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.     

Minute Depressed-Type Submucosal Invasive Cancer–5 mm in Diameter with Intermediate Lymph-Node Metastasis: Report of a Case

We report a rare case of colon cancer in which a depressed-type tumor only 5 mm in diameter invaded the submucosal layer and produced intermediate lymph node metastasis. A 47-year-old male received a total colonoscopy for a depressed-type lesion with marginal elevation in the sigmoid colon. The lesion measured 5 mm in diameter. On chromoendoscopic examination, the depression was clearly demarcated and an irregular pit pattern was identified in the demarcated area by magnification suggesting invasion of the submucosal layer requiring surgery. Laparoscopic-assisted sigmoidectomy was performed and the resected specimen demonstrated well-differentiated adenocarcinoma. The depth of invasion was only 900 μm. There was no lymphovascular invasion although not only paracolic, but also intermediate lymph node metastasis was detected. There have been some reports about small depressed-type colorectal cancer invading the submucosal layer; however, intermediate LN metastasis is very rare in submucosal colorectal cancer. In this case, there were two noteworthy points: 1) despite the small size, submucosal invasion could be estimated preoperatively, therefore, a successful lymph node dissection was performed by laparoscopic surgery; and 2) although this depressed-type cancer invaded the submucosal layer only 900 μm and there was no lymphovascular invasion, intermediate lymph node metastasis was detected. Reprints are not available.     

Lymph node metastasis in early gastric cancer with submucosal invasion： Feasibility of minimally invasive surgery

AIM:To explore the feasibility of performing minimally invasive surgery(MIS) on subsets of submucosal gastric cancers that are unlikely to have regional lymph node metastasis.METHOPS:A total of 105 patients underwent radical gastrectomy with lymph node dissection for submucosal gastric cancer at our hospital from January 1995 to December 1995,Besides investigating many clinicopathological features such as tumor size,gross appearance,and differentiation,we measured the depth of invasion into submucosa minutely and analyzed the clinicopathologic features of these patients regarding lymph node metastasis.RESULTS:the rate of lymph node metastasis in cases where the depth of invasion was<500μm,500-200μm,or>2000μm was 9% (2/23),19%(7/36),and 33%(15/46),respectively(P<0.05).In univariate analysis,no significant correlation was found between lymph node metastasis and clinicopathological characteristics such as age,sex,tumor location,gross appearance,tumor differentiation,Lauren‘s classification,and lymphatic invasion,In multivariate analysis,tumor size(>4cm vs≤2cm,odds ratio=4。80,P=0.04)and depth of invasion(>2000μm vs ≤500μm,odds ratio=6.81,P=0.02)were significantly correlated with lymph node metastasis,Combining the depth and size in cases where the depth of invasion was less than 500μm,we found that lymph node metastasis occurred where the tumor size was greater than 4 cm.In cases where the tumor size was less than 2 cm,lymph node metastasis was found only where the depth of tumor invasion was more than 2000μm.CONCLUSION:MIS can be applied to submucosal gastric cancer that is less than 2 cm in size and 500μm in depth.     

Clinicopathological study for reevaluation of the depth of submucosal invasion and histological classification of early colorectal cancer]

The following studies were undertaken using specimens of submucosal invasive colorectal cancer surgically or endoscopically resected from 104 patients: 1) measurement of the depth of submucosal invasion; 2-a) histological reevaluation of colon sm cancer by scoring of the degree of histological differentiation using a modified Gleason's grading system proposed for prostatic cancer; and 2-b) immunohistological evaluation of E-cadherin, a cell adhesion factor. Lymphatic node metastasis occurred in no case with the depth of submucosal invasion of less than 1,000 microns. In the histological reevaluation, high incidence of lymphatic metastasis was noted in the high-score group, while lymphatic node metastasis was not seen in any patients in the low-score group. Immunohistological evaluation of E-cadherin showed that the destructive pattern is correlated with lymphatic metastasis, suggesting that weakening of the cell adhesive factor was related to a decline in the degree of differentiation of the tumor. Findings obtained in the present study suggest that endoscopic therapy is indicated for colon cancer measuring less than 1,000 microns and that its indication can be expanded to colorectal cancer with the depth of submucosal invasion of more than 1,000 microns by adding histological reevaluation.     

Significance of lymphatic invasion and cancer invasion-related proteins on lymph node metastasis in gastric cancer

Background and Aims:  Cancer invasion and metastasis are critical events for patient prognosis; however, the most important step in the whole process of lymph node (LN) metastasis in gastric cancer remains obscure. In this study, the significance of cancer cell behaviors, such as cell detachment, stromal invasion and lymphatic invasion on regional LN metastasis in gastric cancer was investigated by comprehensive immunohistochemistry.
Methods:  A total of 210 cases with gastric cancer were selected. These consisted of 105 cases with regional LN metastasis (LN[+] group) and 105 cases without LN metastasis (LN[–] group). Both groups exhibited the same depth of invasion. Cancer tissues were subjected to immunohistochemistry with antibodies against claudin-3, claudin-4, β-catenin, matrix metalloproteinase (MMP)-1, and MMP-2, as well as endothelial markers of lymphatic vessel endothelial hyaluronan receptor-1 and von Willebrand factor for the objective discrimination between lymphatics and blood vessels. The expression of each protein as well as the histopathological parameters were compared between LN(+) and LN(−) groups.
Results:  Along with lymphatic invasion by cancer cells and gross tumor size, MMP-1 expression in cancer cells at the invasive front of the primary tumor was a significant, independent predictor of LN metastasis. The expression of claudins and β-catenin was associated with the histopathological type of cancer, but not with LN status.
Conclusion:  Among the cancer invasion-related proteins examined, MMP-1 plays a vital role in LN metastasis of gastric cancer. Tumor size, lymphatic invasion and MMP-1 expression level at the invasive front were the predictive factors of LN metastasis of gastric cancer.     

Evaluation of clinical significance of 18F-fluorodeoxyglucose positron emission tomography in superficial squamous cell carcinomas of the thoracic esophagus

SUMMARY.  ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is used for pre-treatment staging and evaluation of response to pre-operative therapy in advanced thoracic esophageal cancers. To evaluate the clinical significance of PET diagnosis of superficial thoracic esophageal cancers, FDG-PET was conducted preoperatively in 41 patients with such cancers without pre-operative therapy. We compared the PET diagnosis with clinicopathological findings with respect to both the primary tumor and lymph node (LN) metastasis. Of the 41 superficial thoracic esophageal cancers, 21 (51.2%) were PET positive for primary tumors. Although tumor length and histological type did not correlate with FDG uptake by primary tumors, non-flat (elevated or depressed) tumors showed significantly stronger FDG uptake than flat ones. Of 28 tumors infiltrating the deep submucosal layer, 19 (67.9%) were PET positive, while only two (15.4%) of 13 tumors infiltrating only the mucosa or shallow submucosal layer were PET positive. M anova identified FDG uptake as the only independent risk factor for deep submucosal invasion (odds ratio, 7.407; P  = 0.0279). In 13 patients with pathological LN metastasis, although no LN metastasis was detected by FDG-PET, FDG uptake by the primary tumors was the only risk factor for LN metastasis ( P  = 0.0318). PET-negative tumors tended to reflect longer disease-free survival than PET-positive tumors, although this was not significant. FDG-PET is useful for detecting tumors infiltrating the middle or deep submucosal layer (sm2/sm3), and for predicting LN metastasis in patients with superficial thoracic esophageal cancers. FDG-PET is helpful for decision-making regarding treatment of such patients.     

MIXED INTESTINAL‐ AND DIFFUSE‐TYPE HISTOLOGY IS A RISK FACTOR FOR LYMPH NODE METASTASIS OF SUBMUCOSAL INVASIVE GASTRIC CANCER

Background: Endoscopic submucosal dissection is expected to increase the number of node‐negative submucosal invasive gastric cancers, particularly differentiated‐type adenocarcinomas that can be treated conservatively. Methods: Two hundred and seven consecutive surgically treated cases of differentiated‐type early gastric cancer with submucosal invasion were analyzed clinicopathologically. Comparison was made between patients with node‐positive (n = 33) and node‐negative cancer (n = 174). Whole sections of surgical specimens were reviewed and reclassified as pure intestinal type or mixed type. The intramucosal and submucosal components were also described histologically, and the depth of invasion from the muscularis mucosae as well as the width of submucosal invasion was measured. Results: Twenty‐four of 33 (73%) node‐positive cases were of the mixed type, whereas 71 of 174 (41%) node‐negative cases were of the mixed type (P < 0.01). As for the intramucosal histology, the ratio of mixed‐type was also higher in the node‐positive group (58% vs 34%; P < 0.05). Other factors associated with lymph node metastasis were larger tumor size (P = 0.003), deeper submucosal invasion (P < 0.001) and wider submucosal extension (P = 0.004), and lymphatic permeation (P < 0.001). Multivariate analysis demonstrated that lymphatic permeation (P = 0.001, OR 4.76), and mixed‐type histology (OR 2.56) were independent risk factors. Conclusions: Histological heterogeneity is a risk factor for metastasis of submucosal invasive gastric cancer to lymph nodes. Heterogeneity of mucosal components is also a significant risk factor and thus a good predictor of lymph node metastasis, potentially useful in distinguishing patients ineligible for conservative therapy.     

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 Differences between Proximal and Distal pT3 Colon Cancer and the Clinical Significance of the Depth of Cancer Invasion beyond the Muscularis Propria

Background/Aims: To investigate differences in clinicopathological features between proximal and distal pT3 colon cancers and to determine whether the depth of the cancer invasion beyond the muscularis propria (DBM) serves as an objective indicator of the depth of tumor invasion in proximal colon cancer and in distal colon cancer. Methodology: A total of 207 patients who underwent surgery for proximal and distal pT3 colon cancer between 1996 and 2001 were included in the analysis. Results: No differences were noted between proximal and distal cancers in lymph node metastasis, distant metastasis, lymphatic/venous invasion, histological type and curability of surgical resection, although proximal cancer patients were significantly older. High-grade malignancy appeared to be more commonly noted in the proximal colon cancer cases but there was no significant difference in prognosis between proximal and distal cancer patients. Conclusions: Regarding the correlation between DBM and prognosis, there was a significant decrease in the 5-year survival rate in patients with proximal lesions of DBM 3000μm or more, and patients with distal lesions of DBM 5000μm or more. DBM is thus an objective indicator of depth of tumor invasion for both proximal and distal lesions, a prognostic factor and a guide to determining whether postoperative adjuvant chemotherapy is indicated for pT3 colon cancer cases.     

Prediction of the indication criteria for endoscopic resection of early gastric cancer

AIM: To find risk factors of lymph node metastasis(LNM) in early gastric cancer(EGC) and to find proper endoscopic therapy indication in EGC.METHODS: We retrospectively reviewed the 2270 patients who underwent curative operation for EGC from January 2001 to December 2008. EGC was defined as malignant lesions that do not invade beyond the submucosal layer of the stomach wall irrespective of presence of lymph node metastasis.RESULTS: Among 2270 enrolled patients, LNM was observed in 217(9%) patients. LNM in intramucosal(M) cancer and submucosal(SM) cancer was detectedin 3 8( 2. 8 %, 3 8 / 1 3 4 0) patients and 1 7 9(19%, 179/930) patients, respectively. In univariate analysis, the risk factors for LNM in EGC were size of tumor, Lauren classification, ulcer, lymphatic invasion, vascular invasion, and depth of invasion. However, in multivariate analysis, size of tumor, lymphatic invasion, vascular invasion, and depth of invasion were risk factors for LNM in EGC. Size of tumor, lymphatic invasion, vascular invasion, and depth of invasion were risk factors for LNM in cases of intramucosal cancer and submucosal cancer. In particular, there was no lymph node metastasis in cases of well differentiated early gastric cancer below 1 cm in size without ulcer regardless of lymphovascular invasion.CONCLUSION: Tumor size, perilymphatic-vascular invasion, and depth of invasion were risk factors for LNM in EGC. There was no LNM in EGC below 1 cmregardless risk factors.     

The oncologic benefit of high ligation of the inferior mesenteric artery in the surgical treatment of rectal or sigmoid colon cancer

PURPOSE: It remains controversial as to whether high ligation of the inferior mesenteric artery (IMA) should be performed during surgical treatment for sigmoid colon or rectal cancer. The purpose of this study is to attempt to clarify the extent of the oncologic benefit of high ligation of the IMA. MATERIALS AND METHODS: From January 1995 to July 2001, a total of 1,389 patients underwent high ligation of the IMA; 387 patients featured non-disseminated sigmoid colon cancer and 1,002 patients had rectal cancer. Pathology of the primary tumors, IMA nodes, and clinical outcome were reviewed. RESULTS: Forty-three patients (3.1%) revealed IMA node metastasis. Of these 43 patients, 29 (67.4%) featured tumor recurrences/metastases. After a minimum 5-year follow-up, 11 of these 43 patients (25.6%) were alive and disease free. Of these 43 patients, the 5-year disease-free survival rate for patients featuring sigmoid cancer was 50% and for patients with rectal cancer 13.8%. The beneficial rate of high ligation of the IMA for non-disseminated sigmoid colon cancer and rectal cancer was 0.8%, for non-disseminated sigmoid colon cancer 1.8%, and for non-disseminated rectal cancer, the rate was only 0.4%. The rates of IMA metastasis in patients with T stage tumors were 0% (pT1), 1.0% (pT2), 2.6% (pT3), and 4.3% (pT4). CONCLUSIONS: Although patients afflicted with IMA node metastasis revealed a rather high incidence of tumor recurrence/metastasis, 25.6% of these patients remained disease free following IMA node dissection after a minimum 5-year follow-up. We consider that IMA node dissection is more beneficial in patients with non-disseminated sigmoid pT4 tumor.     

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.     

Clinicopathologic features of early rectal carcinoma and indications for endoscopic treatment

PURPOSE: This study was undertaken to clarify the indications for endoscopic treatment. METHODS: Clinical and pathologic features of 191 lesions in 180 patients with early rectal carcinoma were examined, including 110 intramucosal carcinomas and 81 carcinomas with submucosal invasion (submucosal carcinomas). All lesions had been endoscopically or surgically resected at the National Cancer Center Hospital between 1976 and 1990. RESULTS: Metastasis to regional lymph nodes (LN metastasis) was seen in 0 percent (0/39) of intramucosal carcinomas and 9.2 percent (6/65) of submucosal carcinomas in the surgically treated patients. The incidence of LN metastasis was higher for lesions larger than 10 mm in diameter, for those showing massive submucosal invasion, and for moderately differentiated adenocarcinomas. LN metastases were associated significantly with lymphatic invasion. CONCLUSIONS: These results suggest that early rectal carcinomas should be resected surgically if they 1) show massive submucosal invasion, 2) are classified as moderately differentiated adenocarcinomas, and 3) are larger than 10 mm in diameter. In patients with both scanty submucosal invasion and features of well-differentiated adenocarcinoma or intramucosal carcinoma and if no other risk factors for LN metastasis are present, such as lymphatic invasion by the primary lesion, surveillance may suffice after endoscopic resection.     

Vascular endothelial growth factor-C (VEGF-C) is a more specific risk factor for lymph node metastasis than VEGF-D in submucosal colorectal cancer

BACKGROUND/AIMS: It is useful to decide whether lymphatic involvement or lymph node metastasis exists before polypectomy or operation in submucosal colorectal cancer. Whether vascular endothelial growth factor-C (VEGF-C) or VEGF-D could predict lymph node metastasis and lymphatic involvement is uncertain. METHODOLOGY: Expression of the VEGF-C and VEGF-D in human submucosal colorectal cancers was investigated in paraffin-embedded stepwise sections by means of immunohistochemistry, and the correlation between immunohistochemical expression pattern and clinicopathological features was also evaluated. RESULTS: The results showed that VEGF-C overexpression correlated with lymphatic involvement (P = 0.01) and lymph node metastasis (P = 0.02), but VEGF-D overexpression did not correlate significantly. In multivariate analysis lymphatic invasion was the predictive factor (P = 0.0129), but VEGF-C positivity was not predictive (P = 0.3437). CONCLUSIONS: These results may suggest that VEGF-C is a more specific risk factor for lymph node metastasis than VEGF-D in submucosal colorectal cancer.     

Computed tomography and magnetic resonance imaging evaluation of lymph node metastasis in early colorectal cancer

AIM: To assess the role of computed tomography(CT) and magnetic resonance imaging(MRI) and establish imaging criteria of lymph node metastasis in early colorectal cancer.METHODS: One hundred and sixty patients with early colorectal cancer were evaluated for tumor location, clinical history of polypectomy, depth of tumor invasion, and lymph node metastasis. Two radiologists assessed preoperative CT and/or MRI for the primary tumor site detectability, the presence or absence of regional lymph node, and the size of the largest lymph node. Demographic, imaging, and pathologic findings were compared between the two groups of patients based on pathologic lymph node metastasis and optimal size criterion was obtained.RESULTS: The locations of tumor were ascending, transverse, descending, sigmoid colon, and rectum. One hundred and sixty early colorectal cancers were classified into 3 groups based on the pathological depth of tumor invasion; mucosa, submucosa, and depth unavailable. A total of 20(12.5%) cancers with submucosal invasion showed lymph node metastasis. Lymph nodes were detected on CT or MRI in 53 patients. The detection rate and size of lymph nodes were significantly higher(P = 0.000, P = 0.044, respectively) in patients with pathologic nodal metastasis than in patients without nodal metastasis. Receiver operating curve analysis showed that a cut-off value of 4.1 mm is optimal with a sensitivity of 78.6% and specificity of 75%.CONCLUSION: The short diameter size criterion of≥ 4.1 mm for metastatic lymph nodes was optimal for nodal staging in early colorectal cancer.     

Lymph node metastasis as a significant prognostic factor in gastric cancer: a multiple logistic regression analysis

BACKGROUND: In Japan, the standard treatment policy for all potentially curable patients with gastric cancer is radical resection including extensive lymphadenectomy. This treatment strategy has been used for both early and advanced gastric cancers, and substantial increases in survival time have been reported. In advanced gastric cancer, lymphatic spread is reported to be one of the most relevant prognostic factors for gastric cancer resected for cure. The purpose of this study was to determine the factors affecting lymph node involvement and to establish guidelines for the extent of lymph node dissection most appropriate for the treatment of gastric cancer. METHODS: The clinicopathological features of 926 patients with gastric cancer were reviewed. Information on the clinicopathological features was obtained from the database of gastric cancer at the Department of Gastroenterological Surgery, Sendai National Hospital. Univariate and multivariate analyses of data for patients with gastric cancer tumors were performed to evaluate the prognostic significance of clinicopathological features. The independent risk factors influencing lymph node metastasis were determined by multiple logistic regression analysis. RESULTS: The following clinicopathologic factors were found to be correlated with prognosis of gastric cancer: (1) macroscopic type, (2) depth of invasion, (3) cancer-stromal relationship, (4) histological growth pattern, (5) lymph node involvement, (6) lymphatic invasion, (7) vascular invasion and (8) tumor site. However, a multivariate analysis revealed that macroscopic type, depth of invasion, lymph node involvement and tumor site are independent risk factors for the prognosis of gastric cancer patients. Among these factors, the prognosis of patients with gastric cancer was most strongly influenced by lymph node involvement (odds ratio, 4.632). According to a multiple logistic regression model, depth of cancer invasion and lymphatic invasion was significantly correlated with lymph node metastases. CONCLUSIONS: Lymph node involvement has the strongest influence on the prognosis of gastric cancer. Among the clinicopathological factors, depth of invasion and microscopically lymphatic invasion are important factors in predicting lymph node metastases. Thus, the ability to perform gastrectomy with dissection of lymph nodes is a basic requirement for gastric cancer surgeons.     

Invasive front of colorectal cancer： Dynamic interface of pro-/anti-tumor factors

Tumor-host interaction at the invasive front of colorectal cancer represents a critical interface encompassing a dynamic process of de-differentiation of colorectal carcinoma cells known as epithelial mesenchymal transition (EMT). EMT can be identified histologically by the presence of "tumor budding", a feature which can be highly specific for tumors showing an infiltrating tumor growth pattern. Importantly, tumor budding and tumor border configuration have generated considerable interest as additional prognostic factors and are also recognized as such by the International Union Against Cancer. Evidence seems to suggest that the presence of tumor budding or an infiltrating growth pattern is inversely correlated with the presence of immune and inflammatory responses at the invasive tumor front. In fact, several tumor-associated antigens such as CD3, CD4, CD8,CD20, Granzyme B, FOXP3 and other immunological or inflammatory cell types have been identified as potentially prognostic in patients with this disease. Evidence seems to suggest that the balance between pro-tumor(including budding and infiltrating growth pattern) and anti-tumor (immune response or certain inflammatory cell types) factors at the invasive front of colorectal cancer may be decisive in determining tumor progression and the clinical outcome of patients with colorectal cancer. On one hand, the infiltrating tumor border con-figuration and tumor budding promote progression and dissemination of tumor cells by penetrating the vascular and lymphatic vessels. On the other, the host attempts to fend off this attack by mounting an immune response to protect vascular and lymphatic channels from invasion by tumor buds. Whereas standard pathology reporting of breast and prostate cancer involves additional prognostic features, such as the BRE and Gleason scores, the ratio of pro- and anti-tumor factors could be a promising approach for the future development of a prognostic score for patients with colorectal cancer which could complement tumor node metastasis staging to improve the clinical management of patients with this disease.     

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     

Modes of spread in early ampullary cancer in terms of establishing proper indications for endoscopic papillectomy

Background: Endoscopic papillectomy for adenomas of the ampulla of Vater has been reported and is gaining acceptance as an alternative to surgery in the treatment of early ampullary cancer. However, whether endoscopic treatment is justified as a treatment of choice for early ampullary cancer remains controversial. The aim of the present study was to elucidate the possibility of endoscopic papillectomy as a treatment of early ampullary cancer from the review of pathology of cases treated by surgical resection. Patients and methods: Twenty‐three cases of early ampullary cancer (m—tumor limited to the mucosa of the ampulla 14; od—tumor that invades Oddi's sphincter, 9) treated by surgical resection from January 1984 to March 2003 were investigated as to the following: (i) macroscopic type, maximum size, and histological type of tumor; (ii) main location and extension of tumor; (iii) prevalence of extension into the lower bile duct or pancreatic duct, and relationship between ductal infiltration and macroscopic type, maximum size, main location, or depth of invasion of tumor; (iv) lymphatic permeation, vascular invasion, and lymph node metastasis; and (v) prognosis. Results: All cases were classified macroscopically as exposed‐tumor type or non‐exposed‐tumor type without ulceration. Extension into the lower bile duct or the pancreatic duct was observed in 43% of the cases. There was no correlation between ductal infiltration and macroscopic type, maximum tumor size, main tumor location, or tumor depth. No lymphatic permeation, vascular invasion, or lymph node metastasis were proven in cases with ampullary cancer confined to the mucosa. In the nine cases with involvement of Oddi's sphincter, lymphatic permeation and lymph node metastasis were observed in two cases and one case, respectively. Conclusion: Endoscopic treatment for early ampullary cancer confined to the mucosa without spread to the bile duct or pancreatic duct is justified as a treatment of choice if detailed histological examination of the resected specimen indicated no invasion beyond its margin.     

What types of colorectal cancer overexpress the MAGE protein?

BACKGROUND/AIMS: Tumor-specific antigens such as Melanoma-associated antigens could be attractive targets for immunotherapy. It will be a great help for cancer immunotherapy to distinguish what types of tumor expresses tumor-specific antigen. METHODOLOGY: We investigated the expression pattern of MAGE-A1 by immunohistochemical typing methods in human colorectal cancers obtained from consecutive patients undergoing surgical treatment at the hospital of the University of Tokyo. RESULTS: In 35 of 89 cases (39%), MAGE-A1 positive immunoreactivity was detected in the malignant glands. MAGE-A1 positive immunoreactivity was significantly higher among the patients under the age of 70 than among those 70 years of age and older (p=0.04). Among the patients under the age of 70, the tumors located in the distal colon (descending colon, sigmoid colon and rectum) showed significantly more positive MAGE-A1 immunoreactivity than those in the proximal colon (cecum, ascending colon and transverse colon) (p=0.04). The expression pattern of MAGE-A1 was not associated with gender, size, depth, histological type, vessel invasion, lymphatic invasion, lymph nodal invasion or stage of disease. CONCLUSIONS: Relatively better results can be expected with MAGE-A1 immunotherapy among patients with distal colon cancer under the age of 70.