Predictive Histopathologic Factors for Lymph Node Metastasis in Patients With Nonpedunculated Submucosal Invasive Colorectal Carcinoma

PURPOSE Risk factors for lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma remain to be characterized. This study examines the relationship between lymph node metastasis and clinicopathologic factors in nonpedunculated submucosal invasive colorectal carcinoma.METHODS The study cohort comprised 155 patients who had undergone surgical treatment for nonpedunculated submucosal invasive colorectal carcinoma. The clinicopathologic factors investigated included gender, age, tumor location, macroscopic type, tumor size, histologic type and grade, intramucosal growth pattern, lymphatic invasion, venous invasion, degree of focal dedifferentiation at the submucosal invasive front, status of the remaining muscularis mucosa, and the depth and width of submucosal invasion.RESULTS Lymph node metastases were found in 19 patients (12.3 percent). Univariate analysis showed that lymphatic invasion, focal dedifferentiation at the submucosal invasive front, status of the remaining muscularis mucosa, and depth of submucosal invasion all had a significant influence on lymph node metastasis. Multivariate analysis showed lymphatic invasion (P = 0.014) and high-grade focal dedifferentiation at the submucosal invasive front (P = 0.049) to be independent factors predicting lymph node metastasis. No lymph node metastasis was found in tumors with a depth of submucosal invasion of <1.3 mm.CONCLUSIONS Lymphatic invasion and high-grade focal dedifferentiation at the submucosal invasive front are important predictors of lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma. Depth of submucosal invasion can be used as an identifying marker for patients who do not require subsequent surgery after endoscopic resection.Supported in part by a grant-in-aid for cancer research from the Ministry of Health and Welfare of Japan.     

Clinicopathological study of lymph-node metastasis in 1,389 patients with early gastric cancer: assessment of indications for endoscopic resection

BACKGROUND: The endoscopic resection of early gastric cancers (EGC) is a standard technique in Japan and is increasingly used throughout the world. Further experience in the treatment of EGC and a clearer delineation of the factors related to lymph‐node metastasis would permit a more accurate assessment of endoscopic resection. METHODS: The study group comprised 1389 patients with EGC who underwent gastrectomy with lymph‐node dissection. We evaluated the relations of lymph‐node metastasis to clinicopathological factors. RESULTS: Of the 718 patients with intramucosal carcinomas, 14 (1.9%) had lymph‐node metastasis. All cases of lymph‐node metastasis were associated with ulceration. No lymph‐node metastasis was found in patients with intramucosal carcinomas without ulceration, irrespective of tumor size and histological type. Lymph‐node metastasis was present in 14 (4.7%) of the 296 patients who had cancer with a submucosal invasion depth of less than 500 μm (sm1). Significantly increased rates of lymph‐node metastasis were associated with undifferentiated types, ulcerated lesions and lymphatic invasion. No lymph‐node metastasis was found in patients with differentiated sm1 carcinomas 30 mm or less in diameter without ulceration. Lymph‐node metastasis occurred in 29% of the patients who had cancer with a submucosal invasion depth of 500 μm or more (sm2). CONCLUSION: This large series of patients with EGC provides further evidence supporting the expansion of indications for endoscopic treatment, as well as warns against potential risks.     

Risk factors for lymph node metastasis of submucosal invasive differentiated type gastric carcinoma: clinical significance of histological heterogeneity

Background. The use of endoscopic resection for submucosal invasive gastric carcinoma (Sm-ca) with histologically differentiated type has been expected. However, the treatment criteria remain controversial. The purpose of this study was to clarify the relationship between lymph node metastasis and the histologic features of differentiated Sm-ca. Methods. The clinicopathologic features of 35 patients with node-positive differentiated Sm-ca were compared with those of 221 patients with node-negative differentiated Sm-ca by multivariate analysis with logistic regression. To clarify the metastatic behavior of differentiated Sm-ca, we examined mucin-histochemical expression and immunohistochemical staining, using Ki-67, p53, and c-erbB2. Results. The rate of lymph node metastasis was significantly higher in differentiated Sm-ca with histologi-cal heterogeneity (combined differentiated type, with poorly differentiated component) than in that without histological heterogeneity (27% vs 7%; P < 0.001). Multivariate analysis revealed that lymphatic vessel invasion was the most significant determinant (odds ratio, 8.68) for lymph node metastasis. Histological heterogeneity (odds ratio, 3.88) was next, followed by papillary adenocarcinoma (odds ratio, 3.28), and submucosal invasion level (odds ratio, 2.34). The mean value of the Ki-67 labeling index for node-positive differentiated Sm-ca was higher than that of node-negative differentiated Sm-ca (47% vs 39%; P < 0.05). Conclusions. When the extension of endoscopic surgery to differentiated Sm-ca is considered, this therapeutic technique should be limited to the differentiated type of Sm-ca without histological heterogeneity. The Ki-67 labeling index provides useful information for identifying those patients with a high risk of lymph node metastasis. Received: January 9, 2001 / Accepted: April 13, 2001     

Predictive factors for lymph node metastasis and endoscopic treatment strategies for undifferentiated early gastric cancer

Background and Aim: Although more than 80% of undifferentiated early gastric cancers (EGC) are not associated with lymph node metastasis, endoscopic mucosal resection is not generally accepted as a means of curative treatment because of an abundance of conflicting data concerning clinicopathological characteristics and prognoses. The aim of this study was to define a subgroup of undifferentiated EGC that could be cured by endoscopic treatment without the risk of lymph node metastasis. Method: A total of 591 patients surgically resected for undifferentiated EGC between January 1999 and March 2005 were reviewed. Associations between various clinicopathological factors and the presence of lymph node metastasis were analyzed to identify the risk factors of lymph node metastasis. Results: Lymph node metastasis was found in 79 patients (13.4%). By multivariate logistic regression analysis, a tumor diameter 2.5 cm or larger, invasion into the middle third of the submucosal layer or deeper, and lymphatic involvement were identified as independent risk factors of lymph node metastasis (P < 0.001, respectively). Lymph node metastasis was not found in any patient with undifferentiated EGC smaller than 2.5 cm confined to the mucosa or upper third of the submucosal layer without lymphatic involvement. Conclusions: Undifferentiated intramucosal EGC smaller than 2.5 cm without lymphatic involvement was not associated with lymph node metastasis. Thus, we propose in this circumstance that endoscopic mucosal resection could be considered a definitive treatment without compromising the possibility of cure.     

Treatment strategy for rectal carcinoids: A clinicopathological analysis of 229 cases at a single cancer institution

Background and Aim: A treatment strategy for tumors with only venous invasion and characteristics of small rectal carcinoids with metastasis have not been clearly documented. The present study aims to determine the risk factors for lymph node metastasis and to elucidate characteristics of small tumors with metastasis. Methods: We investigated a total of 229 patients with rectal carcinoids. The relationship between each clinicopathological variable and the presence of lymph node metastasis was evaluated. Results: Tumor size (larger than 10 mm), presence of central depression, depth of tumor invasion, lymphatic invasion, and venous invasion were significantly associated with the incidence of lymph node metastasis (P < 0.001). Multivariate analysis revealed that tumor size (odds ratio: 63.3, P < 0.001) and venous invasion (odds ratio: 40.9, P < 0.001) were independently predictive of lymph node metastasis. In 204 patients with small (no larger than 10 mm) tumors, 10 patients had lymph node metastasis. All 10 tumors had low proliferation values indicated by mitosis and Ki‐67 index. Multivariate analysis for the 204 patients revealed that only venous invasion was independently associated with metastasis (odds ratio: 40.1, P < 0.001). Five‐year disease free survival rates of the total patients with metastasis and without metastasis were 81.1% and 95.5%, respectively (P < 0.001, log‐rank test). Conclusions: Venous invasion as well as tumor size and lymphatic invasion indicates high malignant potential to metastasize to lymph node and would provide useful information in considering the addition of radical surgery. Postoperative pathological examinations of specimens obtained by local resection are very important to avoid underestimation.     

Feasibility study on expanded indication for endoscopic submucosal dissection of intramucosal poorly differentiated early gastric cancer

AIM: To identify clinicopathological factors predictive of lymph node metastasis (LNM) in intramucosal poorly differentiated early gastric cancer (EGC), and further to expand the possibility of using endoscopic submucosal dissection (ESD) for the treatment of intramucosal poorly differentiated EGC.METHODS: Data for 81 surgically treated patients with intramucosal poorly differentiated EGC were collected, and the association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Several clinicopathologic factors were investigated to identify predictive factors for lymph nodes metastasis, including gender, age, family history of gastric cancer, number of tumors, tumor location, ulceration, tumor size, macroscopic type, lymphatic vessel involvement, and signet-ring-cell component.RESULTS: Tumor size (OR = 7.273, 95%CI: 1.246-29.918, P = 0.042), lymphatic vessel involvement (OR = 42.219, 95%CI: 1.923-97.052, P = 0.018) and signet-ring-cell component (OR = 17.513, 95%CI: 1.647-77.469, P = 0.034) that were significantly associated with LNM by univariate analysis, were found to be significant and independent risk factors for LNM by multivariate analysis. However, gender, age, family history of gastric cancer, number, location, ulceration and macroscopic type of tumor were found not to be associated with LNM. Of these 81 patients diagnosed with intramucosal poorly differentiated EGC, 7 (8.6%) had LNM. The LNM rates were 9.1%, 22.2% and 57.1%, respectively, in cases with one, two and three of the risk factors. There was no LNM in 54 patients without the three risk clinicopathological factors.CONCLUSION: Tumor size, lymphatic vessel involvement and signet-ring-cell component are independently associated with the presence of LNM in intramucosal poorly differentiated EGC. Thus, these three risk factors may be used as a simple criterion to expand the possibility of using ESD for the treatment of intramucosal poorly differentiated EGC.     

Predictive factors for lymph node metastasis of differentiated submucosally invasive gastric cancer

BACKGROUND: For early gastric cancer, submucosal invasion may be unrecognized until histopathologic examination of the specimen obtained by EMR. Gastrectomy with lymphadenectomy is the standard treatment for such submucosal cancers. However, approximately 80% of submucosal cancers do not have lymph node metastasis. Unnecessary surgery could be avoided if a subgroup of patients with submucosal cancer with negligible risk of lymph node metastasis can be defined. This study was conducted to define such a subgroup. METHODS: Data from 104 patients surgically treated for differentiated submucosal cancers were retrospectively collected. A multivariate analysis of clinicopathologic factors was performed to identify predictive factors for lymph node metastasis. RESULTS: Three independent risk factors, namely, female gender (p=0.0174), deep invasion (> or =500 microm) into the submucosal layer (p=0.001), and presence of lymphatic involvement (p < 0.0001) were associated with lymph node metastasis. Lymph node metastasis was not observed in any patient who had limited submucosal invasion and absence of lymphatic involvement. The rate of lymph node metastasis was calculated to be 80% in patients who had both deep submucosal invasion and lymphatic involvement. CONCLUSIONS: If endoscopic resection specimens exhibit no deep penetration (<500 microm) into the submucosal layer and lymphatic involvement is absent, EMR may be sufficient treatment for submucosal well-differentiated early gastric cancers. A long-term follow-up study of patients with such lesions treated by EMR alone is required.     

Higher frequencies of numerical aberrations of chromosome 17 in primary gastric cancers are associated with lymph node metastasis

We investigated the correlation between the frequency of numerical aberrations of chromosome 17 and clinicopathological features of gastric cancer. The copy number of chromosome 17 was examined with fluorescence in-situ hybridization (FISH) in frozen specimens from 100 primary gastric cancers. Chromosomal numerical aberrations were diagnosed as chromosomal loss (single signal) or gain (triple or more signals), in each cell. The frequency of numerical aberrations of chromosome 17 correlated significantly with the depth of invasion (P < 0.01), lymph node metastasis (P < 0.0001), lymphatic invasion (P < 0.001), and venous invasion (P < 0.01). Numerical aberrations of chromosome 17 were associated with lymph node metastasis in 32 early gastric cancers. Multiple regression analysis identified the depth of invasion and numerical aberrations of chromosome 17 as independent significant determinants of lymph node metastasis. Our findings suggest that alterations in chromosome 17 may be linked with tumor progression in primary gastric cancer. Our results also indicate that numerical aberrations of chromosome 17 detected by FISH provide important information about the malignant potential (in particular, lymph node metastasis) of primary gastric cancer. (Received Feb. 22, 1998; accepted July 24, 1998)     

Clinical utility of grading criteria for submucosal invasion in the prognosis of T1 colorectal carcinomas

Background: The clinical utility of relative and absolute grading criteria for submucosal invasion in T1 colorectal carcinomas has been controversial. Methods: In 51 T1 colorectal carcinomas, depth of submucosal invasion was graded either according to a modified Haggitt's classification (a relative criterion) or by direct measurement using a micrometer (an absolute criterion), and immunostaining for E-cadherin, α-catenin, β-catenin, matrilysin, and CD44 variant 6 was performed on formalin-fixed, paraffin-embedded sections. The associations between lymph node metastasis or local recurrence (locoregional failure) and tumor budding, and clinicopathologic parameters and immunoreactivity were examined statistically. Results: By univariate analysis, tumor budding, histology, and the co-expression pattern of nuclear β-catenin and CD44 variant 6 were significantly associated with locoregional failure. The relative and absolute grading of submucosal invasion were not significantly associated with locoregional failure. Multivariate analysis showed that tumor budding alone was significantly associated with locoregional failure, and the association between the co-expression pattern of nuclear β-catenin and CD44 variant 6, and locoregional failure was marginally significant (P = 0.0502). Lymphatic invasion and absolute grading of depth and width of submucosal invasion were significantly associated with tumor budding, and the associations between tumor budding, and histologic differentiation and membranous α-catenin expression were marginally significant (P = 0.06; P = 0.08), whereas, a relative grading of submucosal invasion was not significant (P = 0.58). Analysis of variance showed that histologic differentiation and lymphatic invasion were independently and significantly associated with tumor budding (P = 0.005; P < 0.001). Conclusions: These results suggest that the grading of submucosal invasion, either relative or absolute, may not be a useful risk factor for lymph node metastasis or local recurrence in T1 colorectal carcinomas. Received: January 16, 2002 / Accepted: May 17, 2002 Acknowledgements. We thank Drs. Y. Shimada, K. Nunomura, and S. Uchiyama for providing tissue blocks. For expert technical assistance we thank Ms. N. Shiota and Ms. K. Ooshima. Reprint requests to: T. Masaki     

Indications and Techniques for Endoscopic Mucosal Resection in the Lesions of A Colorectal Tumor

We evaluated the possibility of an extended application of endoscopic treatment for submucosal‐invading colorectal cancers, and describe the method of endoscopic mucosal resection (EMR) using a one channel colonoscope. A total of 328 submucosal‐invading cancers were examined from July 1985 to September 2002. The patterns of infiltrating growth into the submucosal layer were further divided into two groups: expanding growth, and infiltrating growth. Lymph node metastasis occurred in sm2 and extension cancer in more advanced stages. The lowest measurement of submucosal invading cancer with lymph node metastasis was 1250 µm. As for patterns of invasion, the frequencies of lymph node metastasis in the groups of expanding growth and infiltrating growth were 0% (0/87) and 14.5% (16/110), respectively, (P = 0.0002, Fisher's direct method). Results showed that endoscopic treatment is suitable for sm1 extension without vessel invasion, but there is a possibility that some sm2 extension cancers can be cured radically when the pattern of submucosal invasion shows expanding growth with a distinct border.     

Clinicopathological features associated with lymph node metastasis in early gastric cancer: Analysis of a single-institution experience in China

BACKGROUND:

An accurate assessment of potential lymph node metastasis is an important issue for the appropriate treatment of early gastric cancer. Minimizing the number of invasive procedures used in cancer therapy is critical for improving the patient’s quality of life.

OBJECTIVE:

To evaluate the clinicopathological features associated with lymph node metastasis of early gastric cancer in patients from a single institution in China.

METHODS:

A retrospective review of data from 410 patients surgically treated for early gastric cancer at the First Affiliated Hospital (Nanjing, China) between 1998 and 2007, was conducted. The clinicopathological variables associated with lymph node metastasis were evaluated.

RESULTS:

Lymph node metastasis was observed in 12.20% of patients. The macroscopic type, tumour size, location in the stomach, depth of gastric carcinoma infiltration, and presence of vascular or lymphatic invasion showed a positive correlation with the incidence of lymph node metastasis by univariate analysis. Multivariate analyses revealed histological classification, macroscopic type, tumour size, depth of gastric carcinoma infiltration, and the presence of vascular or lymphatic invasion to be significantly and independently related to lymph node metastasis. The depth of gastric carcinoma infiltration was the strongest predictive factor for lymph node metastasis. For intramucosal cancer, tumour size was the unique risk factor for lymph node metastasis. For submucosal cancer, histological classification and tumour size were independent risk factors for lymph node metastasis.

CONCLUSIONS:

Histological classification, macroscopic type, tumour size, depth of gastric carcinoma infiltration, and the presence of vascular or lymphatic invasion are independent risk factors for lymph node metastasis in patients with early gastric cancer in China. Minimal invasive treatment, such as endoscopic mucosal resection, may be possible for highly selected cancers.     

分化不良型早期胃癌淋巴结转移的危险因素分析

目的评估分化不良型早期胃癌患者淋巴结转移的危险因素,探讨其内镜治疗的可能性。方法回顾性分析2002年9月-2008年12月经手术证实的100例分化不良型早期胃癌患者,对其年龄、性别、肿瘤大小、部位、大体类型、溃疡、组织学类型、浸润深度及淋巴管肿瘤浸润与淋巴结转移的关系进行单因素和多因素分析。结果分化不良型早期胃癌的淋巴结转移率达18．00％。多变量分析显示肿瘤大小（〉2cm）、侵犯至黏膜下层、淋巴管肿瘤浸润均是分化不良型早期胃癌淋巴结转移的独立危险因素（P〈0．05）。肿瘤大小和淋巴管肿瘤浸润是分化不良型黏膜内早期胃癌的淋巴结转移的独立危险因素。在直径≤2cm且无淋巴管肿瘤浸润的分化不良型黏膜内早期胃癌中未发现淋巴结转移。结论直径≤2cm且无淋巴管肿瘤浸润的分化不良型黏膜内癌患者可考虑内镜治疗,术后需密切随访。     

Independent histological risk factors for lymph node metastasis of superficial esophageal squamous cell carcinoma; implication of claudin‐5 immunohistochemistry for expanding the indications of endoscopic resection

Endoscopic resection is curative for superficial esophageal squamous cell carcinoma (ESCC) limited to the lamina propria. Endoscopic resection is not recommended for superficial ESCC invading muscularis mucosa or submucosa, however, because of the high frequency of lymph node metastasis (LNM) in such patients. Methods to more accurately predict LNM by analysis of endoscopically resected specimens are needed. Patients with superficial ESCC who underwent surgery without prior chemoradiotherapy (n= 110) were retrospectively examined to determine whether LNM correlated with immunohistochemical parameters and conventional histological parameters, including depth of invasion and vascular permeation. Cancer cell expression of claudins‐1, 5, and 7, E‐cadherin, β‐catenin, and matrix metalloproteinase 7 was evaluated. Univariate analysis revealed that LNM correlated with claudin‐5 expression, but not any other immunohistochemical parameter examined. Multivariate analysis revealed three independent risk factors for LNM: aberrant claudin‐5 expression in cancer cells (odds ratio; OR [95% confidence interval]= 4.61[1.44–14.77]), depth of submucosal invasion greater than 200 µm (3.55 [1.02–13.17]), and positive lymphatic permeation (3.34 [1.22–9.15]). LNM was found in one of 29 (3.4%) patients with none of these three risk factors, and in 32 of 81 (39.5%) patients with one or more of these risk factors. In superficial ESCC, routine analysis of claudin‐5 expression in cancer cells together with depth of invasion and lymphatic permeation may be useful for predicting LNM and thereby reducing the number of patients undergoing additional surgery after successful endoscopic resection.     

Immunohistochemical localization of carcinoembryonic antigen as a predictor of lymph node status in submucosa-invasive colorectal carcinoma

PURPOSE: Submucosa-invasive colorectal carcinoma is a colorectal carcinoma extending only into the submucosal layer. To clarify the metastatic potential of submucosa-invasive colorectal carcinoma, we studied the relationship between the immunohistochemical staining pattern of carcinoembryonic antigen (CEA) and that of lymphatic invasion/ lymph node metastasis. METHODS: We investigated 49 submucosa-invasive colorectal carcinomas resected surgically or endoscopically. CEA distribution patterns of the neoplastic tissues were divided into three patterns: Pattern 1 = luminal type; Pattern 2 = apical cytoplasmic type; and Pattern 3 = diffuse cytoplasmic type. We also observed the submucosal stromal staining of CEA. RESULTS: Lymphatic invasion and lymph node metastasis were found in 48.8 percent (21/43) and 11.6 percent (5/43) of the Pattern 2/Pattern 3 cases, whereas these were seen in none (0/6) of Pattern 1 cases. Lymphatic invasion and lymph node metastasis were found in 63.3 percent (19/30) (chi-squared =21.94;P <0.001) and 16.7 percent (5/30) of the positive stromal CEA cases, whereas these were seen in 10.5 percent (2/19) and none (0/14) of the negative stromal CEA cases, respectively. CONCLUSION: Pattern 2/Pattern 3 and stromal CEA can be predictors of the lymph node metastasis with 11.6 percent and 16.7 percent risks.Read at the meeting of the Japanese Society of Gastroenterological Surgery, Tokyo, Japan, February 24 to 25, 1994.     

Expression of urokinase-type plasminogen activator receptor and plasminogen activator inhibitor-1 in gastric cancer

In gastric cancer, the urokinase-type plasminogen activator (uPA) system plays important roles in invasion and metastasis, processes which entail proteolysis and adhesion. Both the urokinasetype plasminogen activator receptor (uPAR) and the plasminogen activator inhibitor-1 (PAI-1) are thought to be important factors in this system. To clarify the relationship between these two factors and gastric cancer invasiveness, we evaluated the expression of uPAR and PAI-1 in 91 cases of gastric cancer by immunohistochemistry and in situ hybridization. Urokinase-type plasminogen activator receptor-mRNA, PAI-1-mRNA, uPAR and PAI-1 protein were diffusely distributed in the cytoplasm of the cancer cells and concentrated at invasive foci. Urokinase-type plasminogen activator receptor protein expression correlated with lymphatic, venous invasion (P<.01) and lymph node metastasis (P<0.05); uPAR-mRNA expression correlated with lymphatic, venous invasion and lymph node metastasis (P<0.05). Plasminogen activator inhibitor-1 protein expression correlated with lymphatic, venous invasion, lymph node metastasis and depth of invasion (P<0.01); PAI-1-mRNA expression was linked to lymphatic, venous invasion (P<0.01), lymph node metastasis and depth of invasion (P<0.05). This suggests that the proteolytic activity of uPAR and the cellular motility of PAI-1 in gastric cancer cells may determine penetration of lymphatic and blood vessels, whereby lymph node metastasis may be promoted and that the promotion of cellular motility by PAI-1 may influence the depth of cancer invasion.     

Predictive value of histology at the invasive margin in the prognosis of early invasive colorectal carcinoma

To accurately select patients with malignant colorectal polyps who are at high risk of adverse outcome, we examined the predictive value of clinicopathological factors, with special attention paid to the histology at the invasive margin. We examined 75 submucosal carcinomas from 75 patients, initially resected by polypectomy, including endoscopic, trans-anal, trans-sacral, and trans-sphincteric local excision. The associations between clinicopathological features such as sex and age; tumor size, location, shape, depth of submucosal invasion, vascular invasion, histology at the central part, and histology at the invasive margin; and the presence or absence of a residual adenomatous component and adverse outcome were examined by univariate and multivariate logistic regression analyses. Lymph node metastases were found in 2 patients, local recurrence in 4, and distant metastases in 2. Univariate logistic regression analysis showed that unfavorable histology at the invasive margin was significantly associated with lymph node metastasis or local recurrence (P = 0.0373), whereas the association of lymphatic invasion and vascular (lymphatic or venous) invasion with lymph node metastasis or local recurrence had marginal significance (P = 0.0785; P = 0.0990). Multivariate logistic regression analysis, with unfavorable histology at the invasive margin and lymphatic invasion as independent variables, showed that unfavorable histology alone had significance (P = 0.0373) in predicting adverse outcome. Widely accepted criteria such as massive submucosal invasion, positive vascular invasion, and poorly differentiated histology, were less useful in predicting adverse outcome. These results suggest that unfavorable histology at the invasive margin is a useful risk factor for predicting lymph node metastasis or local recurrence in patients with malignant colorectal polyps. Received: March 23, 1999 / Accepted: August 27, 1999     

New indication for endoscopic treatment of colorectal carcinoma with submucosal invasion

BACKGROUND AND AIMS: Although an increasing number of early colorectal cancers (CRC) have been curatively treated by endoscopy, there have been no definitive criteria to decide the effectiveness of such therapy. We retrospectively analyzed clinicopathological factors to establish criteria for curative endoscopic treatment of early CRC. METHODS: First, risk factors of lymph node metastasis were analyzed in 171 patients who received surgery with postoperative histology of CRC submucosal invasion. The resultant new criteria were evaluated in another 60 patients who experienced endoscopic resection of CRC and surgery according to the current criteria most often used in Japan. RESULTS: In the first substudy, lymph node metastasis was present in 18 of 171 patients (10.5%). Lymphatic permeation, sprouting and infiltrative growth of cancer cells were identified as histological factors significantly related to lymph node metastasis, and observed in much higher rates when the depth of submucosal invasion was beyond 1,500 micron. The minimum depth with positive lymph nodes was 1,075 micron. In the second group of 60 patients, lymph node metastasis was recorded in none of nine patients who met our new criteria of complete endoscopic treatment: submucosal invasion below 1,500 micron in depth, and no lymphatic permeation, sprouting or infiltrative growth pattern on tumor histology. Lymph node metastasis was positive in three of the other cases who did not meet our new criteria. CONCLUSIONS: The present study showed that endoscopic treatment of early CRC may be considered complete when submucosal invasion beyond 1,500 micron, lymphatic permeation, sprouting, and infiltrating growth are all denied.     

Epstein–Barr virus positivity among surgically resected intramucosal gastric cancer

Epstein–Barr virus‐associated gastric cancer (EBV‐GC) accounts for approximately 8% of gastric cancers. However, little is known regarding intramucosal EBV‐GC. The present study aimed to evaluate endoscopic and clinicopathological characteristics of intramucosal EBV‐GC. Pathological data of 172 patients with 173 intramucosal gastric cancers who received gastrectomy with lymph node dissection were obtained for review. EBV‐encoded small RNA in situ hybridization (EBER‐ISH) was carried out using a tissue microarray block. Eight intramucosal early gastric cancers (4.6%) were EBER‐ISH positive in which no cases had any lymph node metastasis. Macroscopic types were either depressed or flat, dominant histology was mixed type of moderate and poorly differentiated adenocarcinoma. In detail, histological features of “lace pattern” or “lymphocyte infiltration into the stroma or cancer nests” were observed.     

Risk factors of lymph node metastasis in T1 esophageal squamous cell carcinoma

Background and Aim: To perform endoscopic mucosal resection (EMR) for T1 esophageal cancer, it is essential to estimate the lymph node status exactly. In order to evaluate the feasibility of EMR for esophageal cancers, we evaluated the clinicopathological features of T1 esophageal squamous carcinomas with an emphasis on the risk factors and distribution patterns of lymph node metastasis. Methods: From 1994 to 2006, a total of 200 patients with T1 esophageal carcinoma were treated surgically in our institution. Among them, clinicopathological features were evaluated for 197 consecutive patients with T1 squamous cell carcinoma. Results: The frequency of lymph node involvement was 6.25% (4/64) in mucosal cancers and 29.3% (39/133) in submucosal cancers (P < 0.001). In patients with M1 (n = 32) and M2 (n = 14) cancers, no lymph node metastasis was found. In multivariate analysis, size larger than 20 mm, endoscopically non‐flat type, and endo‐lymphatic invasion were significant independent risk factors for lymph node metastasis. The differentiation of tumor cell was not a risk factor for lymph node metastasis. Conclusions: We suggest that EMR may be attempted for flat superficial squamous esophageal cancers smaller than 20 mm. After EMR, careful histological examination is mandatory.     

Assessment of vascular invasion in gastric cancer: A comparative study

AIM: To evaluate and compare detection of lymphatic and blood vessel invasion (LVI and BVI) by hematox-ylin-eosin (HE) and immunohistochemistry (IHC) in gastric cancer specimens, and to correlate with lymph node status. METHODS: IHC using D2-40 (a lymphatic endothelial marker) and CD34 (a pan-endothelial marker) was performed to study LVI and BVI in surgical specimens froma consecutive series of 95 primary gastric cancer cases. The results of the IHC study were compared with the detection by HE using McNemar test and kappa index. The morphologic features of the tumors and the presence of LVI and BVI were related to the presence of lymph node metastasis. A χ2 test was performed to obtain associations between LVI and BVI and other prognostic factors for gastric cancer. RESULTS: The detection rate of LVI was considerably higher than that of BVI. The IHC study identified eight false-positive cases and 13 false-negative cases for LVI, and 24 false-positive cases and 10 false-negative cases for BVI. The average Kappa value determined was moderate for LVI (k=0.50) and low for BVI (k=0.20). Both LVI and BVI were statistically associated with the presence of lymph node metastasis (HE: P=0.001, P=0.013, and IHC: P=0.001, P=0.019). The mor-phologic features associated with LVI were location of the tumor in the distal third of the stomach (P=0.039), Borrmann’s macroscopic type (P=0.001), organ inva-sion (P=0.03) and the depth of tumor invasion (P=0.001). The presence of BVI was related only to the depth of tumor invasion (P=0.003). CONCLUSION: The immunohistochemical identification of lymphatic and blood vessels is useful for increasing the accuracy of the diagnosis of vessel invasion and for predicting lymph node metastasis.