Risk Factors for Occult Lymph Node Metastasis of Colorectal Cancer Invading the Submucosa and Indications for Endoscopic Mucosal Resection

Purpose Although risk factors for histologically overt lymph node metastasis in patients with early-stage colorectal cancer have been clarified, the risk factors for occult lymph node metastasis are not clear. This study was designed to clarify risk factors for lymph node metastasis, including occult metastasis, in patients with colorectal cancer invading the submucosa and to determine the criteria for endoscopic resection of early colorectal cancer. Methods The risk factors for lymph node metastasis, including occult metastasis, were analyzed in 86 cases of surgically resected colorectal cancer invading the submucosa. The lymph nodes were assessed by immunohistochemistry with cytokeratin antibody CAM5.2. Results The frequencies of overt and occult metastasis to the lymph nodes were 13 percent (11/86) and 13 percent (10/75), respectively. Multivariate analysis showed vascular invasion (P = 0.001) and tumor budding (P = 0.003) to be independent risk factors for lymph node metastasis, including occult metastasis. For tumors with submucosal invasion ≤1,000 μm, no lymph node metastasis was found. The frequencies of lymph node metastasis for tumors with submucosal invasion of 1,000 to 2,000 μm and >2,000 μm were 21 and 37 percent, respectively. In considering combinations of risk factors, there was no lymph node metastasis in tumors having neither vascular invasion nor tumor budding and submucosal invasion of ≤3,000 μm. Conclusions Vascular invasion, tumor budding, and the degree of submucosal invasion were significant risk factors for lymph node metastasis, including occult metastasis. These three factors can be used in combination to identify patients requiring additional surgery after endoscopic resection. Supported in part by a Grant-in-Aid for Scientific Research (no. 15390401) from the Japanese Ministry of Education, Science, and Culture. Presented at the Congress of Japan Surgery Society, Tokyo, Japan, March 29 to 31, 2006. Reprints are not available.     

MID‐TERM PROGNOSIS AFTER ENDOSCOPIC RESECTION FOR SUBMUCOSAL COLORECTAL CARCINOMA: SUMMARY OF A MULTICENTER QUESTIONNAIRE SURVEY CONDUCTED BY THE COLORECTAL ENDOSCOPIC RESECTION STANDARDIZATION IMPLEMENTATION WORKING GROUP IN JAPANESE SOCIETY FOR CANCER OF THE COLON AND RECTUM

We carried out a retrospective questionnaire survey of 792 submucosal colorectal carcinoma (CRC) cases from 15 institutions affiliated with the Colorectal Endoscopic Resection Standardization Implementation Working Group in Japanese Society for Cancer of the Colon and Rectum. In these cases, endoscopic resection (ER) and surveillance was carried out without additional surgical resection. Local recurrence or metastasis was observed in 18 cases. Local submucosal recurrence was observed in 11 cases, and metastatic recurrence was observed in 13 cases. Among the 15 cases in which the depth of submucosal invasion was measured, two cases showed depth less than 1000 µm, which has other risk factors for metastasis. Metastatic recurrence was observed in the lung, liver, lymph node, bone, adrenal glands, and the brain; in some cases, metastatic recurrence was observed in multiple organs. Death due to primary disease was observed in six cases. The average interval between ER and recurrence was 19.7 ± 9.2 months. In 16 cases, recurrence was observed within 3 years after ER. Thus, validity of ER without additional surgical resection for cases with the conditions that the depth of submucosal invasion is less than 1000 µm and the histological grade is well or moderately differentiated adenocarcinoma with no lymphatic and venous involvement was proven.     

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.     

Novel risk factors for lymph node metastasis in early invasive colorectal cancer: a multi-institution pathology review

Background

Novel risk factors for lymph node metastasis (LNM) in T1 colorectal cancer (CRC) have been recently proposed, but most have not been implemented because of the lack of validation. Here we determined the value of poorly differentiated clusters (PDCs) in a multi-institutional cohort of T1 CRC cases.

Methods

A pathology review involving 30 institutions was conducted for 3556 T1 CRCs. PDC was defined as malignant clusters comprising ≥5 cells and lacking a glandular formation. The ability to identify LNM risk was compared using Akaike’s information criterion (AIC).

Results

PDC was observed in 1401 tumors (39.4 %), including 94 (17.8 %) with <1000 µm submucosal invasion and 1307 (43.2 %) with ≥1000 µm submucosal invasion (P < 0.0001). The incidence of LNM was higher in PDC-positive tumors (17.4 %) than in PDC-negative tumors (6.9 %; P < 0.0001), and PDCs had an adverse impact on LNM irrespective of the degree of submucosal invasion. Grade 3, vascular invasion, budding, and submucosal invasion depth were also significant factors (all, P < 0.0001). AIC of risk factor to identify LNM risk was most favorable for vascular invasion (2273.4), followed by PDC (2357.4); submucosal invasion depth (2429.1) was the most unfavorable. Interinstitutional judgment disparities were smaller in PDC (kappa, 0.51) than vascular invasion (0.33) or tumor grade (0.48).

Conclusions

PDC is a promising new parameter with good ability to identify LNM risk. Use of its appropriate judgment criteria will enable us determine whether an observational policy can be safely applied following local tumor excision in T1 CRC cases.     

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.     

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.     

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.     

Endoscopic treatment of submucosal invasive colorectal carcinoma with special reference to risk factors for lymph node metastasis

A clinicopathological analysis of the risk factors for lymph node metastasis was performed in 177 patients with submucosal invasive colorectal carcinoma (CRC). The submucosal deepest invasive portion was histologically subclassified as well (W), moderately (M), or poorly (Por) differentiated. M type was further subdivided into moderately-well (Mw) and moderatelypoorly (Mp) differentiated. The pattern of tumor growth was classified as polypoid growth (PG) and non-polypoid growth (NPG). Lymph node metastasis was detected in 21 (12%) of the 177 patients. Macroscopically, type IIc and IIa+IIc lesions showed a significantly higher incidence of lymph node metastasis (44% and 30%) than type IIa and I (4% and 8%). Regarding the histologic subclassification, Por and Mp lesions showed a significantly higher incidence of lymph node metastasis (67% and 37%) than W and Mw lesions (4% and 14%). NPG tumors showed a significantly higher incidence of lymph node metastasis (29%) than PG tumors (7%). The depth of submucosal invastion and lymphatic invasion (ly) were also significantly correlated with incidence of lymph node metastasis (submucosal scanty (sm-s) invasion 4%, massive invasion 20%; ly(+) 23%, ly(?) 5%). None of the lesions with both sm-s invasion and of W or Mw type showed lymph node metastasis. These results indicate that submucosal invasive CRC with both sm-s invasion and of W or Mw type, which shows no ly, is the appropriate indication for endoscopic curative treatment.     

MUC-1 expression as a predictor of the curative endoscopic treatment of submucosally invasive colorectal carcinoma

PURPOSE: This study was undertaken to clarify the clinical significance of MUC-1 expression in the endoscopic treatment of colorectal carcinoma with submucosal invasion. METHODS: One hundred eighty-four colorectal carcinomas with submucosal invasion were examined. The depth of submucosal invasion was classified as scanty or massive. The histologic subclassfication at the deepest invasive portion was defined as well-differentiated, moderately well-differentiated, moderately to poorly differentiated, poorly differentiated, or mucinous adenocarcinoma. MUC-1 expression was examined immunohistochemically at the deepest invasive portion. In addition, the Ki67 labeling index was also examined immunohistochemically. RESULTS: Lymph node metastases were detected in 28 (15.2 percent) of 184 lesions. Lesions with both scanty submucosal invasion and well-differentiated or moderately well-differentiated adenocarcinomas had no lymph node metastases. MUC-1 expression was detected in 88 (47.8 percent) of 184 lesions and correlated significantly with the presence of lymph node metastases. The Ki67 labeling index also correlated significantly with lymph node metastases. Furthermore, lesions with both MUC-1-negative and low Ki67 labeling index showed no lymph node metastases, even in lesions with massive submucosal invasion. Multivariate analysis indicated that MUC-1 expression was one of the most important risk factors for lymph node metastases and histologic grade among the clinicopathologic factors usually examined. CONCLUSION: MUC-1 expression is one of the accurate predictors of the presence of lymph node metastases among the clinicopathologic factors commonly used. Combined analysis of MUC-1 expression and Ki67 labeling index may be a useful indicator of lymph node metastases and may broaden the indications for the curative endoscopic treatment of carcinoma with massive submucosal invasion.     

Recurrent colorectal cancer after endoscopic resection when additional surgery was recommended

AIM: To evaluate the type of recurrence after endoscopic resection in colorectal cancer patients and whether rescue was possible by salvage operation.METHODS: Among 4972 patients who underwent surgical resection at our institution for primary or recurrent colorectal cancers from January 2005 to February 2015, we experienced eight recurrent colorectal cancers after endoscopic resection when additional surgical resection was recommended.RESULTS: The recurrence patterns were: intramural local recurrence(five cases), regional lymph node recurrence(three cases), and associated with simultaneous distant metastasis(three cases). Among five cases with lymphatic invasion observed histologically in endoscopic resected specimens, four cases recurred with lymph node metastasis or distant metastasis. All cases were treated laparoscopically and curative surgery was achieved in six cases. Among four cases located in the rectum, three cases achieved preservation of the anus. Postoperative complications occurred in two cases(enteritis).CONCLUSION: For high-risk submucosal invasive colorectal cancers after endoscopic resection, additional surgical resection with lymphadenectomy is recommended, particularly in cases with lymphovascular invasion.     

The risk of lymph node metastasis in T1 colorectal carcinoma

BACKGROUND/AIMS: The purpose of this study was to evaluate the risk of lymph node metastasis in patients with T1 colorectal carcinoma based on a uniform histopathology system, and to accomplish guidelines for additional surgery for endoscopically or locally removed T1 colorectal carcinoma. METHODOLOGY: A review was performed of 301 patients who underwent curative resection for T1 colorectal carcinoma between January 1970 and March 2001. The following clinicopathologic variables were evaluated using univariate and multivariate analysis: sex, age, location, size of tumor, macroscopic appearance, depth of submucosal invasion, lymphovascular invasion, and histologic grade. Lesions were subdivided according to the depth of submucosal invasion: sm1, submucosal invasion up to 500 microm from the muscularis mucosa; sm2, submucosal invasion between 500 and 1000 microm; sm3, submucosal invasion beyond 1000 microm. RESULTS: The overall lymph node metastasis rate was 6.3 per cent (19 of 301). Depth of submucosal invasion (sm3) and presence of lymphovascular invasion were significant risk factors for lymph node metastasis both univariately and multivariately. CONCLUSIONS: The findings of the current study demonstrated that significant risk factors for lymph node metastasis were level of submucosal invasion (sm3) and the presence of lymphovascular invasion. Surgery is indicated for patients with adverse factors.     

Size does not determine the grade of malignancy of early invasive colorectal cancer

AIM： To clarify the clinicopathological characteristics of small and large early invasive colorectal cancers （EI-CRCs）, and to determine whether malignancy grade depends on size. METHODS： A total of 583 consecutive EI-CRCs treated by endoscopic mucosal resection or surgery at the National Cancer Center Hospital between 1980 and 2004 were enrolled in this study. Lesions were classified into two groups based on size： small （≤10 ram） and large （〉10 ram）. Clinicopathological features, incidence of lymph node metastasis （LNM） and risk factors for LNM, such as depth of invasion, lymphovascular invasion （LVI） and poorly differentiated adenocarcinoma （PDA） were analyzed in all resected specimens. RESULTS： There were 120 （21%） small and 463 （79%） large lesions. Histopathological analysis of the small lesion group revealed submucosal deep cancer （sin： 1〉1000 μm） in 90 （75%） cases, LVI in 26 （22%） cases, and PDA in 12 （10%） cases. Similarly, the large lesion group exhibited submucosal deep cancer in 380 （82%） cases, LVI in 125 （27%） cases, and PDA in 79 （17%） cases. The rate of LNM was 11.2% and 12.1% in the small and large lesion groups, respectively.CONCLUSION： Small EI-CRC demonstrated the same aggressiveness and malignant potential as large cancer.     

Lymph node metastasis in early gastric cancer: a clinicopathological analysis

BACKGROUND/AIMS: Endoscopic mucosal resection and laparoscopic wedge resection have become more common in the treatment of early gastric cancer. However, lymph node metastasis is a major poor prognostic factor influencing tumor recurrence and survival. To predict the risk of lymph node metastasis in early gastric cancer, the authors conducted a study to investigate the clinicopathologic characteristics of early gastric cancer with lymph node metastasis. METHODOLOGY: From 1982 to 1998, 181 patients of early gastric cancer underwent primary surgery and were included in the study. Patient data was postoperatively reviewed regarding age, gender, tumor size, depth of invasion, histologic differentiation, macroscopic classification and anatomic level of lymph node metastasis. The chi 2 test or Student's t test was used for statistical analysis. Logistic regression analysis was used to evaluate the independent risk factors for lymph node metastasis. RESULTS: Lymph node metastasis was observed in 19 cases (11%). Early gastric cancer with size larger than 4 cm (P < 0.05), with submucosal invasion (P < 0.01), and with poor differentiation (P < 0.05) was associated with higher risk of lymph node metastasis. The macroscopic classification had no predictive value. Multivariate analysis showed that submucosal invasion correlated best with lymph node spread (OR 10.25, 95% CI: 2.10-49.96), followed by tumor size larger than 4 cm (OR 4.99, 95% CI: 1.46-17.05), and poorly differentiated histological subtype (OR 3.31, 95% CI: 1.16-9.45). CONCLUSIONS: Poor differentiation, submucosal invasion and large tumor size were independent risk factors for lymph node metastasis in early gastric cancer. Macroscopic classification was not correlated with lymph node metastasis.     

Actual number of tumor budding as a new tool for the individualization of treatment of T1 colorectal carcinomas

BACKGROUND AND AIM: Treatment of T1 colorectal carcinomas, either local excision including endoscopic polypectomy or radical surgery, has always been problematic in everyday practice. Although previous studies have revealed that tumor budding at the invasive margin can be a marker for the malignant potential of T1 colorectal carcinomas, the evaluation of tumor budding has not been standardized as yet. In the present study, we attempted to apply the actual number of tumor budding units for the individualization of treatment in T1 colorectal carcinomas. METHODS: In 76 T1 colorectal carcinomas, associations between lymph node metastasis and clinicopathological parameters were examined statistically. A mathematical formula for predicting the risk of lymph node metastasis was constructed and decision analysis was attempted to determine individually the indication for additional surgery after endoscopic mucosal resection of T1 colorectal carcinomas. RESULTS: Of the clinicopathological parameters examined, multivariate analysis showed that the actual number of tumor budding units alone was significantly associated with lymph node metastasis. The probability of lymph node metastasis was calculated as Z = 0.07 x (budding counts) - 3.726, probability = 1/1 + e(-Z). The more the budding counts, the higher the probability of lymph node metastasis. This formula was able to accurately predict lymph node metastasis in successive cases. The actual number of tumor budding units can be applied to decision analysis in determining an indication for additional surgery after endoscopic mucosal resection of T1 colorectal carcinomas. CONCLUSIONS: The actual number of tumor budding units may be useful in the decision making for patient-oriented treatment of T1 colorectal carcinomas.     

Immunohistochemical molecular markers as predictors of curability of endoscopically resected submucosal colorectal cancer

AIM： To clarify the usefulness of immunohistochemical molecular markers in predicting lymph node metastasis of submucosal colorectal cancer.
METHODS： We examined microvessel density, lymphatic vessel density, the Ki-67 labeling index, expression of MUC1 and Matrix metalloproteinase-7 （MMP-7） in tumor cells, and expression of cathepsin D in stromal cells at the invasive front by immunostaining of samples resected from 214 patients with submucosal colorectal cancer. Pathologic features were assessed on hematoxylin-eosinstained samples. We evaluated the relations between clinicopathologic/immunohistochemical features and lymph node metastasis.
RESULTS： Lesions of the superficial type, with an unfavorable histologic grade, budding, lymphatic involvement, high microvessel density （≥ 40）, high lymphatic vessel density （≥9）, high Ki-67 labeling index （≥ 42）, and positivity of MUC1, cathepsin D, and MMP-7 showed a significantly high incidence of lymph node metastasis. Multivariate analysis revealed that high microvessel density, unfavorable histologic grade, cathepsin D positivity, high lymphatic vessel density, superficial type, budding, and MUC1 positivity were independent risk factors for lymph node metastasis.A combined examination with four independent immunohistochemical markers （microvessel density, cathepsin D, lymphatic vessel density, and MUC1） revealed that all lesions that were negative for all markers or positive for only one marker were negative for lymph node metastasis.
CONCLUSION： Analysis of a combination of immuno- histochemical molecular markers in endoscopically resected specimens of submucosal colorectal cancer allows prediction of curability regardless of the pathologic features visible of hematoxylin-eosin-stained sections.     

Additional colectomy after colonoscopic polypectomy for T1 colon cancer: a fine balance between oncologic benefit and operative risk

Purpose

The treatment of early-stage colorectal cancers removed endoscopically depends on histopathologic findings. This study aimed to assess the benefit–risk balance for patients who underwent additional surgery after endoscopic resection of a T1 carcinoma with unfavorable histology.

Methods

From 2000 to 2010, 64 consecutive patients were included in this retrospective study. Specimens resected after endoscopic polypectomy showed at least one of the following unfavorable factors: no free margin, lymphovascular invasion, poorly differentiated grade, SM2–3 involvement (submucosal invasion greater than 300?μm from the muscularis mucosae), tumor budding, sessile morphology, and piecemeal resection. The main objective was to assess the benefit–risk balance of an oncological resection performed after the polypectomy. Oncological benefit was measured by the lymph node metastasis rate and the persistence of a residual adenocarcinoma on the specimen. The risk was measured by the occurrence of severe complications of grade III–IV or death. The associations between these end points and clinicopathologic variables were evaluated by univariate analysis and logistic regression.

Results

Five patients (7.8?%) had lymph node metastases and two (3.1?%) had residual carcinomas. Eight patients (12.5?%) had grade III–IV morbidity. There were no deaths. Oncological benefit was associated by logistic regression analysis with patients who presented multiple criteria (≥2) that led to surgery (p?=?0.031). The benefit–risk balance was favorable only for those patients.

Conclusions

Additional surgery is required for patients who present multiple adverse histological criteria. If only one criterion is selected, the indication should be discussed, especially for patients with multiple comorbidities.     

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     

Feasible endoscopic therapy for early gastric cancer

AIM: To analyze the relationship between lymph node metastasis and clinical pathology of early gastric cancer(EGC) in order to provide criteria for a feasible endoscopic therapy.METHODS: Clinical data of the 525 EGC patients who underwent surgical operations between January 2009 and March 2014 in the West China Hospital of Sichuan University were analyzed retrospectively. Clinical pathological features were compared between different EGC patients with or without lymph node metastasis, and investigated by univariate and multivariate analyses for possible relationships with lymph node metastasis.RESULTS: Of the 2913 patients who underwent gastrectomy with lymph node dissection, 529 cases were pathologically proven to be EGC and 525 cases were enrolled in this study, excluding 4 cases of gastric stump carcinoma. Among 233 patients with mucosal carcinoma, 43(18.5%) had lymph node metastasis. Among 292 patients with submucosal carcinoma, 118(40.4%) had lymph nodemetastasis. Univariate analysis showed that gender, tumor size, invasion depth, differentiation type and lymphatic involvement correlated with a high risk of lymph node metastasis. Multivariate analysis revealed that gender(OR = 1.649, 95%CI: 1.091-2.492, P = 0.018), tumor size(OR = 1.803, 95%CI: 1.201-2.706, P = 0.004), invasion depth(OR = 2.566, 95%CI: 1.671-3.941, P = 0.000), histological differentiation(OR = 2.621, 95%CI: 1.624-4.230, P = 0.000) and lymphatic involvement(OR = 3.505, 95%CI: 1.590-7.725, P = 0.002) wereindependent risk factors for lymph node metastasis. Comprehensive analysis showed that lymph node metastasis was absent in patients with tumor that was limited to the mucosa, size ≤ 2 cm, differentiated and without lymphatic involvement.CONCLUSION: We propose an endoscopic therapy for EGC that is limited to the mucosa, size ≤ 2 cm, differentiated and without lymphatic involvement.     

Budding as a risk factor for lymph node metastasis in pT1 or pT2 well-differentiated colorectal adenocarcinoma

PURPOSE: Lymph node metastasis is an important indicator of tumor stage and prognosis in pT1 and pT2 colorectal adenocarcinomas. Lymphovascular invasion is an established risk factor of lymph node metastasis, whereas budding at the invasive front of tumors is also reported to correlate with lymph node metastasis. We examined whether the coexistence of lymphovascular invasion and budding provides any better information than lymphovascular invasion alone in the prediction of lymph node metastasis of pT1 or pT2 well-differentiated colorectal adenocarcinomas. METHODS: Surgically resected specimens of 101 pT1 or pT2 well-differentiated colorectal adenocarcinomas were studied. Using sections stained with hematoxylin-eosin, we examined lymphovascular invasion and budding according to Morodomis definition. RESULTS: Lymphovascular invasion was present in 39 lesions (38 percent), whereas budding was found in 42 lesions (41 percent). Budding was more frequently detected in pT2 tumors than in pT1 tumors. The presence of budding significantly correlated with lymphovascular invasion. Sensitivity, specificity, positive predictive value, and negative predictive value of lymphovascular invasion alone for lymph node metastasis were 79, 76, 34, and 96 percent, respectively, whereas those of the combination of lymphovascular invasion and budding (either lymphovascular invasion or budding) were 93, 52, 24, and 98 percent, respectively. CONCLUSION: Because the risk of lymph node metastasis in pT1 or pT2 well-differentiated colorectal adenocarcinomas having neither lymph node metastasis nor budding is very low, budding in combination with lymphovascular invasion seems to be a simple and inexpensive pathologic marker in predicting lymph node metastasis. Therefore, the presence or absence of budding should be examined in the routine pathologic diagnosis of pT1 or pT2 well-differentiated colorectal adenocarcinomas.     

Predictive factors for lymph node metastasis in t1 stage colorectal Carcinomas

Purpose Selective endoscopie resection may cure early colorectal cancer (Tl), but the management is controversial. There is concern about the small risk of lymph node metastasis, which will not be treated by endoscopie resection alone. The authors sought predictive markers of lymph node metastasis to assist patient management. METHODS: The authors retrospectively analyzed consecutive cases of Tl stage colorectal cancer resected using endoscopie resection or bowel surgery over the period 1979 to 2000. The risk of lymph node metastasis was analyzed using logistic regression model for the markers selected by univariate analysis: the type of initial treatment, depth of submucosal invasion, lymphatic channel invasion, differentiation of histology, and invasive front histology. RESULTS: Two hundred seventy-eight patients were available for study. Twenty-one had lymph node metastasis. Depth of submucosal invasion (2 2,000 yum) and lymphatic channel invasion significantly predicted risk of lymph node metastasis in multivariate analysis. When these two factors were adopted for the prediction of lymph node metastasis, sensitivity, specificity, positive predictive value, and negative predictive value were 100, 55.6, 15.6, and 100 percent, respectively. CONCLUSIONS: Depth of submucosal invasion and lymphatic channel invasion were accurate predictive factors for lymph node metastasis. These two factors could be used in selecting appropriate cases for surgery after endoscopie resection. Poster presentation at meeting of the American Society of Colon and Rectal Surgeons, San Diego, California, June 2 to 7, 2001.