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15 What Are theOptions forManagement ofLarge Colonic Polyps?
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Quality of
evidence
High
N/A
N/A
N/ANSp=0.015
12.5% vs. 18.8%
0% vs. 0%
43.8% vs. 25%
0% vs. 6.3%
9.5±0.7 vs.
7.3±0.6
Moderate
SignicantNSSignicant
28.6% vs. 4.8%
52.4% vs. 69.1%
Low
p=0.038NSNS
17.7±9.3 vs.
12±7.4
5.7% vs. 15.9%
p<0.001
p<0.001
0% vs. 2.9%
0% vs. 2.9%
42.9% vs. 65.2%
32.9% vs. 59.4%
p<0.001
25.7% vs. 3.1%
185
Complication (other)
En bloc resection
Incomplete resection
Procedure time, min
En bloc resection
Procedure time, min
Complication (any)
Bleeding
Perforation
En bloc resection
(69)
Intervention
group Control group Outcome measures Results Signicance
Study Design
RCT EMR (12) CP (11) Complete resection 75% vs. 18% p=0.006 High
RCT EMR (16) U-EMR (16) Immediate bleeding
a
Study
Horiuchi 2015
[21]
Table 15.3 Summary of studies comparing EMR with other techniques
Yen etal. [22]
EMR (42) U-EMR (42) Bleeding
Retrospective
Cohort
b
Chien etal. [23]
EMR (140) Hybrid ESD
Cohort
Lee 2011 [14] Retrospective
R0 resection
Recurrence
EMR (310) Surgery (81) Complication (any) 0.6% vs. 22.2% p=0.00001 Low
Cohort
Patel 2019 [24] Retrospective
Controlled Trial, U-EMR Underwater EMR
En bloc resection: resection of a polyp in one-piece. R0 resection: resection of a polyp in one-piece with histologically proven negative margins. Complete
resection: resection of a polyp with histologically proven negative margins (not necessarily in one-piece). Incomplete resection: histologically proven margin
CP Conventional Polypectomy, EMT Endoscopic Mucosal Resection, ESD Endoscopic Submucosal Dissection, NS Non-signicant, RCT Randomized
positivity
Difference (%95 CI) levels for bleeding and procedure time are -23.8 ([-38.9]-[-8.7]) and -5.2 ([-8.9]-[-1.6]), respectively
Model failed to converge to assess the signicance level for immediate bleeding, complications, and en bloc resection
a
b
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ESD vs. CP+EMR.Studies comparing ESD with EMR reported conicting results on perforation rates [1016]. Some studies reported signicantly higher perforation rates with ESD (when compared with EMR) [12, 13, 16], whereas some [10, 11, 14,
15] reported no signicant difference. When Hybrid ESD was compared to EMR [12]
and ESD [1719], there was no signicant difference in perforation rates, with the exception of 1 study, in which ESD was associated with higher perforation rates [12].
S. Yilmaz and E. Gorgun
Tumor Recurrence
7 studies reported tumor recurrence rates [9, 1116]. Compared with CP+EMR [9] and EMR [1115], ESD was associated with signicantly lower local recurrence rates. No signicant difference was observed when ESD and U-EMR were com­pared with each other [16]. Compared to EMR, Hybrid ESD was associated with lower recurrence rates [12].
Secondary Outcomes
[10] [11, 13, 1520, 22, 23], studies evaluated the procedure time. ESD, when com- pared with EMR and Hybrid ESD, was associated with signicantly higher proce­dure time [11, 13, 1519]. Gamaleldin etal. [20] compared procedure times between ESD and surgery (laparoscopic resection) and found no signicant difference. U-EMR achieved signicantly shorter procedure times than EMR [22, 23].
[3] [14, 15, 20], studies assessed the length of hospital stay. Among 2 studies comparing EMR and ESD [14, 15], Soliman etal. [14] reported signicantly higher length of hospital stay associated with ESD, whereas Ham etal. [15] reported no signicant difference. Compared to surgery, ESD was associated with shorter length of hospital stay in one study [20], but the result was not statistically signicant.
Ham etal. [15] compared the cost of initial resection between ESD and EMR (piecemeal), and reported that ESD was associated with signicantly higher cost. However, patients undergoing EMR needed signicantly higher number of follow­ up colonoscopies, which in turn evened up the cumulative costs associated with two procedures. Gamaleldin et al. [20] compared the technical costs associated with ESD vs. surgery and reported that the cost of ESD was 60% of the cost of surgery. This result was statistically signicant.
Recommendation
Management of large colonic polyps (2cm) require more invasive techniques than CP (Evidence: moderate; Recommendation: strong). ESD is associated with higher en-bloc and R0 resection, and lower recurrence rates than EMR. Therefore, for the management of colonic polyps 2cm, ESD should be considered (Evidence: low­moderate; Recommendation: strong).
15 What Are theOptions forManagement ofLarge Colonic Polyps?
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Compared to surgery, EMR and ESD are associated with lower complication rates and cost. Furthermore, some patients might be poor surgical candidates (e.g., patients with severe comorbidities). Therefore, when possible, EMR and ESD should be preferred rather than surgery (Evidence: low, Recommendation: strong).
Hybrid ESD is an alternative option for the management of large colonic polyps, providing shorter procedure times than ESD with equal or lower complication rates. However, it can be associated with lower en-bloc and R0 resection rates. Therefore, it can be an option in the treatment of large colonic polyps in certain situations (Evidence: low, Recommendation: weak).
187
Personal View
Early detection and removal of colorectal neoplasms with colonoscopic polypec­tomy is a well-established means of decreasing colorectal cancer incidence and mor­tality [25, 26]. In general, majority of colorectal neoplasms are 1cm and can safely and effectively be removed with standard polypectomy [4]. However, 2–15% of pol­yps are not amenable for conventional colonoscopic removal due to a variety of rea­sons such as large size, difcult location, previous resection attempts etc [27, 28]
Traditionally, treatment of endoscopically unresectable tumors has required sur­gical resection / colectomy due to limited availability of management options and concerns for malignancy. However, we have previously reported that only 8.4% of these specimens harbor malignancy [28]. Moreover, colectomy for endoscopically unresectable tumors is associated with 17–25.3% morbidity and 0.8–1.5% mortality risk [29, 30].
Advanced endoscopic resection techniques such as EMR, ESD and Hybrid ESD have been introduced for removal of these complex lesions while allowing patients to avoid the morbidity and mortality of surgical resection [31, 32]. EMR is highly effective in the treatment of colorectal lesions <2cm, achieving 86–97.5% en-bloc and 76.6–95.5% R0 resection rates [33, 34]. When EMR is used to resect large lesions, en-bloc and R0 resection rates range 26.3–54% [1014, 35] and 26.3–37% [10, 12, 14], respectively. Luigiano et al. [35] reported their outcomes with 174 EMRs performed for lesions larger than 2cm, and mentioned that en-bloc resection was possible only for lesions <3 cm. Iizuka et al. [10] reported that tumor size 2 cm is an independent risk factor for piecemeal resection following EMR.Piecemeal resection reduces the reliability of the histopathological assess­ment, and is associated with higher local recurrence rates [15, 36]. Given that increased polyp size is a predictor for malignancy [6, 37], en-bloc resection is pre­ferred to allow accurate histopathological assessment and curative resection [5]. U-EMR uses oating effect of water submersion instead of submucosal injection. Water submersion helps mucosa and submucosa to be separated from the muscula­ris layer, hence enables snaring of the polyp [38]. A meta-analysis published in 2020 [39] showed that U-EMR is associated with higher en-bloc resection and lower recurrence rates, and shorter procedure time without any difference in com­plication rates when compared with conventional EMR.
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S. Yilmaz and E. Gorgun
Colorectal ESD is an endoscopic resection technique which allows for en-bloc resection of a neoplasm regardless of its size [8]. For treatment of polyps larger than 2cm, several case series and comparative studies reported 83.5–100% [9, 1119,
40, 41] en-bloc and 73–94.9% [12, 1419, 40, 41] R0 resection rates with
ESD. Consequently, tumor recurrence rates following ESD range from 0.5% to
7.6% [9, 11, 1315], which is signicantly lower compared to EMR [11, 12, 14, 16] and CP [9]. Despite these advantages, colorectal ESD has not been widely accepted in clinical practice because it is a technically challenging procedure given the trou­blesome anatomy of the colon with its folds, exures, thinner wall and narrower lumen. In fact, perforation rates following ESD can be as high as 10.7% [42].
Colorectal ESD requires a high level of skill. In 2011, Nakajima etal. [43] evalu­ated the learning curve for ESD in trainees who are experienced in gastric ESD. They reported that after experience with 30 cases, trainees were able to perform colorec­tal ESD without signicant complications. In their systematic review, Rajendran etal. [44] assessed learning curves for colorectal polyp resection techniques. They concluded that to achieve en-bloc resection rate of 80% and R0 resection rate of 70%, a trainee must perform 20–40 cases. Competency in safety was achieved at 20–200 cases. Compared to other techniques, ESD requires a longer procedure time [11, 13, 1619]. Rajendran etal. [44] also reported that procedural speed increases after 30 cases. Nevertheless, for lesions >4cm, ESDmust be performed by experi­enced endoscopists, due to the longer procedure time [9]. In our experience and based on our unpublished data, prociency in performing ESD was achieved after completing around 100 cases.
Hybrid ESD involves circumferential mucosal incision followed by submucosal dissection to a certain degree and snare resection of the polyp. Since it is a technique that can use the advantages of both ESD and snaring, it is an attractive method to achieve safe, rapid, en-bloc resection of colorectal neoplasms [18]. While studies agree on Hybrid ESD being performed faster [1719] than ESD, it might be inferior in terms of achieving en-bloc & R0 resection of large polyps [12, 17].
In conclusion, large polyps are not amenable to be resected with CP. EMR is an attractive option for the management of polyps that are unsuitable for CP, however, its efcacy is limited for lesions larger than 2cm [5]. ESD achieves higher en-bloc and R0 resection and lower tumor recurrence rates. However, it is a technically chal­lenging procedure and might be associated with higher perforation rates. Nevertheless, it remains to be safer and more cost-effective than surgery [20].
References
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15 What Are theOptions forManagement ofLarge Colonic Polyps?
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4. Ma MX, Bourke MJ.Complications of endoscopic polypectomy, endoscopic mucosal resec­tion and endoscopic submucosal dissection in the colon. Best Pract Res Clin Gastroenterol. 2016;30(5):749–67.
5. Pimentel-Nunes P, Dinis-Ribeiro M, Ponchon T, et al. Endoscopic submucosal dissec­tion: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy. 2015;47(9):829–54.
6. He X, Wu K, Ogino S, Giovannucci EL, Chan AT, Song M.Association between risk factors for colorectal cancer and risk of serrated polyps and conventional adenomas. Gastroenterology. 2018;155(2):355–373.e18.
7. Gotoda T, Kondo H, Ono H, et al. A new endoscopic mucosal resection procedure using an insulation-tipped electrosurgical knife for rectal at lesions: report of two cases. Gastrointest Endosc. 1999;50(4):560–3.
8. Hashiguchi Y, Muro K, Saito Y, et al. Japanese Society for Cancer of the colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol. 2020;25(1):1–42.
9. Oka S, Tanaka S, Saito Y, etal. Local recurrence after endoscopic resection for large colorectal neoplasia: a multicenter prospective study in Japan. Am J Gastroenterol. 2015;110(5):697–707.
10. Iizuka H, Okamura S, Onozato Y, Ishihara H, Kakizaki S, Mori M. Endoscopic submucosal dissection for colorectal tumors. Gastroenterol Clin Biol. 2009;33(10–11):1004–11.
11. 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(2):343–52.
12. Lee EJ, Lee JB, Lee SH, Youk EG. Endoscopic treatment of large colorectal tumors: com­parison of endoscopic mucosal resection, endoscopic mucosal resection-precutting, and endo­scopic submucosal dissection. Surg Endosc. 2012;26(8):2220–30.
13. Tajika M, Niwa Y, Bhatia V, et al. Comparison of endoscopic submucosal dissection and endoscopic mucosal resection for large colorectal tumors. Eur J Gastroenterol Hepatol. 2011;23(11):1042–9.
14. Soliman H, Brieau B, Guillaumot MA, etal. Invasive pit pattern, macronodule and depression are predictive factors of submucosal invasion in colorectal laterally spreading tumours from a Western population. United European Gastroenterol J. 2018;6(10):1569–77.
15. Ham NS, Kim J, Oh EH, etal. Cost of endoscopic submucosal dissection versus endoscopic piecemeal mucosal resection in the Colorectum. Dig Dis Sci. 2020;65(4):969–77.
16. Inoue T, Nakagawa K, Yamasaki Y, etal. Underwater endoscopic mucosal resection versus endoscopic submucosal dissection for 20-30mm colorectal polyps. J Gastroenterol Hepatol. 2021;36(9):2549–57.
17. Byeon JS, Yang DH, Kim KJ, etal. Endoscopic submucosal dissection with or without snaring for colorectal neoplasms. Gastrointest Endosc. 2011;74(5):1075–83.
18. Bae JH, Yang DH, Lee S, et al. Optimized hybrid endoscopic submucosal dissection for colorectal tumors: a randomized controlled trial. Gastrointest Endosc. 2016;83(3):584–92.
19. Yang DH, Kwak MS, Park SH, etal. Endoscopic mucosal resection with circumferential muco­sal incision for colorectal neoplasms: comparison with endoscopic submucosal dissection and between two Endoscopists with different experiences. Clin Endosc. 2017;50(4):379–87.
20. Gamaleldin M, Benlice C, Delaney CP, Steele S, Gorgun E. Management of the colorectal polyp referred for resection: a case-matched comparison of advanced endoscopic surgery and laparoscopic colectomy. Surgery. 2018;163(3):522–7.
21. Horiuchi A, Makino T, Kajiyama M, Tanaka N, Sano K, Graham DY.Comparison between endoscopic mucosal resection and hot snare resection of large nonpedunculated colorectal polyps: a randomized trial. Endoscopy. 2016;48(7):646–51.
22. Yen AW, Leung JW, Wilson MD, Leung FW. Underwater versus conventional endoscopic resection of nondiminutive nonpedunculated colorectal lesions: a prospective randomized controlled trial (with video). Gastrointest Endosc. 2020 Mar;91(3):643–654.e2.
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23. Chien HC, Uedo N, Hsieh PH.Comparison of underwater and conventional endoscopic muco­sal resection for removing sessile colorectal polyps: a propensity-score matched cohort study. Endosc Int Open. 2019;7(11):E1528–36.
24. Patel M, Haque M, Kohli D, et al. Endoscopic resection reduces morbidity when com­pared to surgery in veterans with large and complex colorectal polyps. Surg Endosc. 2021;35(3):1164–70.
25. Winawer SJ, Zauber AG, Ho MN, etal. Prevention of colorectal cancer by colonoscopic polyp­ectomy. The National Polyp Study Workgroup. N Engl J Med. 1993;329(27):1977–81.
26. Lin JS, Perdue LA, Henrikson NB, Bean SI, Blasi PR.Screening for colorectal cancer: updated evidence report and systematic review for the US preventive services task force [published cor­rection appears in JAMA. 2021 Jul 20;326(3):279]. JAMA. 2021;325(19):1978–98.
27. Zhang M, Shin EJ. Successful endoscopic strategies for difcult polypectomy. Curr Opin Gastroenterol. 2013;29(5):489–894.
28. Gorgun E, Benlice C, Church JM.Does cancer risk in colonic polyps unsuitable for polypectomy support the need for advanced endoscopic resections? J Am Coll Surg. 2016;223(3):478–84.
29. Vu JV, Sheetz KH, De Roo AC, Hiatt T, Hendren S.Variation in colectomy rates for benign polyp and colorectal cancer. Surg Endosc. 2021;35(2):802–8.
30. Ma C, Teriaky A, Sheh S, et al. Morbidity and mortality after surgery for nonmalignant colorectal polyps: a 10-year Nationwide analysis. Am J Gastroenterol. 2019;114(11):1802–10.
31. Shirai M, Nakamura T, Matsuura A, Ito Y, Kobayashi S.Safer colonoscopic polypectomy with local submucosal injection of hypertonic saline-epinephrine solution. Am J Gastroenterol. 1994;89(3):334–8.
32. Yamamoto H, Kawata H, Sunada K, etal. Successful en-bloc resection of large supercial tumors in the stomach and colon using sodium hyaluronate and small-caliber-tip transparent hood. Endoscopy. 2003;35(8):690–4.
33. Zhang XQ, Sang JZ, Xu L, et al. Endoscopic mucosal resection-precutting vs conven­tional endoscopic mucosal resection for sessile colorectal polyps sized 10-20mm. World J Gastroenterol. 2022;28(45):6397–409.
34. Li D, Wang W, Xie J, etal. Efcacy and safety of three different endoscopic methods in treat­ment of 6-20mm colorectal polyps. Scand J Gastroenterol. 2020;55(3):362–70.
35. Luigiano C, Consolo P, Scafdi MG, et al. Endoscopic mucosal resection for large and giant sessile and at colorectal polyps: a single-center experience with long-term follow-up. Endoscopy. 2009;41(10):829–35.
36. Mandic O, Jovanovic I, Cvetkovic M, etal. Factors predicting malignant occurrence and polyp recurrence after the endoscopic resection of large colorectal polyps: a single center experience. Medicina (Kaunas). 2022;58(10):1440.
37. Bujanda L, Cosme A, Gil I, Arenas-Mirave JI. Malignant colorectal polyps. World J Gastroenterol. 2010;16(25):3103–11.
38. Nett A, Binmoeller K.Underwater endoscopic mucosal resection. Gastrointest Endosc Clin N Am. 2019;29(4):659–73.
39. Choi AY, Moosvi Z, Shah S, etal. Underwater versus conventional EMR for colorectal polyps: systematic review and meta-analysis. Gastrointest Endosc. 2021;93(2):378–89.
40. Xu MD, Wang XY, Li QL, etal. Colorectal lateral spreading tumor subtypes: clinicopathology and outcome of endoscopic submucosal dissection. Int J Color Dis. 2013;28(1):63–72.
41. Draganov PV, Aihara H, Karasik MS, et al. Endoscopic submucosal dissection in North America: a large prospective multicenter study. Gastroenterology. 2021;160(7):2317–2327.e2.
42. Tanaka S, Oka S, Chayama K.Colorectal endoscopic submucosal dissection: present status and future perspective, including its differentiation from endoscopic mucosal resection. J Gastroenterol. 2008;43(9):641–51.
43. Sakamoto T, Saito Y, Fukunaga S, Nakajima T, Matsuda T.Learning curve associated with colorectal endoscopic submucosal dissection for endoscopists experienced in gastric endo­scopic submucosal dissection. Dis Colon Rectum. 2011;54(10):1307–12.
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S. Yilmaz and E. Gorgun
Management oftheMalignant Colon
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Polyp: Resection or Surveillance?
AhmedA.Eltahir andRadhikaK.Smith
Introduction
Malignant polyps are dened as polyps containing cancer cells that invade into but not through the submucosa of the colon [1]. Malignant polyps make up to 11% of colorectal polyps [24]. Over the last 20 years, participation in age appropriate colonoscopy screening has more than doubled leading to a 60% increase in the detection of malignant polyps [5]. With the adoption of advanced endoscopic tech­niques such as endoscopic mucosal resection (EMR) and, more recently, endoscopic submucosal dissection (ESD), complete polypectomy at the time of endoscopy is becoming more commonplace. When these polyps are completely removed at the time of endoscopy it questions the need for an oncologic resection at these very early stages of malignancy. Complete endoscopic removal could potentially avoid the morbidity and mortality associated with subsegmental colectomies and lymphadenectomy.
When weighing the risks and benets of surgical resection versus ongoing sur­veillance after polypectomy, the main clinical dilemma to consider is the potential for regoinal spread to the lymph nodes. It is assumed that malignant polyps are all very early cancers but our current locoregional staging relies on lymphadenectomy. The submucosal plane houses the lymphatics and vasculature, and invasive cells in this layer allow for the potential for regional lymph node metastasis [6]. There are also certain histological characteristics such as positive margins, poor differentia­tion, lymphovascular invasion, tumor budding, and deep submucosal invasion which are associated with lymph node spread and worse outcomes [7, 8]. The
16
A. A. Eltahir (*) · R. K. Smith (*) Washington University St. Louis, St. Louis, MO, USA e-mail: a.a.eltahir@wustl.edu; radhikasmith@wustl.edu
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 K. Umanskiy, N. Hyman (eds.), Difcult Decisions in Colorectal Surgery, Difcult Decisions in Surgery: An Evidence-Based Approach,
https://doi.org/10.1007/978-3-031-42303-1_16
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consideration of these factors, in addition to patients’ underlying health and prefer­ences, should drive the conversation for management of malignant polyps.
A. A. Eltahir and R. K. Smith
Search Strategy
A comprehensive search of PUBMED, Cochrane Library, and the Embase database was completed to identify cohort studies, reviews, meta-analysis, and other articles pertaining to malignant colon polyps. The search was limited to articles published in English between 2002 and 2022. The following keywords were used: malignant, colon, polyp, carcinoma, pT1, endoscopic resection, and surveillance.
Studies were included if they examined histological characteristics and their association with mortality, lymph node spread, residual disease, recurrence, or adverse outcomes. Studies which had incomplete histological evaluations of speci­men were excluded. Studies which included benign polyps or advanced carcinomas in their analysis were also excluded. If articles were published using the same data, only the most recent article was included.
Results
Malignant polyps account for up to 11% of colorectal polyps [24]. Their lymph node metastatic potential ranges from 6.6 to 16% [912]. A variety of retrospective and prospective studies were conducted to better prognosticate the risks of these early malignancies to spread to the regional lymph nodes. These data could better inform clinicians on how to best manage these polyps and potentially avoid over­treatment with surgical resection. Studies published over the last several decades have reported on the metastatic risk to the lymph node of malignant polyps, differ­entiating them into low and high risk features [13].
Depth ofInvasion
Polyp morphology has been linked to risk for nodal invasion with sessile polyps having a higher likelihood of lymph node spread when compared to pedunculated polyps. Different classications are used to grade the level of invasion of peduncu­lated and sessile polyps. The Haggitt classication is used for pedunculated polyps as seen in Fig.16.1. Overall incidence of lymph node spread in pedunculated polyps is approximately 6%. Many studies have shown that risk of lymph node spread is <1% of polyps with Haggitt level 1,2, and 3 invasion when the polyp is completely removed. Level four invasion, however, is associated with a lymph node metastasis risk of up to 27% [14, 15]. Depth of submucosal invasion in sessile polyps on the other hand are divided into thirds according to the Kikuchi classication as seen in Fig.16.2, which can also be seen in the histology slides in Figs.16.3, 16.4 and 16.5. SM1 polyps carry a risk of lymph node spread of 1–3%, SM2 have an 8% risk, and
Muscularis mucosa
Adenocarcinoma
4
Submucosa
Adenocarcinoma
SM1 SM2 SM3
16 Management oftheMalignant Colon Polyp: Resection or Surveillance?
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193
Adenomatous epithelium
Mucosa
Submucosa
Muscularis propria
Level 0
Level 1
Level 2
Level 3
Level
Fig. 16.1 Haggitt classication of pedunculated polyp. (This gure was illustrated by Shawna Duan)
Adenomatous epithelium
Mucosa
Muscularis mucosa
Muscularis propria
Fig. 16.2 Kikuchi classication of sessile polyp. (This gure was illustrated by Shawna Duan)
SM3 have a risk of 23–27% [16, 17]. It is hard to measure relative invasion of endo­scopically resected polyps as the whole submucosa is usually not resected. Therefore, studies have looked at the degree of invasion with invasion of more than 1mm associated with a higher risk of lymph node spread [7].
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Fig. 16.3 Kikuchi SM 1. (This gure produced thanks to Dr. Kathleen Byrnes and Washington University in St. Louis Pathology Department)
Fig. 16.4 Kikuchi SM 2. (This gure produced thanks to Dr. Kathleen Byrnes and Washington University in St. Louis Pathology Department)
A. A. Eltahir and R. K. Smith
Margin Positivity
Histologically incomplete resection of malignant polyps is associated with both lymph node metastasis and residual disease. Boenicke etal. retrospectively studied 105 patients with malignant polyps. They found that histologically incomplete removal was signicantly associated with lymph node spread with an odds ratio of
10.2 [18]. A meta-analysis encompassing 815 patients found that tumors with lymph node spread had a 2.36 odds of having positive margins [19]. Butte etal. found that 16% of patients with less than 1mm margins had residual disease while no patients with a margin 1mm or greater had residual disease [20]. Kim etal. also found that positive margins were twice as likely to have residual disease [21].