**4. Correlations between lymph node metastasis and depth of submucosal invasive colorectal carcinoma**

**Histological type at the deepest portion**

LNM (+) Ly (+) V (+) Sp (+) wel, mod por Identified

Desmoplastic Reaction in Biopsy Specimens of T1 Stage Colorectal Cancer Plays a Critical Role in Defining the Level...

0 (0) 5 (7.7) 3 (4.6) 9 (13.8) 64 (98.5) 1 (1.5) 64 (98.5) 1 (1.5)

0 (0) 12 (20.7) 7 (12.1) 7 (12.1) 58 (100) 0 (0) 51 (87.9) 7 (12.1)

6 (11.5) 16 (30.8) 12 (23.1) 16 (30.8) 51 (98.1) 1 (1.9) 36 (69.2) 16 (30.8)

10 (12.2) 27 (32.9) 16 (19.5) 37 (45.1) 82 (100) 0 (0) 48 (58.5) 34 (41.5)

13 (15.5) 28 (33.3) 21 (25.0) 42 (50.0) 78 (92.9) 6 (7.1) 31 (36.9) 53 (63.1)

8 (11.3) 29 (40.8) 16 (22.5) 38 (53.5) 71 (100) 0 (0) 20 (28.2) 51 (71.8)

5 (6.9) 26 (36.1) 15 (20.8) 35 (48.6) 69 (95.8) 3 (4.2) 16 (22.2) 56 (77.8)

35 (14.6) 92 (38.3) 74 (30.8) 133 (55.4) 237 (98.8) 3 (1.2) 48 (20.0) 192 (80.0)

**Table 3.** Relationship between clinicopathological factors and the rate of lymph node metastasis according to SM

Suprisingly, Japanese collaborative retrospectively nationwide survey shows both of Ip type (pedunculated lesion) and non-Ip type (nonpedunculated lesion) of early colorectal carcino‐ ma with rate of lymph node metastasis was also 0% if submucosal invasion depth was <1000 µm (Table 4). It is easy to measure one southern micrometer using by small ruler under mi‐ croscopy for surgical pathologist. When if submucosal invasion depth was 1000 µm ≤, surgi‐ cal pathologist should be advice to gastrointestinal endoscopist. And recently Japanese large-scale multicenter retrospectively study for 384 (head invasion: 240, stalk invasion: 144) pedunculated (Ip type) SICCs demonstrated that incidence of lymph node metastasis was 3.5%. the incidence of lymph node metastasis was 0.0% inpatients with head invasion, as‐ compared with 6.2% in patients with stalk invasion (Tabel 4). Pedunculated type early inva‐ sive colorectal cancers pathologically diagnosed as head invasion can be only treated by

depth in nonpedunculated (non-Ip type) SICC (adapted from [3])

SM depth (µm) (%) (%) (%) (%) (%) (%) (%) (%)

0 <X<500 (n=65)

500≤X<1000 (n=58)

1000≤X<1500 (n=52)

1500≤X<2000 (n = 82)

2000 ≤X<2500 (n= 84)

2500≤X< 3000 (n= 71)

3000 ≤X<3500 (n= 72)

endoscopic resection.

3500 ≤X (n= 240) **Status of muscularis mucosae**

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Not identified 167

The Japanese collaborative retrospectively study for 865 SICCs. This nationwide survey not on‐ ly represents a first for Japan, but reviewing the literature using PubMed revealed no similar surveys from anywhere in the world at that time [3] This study reported that pedunculated (Ip type) SICC, rate of lymph node metastasis was never in head invasion cases and stalk invasion cases with submucosal invasion depth < 3000 µm if lymphatic invasion was negative (Table 2).

And, For nonpedunculated (non-Ip type) SICC, rate of lymph node metastasis was also 0% if submucosal invasion depth was <1000 µm (Table 3). In multivariate analysis, SM depth <1000µm (P <0.006), sprouting (P <0.002), and lymphatic invasion (P<0.0001) represented significant risk factors, with odds ratios of 5.404, 2.276, and 4.691, respectively. Several priv‐ iously reports suggested that prognosis in patients with early colorectal carcinoma based on Haggitt's classification, finding that level 4 which is carcinoma invading the submucosa of the bowel wall below the stalk of the polyp but above the muscularis propria, represented the most important factor for lymph node metastasis [9, 10]. Therefore, these results re‐ vealed that submucosal invasion could be an important of predicting lymph node metastasis potential.


SICC, submucosal invasive colorectal carcinoma; SM depth, depth of submucosal invasion of SICC; LNM, lymph node metastasis; Ly, lymphatic invasion; V, venous invasion; Sp, sprouting; wel, well-differentiated adenocarcinoma; mod, moderately differentiated adenocarcinoma; por, poorly differentiated adenocarcinoma

**Table 2.** Relationship between clinicopathological factors and the rate of lymph node metastasis according to SM depth in pedunculated (Ip type) SICC (adapted from [3])

**4. Correlations between lymph node metastasis and depth of submucosal**

The Japanese collaborative retrospectively study for 865 SICCs. This nationwide survey not on‐ ly represents a first for Japan, but reviewing the literature using PubMed revealed no similar surveys from anywhere in the world at that time [3] This study reported that pedunculated (Ip type) SICC, rate of lymph node metastasis was never in head invasion cases and stalk invasion cases with submucosal invasion depth < 3000 µm if lymphatic invasion was negative (Table 2).

And, For nonpedunculated (non-Ip type) SICC, rate of lymph node metastasis was also 0% if submucosal invasion depth was <1000 µm (Table 3). In multivariate analysis, SM depth <1000µm (P <0.006), sprouting (P <0.002), and lymphatic invasion (P<0.0001) represented significant risk factors, with odds ratios of 5.404, 2.276, and 4.691, respectively. Several priv‐ iously reports suggested that prognosis in patients with early colorectal carcinoma based on Haggitt's classification, finding that level 4 which is carcinoma invading the submucosa of the bowel wall below the stalk of the polyp but above the muscularis propria, represented the most important factor for lymph node metastasis [9, 10]. Therefore, these results re‐ vealed that submucosal invasion could be an important of predicting lymph node metastasis

SM depth (µm) (%) (%) (%) (%) (%) (%) X=0 (n=53) 3 (5.7) 15 (28.3) 9 (17.0) 15 (28.3) 51 (96.2) 2 (3.8) 0 <X<500 (n=10) 0 (0) 2 (20.0) 0 (0) 3 (33.3) 10 (100) 0 (0) 500≤X<1000 (n=7) 0 (0) 1 (14.3) 0 (0) 2 (28.6) 7 (100) 0 (0) 1000≤X<1500 (n=11) 1 (9.1) 2 (18.2) 3 (27.3) 7 (63.6) 11 (100) 0 (0) 1500≤X<2000 (n = 7) 1 (14.3) 4 (57.1) 0 (0) 5 (71.4) 7 (100) 0 (0) 2000 ≤X<2500 (n= 10) 1 (10.0) 4 (40.0) 3 (30.0) 1 (10.0) 9 (90.0) 1 (10.0) 2500≤X< 3000 (n= 4) 0 (0) 0 (0) 2 (50) 1 (25.0) 4 (100) 0 (0) 3000 ≤X<3500 (n= 9) 2 (22.2) 4 (44.4) 3 (33.3) 5 (55.6) 8 (88.9) 1 (11.1) 3500 ≤X (n= 30) 2 (6.7) 9 (30.0) 10 (33.3) 10 (33.3) 28 (93.3) 2 (6.7)

SICC, submucosal invasive colorectal carcinoma; SM depth, depth of submucosal invasion of SICC; LNM, lymph node metastasis; Ly, lymphatic invasion; V, venous invasion; Sp, sprouting; wel, well-differentiated adenocarcinoma; mod,

**Table 2.** Relationship between clinicopathological factors and the rate of lymph node metastasis according to SM

moderately differentiated adenocarcinoma; por, poorly differentiated adenocarcinoma

depth in pedunculated (Ip type) SICC (adapted from [3])

LNM (+) Ly (+) V (+) Sp (+) wel, mod por

**Histological type at the deepest portion**

**invasive colorectal carcinoma**

166 Colonoscopy and Colorectal Cancer Screening - Future Directions

potential.


**Table 3.** Relationship between clinicopathological factors and the rate of lymph node metastasis according to SM depth in nonpedunculated (non-Ip type) SICC (adapted from [3])

Suprisingly, Japanese collaborative retrospectively nationwide survey shows both of Ip type (pedunculated lesion) and non-Ip type (nonpedunculated lesion) of early colorectal carcino‐ ma with rate of lymph node metastasis was also 0% if submucosal invasion depth was <1000 µm (Table 4). It is easy to measure one southern micrometer using by small ruler under mi‐ croscopy for surgical pathologist. When if submucosal invasion depth was 1000 µm ≤, surgi‐ cal pathologist should be advice to gastrointestinal endoscopist. And recently Japanese large-scale multicenter retrospectively study for 384 (head invasion: 240, stalk invasion: 144) pedunculated (Ip type) SICCs demonstrated that incidence of lymph node metastasis was 3.5%. the incidence of lymph node metastasis was 0.0% inpatients with head invasion, as‐ compared with 6.2% in patients with stalk invasion (Tabel 4). Pedunculated type early inva‐ sive colorectal cancers pathologically diagnosed as head invasion can be only treated by endoscopic resection.


**5. The treatment of colorectal carcinoma with submucosal invasion state**

Desmoplastic Reaction in Biopsy Specimens of T1 Stage Colorectal Cancer Plays a Critical Role in Defining the Level...

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169

Many new treatment methods have been developed over the last few decades. The Japanese Society for Cancer of the Colon and Rectum guidelines 2010 for the treatment of colorectal cancer (JSCCR Guidelines 2010 [13]) have been prepared to show standard treatment strat‐

**Figure 6.** Guide line for the treatment of colorectal carcinoma with submucosal invasion state after endoscopic resection. (adapted from JSCCR Guidelines 2010 [13] with minor modifications );; Pap: papillary adenocarcinoma, Tub: tub‐ ular adenocarcinoma, Por: poorly differentiated adenocarcinoma, Sig: signet-ring cell carcinoma, Muc: mucinous adenocarcinoma, SM: submucosal invasion, Budding: tumor budding. The tumor budding denotes that at the invasion front of colorectal adenocarcinomas tumour cells, and the potential of tumour budding as a prognostic factor

**after endoscopic resection**

egies for submucosal invasive colorectal cancer (Figure. 6).

(G1:Grade 1 to G3: Grade 3) for routine surgical pathology [14,15])

a) Endoscopic finding (b) Stereomicroscopic

macroscopically. (White bar: mucosal invasion, Red bar: submucosal invasion) (c),

finding

**Figure 7.** Endoscopic, stereomicroscopic, macroscopic findings of the early colorectal carcinoma. Endoscopic finding of the pedunculated(Non-Ip) type (a), several pits are arranged irregularly in the stereomicroscopic view (b), macroscopic appearance of SICC, post formalin-fixed. Most of the endoscopic detectable lesions were the irregular elevated type

(c) Macroscopic

finding

Ip type: pedunculated lesion. Non-Ip type: nonpedunculated lesion

\*: vessels invasion

**Table 4.** Relationship between clinicopathological factors and the rate of the lymph node metastasis according to SM depth (summarized of Table 2 and 3, adapted from [11]. English translated version]


Lymphatic and ⁄or venous invasion. CI, confidence interval

**Table 5.** Histopathological characteristics of 384 cases of pedunculated type early invasive colorectal cancer (adapted from [12])
