1. Malignant colonic polyp: endoscopic treatment updates
CHAN Ka-man, Fiona
Kwong Wah Hospital
Joint Hospital Surgical Grand Round
18th April, 2015

2. Prevalence Screen detected adenoma
21-58% from years
Malignant polyps in endoscopically removed polyps
0.2-11%
Screening colonoscopies continue to be performed in the hope of removing benign polyps prior to malignant degeneration through the well-recognized adenoma–carcinoma sequence. According to the adenoma carcinoma sequence, early detection and resection of colorectal neoplasm is essential for improving cancer mortality
Williams AR, Balasooriya BA, Day DW. Polyps and cancer of the large bowel: a necropsy study in Liverpool. Gut 1982; 23: 835–42.
Management of colorectal polyps.Markowitz AJ, Winawer SJ
CA Cancer J Clin Mar-Apr; 47(2):
Gastroenterology Feb; 98(2):371
[4] Netzer P. Risk factor assessment of endoscopically removed malignant colorectal
polyps. Gut 1998;43:
[5] Volk EE. Management and outcome of patients with invasive carcinoma arising in
colorectal polyps. Gastroenterology 1995;109:
[6] Nusko G. Invasive carcinoma in colorectal adenomas: multivariate analysis of patient
and adenoma characteristics. Endoscopy 1997;29:
Markowitz AJ. CA Cancer J Clin 1997;47:93-112
Nusko G. Endoscopy 1997;29:
Williams AR. Gut 1982;23:835-42

3. Superficial neoplastic lesion
Malignant colonic polyp
Neoplasm that penetrates the muscularis mucosae into submucosa
Carcinoma in-situ/High-grade intraepithelial neoplasia
Neoplasm that are confined to the epithelium or invade the lamina propria alone and lack invasion through the muscularis mucosae
Early colorectal carcinoma/superficial neoplasia
Carcinoma that is confined to the mucosa and submucosa
Wolff WI, Shinya H. Definitive treatment of “malignant” polyps of the colon. Annals of Surgery. 1975;182(4):
Japanese Society for Cancer of the Colon and Rectum, editor. Japanese Classification of Colorectal Carcinoma. 2nd ed. Tokyo: Kanehara & Co., Ltd; 2009
Hamilton SR, Aaltonen LA, editors . World Health Organization classification of tumors. Pathology and genetics of tumours of the digestive system. Lyon, France: IARC Press; pp. 104–109.
According to the classification published by The World Health Organization (WHO),2 only epithelial tumors that have penetrated through the muscularis mucosae into the submucosa are considered malignant in the colon or rectum.
Lesions with the morphological characteristics of adenocarcinoma that are confined to the epithelium or invade the lamina propria alone and lack invasion through the muscularis mucosae into the submucosa have virtually no risk of metastasis. Therefore, ‘high-grade intraepithelial neoplasia’ is a more appropriate term than ‘adenocarcinoma in-situ’, and ‘intramucosal neoplasia’ is more appropriate than ‘intramucosal adenocarcinoma’.
Wolff WI. Annals of Surgery 1975;182:
Japanese Society for Cancer of the Colon and Rectum. 2009
World Health Organization classification of tumors pp. 104–109

4. Why is endoscopic treatment feasible?
Risk of lymph node metastasis in Tis is negligible
Risk of lymph node metastasis in submucosal lesion
Risk 6-12% in general
Pedunculated lesions
Rate of lymph node metastasis was 0% in head invasion cases and stalk invasion cases with SM depth <3000 µm if lymphatic invasion was negative.
Non-pedunculated lesions
Rate of lymph node metastasis was also 0% if SM depth was <1000 µm.
In multivariate analysis, SM depth 1000μm (P 0.006), sprouting (P ), and lymphatic invasion (P ) represented significant risk factors, with odds
ratios of 5.404, 2.276, and 4.691, respectively
Kitajima K, Fujimori T, Fujii S et al. Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study. J. Gastroenterol. 2004; 39: 534–43.

5. Classification Paris Classification Japan Classification
Especially type 0-IIc lesions have a substantial risk of penetration into the submucosa with a reported incidence of 40%.
predict the depth of invasion of a superficial carcinoma and predict the risk of lymph node metastasis
Jap: kudo classified polyps into protruding and flat ones in 1983 (JAPANESE research society for cancer of the colon and rectum)
Paris classfication 2002
Flat adenomas 40% of all adenoma. They had 2.7 times incraesed risk of high grade dysplasia or submucosal carcinoms (OR=2.7; CI : p<0.05)
Flat elevated in paris classification: height less than closed cups of biopsy forceps 2.5mm
Gastrointest Endosc 2003; 58(Suppl. 6): S3–43
Japanese Classification of Colorectal Carcinoma. 1997

6. Lateral spreading tumour (LST)
Neoplasm with horizontal extending growth pattern
>10mm
Granular type (LST-G)
Non-granular type (LST-NG)
High possibility of deep submucosal invasion 14% versus 7% in glandular type (p<0.01)
30-56% have multifocal invasion
LST‐NG type had a significantly higher frequency of sm invasion (14% (32/224) v 7% (19/287), respectively; p<0.01).
Subtypes of laterally spreading tumors (LST) (classification should be done on the basis of imagesobtained by using indigocarmine dye spraying)
Implication:
NG not for EMR
Endoscopic appearance of exophytic and flat elevated tumors (Japanese classification of colorectal carcinoma (8th ed.)) [30]. (a) Exophytic type: Ip = pedunculated type; Isp = semipedunculated type; Is = sessile type; and (b) Flat elevated type: IIa = superficial elevated type; LST-G = laterally spreading tumor, granular type; LST-NG = laterally spreading tumor, non-granular type.
Japanese Classification of Colorectal Carcinoma. 1997

7. Endoscopic treatment options
Participants in the Paris Workshop. The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, Gastrointest Endosc 2003; 58(Suppl. 6): S3–43.
Based on morphorology, chromoendoscopy, NCI assessment, polyp location, patient factors
The primary role for endoscopic staging is to predict the risk of submucosal invasion and the associated risk of nodal metastases.
As LST‐NG type ⩾20 mm are technically more difficult to remove en bloc by conventional EMR techniques2,3,27 and LST‐NG type have a higher malignancy potential than LST‐G type, we believe that endoscopic submucosal dissection (ESD)28,29,30,31 or laparoscopy assisted colectomy should be the techniques of choice for en bloc resection of LST‐NG type ⩾20 mm.
indications for ESD [24] as an LST
nongranular (LST-NG)-type lesion [20 mm and an LST
granular (LST-G)-type lesion[40 mm because they both
had a higher sm invasion rate and were difficult to treat
even by endoscopic piecemeal mucosal resection (EPMR
Williams. Colorectal Disease 2013;15:1–38

8. Exclusion of lesion for endoscopic treatment
Chromoendoscopy
Narrow band imaging
Magnifying endoscopies
Level of invasiveness
Kudo. Gastrointest Endosc 1996;44:8-14
Sano. Digest Endosc, Vol. 18.S44–51

9. Endoscopic treatment Snare polypectomy
Endoscopic mucosal resection (EMR)
Endoscopic submucosal dissection(ESD)
Curative
Minimally invasive
Diagnostic

10. Well established method world wide for removal of superficial neoplastic lesions.
Norman E. Upper Endoscopy, Advanced Digestive Endoscopy

11. Piecemeal EMR
This violates the principle of en-bloc resection but might prove adequate for local control in an unfit person.
The histopathology specimens are more difficult to interpret, and prediction of prognosis is harder still. On this basis, when a lesion has any features suspicious for malignancy this should not be the preferred treatment modality.
Local recurrence rate %
Piecemeal EMR:
piecemeal EMR was also effective in treating many LST-G ≥20 mm and the perforation rate was lower than ESD (N.S.), but three cases (1.3%) required surgery after such piecemeal resections including two cases of invasive cancer recurrence. A third piecemeal resection also required surgery because of technical difficulty in carrying out another EMR after recurrence of intramucosal cancer
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. Surg. Endosc. 2010; 24: 343–352.
the first tocompare clinical outcomes for colorectal ESD with EMR/
EPMR including mid-term follow-up.
John Hopkins colon cancer center

12. Efficacy of EMR
En bloc resection: 66.5–80% when the tumor sizes were <20 mm
When the tumor sizes were ≥20 mm, the en bloc resection rate significantly decrease to 20-48%
Local recurrence
3% en bloc resection
20% piecemeal resection
Piecemeal resection was the only independent risk factor for recurrence.
Toyonaga T, Man IM, Morita Y et al. The new resources of treatment for early stage colorectal tumors: EMR with small incision and simplified endoscopic submucosal dissection. Dig. Endosc. 2009; 21: 31–7.
Saito Y, Matsuda T, Fujii T. Endoscopic submucosal dissection of non-polypoid colorectal neoplasms. Gastrointest
Endosc Clin N Am 2010; 20: 515–24.
Jin, HY.; Wu, K.; Ye, H.; Zhu, Y.; Zhang, J. & Ding, Y. (2009). Size over 20mm is an
independent risk factor of endoscopic mucosa resection (EMR) for colorectal lateral
spread tumor (LST): A prospective study and multivariate analysis. Cancer Therapy,
Vol. 7. pp
125 Tanaka S, Oka S, Chayama K. Endoscopic mucosal resection
for superficial early colorectal carcinoma – indication, choice
of methods and outcome. Gastroenterol. Endosc. 2004; 46:
243–52. (in Japanese with English abstract.)
126 Moss A, Bourke MJ, Williams SJ et al. Endoscopic mucosal
resection outcomes and prediction of submucosal cancer from
advanced colonic mucosal neoplasia. Gastroenterology 2011;
140: 1909–18.
127 Wada Y, Kudo S, Hayashi T et al. Indication for endoscopic
submucosal dissection from the standpoint of growth type, size
and pit pattern diagnosis in colorectal tumors. Application of
colorectal ESD according to the type and size of tumor.
Stomach Intestine 2013; 48: 134–44. (in Japanese with English
abstract.)
128 Walsh RM, Ackroyd FW, Shellito PC. Endoscopic resection of
large sessile colorectal polyps. Gastrointest. Endosc. 1992; 38:
303–9.
Most adenomas and intramucosal cancers can be resected by EMR; however, tumors greater than 20 mm in diameter are considered difficult candidates for en bloc resection[19-24]. The rates of en bloc and complete resection have been reported to be 62.85% and 58.66%, respectively[6].
Although piecemeal EMR enables the removal of large colorectal tumors, it has a high rate of local recurrence (7.9%-21.4%)
Yoshida N, Naito Y, Yagi N, Yanagisawa A. Importance of histological evaluation in endoscopic resection of early colorectal cancer. World Journal of Gastrointestinal Pathophysiology. 2012;3(2): doi: /wjgp.v3.i2.51.
Enbloc resection is essential for accurate histopathological evaluation of resection margin, level of tumour invasion
Wada. Stomach Intestine 2013;48:134–44
Walsh. Gastrointest Endosc 1992;38:303–9
Saito. Gastrointest Endosc Clin N Am 2010;20:515–24
Jin. Cancer Therapy. Vol. 7. pp

13. Endoscopic submucosal dissection (ESD)
ESD served to resect large lesions enbloc
ESD was first described in 1988 as a technique to treat early gastric neoplasia nonoperatively.
For many years, conventional EMR and surgery were the only available treatments for large colorectal tumors, even those detected at an early stage. Conventional EMRs usually resulted in EPMRs particularly for large LSTs C20 mm with reports of local recurrence rates ranging from 7.4% to 17%
(Understanding ESDs: A Procedure for Treating Cancer Without Major Surgery) (Kōdansha, 2011).
Commenced late 1990
The technical difficulty and complications of ESD preclude the standardization of this novel procedure. Colorectal ESD, at present, is only practiced in Japan, Korea, and a few facilities in other countries.
Lesions are dissected directly along the submucosal layer using an electrosurgical knife, resulting in an en-bloc resection of even large lesions
but because it has a higher rate of perforation and bleeding complications than conventional EMR, a greater degree of endoscopic skill and experience
Longer procedure
Kōdansha. Understanding ESDs: A Procedure for Treating Cancer Without Major Surgery. 2011

14. Efficacy of ESD Meta-analysis of ESD of 1314 large flat polyps
En-bloc resection rates 88%-90.5%
Histological R0 resection rate 76.9%-89%
Local tumor recurrence 1.9%
Tanaka S, Terasaki M, Kanao H et al. Current status and future perspectives of endoscopic submucosal dissection for colorectal tumors. Dig. Endosc. 2012; 24 (Suppl 1): 73–79.
Saito Y, Uraoka T, Yamaguchi Y et al. A prospective, multicenter study of 1111 colorectal endoscopic submucosal dissections (with video). Gastrointest. Endosc. 2010; 72: 1217–1225
Perforation 4.9%-5.4%
Postoperative bleeding 1.8%
Tanaka S. Dig Endosc 2012; 24(Suppl 1):73–79
Saito. Gastrointest Endosc 2010;72:1217–1225
Puli SR. Ann Surg Oncol 2009;16:

15. ESD vs. EMR Larger resected specimens (37 mm vs. 28mm; p=0.0006)
Higher en-bloc resection rate(94.5% vs. 56.9%; p<0.01)
Less recurrences (2% vs. 14%; p<0.0001)
Longer procedure time ( min vs min; p<0.0001)
Higher perforation rate (6.2% vs. 1.3%)
Multicenter prospective study with 18 centre , 1845 patient
This was a retrospective case-controlled study performed at the National Cancer Center Hospital in Tokyo, Japan involving 373 colorectal tumors C20 mm
determined histologically to be curative resections
Most perforations can be managed endoscopically with clipping
Nakajima. Surg Endosc 2013
Saito. Surg Endosc 2010;24:343–352

16. ESD versus laparoscopic colectomy
Limited comparative data
Shorter procedure time (95 vs. 185 mins; p<0.001)
Shorter hospital stay (5 vs. 10days; p<0.001)
Less analgesic requirement
Early resumption of diet and mobility
The 3-year overall survival rate exceeded 99% in both the ESD and LAC groups
Results of local prospective randomized controlled trials pending
Prospective case control The en bloc and curative resection rates with ESD were 87% and 80%
ESD was safe with excellent prognosis
The indications for ESD and LAC are different.
Quality of life following treatment would likely be better with ESD
Before the development of ESD, LAC are inidcated for treatment of these lesions.
Simple comparison between ESD and LAC is problematic because each indication differs in Japan, as do procedures. ESD is used as a local treatment without lymph node dissection for adenoma, intramucosal or SM-s carcinomas, whereas LAC is performed for SM-d carcinomas and includes lymph node dissection. Worldwide, however,
LAC is performed as the standard for lesions that are a good indication for colorectal ESD in Japan. The reasons are as follows: LAC is a low-invasive procedure compared
with laparotomy and maintains QOL. ESD, on the other hand, seems to be a difficult and hazardous procedure for non-expert endoscopists.
Endoscopic diagnosis of T stage invasion depth based on conventional and magnifying colonoscopy in early cancer is also a hurdle and controversy, especially in western countries.
Background and study aims: Endoscopic submucosal dissection (ESD) is increasingly being used to resect early colorectal carcinoma, despite the technical difficulties associated with the procedure. Laparoscopic-assisted colorectal surgery (LAC) is an alternative to open surgery for colorectal cancers, and ESD was recently introduced as another alternative. In this study, we compared ESD with LAC as minimally invasive treatments for early colorectal cancer.
Patients and methods: The study included 589 patients (297 patients with colorectal intramucosal or slightly submucosal invasive cancers undergoing ESD; 292 patients with T1 colorectal cancers undergoing LAC) who were treated at National Cancer Center Hospital in Tokyo, Japan, between January 1998 and September 2008. The clinical outcomes of ESD and LAC were evaluated retrospectively and compared on the basis of data that were originally collected prospectively.
Results: In the ESD group, mean tumor size was 37 mm, mean procedure time was 106 minutes, and the en bloc and curative resection rates were 87 % and 80 %, respectively. There were 14 perforations (4.7 %) and 5 cases of postprocedure bleeding (1.7 %); all complications were successfully managed endoscopically except for one of the perforations, which required emergency surgery. In the LAC group, mean tumor size was 20 mm, mean operation time was 206 minutes, and complications included 31 wound infections, 2 pelvic abscesses, 3 anastomotic leakages, and 1 anastomotic bleed. Stomas were necessary in 93 % of the patients who underwent LAC for rectal cancers located below the peritoneal reflection.
Conclusions: ESD was associated with a lower complication rate than LAC, with favorable en bloc and curative resection rates. The safety profile and possibility of curative treatment with colorectal ESD provide advantages for the treatment of early colorectal cancers with nul risk of lymph node metastasis
We propose to conduct a prospective randomized trial to compare the short-term clinical outcomes and systemic inflammatory/cytokine responses of ESD versus laparoscopic resection for early colorectal neoplasms that are not amenable to en bloc endoscopic resection with conventional techniquesWe propose to conduct a prospective randomized trial to compare the short-term clinical outcomes and systemic inflammatory/cytokine responses of ESD versus laparoscopic resection for early colorectal neoplasms that are not amenable to en bloc endoscopic resection with conventional techniques
Nakamura F1, Saito Y, Sakamoto T, Otake Y, Nakajima T, Yamamoto S, Murakami Y, Ishikawa H, Matsuda T.
Surg Endosc Mar;29(3): doi: /s Epub 2014 Jul 19.
Potential perioperative advantage of colorectal endoscopic submucosal dissection versus laparoscopy-assisted colectomy.
Kiriyama S. Endoscopy 2012; 44:1024–1030
Nakamura. Surg Endosc 2015;29:

17. Difficulty in ESD Anatomical difficulties Steep learning curve
Longer length, narrower lumen, extensive flexion and thinner walls
Steep learning curve
Animal models
20 gastric ESD → rectal ESD → colon ESD
Complication
Perforation rate 4-10%
Bleeding rate %
Limited data on flat polyps in western countries
Lateral spreading tumour are much less reported in western literature ? Overlooked/ prevalence is less in the west
knowledge on chrmooendoscopy and NBi for accrate identification of leisons for resection
Time consuming
Perforation rate higher than EMR
Puli SR. Successful complete cure en-bloc resection of large nonpedunculated colonic polyps by endoscopic submucosal dissecion: a meta-analysis and systemic review. Ann Surg Oncol 2009;16:
Uroka. Journal of Gastroenterology and Hepatology (2013) 406–414

18. Curative endoscopic resection
Lateral and vertical margins of the specimen were free
Submucosal invasion less than 1,000 μm
No lymphovascular involvement
No poorly differentiated component
Tumor budding grade 1 (low grade)
Budding is defined as cancer nests comprising less than 5 cancer cells and invading the interstitial tissue of the cancer growth front. The area where budding appears most
frequently is selected and the number of instances is counted in a ×200 field. Budding is classified into 3 groups (grade 1, 0–4 pieces; grade 2, 5–9 pieces; and grade 3, ≥10 pieces),
and grades 2 and 3 are risk factors for lymph node metastasis.
An adenoma with an unknown lateral margin was also considered to be a curative resection provided that such adenoma met all the other criteria
In surgically resected specimens from the stomach and the colon, the semiquantitative evaluation of the invasion in the submucosa (divided in two or 3 sectors) is less and less used. Currently, the quantitative micrometric measure is the common guideline for the specimens issued from a surgical or an endoscopic resection. The categorization of cancer invasion as superficial or deep in the submucosa is determined by an organ-specific limit fixed at a certain depth. With the quantitative method of measurement, sm1 means ‘‘less invasive than the cutoff limit,’’ and sm2 means ‘‘deeper than the cutoff limit.’’ In Japan, the pathologists have established distinct empirical cutoff limits for columnar neoplasia
in the stomach128 and columnar neoplasia in the large bowel.129,130 Application of these categories to surgical specimens is the only way to achieve comparability between EMR and surgical resections.
Kitajima K, Fujimori T, Fujii S, Takeda J, Ohkura Y, Kawamata
H et al (2004) Correlations between lymph node metastasis and
depth of submucosal invasion in submucosal invasive colorectal
carcinoma: a Japanese collaborative study. J Gastroenterol 39:
534–543
Yokoyama J, Ajioka Y, Watanabe H, Asakura H. Lymph node metastasis and micrometastasis of submucosal invasive colorectal carcinoma: an indicator of the curative potential of endoscopic treatment. Acta Medica Biologica 2002;50:1-8.
Kitajima. J Gastroenterol 2004; 39:534–543

19. Endoscopic surveillance
Detection of recurrence
Metachronous adenoma and early carcinoma were detected in 54.8% and in 11.9% of surveillance endoscopy
No evidence-based consensus
First surveillance at 3-6 months, then regular surveillance in 3-5 years
Oka S, Tanaka S, Kaneko I et al. Conditions of curability after endoscopic treatment for colorectal carcinoma with submucosal invasion: Assessments of prognosis in cases with submucosal invasive carcinoma resected endoscopically. Stomach Intestine 2004; 39: 1731–43.
A complete surveillance colonoscopy within 3 years of the initial polypectomy Burnstein M J, Hicks T C. In: Wolff BG, Fleshman JW, Beck DE, Pemberton JH, Wexner SD, editor. The ASCRS Textbook of Colon and Rectal Surgery. New York: Springer; Polyps. pp. 366–368
Martínez ME. Adenoma characteristics as risk factors for recurrence of advanced adenomas.
Gastroenterology 2001;120:
Repici A, Pellicano R, Strangio G, Danese S, Fagoonee S, Malesci A. Endoscopic mucosal resection for early colorectal neoplasia: pathologic basis, procedures, and outcomes. Dis Colon Rectum 2009; 52: 1502–15.
Repici .Dis Colon Rectum 2009; 52: 1502–15

20. Conclusion
Malignant colonic polyps can be managed by endoscopic resection
ESD enables en-bloc resection of large superficial tumours
Regular surveillance aids detection of recurrence which can be managed endoscopically

21. Reference
Wolff WI, Shinya H. Definitive treatment of “malignant” polyps of the colon. Annals of Surgery. 1975;182(4):
Japanese Society for Cancer of the Colon and Rectum, editor. Japanese Classification of Colorectal Carcinoma. 2nd ed. Tokyo: Kanehara & Co., Ltd; 2009
Kitajima K, Fujimori T, Fujii S et al. Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study. J. Gastroenterol ; 39: 534–43.
Participants in the Paris Workshop. The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, Gastrointest Endosc 2003; 58(Suppl. 6): S3–43.
Oka S, Tanaka S, Kaneko I et al. Conditions of curability after endoscopic treatment for colorectal carcinoma with submucosal invasion: Assessments of prognosis in cases with submucosal invasive carcinoma resected endoscopically. Stomach Intestine 2004; 39: 1731–43.

23. Polyp morphology relation to size and risk of submucosal invasion
Participants in the Paris Workshop. The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, Gastrointest Endosc 2003; 58(Suppl. 6): S3–43.
The primary role for endoscopic staging is to predict the risk of submucosal invasion and the associated risk of nodal metastases.
The Paris endoscopic classification of superficial neoplastic lesions. Gastrointest Endosc 2003; 58(Suppl. 6): S3–43

25. Pit pattern and histological correlation
Kashida H, Kudo SE. Early colorectal cancer: concept,
diagnosis, and management. Int J Clin Oncol 2006; 11:
1–8.