing it with EMR-S.

Description:

Colorectal carcinoma (CRC) is the second cause of death for cancer in industrialized countries, with annual incidence and mortality of about one million and 500.000 case respectively.

It's well known that most of CRC follow the path adenoma-carcinoma: early diagnosis and endoscopic removal of colonic polyps has been proved to be useful in preventing cancer.

Most of colorectal polyps are smaller than 1 cm and can be successfully resected with a standard polypectomy. However, between 0.8% and 5% of patients develop sessile polyps or lesions larger than 20 mm, of which removal can be difficult, requiring high endoscopic experience.

Recent prospective studies report that 7%-36% of CRC have a flat or depressed morphology and are more likely to infiltrate the submucosa compared with polypoid ones.

A univariate analysis has proved that the size of the lesion is the only significant risk factor associated with malignant evolution.

Contrary to sessile polyps (SP) that are protruding lesions without a peduncle and whose base has almost the same dimension of the head, "Lateral Spreading Tumors" (LSTs) are dysplastic lesions whose protrusion within the lumen is not more than twice as compared to the surrounding non-dysplastic mucosa. According to Kudo classification they are larger than 1 cm in size, slightly elevated and extending laterally along the intestinal wall.

They can be divided into two groups (according to Paris Classification, 2005, updated for the colon in Kyoto Classification 2008):

• Granular type (LST-G) characterized by nodular aggregates and sub-classified into homogeneous (0-IIa according to Paris Classification) and mixed nodular (0-IIa, 0-Is + IIa, 0-II+ Is) subtypes.

• Non Granular type (LST-NG) characterized by a non nodular surface and sub-classified into elevated (0-IIa) and pseudo-depressed (0-IIa + 0-IIc, 0-IIc +0- IIa) subtypes.

The risk of developing cancer is different between the two types (57.7% in LST-NG vs 32.7% in LST-G). LST-NG are more likely to invade the submucosa compared to LST-G (14% vs 7%). Within the LST-G group, lesions with a mixed nodular morphology have a greater tendency to infiltrate the submucosa compared to the homogeneous ones.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are currently the most used techniques to resect this type of lesions. Compared to other methods of tissue ablation, EMR allows to carry out the histological evaluation of the resected fragments and ESD of the lesion in toto ("en bloc").

EMR allows the resection of superficial neoplasia of gastro-intestinal tract (GI) confined to the mucosa, in the absence of vascular and/or lymphatic invasion.

ESD compared with EMR allows to remove "en bloc" lesions ≥20 mm in size. It should be preferred for lesions with higher risk of invasiveness or when the removal of the deepest layers or of the whole submucosa is desired, despite the size of the lesion. However, ESD is a complex procedure which requires a long training period and it is associated with higher risk of perforation compared with EMR (6.2% vs 1.3%). Furthermore, ESD requires a longer execution time.

Therefore, EMR is currently the most used technique for removal of LST, but for lesions of ≥ 30 mm the resection is performed "piecemeal", i.e. fragmentary. This can compromise an adequate histological evaluation of the lateral and deep margins of the lesion.

Piecemeal resection increases the risk of residual disease that ranges from 12% to 20% compared with 5% described after "en bloc" removal while the percentage of recurrence reported for polypoid lesions ≥ 20 mm is on average 25% (21) and reaches 55% in some studies.

Colonic EMR is usually performed using a polypectomy snare, after lifting the lesion from the underlying layers with a submucosal injection of liquid (EMR standard or "inject-and-cut"). The aspiration of the lesion inside a plastic cap preloaded on the tip of the colonoscope ("cap-assisted EMR" - EMR-C) is almost exclusively used for the treatment of gastric and esophageal lesions. Its use for lesions of the colon and duodenum has been reported in limited experiences.

The advantage of diagnostic "cap-assisted colonoscopy" (CAC) is the higher chance of reaching cecum even by less experienced endoscopists in a shorter time, with less pain for the patients and a better observation of the mucosa behind the folds and at the flexures. There are not enough concordant data about the percentage of missing lesions, especially if small in size (27, 28). The cap makes the position of the instrument more stable during standard "inject-and-cut" technique (EMR-S), and reduces execution time. However, the realization of the EMR-C for colonic lesions isn't reported (29).

The use of EMR-C in colon is controversial because of the risk of entrapping the muscular layer in the polypectomy snare with risk of perforation.

The advantage of using the cap is represented by the possibility to perform mucosectomy of lesions located in difficult positions (between haustra, near or involving the ileo-caecal valve), thanks to the improved visibility on the operative field.

Our group has reported a 4% of residual disease/recurrence rate, much lower than those reported by other authors who performed EMR-S. We had a perforation and bleeding rate of 0% and 7% respectively vs 0.4% and 11% as reported in literature with EMR-S.

More recently, a study of 134 lesions treated with EMR-C reported a recurrence rate of 1.8% on 82 lesions treated, with a mean of 4.2 months follow-up.

The principal aim of this study is to evaluate the efficacy and the safety of the EMR-C for the removal of large colonic granular and non-granular Lateral Spreading Tumors (LST-G, LST-NG), comparing it with EMR-S.

Patients with colorectal LST-G/NG ≥30 mm will be included. Patients who refuse endoscopic follow up will be excluded from the study. The total enrollment period will be 6 months Endoscopic evaluation in patients without invasive carcinoma will be performed at 3, 6 and 12 months, and then annually Follow-up period will last 12 months from the enrollment of the last patient.

Will be defined as:

Residual lesion: the presence of adenomatous tissue endoscopically visible at follow-up colonoscopies within the first year from EMR.

Recurrent lesion: the presence of adenomatous tissue endoscopically visible after 2 (at 3 and 6 months from EMR) previous negative colonoscopies.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: September 15, 2019
• Est. primary completion date: September 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients =18 years Colonic LST-G/NG () = 30 mm in size. Patients able to undergo all follow up procedures as indicated in the protocol and to provide written informed consent, at least 48 hours before the intervention (reasoned consent).

Exclusion Criteria:

• Presence of sessile polyps Non polypoid lesions 0-III according to Paris Classification Lesions with suspicion of malignancy (rigidity, non-lifting lesions, mucosal fragility, ulceration) Patients unable to provide informed consent Patients with coagulopathy and INR >1.5 (not corrected with replacement therapy, such as enoxaparin).

Patients who have undergone previous attempt of lesion resection (residual disease, local recurrence).

Patients with histological diagnosis of submucosal invading neoplasia who will be sent to surgery and excluded from follow-up.

Related Conditions & MeSH terms

• Endoscopic Mucosal Resection

Intervention

Device:
• cap for mucosectomy
endoscopic mucosal resection of colonic lesions with a plastic cap for mucosectomy
• standard snare for polypectomy
endoscopic mucosal resection of colonic lesions with standard inject and cut mucosectomy

Locations

Country	Name	City	State
Italy	AOUSenese	Siena

Sponsors (3)

Lead Sponsor	Collaborator
Azienda Ospedaliera Universitaria Senese	Azienda Ospedaliera Niguarda Cà Granda, Azienda USL 1 Imperiese

Country where clinical trial is conducted

Italy, 

References & Publications (31)

Belderbos TD, Leenders M, Moons LM, Siersema PD. Local recurrence after endoscopic mucosal resection of nonpedunculated colorectal lesions: systematic review and meta-analysis. Endoscopy. 2014 May;46(5):388-402. doi: 10.1055/s-0034-1364970. Epub 2014 Mar — View Citation

Binmoeller KF, Bohnacker S, Seifert H, Thonke F, Valdeyar H, Soehendra N. Endoscopic snare excision of "giant" colorectal polyps. Gastrointest Endosc. 1996 Mar;43(3):183-8. — View Citation

Buchner AM, Guarner-Argente C, Ginsberg GG. Outcomes of EMR of defiant colorectal lesions directed to an endoscopy referral center. Gastrointest Endosc. 2012 Aug;76(2):255-63. doi: 10.1016/j.gie.2012.02.060. Epub 2012 May 31. — View Citation

Conio M, Blanchi S, Filiberti R, Ruggeri C, Fisher DA. Cap-assisted endoscopic mucosal resection of large polyps involving the ileocecal valve. Endoscopy. 2010 Aug;42(8):677-80. doi: 10.1055/s-0030-1255565. Epub 2010 Jun 30. — View Citation

Conio M, Blanchi S, Repici A, Ruggeri C, Fisher DA, Filiberti R. Cap-assisted endoscopic mucosal resection for colorectal polyps. Dis Colon Rectum. 2010 Jun;53(6):919-27. doi: 10.1007/DCR.0b013e3181d95a54. — View Citation

Conio M, De Ceglie A, Filiberti R, Fisher DA, Siersema PD. Cap-assisted EMR of large, sporadic, nonampullary duodenal polyps. Gastrointest Endosc. 2012 Dec;76(6):1160-9. doi: 10.1016/j.gie.2012.08.009. Epub 2012 Sep 26. — View Citation

Conio M, Repici A, Demarquay JF, Blanchi S, Dumas R, Filiberti R. EMR of large sessile colorectal polyps. Gastrointest Endosc. 2004 Aug;60(2):234-41. — View Citation

Hewett DG, Rex DK. Cap-fitted colonoscopy: a randomized, tandem colonoscopy study of adenoma miss rates. Gastrointest Endosc. 2010 Oct;72(4):775-81. doi: 10.1016/j.gie.2010.04.030. Epub 2010 Jun 25. — View Citation

Jass JR, Sobin LH, Watanabe H. The World Health Organization's histologic classification of gastrointestinal tumors. A commentary on the second edition. Cancer. 1990 Nov 15;66(10):2162-7. — View Citation

Jung M. The 'difficult' polyp: pitfalls for endoscopic removal. Dig Dis. 2012;30 Suppl 2:74-80. doi: 10.1159/000341898. Epub 2012 Nov 23. — View Citation

Kashani A, Lo SK, Jamil LH. Cap-assisted Endoscopic Mucosal Resection is Highly Effective for Nonpedunculated Colorectal Lesions. J Clin Gastroenterol. 2016 Feb;50(2):163-8. doi: 10.1097/MCG.0000000000000315. — View Citation

Khashab M, Eid E, Rusche M, Rex DK. Incidence and predictors of "late" recurrences after endoscopic piecemeal resection of large sessile adenomas. Gastrointest Endosc. 2009 Aug;70(2):344-9. doi: 10.1016/j.gie.2008.10.037. Epub 2009 Feb 27. — View Citation

Kim WH, Suh JH, Kim TI, Shin SK, Paik YH, Chung HW, Kim DY, Jeong JH, Kang JK, Kim H, Kim NK. Colorectal flat neoplasia. Dig Liver Dis. 2003 Mar;35(3):165-71. — View Citation

Kudo S, Kashida H, Tamura T, Kogure E, Imai Y, Yamano H, Hart AR. Colonoscopic diagnosis and management of nonpolypoid early colorectal cancer. World J Surg. 2000 Sep;24(9):1081-90. — View Citation

Kudo S. Endoscopic mucosal resection of flat and depressed types of early colorectal cancer. Endoscopy. 1993 Sep;25(7):455-61. Review. — View Citation

Mahadeva S, Rembacken BJ. Standard "inject and cut" endoscopic mucosal resection technique is practical and effective in the management of superficial colorectal neoplasms. Surg Endosc. 2009 Feb;23(2):417-22. doi: 10.1007/s00464-008-9983-z. Epub 2008 Sep — View Citation

Moss A, Bourke MJ, Williams SJ, Hourigan LF, Brown G, Tam W, Singh R, Zanati S, Chen RY, Byth K. Endoscopic mucosal resection outcomes and prediction of submucosal cancer from advanced colonic mucosal neoplasia. Gastroenterology. 2011 Jun;140(7):1909-18. — View Citation

Muto T, Bussey HJ, Morson BC. The evolution of cancer of the colon and rectum. Cancer. 1975 Dec;36(6):2251-70. — View Citation

Othman MO, Wallace MB. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) in 2011, a Western perspective. Clin Res Hepatol Gastroenterol. 2011 Apr;35(4):288-94. doi: 10.1016/j.clinre.2011.02.006. Epub 2011 Mar 31. Review. — View Citation

Park SY, Kim HS, Yoon KW, Cho SB, Lee WS, Park CH, Joo YE, Choi SK, Rew JS. Usefulness of cap-assisted colonoscopy during colonoscopic EMR: a randomized, controlled trial. Gastrointest Endosc. 2011 Oct;74(4):869-75. doi: 10.1016/j.gie.2011.06.005. Epub 20 — View Citation

Rembacken BJ, Fujii T, Cairns A, Dixon MF, Yoshida S, Chalmers DM, Axon AT. Flat and depressed colonic neoplasms: a prospective study of 1000 colonoscopies in the UK. Lancet. 2000 Apr 8;355(9211):1211-4. — View Citation

Saito Y, Fukuzawa M, Matsuda T, Fukunaga S, Sakamoto T, Uraoka T, Nakajima T, Ikehara H, Fu KI, Itoi T, Fujii T. Clinical outcome of endoscopic submucosal dissection versus endoscopic mucosal resection of large colorectal tumors as determined by curative — View Citation

Saitoh Y, Waxman I, West AB, Popnikolov NK, Gatalica Z, Watari J, Obara T, Kohgo Y, Pasricha PJ. Prevalence and distinctive biologic features of flat colorectal adenomas in a North American population. Gastroenterology. 2001 Jun;120(7):1657-65. — View Citation

Sanchez-Yague A, Kaltenbach T, Yamamoto H, Anglemyer A, Inoue H, Soetikno R. The endoscopic cap that can (with videos). Gastrointest Endosc. 2012 Jul;76(1):169-78.e1-2. doi: 10.1016/j.gie.2012.04.447. Review. — View Citation

Schlemper RJ, Riddell RH, Kato Y, Borchard F, Cooper HS, Dawsey SM, Dixon MF, Fenoglio-Preiser CM, Fléjou JF, Geboes K, Hattori T, Hirota T, Itabashi M, Iwafuchi M, Iwashita A, Kim YI, Kirchner T, Klimpfinger M, Koike M, Lauwers GY, Lewin KJ, Oberhuber G, — View Citation

The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, 2002. Gastrointest Endosc. 2003 Dec;58(6 Suppl):S3-43. Review. — View Citation

Tsuda S, Veress B, Tóth E, Fork FT. Flat and depressed colorectal tumours in a southern Swedish population: a prospective chromoendoscopic and histopathological study. Gut. 2002 Oct;51(4):550-5. — View Citation

Uraoka T, Saito Y, Matsuda T, Ikehara H, Gotoda T, Saito D, Fujii T. Endoscopic indications for endoscopic mucosal resection of laterally spreading tumours in the colorectum. Gut. 2006 Nov;55(11):1592-7. Epub 2006 May 8. — View Citation

Woodward TA, Heckman MG, Cleveland P, De Melo S, Raimondo M, Wallace M. Predictors of complete endoscopic mucosal resection of flat and depressed gastrointestinal neoplasia of the colon. Am J Gastroenterol. 2012 May;107(5):650-4. doi: 10.1038/ajg.2011.473 — View Citation

Xu MD, Wang XY, Li QL, Zhou PH, Zhang YQ, Zhong YS, Chen WF, Ma LL, Qin WZ, Hu JW, Yao LQ. Colorectal lateral spreading tumor subtypes: clinicopathology and outcome of endoscopic submucosal dissection. Int J Colorectal Dis. 2013 Jan;28(1):63-72. doi: 10.1 — View Citation

Zlatanic J, Waye JD, Kim PS, Baiocco PJ, Gleim GW. Large sessile colonic adenomas: use of argon plasma coagulator to supplement piecemeal snare polypectomy. Gastrointest Endosc. 1999 Jun;49(6):731-5. — View Citation

* Note: There are 31 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with residual lesions within 12 months.	Patients with non invasive lesions will undergo follow-up colonoscopies at 3, 6, 12 months and thereafter annually after both EMR-C and EMR-S..; The presence of adenomatous tissue endoscopically visible at follow-up colonoscopies within the first year from EMR will be considered as residual lesion.	within 12 months
Primary	Proportion of patients with recurrence at 12 months.	The presence of adenomatous tissue endoscopically visible after two previous negative colonoscopies will be defined as recurrence. "	at 12 months
Secondary	Proportion of patients with early complications within 48 hours and late complications after 48 hours from both endoscopic procedures.	Complications are defined as: intraprocedural early: within 48 hours; late: after 48 hours from the endoscopic procedure; Type of complications: Bleeding (intraprocedural, loss of blood from rectum; Perforation (documented with the presence of free air in abdomen by RX and/or CT); Post polipectomy syndrome (abdominal pain with or without fever, without any free air in abdomen reported by radiological investigations)	at the time of the procedure, within 48 hours, within 12 months