Management of T1 Colorectal Carcinoma
This study involved 499 patients with T1 colorectal carcinoma who had undergone surgical resection with lymph node dissection to confirm LN metastasis at Hiroshima University Hospital, or an affiliated hospital, during the period of January 1981 through December 2008. They represented a consecutive and unselected cohort of patients. A total of 368 tumors were primarily treated by surgery with nodal dissection, and 150 tumors were initially treated with endoscopic resection prior to additional surgery. To evaluate precise pathologic findings of primary lesion and to determine exact evidence of LN metastasis we excluded eight cases that were accompanied by advanced cancer and 19 cases showing positive vertical margin of tumor after endoscopic resection (Fig. 1).
(Enlarge Image)
Figure 1.
Flow chart of study subjects. CRC, colorectal carcinoma; LN, lymph node.
Lymph node metastasis was observed by pathologic examination in 8.2% (41/499) of patients. Mean (± standard deviation [SD]) patient age was 63.0 ± 11.0 years (range 32–90 years) and mean tumor size was 18.2 ± 10.7 mm (range 3–100 mm). Macroscopically, 298 of the tumors appeared to be of the protruded type (0-Ip, Isp, Is), and 201 appeared to be of the superficial type (0-IIa, IIc, IIa + IIc, IIc + IIa). None of the patients had received preoperative radiotherapy or neoadjuvant chemotherapy.
Resected specimens were pinned to a board and fixed in 10% buffered formalin for 12–48 h. Surgical specimens were then cut into parallel 3–4 mm thick sections, whereas endoscopic specimens were cut into 2 mm thick sections. Specimens were examined retrospectively by a pathologist.
The rectum was defined as the area located between the lower border of the second sacral vertebra and the upper border of the anal canal.
Pathologic examination was performed under hematoxylin and eosin staining. Pathologic features including depth of submucosal invasion (< 1800 μm vs≥ 1800 μm), histologic characteristics, tumor budding grade, and vessel invasion were analyzed in relation to LN metastasis. The invasion depth cut-off value of 1800 μm was used because, without the presence of other risk factors, LN metastasis was not seen with invasion depths of < 1800 μm. Histologic diagnosis was based on World Health Organization criteria. We measured the depth of submucosal invasion according to the 2010 JSCCR guidelines for the treatment of colorectal cancer (Fig. 2). In brief, if the level of the muscularis mucosae could be identified or presumed, we measured from the muscularis mucosae to the tumor apex. If the level of the muscularis mucosae could not be identified or presumed, we measured from the surface of the tumor to its apex. If a 0-Ip type polyp involved the muscularis mucosae, as in the case of a Peutz-Jeghers polyp, we measured from the neck of the polyp to the tumor apex (deeper than Haggitt level 2). In these cases head invasion was defined as a submucosal invasion depth of 0 μm (Haggitt level 1). In addition, tumor budding was graded according to the same 2010 JSCCR guidelines. A bud was defined as a single cancer cell or a cluster of fewer than five cells along the invasive margin, and budding was graded per microscopic field at 200 × magnification: grade 1, 0–4 buds; grade 2, 5–9 buds; or grade 3, 10 or more buds.
(Enlarge Image)
Figure 2.
Measurement of the depth of submucosal invasion of colorectal carcinoma. (a) When the level of the muscularis mucosae can be detected or presumed, the distance from the muscularis mucosae to the tumor apex is measured. (b,c) When the level of the muscularis mucosae cannot be detected or presumed, the distance from the tumor surface to the tumor apex is measured. (b, sessile polyp; c, pedunculated polyp). (d) If a pedunculated polyp involves the muscularis mucosae (such as a Peutz-Jeghers polyp), the distance from the neck to the tumor apex is measured (deeper than Haggitt level 2).
Incidences of LN metastasis were examined in relation to various histopathologic features, and differences were analyzed by χ tests. Statistical significance was defined as P < 0.05. Multivariate analysis with logistic regression was used to identify risk factors for LN metastasis, with P < 0.05 being considered significant. Odds ratios were calculated to estimate the relative risk of LN metastasis when various factors were present. All statistical analyses were performed with PASW 18 statistical software (SPSS Inc., Chicago, IL, USA).
Methods
Patients and Surgical Specimens
This study involved 499 patients with T1 colorectal carcinoma who had undergone surgical resection with lymph node dissection to confirm LN metastasis at Hiroshima University Hospital, or an affiliated hospital, during the period of January 1981 through December 2008. They represented a consecutive and unselected cohort of patients. A total of 368 tumors were primarily treated by surgery with nodal dissection, and 150 tumors were initially treated with endoscopic resection prior to additional surgery. To evaluate precise pathologic findings of primary lesion and to determine exact evidence of LN metastasis we excluded eight cases that were accompanied by advanced cancer and 19 cases showing positive vertical margin of tumor after endoscopic resection (Fig. 1).
(Enlarge Image)
Figure 1.
Flow chart of study subjects. CRC, colorectal carcinoma; LN, lymph node.
Lymph node metastasis was observed by pathologic examination in 8.2% (41/499) of patients. Mean (± standard deviation [SD]) patient age was 63.0 ± 11.0 years (range 32–90 years) and mean tumor size was 18.2 ± 10.7 mm (range 3–100 mm). Macroscopically, 298 of the tumors appeared to be of the protruded type (0-Ip, Isp, Is), and 201 appeared to be of the superficial type (0-IIa, IIc, IIa + IIc, IIc + IIa). None of the patients had received preoperative radiotherapy or neoadjuvant chemotherapy.
Resected specimens were pinned to a board and fixed in 10% buffered formalin for 12–48 h. Surgical specimens were then cut into parallel 3–4 mm thick sections, whereas endoscopic specimens were cut into 2 mm thick sections. Specimens were examined retrospectively by a pathologist.
The rectum was defined as the area located between the lower border of the second sacral vertebra and the upper border of the anal canal.
Pathologic Evaluation
Pathologic examination was performed under hematoxylin and eosin staining. Pathologic features including depth of submucosal invasion (< 1800 μm vs≥ 1800 μm), histologic characteristics, tumor budding grade, and vessel invasion were analyzed in relation to LN metastasis. The invasion depth cut-off value of 1800 μm was used because, without the presence of other risk factors, LN metastasis was not seen with invasion depths of < 1800 μm. Histologic diagnosis was based on World Health Organization criteria. We measured the depth of submucosal invasion according to the 2010 JSCCR guidelines for the treatment of colorectal cancer (Fig. 2). In brief, if the level of the muscularis mucosae could be identified or presumed, we measured from the muscularis mucosae to the tumor apex. If the level of the muscularis mucosae could not be identified or presumed, we measured from the surface of the tumor to its apex. If a 0-Ip type polyp involved the muscularis mucosae, as in the case of a Peutz-Jeghers polyp, we measured from the neck of the polyp to the tumor apex (deeper than Haggitt level 2). In these cases head invasion was defined as a submucosal invasion depth of 0 μm (Haggitt level 1). In addition, tumor budding was graded according to the same 2010 JSCCR guidelines. A bud was defined as a single cancer cell or a cluster of fewer than five cells along the invasive margin, and budding was graded per microscopic field at 200 × magnification: grade 1, 0–4 buds; grade 2, 5–9 buds; or grade 3, 10 or more buds.
(Enlarge Image)
Figure 2.
Measurement of the depth of submucosal invasion of colorectal carcinoma. (a) When the level of the muscularis mucosae can be detected or presumed, the distance from the muscularis mucosae to the tumor apex is measured. (b,c) When the level of the muscularis mucosae cannot be detected or presumed, the distance from the tumor surface to the tumor apex is measured. (b, sessile polyp; c, pedunculated polyp). (d) If a pedunculated polyp involves the muscularis mucosae (such as a Peutz-Jeghers polyp), the distance from the neck to the tumor apex is measured (deeper than Haggitt level 2).
Statistical Analysis
Incidences of LN metastasis were examined in relation to various histopathologic features, and differences were analyzed by χ tests. Statistical significance was defined as P < 0.05. Multivariate analysis with logistic regression was used to identify risk factors for LN metastasis, with P < 0.05 being considered significant. Odds ratios were calculated to estimate the relative risk of LN metastasis when various factors were present. All statistical analyses were performed with PASW 18 statistical software (SPSS Inc., Chicago, IL, USA).
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