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.     

Vascular endothelial growth factor C and D expression correlates with lymph node metastasis and poor prognosis in patients with resected esophageal cancer

Vascular endothelial growth factors C (VEGF-C) and D (VEGF-D) are important lymphangiogenic factors in human cancers. We studied the expression of VEGF-C and VEGF-D using immunohistochemistry in 73 resected esophageal cancer specimens, and correlated the results with patient clinicopathologic features and survival. High expression of VEGF-C was identified in 40 (54.7%) patients, and it correlated positively with histological grade (p=0.038), tumor stage (p=0.01), depth of tumor invasion (p=0.036) and lymph node metastasis (p=0.001). In 48 of 73 (65.7%) tumors, the VEGF-D protein was also expressed at high levels. VEGF-D immunoreactivity significantly correlated with tumor location (p=0.027), size of tumor (p=0.015), histological grade (p=0.02), depth of invasion (p=0.001) and lymph node metastasis (p=0.018). In logistic multivariate analysis, high expression of VEGF-C (OR 1.941, 95% CI 1.263-7.289, p=0.024) was associated with lymph node metastasis. Calculating the prognostic relevance revealed that both VEGF-C and VEGF-D correlated with decreased overall survival (p=0.01, p=0.003), disease free survival (p=0.02, p=0.006), and cancer-specific survival (p=0.03, p=0.005). In conclusion, our results suggest that high levels of both VEGF-C and VEGF-D proteins are associated with lymph node involvement, and that VEGF-C expression is an independent predictor of risk for lymph node metastasis in esophageal cancer. In locally advanced disease, overexpression of VEGF-C and VEGF-D may be useful in identifying patients who are more likely to have a poor prognosis even after curative resection.     

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.     

VEGFR-3信号途径相关蛋白在胃癌中的表达及意义

目的研究血管内皮生长因子受体（VEGFR）-3信号途径相关蛋白C、D（VEGF—C、VEGF—D）在胃癌中的表达并探讨其与淋巴结转移的关系。方法80例胃癌手术病例分为淋巴结阳性组（n=48）和淋巴结阴性组（n=32）,另设胃溃疡病例为对照组（n=10）。采用ELISA技术进行血清VEGF—C和VEGF-D水平检测,然后应用免疫组织化学EnVisionTM两步法检测胃溃疡组织和胃癌标本VEGF—C、VEGF-D表达。结果胃癌患者血清VEGF-C和VEGF—D水平明显高于对照组（P〈0．05）,胃癌患者血清VEGF-C水平与淋巴结转移有关（P〈0．05）;胃癌组织中VEGF—C、VEGF—D阳性表达率均高于对照组（P〈0．05）,伴淋巴结转移的胃癌组织VEGF-C阳性表达率较无淋巴结转移者更高（P〈0．01）。结论血清VEGF—C可作为胃癌的标记物,对术前判定淋巴结转移具有一定的临床价值。     

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.     

Expression pattern of vascular endothelial growth factor-C in human colorectal normal mucosa and neoplastic mucosa

BACKGROUND/AIMS: Vascular endothelial growth factor-C (VEGF-C) is a potent growth factor stimulating lymphangiogenesis. METHODOLOGY: We examined the expression of VEGF-C immunohistochemically in neoplastic as well as normal mucosa of colorectal tissues, and evaluated the significance of VEGF-C in colorectal carcinogenesis and as a marker to predict the outcome of colorectal cancer. RESULTS: VEGF-C was strongly stained in 70/79 adenomas (89%), but the staining was focal in all cases, and the expression pattern in adenomas was not significantly related to either dysplasia or size of the adenoma. In the 8/8 intramucosal carcinomas within adenomas, both the carcinomatous and adenomatous lesions were stained focally, but in 6 cases (75%), the VEGF-C-positive area was larger in the carcinomatous lesion than in the adenomatous lesion. In most invasive adenocarcinomas, VEGF-C was clearly stained (83/85; 98%), with both a focal (40%) and diffuse (60%) staining pattern. In invasive carcinomas, the expression of VEGF-C was significantly correlated with lymphatic involvement, lymph node metastasis and tumor size, but not with venous involvement or liver metastasis. Survival rate tended to be lower in the high VEGF-C group than in the low group, although statistical significance was not observed. CONCLUSIONS: These results suggest that VEGF-C plays a positive role in lymphatic spread in colorectal carcinomas.     

结肠癌血管生成相关因子的表达及其意义的研究

目的研究VEGF配体及其受体在结肠癌发生、发展、转移中的作用,探讨VEGF家族与结肠癌各个时期病理特征的关系。方法在肿瘤标本,癌旁及正常组织标本中,用半定量RT-PCR方法,测定各种标本中VEGF各配体及VEGF受体表达,以研究它们在结肠癌进程中的作用。同时用免疫组化方法,对上述因子进行研究。结果 (1)与正常组织相比,VEGF-A、VEGF-C在肿瘤组织中显著升高(P<0．01);VEGF-B在肿瘤和正常组织中表达相近,而VEGF-D在肿瘤组织中显著降低;(2)VEGF-A、VEGF-B、VEGF-C在有淋巴结转移的肿瘤中明显升高(P<0．01);VEGF-D在有淋巴结转移的肿瘤中下降,但没有统计学差异。(3)VEGFR-1与Duke's分期,淋巴结转移显著相关(P<0．01);VEGFR-2与淋巴结转移显著相关(P<0．01);VEGFR-3与临床病理特征均不相关;VEGFR-1在肿瘤组织比正常组织升高(P<0．01),但VEGFR-2和VEGFR-3表达在肿瘤进程中没有显著升高。结论 VEGF-A、VEGF-B与结肠癌早期发展过程相关,VEGF-C、VEGFR-1与结肠癌进展过程相关,并和VEGF-D、VEGFR-2共同参与转移过程。     

Lymphatic Vessel Density at the Site of Deepest Penetration as a Predictor of Lymph Node Metastasis in Submucosal Colorectal Cancer

Purpose Lymph node metastasis is an important factor that influences curability after endoscopic treatment of submucosal colorectal cancer. This study was designed to determine the usefulness of identification of lymphatic vessels by immunohistochemistry in predicting lymph node metastasis of submucosal colorectal cancer. Methods Lymphatic involvement was assessed by hematoxylin and eosin staining and podoplanin immunostaining on samples resected from 268 patients with submucosal colorectal cancer. Lymphatic vessel density was estimated by two investigators by average count of three fields (×200) in the area of greatest number of podoplanin-positive capillaries at the site of deepest submucosal penetration. Relations with other clinicopathologic parameters also were investigated. Results Lesions with high lymphatic vessel density (≥9 vessels per field) showed a significantly greater incidence of lymph node metastasis than did those with low lymphatic vessel density (<9 vessels per field; 23.3 vs. 8.4 percent). By multivariate analysis, lymphatic vessel density was determined to be an independent risk factor for lymph node metastasis of submucosal colorectal cancer (P = 0.0044). Lymphatic vessel density also correlated with tumor budding and the degree of inflammation at the invasive front. Conclusions Identification of lymphatic vessels by podoplanin immunostaining provides objective and accurate evaluation of lymphatic involvement. Lymphatic vessel density at the site of deepest penetration is a useful predictor of lymph node metastasis of submucosal colorectal cancer. Supported by a grant from the Japanese Society of Gastroenterological Endoscopy, Chugoku Branch. Presented at the meeting of The Japanese Society of Gastroenterology, Kokura, Fukuoka, Japan, April 20 to 22, 2006. Reprints are not available.     

Expression of vascular endothelial growth factor-C and the relationship between lymphangiogenesis and lymphatic metastasis in colorectal cancer

AIM: To investigate the expression of vascular endothelial growth factor-C (VEGF-C) and the relationship between VEGF-C and lymphangiogenesis, lymph node metastasis in colorectal cancer. METHODS: Fifty six cases of colorectal cancer were selected randomly. Expression of VEGF-C was detected by immunohistochemistry, and lymphatic vessels were stained by enzyme histochemical method. RESULTS: VEGF-C expression was found in 66.7% (37/56) patients. In VEGF-C positive and negative patients, the lymphatic vessel density was 25.16+/-7.52 and 17.14+/-7.22, respectively (P<0.05). The rate of lymph node metastasis in VEGF-C positive patients (81.1%) was significantly higher than that in the negative group (42.1%). CONCLUSION: VEGF-C expression may induce lymphangiogenesis in colorectal cancer, as a result, tumor cells can entry the lymphatic vessels easily. VEGF-C may serve as a useful prognotic factor in colorectal carcinoma.     

VEGF-D expression correlates with colorectal cancer aggressiveness and is downregulated by cetuximab

AIM： To gain mechanistic insights into the role played by epidermal growth factor receptor （EGFR） in the regulation of vascular endothelial growth factors （VEGFs） in colorectal cancer （CRC）. METHODS： The impact of high-level expression of the growth factor receptors EGFR and VEGF receptor （VEGFR）3 and the VEGFR3 ligands VEGF-C and VEGF-D on disease progression and prognosis in human CRC was investigated in 108 patients using immu- nohistochemistry. Furthermore, the expression of the lymphangiogenic factors in response to the modulation of EGFR signalling by the EGFR-targeted monoclonal antibody cetuximab was investigated at the mRNA and protein level in human SW480 and SW620 CRC cell lines and a mouse xenograft model. RESULTS： Human CRC specimens and cell lines displayed EGFR, VEGF-C and VEGF-D expression with varying intensities. VEGF-C expression was associated with histological grade. Strong expression of VEGF-D was significantly associated with lymph node metas- tases and linked to a trend for decreased survival in lymph node-positive patients. EGFR blockade with cetuximab resulted in a significant decrease of VEGF-D expression in vitro and in vivo. CONCLUSION： In conclusion, the expression of VEGF-D in colorectal tumours is significantly associated with lymphatic involvement in CRC patients and such expression might be blocked effectively by cetuximab.     

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.     

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.     

大肠癌组织中生长抑素和血管内皮生长因子-C的表达及其临床意义

目的探讨大肠癌组织中生长抑素（SS）和血管内皮生长因子-C（VEGF-C）的表达及其临床意义。方法采用免疫组化法检测60例大肠癌组织及20例正常大肠黏膜组织中SS蛋白和VEGF-C蛋白的表达，采用VEGF-C受体FLT-4阳性脉管标记淋巴管计数，分析SS与大肠癌淋巴管生成、转移的关系。结果SS蛋白表达阳性率在大肠癌组及正常大肠黏膜组分别为37．7％和65％，VEGF-C在癌及正常组阳性表达率分别为60％和30％，差别均有显著性；SS表达与肿瘤分化程度、淋巴结转移、淋巴管侵犯及远处转移密切相关，与浆面膜受累无关；VEGF-C表达与肿瘤淋巴结转移，淋巴管侵犯及远处转移密切相关，而与肿瘤分化和浆面膜受累无关；大肠癌组织中SS和VEGF-C蛋白表达呈显著负相关。结论SS可能通过对VEGF-C／FLT-4信号通路的阻滞而抑制大肠癌淋巴管生成及转移。     

胃癌组织中VEGF-C、VEGF-D、MMP-9的表达变化及意义

目的观察血管内皮生长因子（VEGF）C、D和基质金属蛋白酶MMP-9在胃癌组织中的表达及其意义。方法采用免疫组织化学染色检测108例胃癌手术切除标本中VEGF-C、D及MMP-9的表达情况,并以正常胃黏膜组织作为对照。结果VEGF-C、VEGF-D及MMP-9在胃癌组织中的阳性表达率分别为55．7％、77．8％、75．0％,而在正常胃黏膜的阳性表达率分别为15．0％、20．0％、10．0％,三者的表达率在两组问均有明显差异（P均〈0．05）。伴淋巴结转移的胃癌病例其VEGF-D及MMP-9阳性表达率（87．0％,83．3％）高于无淋巴结转移者（31．5％,33．3％）,P均〈0．05;而VEGF-C在两组的阳性表达率相近,P〉0．05。结论VEGF-D及MMP-9的表达与胃癌分期、淋巴结转移关系密切,有望成为胃癌治疗的新靶点。     

不同转移潜能的小鼠肝癌淋巴道转移和淋巴管生成的研究

目的探讨小鼠淋巴道高、低转移潜能的肝癌细胞的体内淋巴道转移状况和淋巴管生成对淋巴道转移的影响。方法将淋巴道高、低转移潜能的肝癌细胞接种于Balb／C小鼠，观察成瘤及转移情况，对肿瘤组织进行淋巴管染色，观察淋巴管生成情况。另取高、低转移潜能的细胞株进行体外淋巴管生成实验并进行小鼠肿瘤转移基因芯片检测，对血管内皮细胞生长因子C、D（VEGF—C、D）进行半定量逆转录聚合酶链反应及实时定量聚合酶链反应分析。结果高，低转移细胞在小鼠髂总动脉旁、肾门淋巴结的转移差异有统计学意义（P=0．0l8）。高转移潜能组诱导淋巴管生成的数量大于低转移组和对照组（P=0．032）。高转移组的CD44、E-cadherin．HER2／neu、H—Ras．VEGF—C的表达均高于低转移组，nm23A．nm23-E4、pl6ink4a、CD61等均低于低转移组。半定量逆转录聚合酶链反应表明，高转移组vEGF—C高于低转移组，VEGF—D低于低转移组。实时定量聚合酶链反应分析高转移组的VEGF—D分泌显著小于低转移组，vEGF—C／VEGF—D在高转移组明显高于低转移组。结论肝癌的淋巴道转移与淋巴管生成有关，VEGF—C、D相关基因表达的改变影响淋巴管生成。VEGF—C／VEGF—D比值可能是有效判断并影响肝癌淋巴道转移潜能的指标之一。     

癌组织中VEGF-C及nm23基因蛋白表达与大肠癌浸润转移的关系

目的 探讨血管内皮生长因子c(VEGF-C)及nm23基因蛋白在大肠癌组织中的表达及其与癌局部浸润、淋巴结转移的关系。方法 采用免疫组化SP法,检测93例原发性大肠癌患者手术切除的癌组织中VEGF-C及nm23基因蛋白。结果 VEGF-C基因蛋白阳性表达率与大肠癌组织的分化程度无明显相关性(P>0.05),与癌的浸润深度、淋巴结转移呈正相关(P均<0.05)。nm23基因蛋白在大肠癌淋巴结无转移组中的阳性表达率显著高于有转移组(P<0.05)。结论 VEGF-C及nm23基因蛋白的异常表达在大肠癌的发生、发展和淋巴结转移中可能起重要作用。联合检测癌组织中VEGF-C及nm23基因蛋白,对判断大肠癌的临床分期、淋巴结转移及预后有一定的参考价值。     

Angiogenesis at the site of deepest penetration predicts lymph node metastasis of submucosal colorectal cancer

PURPOSE: Intratumor microvessel count has been reported as a useful prognostic factor in patients with cancer of various organs. This study was undertaken to clarify the relation between microvessel count and lymph node metastasis in submucosal colorectal cancer. METHODS: Microvessel count was estimated in 254 invasive tumors that had been resected from patients with submucosal colorectal cancer. Immunohistochemistry with antibodies against CD34 was performed on archival specimens, and microvessel counts were estimated based on the average count of three fields (original magnification, x400) in the most vascular area at the site of deepest submucosal penetration. RESULTS: Microvessel count ranged from 10 to 98, with a median of 40. Lesions with high microvessel counts (> or =40) had a significantly higher incidence of lymph node metastasis than those with low microvessel counts (<40; 21.8 percent vs. 6.2 percent). None of the 79 lesions with low microvessel counts and submucosal invasion up to a depth of 1,500 microm had metastasized to the lymph nodes. In multivariate analysis, microvessel count was an independent risk factor for lymph node metastasis in submucosal colorectal cancer (P = 0.0026). CONCLUSION: Microvessel count at the site of deepest submucosal penetration can be one of the most useful predictors for lymph node metastasis. Analysis that combines microvessel count and depth of submucosal invasion may predict the occurrence of lesions without lymph node metastasis.     

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。     

Risk of Lymph Node and Distant Metastases in Patients With Early Invasive Colorectal Cancer Classified as Haggitt’s Level 4 Invasion

PURPOSE: Tumor invasion in patients with early invasive colorectal cancer has been classified into four levels proposed by Haggitt. Level 4 invasion into the submucosa has been defined as a risk factor for lymph node metastasis; however, the false-positive rate remains high. This study was designed to determine risk factors for lymph node and distant metastases in addition to Haggitt's Level 4 invasion. METHODS: Seventy-one of 142 patients with submucosa-invasive colorectal cancer underwent intestinal resection as an initial surgical treatment between 1975 and 2000. The subjects of this study were 65 of these 71 patients, all of whom were diagnosed as having Haggitt's Level 4 invasion. The depth, width, and area of submucosal invasion were measured with an image analyzer. RESULTS: Lymph node metastasis was noted in 11 (16.9 percent) of the 65 patients. There were no significant differences in the depth or area of submucosal invasion between node-positive and node-negative patients. However, the width of submucosal invasion was significantly greater in node-positive than in node-negative patients (P = 0.001). When 5-mm-wide submucosal invasion was used as an indicator for intestinal resection, 37 patients were found to have indications for bowel resection, and 11 (29.7 percent) of the 37 had lymph node metastases. Distant metastasis was noted in five patients (7.7 percent). The depth, width, and area of submucosal invasion in patients with distant metastasis did not differ significantly from those without distant metastasis. CONCLUSION: Although further prospective investigation is required, the positive predictive value increases from 17 to 30 percent when the width of submucosal invasion is added to Haggitt's Level 4 as an indicator for bowel resection.