Lymph Node Status in Patients with Submucosal Gastric Cancer

Background The aim of this study was to clarify the lymph node status in patients with submucosal gastric cancer.Methods Between April 1994 and December 1999, 615 patients with histologically proven submucosal gastric cancer who underwent curative resection were included in this study. The results of the surgery and predictive factors for lymph node metastasis were evaluated by univariate and multivariate analyses. The accuracy of the predictive factors was assessed in a second population of a further 186 patients.Results Lymph node metastasis was observed in 119 patients (19.3%). Multivariate analysis showed that pathologic tumor diameter (≥20 mm) and lymphatic invasion were independent predictive factors for lymph node metastasis. The incidence of lymph node metastasis without these 2 predictive factors was 1.8% (2 of 113), and it was 51.2% (85 of 166) with the 2 predictive factors, 9.5% (14 of 148) in tumors <20 mm in diameter, and 5.3% (22 of 414) in tumors without lymphatic invasion. Among patients with a tumor <20 mm in diameter, the incidence of lymph node metastasis was significantly reduced in those with a differentiated tumor: 4.2% (4 of 95). These results were almost identical to those observed in the second population.Conclusions Lymph node status can be accurately predicted on the basis of pathologic tumor diameter <20 mm, lymphatic invasion (absence), and histological type (differentiated) in patients with submucosal gastric cancer. Less extensive surgery for these patients might be reconsidered after confirmation of the reproducibility of the results of this study by an appropriately designed prospective clinical trial.     

Preoperative Serum Angiopoietin-2 Levels Correlate with Lymph Node Status in Patients with Early Gastric Cancer

Background  Lymph node metastasis is the most important factor to consider when deciding on the modality of resection in patients with early gastric cancer. The aim of the present study was to assess the relationship between preoperative serum angiopoietin-2, a lymphangiogenic growth factor, and lymph node metastasis in patients with early gastric cancer. Methods  A total of 62 preoperative serum samples from patients diagnosed with early gastric adenocarcinoma, and 30 serum samples from healthy donors were obtained. The serum levels of angiopoietin-2 (Ang-2) were quantified by immunoassay. Intra- and peritumor lymphatic vessel density (I-LVD and P-LVD) were counted after immunohistochemical staining. The relationship between the serum Ang-2 levels and other prognostic variables (tumor size, histological type, depth of tumor invasion, I-LDV, P-LDV, presence of lymph node involvement, and distant metastasis) were then examined by univariate and multivariate linear regression analyses. Results  The median serum levels of Ang-2 in patients were higher than those of healthy controls [311.1 ng/mL, interquartile range (IQR) 256.7–311.1 ng/mL versus 286.5 ng/mL, IQR 226.9–286.5 ng/mL; Mann–Whitney test, P = 0.016]. Eight patients had metastatic lymph nodes; the Ang-2 levels from the patients with metastatic lymph nodes were higher than from those with negative lymph nodes (297.5 ng/mL, IQR 251.1–385.8 ng/mL versus 416.0 ng/mL, IQR 337.1–485.5 ng/mL; Mann–Whitney test, P = 0.019). Elevated serum Ang-2 levels were associated with positive lymph node involvement and this finding was significant on univariate (P = 0.008) and multivariate logistic regression analysis (P = 0.011). Conclusion  Serum Ang-2 levels were clinically useful markers for lymph node metastasis in patients with early gastric cancer.     

Risk of Limited Lymph Node Dissection in Patients with Clinically Early Gastric Cancer: Indications of Extended Lymph Node Dissection for Early Gastric Cancer

Background

Laparoscopic gastrectomy is usually indicated in T1 N0–1 early gastric cancer (EGC). Limited lymph node dissection, such as D1+, is applied in these cases. However, preoperative staging is not always correct, and the risk of undertreatment thus exists.

Methods

Patients with clinically early gastric cancer (cEGC) who underwent gastrectomy with lymph node dissection of D2 and over were selected from 4,021 patients with gastric cancer. The station numbers of all metastatic lymph nodes (MLNs) were identified, and MLNs were classified into groups 1 and 2 (including lymph nodes of second tier and over) on the basis of the system of the Japanese Gastric Cancer Association, irrespective of the number of MLNs. Clinicopathological data were compared according to the existence of lymph node metastasis and the classification of MLNs.

Results

Of 1,308 patients with cEGC who fulfilled the inclusion criteria, 1,184 (90.5 %) were diagnosed pathologically with EGC. Among 126 patients with cEGC who were diagnosed with lymph node metastasis, 93 patients had only group 1 MLNs and 33 patients had group 2 MLNs. Tumor location in the proximal third of the stomach (odds ratio 5.450) and ulceration (odds ratio 11.928) were significant factors for group 2 metastasis.

Conclusions

Extended lymph node dissection is recommended in cEGC with ulceration or disease located in the proximal third of the stomach.     

Race and Correlations Between Lymph Node Number and Survival for Patients with Gastric Cancer

Background

There is ongoing debate whether extended lymphadenectomy improves survival in gastric cancer patients who undergo surgical resection. We previously observed that Korean–American patients had the highest overall survival in Los Angeles County. Our objective was to assess lymph node (LN) number and its impact on survival for Korean–American gastric cancer patients.

Methods

We utilized the National Cancer Institute’s Surveillance, Epidemiology, and End Results registry to identify Korean–Americans with gastric adenocarcinoma treated with curative-intent gastrectomy between 1988 and 2008. We grouped patients according to examined LN number (1–15 and 16+) and compared characteristics. We performed similar analysis for white patients.

Results

Out of 982 Korean–American patients with gastric adenocarcinoma, most patients had 1–15 examined LNs (60 %). When we compared LN groups, we observed higher overall survival in the 1–15 group than the 16+ group (5-year survival, 59 % vs 52 %, respectively; p?=?0.04). However, LN number was not prognostic of overall survival on stepwise Cox proportional hazards analysis. In contrast, LN number was prognostic for white patients.

Conclusions

Although examined LN number may impact survival for white patients, outcomes of Korean–American gastric cancer patients were independent of LN number. Our data suggest that survival of Korean–American gastric cancer patients are comparable with outcomes from East Asian hospitals and may be independent of surgical technique.     

Central Lymph Node Metastasis in Gastric Cancer Is Predictive of Survival After Preoperative Therapy

Background

It is unclear how preoperative therapy for gastric cancer affects the metastasis rate of lymph nodes (LNs) and whether the location of positive LNs affects survival after preoperative therapy. Therefore, we determined the association between positive central lymph nodes (CnLNs) and disease stage and overall survival (OS).

Methods

We reviewed a prospectively maintained database to identify patients who had undergone resection of gastric adenocarcinoma at our institution from 2005 to 2015. CnLNs were defined as common hepatic, celiac, and proximal splenic artery LNs (stations no. 8, 9, and 11p). The frequency of CnLN metastases and risk factors affecting OS were examined.

Results

We identified 356 patients. Preoperative therapy was administered to 66% of patients. D2 LN dissection was performed in 80% of patients, and the median number of LNs examined was 25 (IQR, 18–34). In 243 patients (68%), CnLNs had undergone separate pathologic examination; the CnLN-positive rate was 9.1% (22 of 243; station no. 8, 4.5%; no. 9, 2.1%; and no. 11p, 4.8%). CnLN metastasis was associated with shorter 3-year OS in patients with pN2/3 disease (33 vs. 62%; p?=?0.004). Among patients who had undergone preoperative therapy, ypT3–4 stage (HR 2.44; p?=?0.01) and positive CnLNs (HR 5.44; p?<?0.001) were negatively associated with OS by multivariate analysis.

Conclusions

CnLN metastases are uncommon in gastric cancer and have an adverse effect on OS in patients who have undergone preoperative therapy. Larger multi-institutional studies are needed to determine whether CnLN positivity requires a separate staging category after preoperative therapy.

     

Appropriate Gastric Resection with Lymph Node Dissection for Early Gastric Cancer

Background The extent of lymphadenectomy (limited vs. extended) and that of gastric resection (partial vs. total) remain controversial issues in the management of early gastric cancer (EGC). A multicentric study was performed to elucidate the appropriate gastric resection with lymph node dissection for early gastric cancer.Methods From 1979 to 1988, 332 patients with EGC underwent surgery in 23 French centers. Clinicopathological data, the extent of resection, and the number of lymph nodes retrieved were reviewed retrospectively and screened for prognostic effect. The mean follow-up for the 332 EGC patients was 80 months.Results Postoperative mortality was correlated to age (odds ratio [OR], 1.1) and extent of gastric resection (OR,10.3). Examination of survival data (excluding postoperative deaths) with univariate analysis and the Cox proportional hazards model showed that the independent factors for excellent prognosis included no lymphatic involvement (P = .005), 10 or more lymph nodes retrieved (P = .003), site of the tumor in the lower third of the stomach (P = .01), and mucosal lesions (P = .04). The extent of resection did not influence long-term survival.Conclusions Our results suggest that because of the associated good prognosis, the appropriate surgical treatment for EGC is partial gastrectomy with lymphadenectomy retrieving 10 or more lymph nodes.     

Lymph Node Micrometastases in Patients With Early Gastric Cancer: Experience With 139 Patients

Background:Although lymph node metastases in patients with early gastric cancer (EGC) is an important prognostic factor, the prognostic relevance of lymph node micrometastases is still uncertain.Methods:The authors studied 1488 lymph nodes, which were histologically confirmed as pN0, dissected from 139 patients who were treated for EGC between 1976–1994. Micrometastases were defined as a single or small cluster of neoplastic cells identifiable only by immunohistochemical methods.Results:Lymph node micrometastases was observed in 24 of the 139 patients (17%). No significant correlation was observed between micrometastases and other clinicopathological characteristics. Analysis of overall survival showed no significant difference between the micrometastases positive and negative groups.Conclusion:The results of our study show that the presence of lymph node micrometastases in EGC does not have an influence on patient prognosis.     

早期胃癌淋巴结转移潜在危险因素分析

目的:探讨影响早期胃癌淋巴结转移的潜在危险因素,指导胃癌淋巴结清扫术(D1或D2)的合理应用。方法:回顾性分析1995年3月—2010年6月经手术治疗的336例早期胃癌患者的临床病理资料,对影响早期胃癌淋巴结转移的潜在危险因素进行单因素及多因素分析。结果:早期胃癌淋巴结转移与性别(P=0.010)、年龄(P=0.013)、肿瘤部位(P=0.042)、有无合并溃疡(P=0.001)、浸润深度(P<0.0001)、有无脉管癌栓(P<0.0001)有关,合并有溃疡(P=0.012)、浸润至黏膜下层(P=0.008)及有脉管癌栓(P=0.001)是淋巴结转移的独立性危险因素;黏膜内癌淋巴结转移与肿瘤部位(P=0.007)及大小(P=0.010)有关,肿瘤直径>20mm(P=0.041)是黏膜内癌淋巴结转移的独立性危险因素。结论:合并有溃疡、浸润至黏膜下层及有脉管癌栓的早期胃癌患者进行手术时,建议行淋巴结清扫(D2)术;肿瘤直径>20mm黏膜内癌也要考虑行淋巴结清扫(D2)术。     

Predictors of Lymph Node Metastasis in Western Early Gastric Cancer

Background

The application of endoscopic and local resection for early gastric cancer (EGC) is limited by the risk of regional lymph node (LN) metastasis. We sought to determine the incidence and predictors of LN metastasis in a contemporary cohort of Western patients with early gastric cancer.

Methods

Sixty-seven patients with pT1 gastric adenocarcinoma underwent radical surgery without neoadjuvant therapy at our institution between 1995 and 2011, and clinicopathologic factors predicting LN metastasis were analyzed.

Results

LN metastases were present in 15/67 (22 %) pT1 tumors, including 1/23 (4 %) T1a tumors and 14/44 (32 %) T1b tumors. Tumor size, site, degree of differentiation, macroscopic tumor sub-classification, perineural invasion status, and depth of submucosal tumor penetration did not predict LN metastasis. The presence of lymphovascular invasion (LVI) and positive nodal status by endoscopic ultrasound (EUS) were the only factors that predicted LN metastasis on multivariate analysis. T1a tumors without LVI had a 0 % rate of positive LN, whereas T1b tumors with LVI had a 64.3 % rate of positive LN.

Conclusions

EGC limited to the mucosa, without evidence of LVI, and N0 on EUS, may be considered for limited resection. However, any EGC with submucosal invasion, LVI, or positive nodes on EUS should undergo radical resection with lymphadenectomy.

     

S-Classification of Sentinel Lymph Node Predicts Axillary Nonsentinel Lymph Node Status in Patients with Breast Cancer

Background One-half of breast cancer patients with positive sentinel lymph node (SN) have no further metastases in the axillary lymph node basin. The aim of the present study was to identify patients with positive SN who are unlikely to have further metastases in the axillary lymph node basin, using a new classification of SN, namely the S-classification. Methods Specimens of positive SN were subjected to a pathological review according to the previously published S-classification. S-stages of positive SN were correlated with the status of further metastases in the axillary lymph node basin after axillary lymph node dissection (ALND). Results Of 117 patients who underwent sentinel lymph node biopsy, 36 (30.8%) had a positive SN and were subjected to level I and II ALND. The occurrence of positive nonsentinel nodes was significantly related to the S-stage of SN. No patient with stage SI had additional metastases in the nonsentinel lymph nodes, while 14.3% of patients with SII stage disease and 60.9 % of patients with SIII disease had other non-SN that were metastatic. Conclusion S-stages of positive SN are highly predictive for axillary nonsentinel node status. Especially patients with SI sentinel node metastases appear to be at low risk for further nonsentinel node metastases.     

Ethnicity Influences Lymph Node Resection in Colon Cancer

The purpose of this study is to determine the association between ethnicity and lymph node retrieval after colon cancer resection. Using the Surveillance Epidemiology and End Results (SEER)–Medicare database, patients who underwent colon cancer resection from 2000–2003 were evaluated. Subjects were classified as having <12 (N = 20,605) or ≥12 (N = 12,358) lymph nodes examined. Multivariate models were used to analyze the relationship between lymph nodes resected and independent variables. Out of a total of 32,936 patients, 62.5% had fewer than 12 lymph nodes resected. In multivariate analysis, Hispanic ethnicity was associated with a significantly lower chance of having ≥12 lymph nodes than the Caucasian population (OR = 0.61; CI, 0.50–0.74). Despite this, there was no understaging: the proportion of stage II and III diagnoses was the same. Both groups received the same rate of cancer-directed surgery and survival was equivalent. During this study period, a majority of colon cancer resections were inadequate based on the current standard of ≥12 nodes. Hispanic patients were less likely to have an adequate node resection when compared to Caucasians. Despite fewer lymph nodes harvested, they had equivalent staging and survival. These results suggest that ethnicity influences the lymph node count.     

Risk Factors for Lymph Node Metastasis in Undifferentiated Early Gastric Cancer

Background Endoscopic surgery has not been accepted as a curative treatment for intramucosal undifferentiated early gastric cancer (EGC). The purpose of this study was to evaluate the predictive factors of lymph node metastasis and explore the possibility of using endoscopic surgery for undifferentiated EGC. Methods We retrospectively analyzed 646 patients with undifferentiated EGC who had undergone gastrectomy with D2 lymphadenectomy from January 2000 to March 2005. We used univariate and multivariate analysis to identify clinicopathological features that were predictive factors for lymph node metastasis. Results The incidence of lymph node metastasis was 4.2% in intramucosal and 15.9% in submucosal undifferentiated EGC. Multivariate analysis revealed that submucosal invasion, larger tumor size (greater than 2 cm), and presence of lymphovascular invasion (LVI), were significantly associated with lymph node metastasis in patients with undifferentiated EGC. Tumor size and LVI were independent risk factors for lymph node metastasis in cases of intramucosal EGC. Lymph node metastasis was found in only one patient (0.5%) who had neither of the two risk factors for intramucosal EGC. Conclusion Complete endoscopic resection may be acceptable as a curative treatment for intramucosal undifferentiated EGC when the tumor size is less than or equal to 2 cm, and when LVI is absent in the postoperative histological examination. Radical gastrectomy should be recommended if LVI or unexpected submucosal invasion is present.     

Prognostic Significance of the Metastatic Lymph Node Ratio in Patients with Gastric Cancer

Background  

In gastric cancer, the classification of lymph node status is still a controversial prognostic factor. Recent studies have proposed a new prognostic factor (metastatic lymph node ratio: MLR) for gastric cancer patients who undergo curative resection. The present study tested the hypothesis that MLR was better than the current pN staging system by analyzing the correlation between MLR and the International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) staging system, by analyzing the correlation between MLR and 5-year overall survival (OS), by comparing area under the curve (AUC), and by performing univariate and multivariate analyses for OS.     

胃黏膜下层癌淋巴结转移临床病理因素分析

【摘要】 目的 研究胃黏膜下层癌淋巴结转移率及其影响因素。 方法 回顾性分析南京医科大学第一附属医院1998年1月至2007年12月手术证实的181例胃黏膜下层癌的临床病理资料,对病人年龄、性别、肿瘤组织学类型、形态学类型、大小、部位、浸润深度、脉管内癌栓等与淋巴结转移的关系进行单因素与多因素分析。 结果 胃黏膜下层癌淋巴结转移率为20.44%。影响胃黏膜下层癌淋巴结转移的因素主要有肿瘤组织学类型（分化型 vs 分化不良型,P =0.0352）、直径大小（＜2cm vs ≥2cm,P =0.0143）、部位（近端胃vs胃体vs远端胃,P =0.0254）及脉管内癌栓（无vs有,P =0.0323）。Logistic回归分析显示肿瘤组织学类型与大小为胃黏膜下层癌淋巴结转移的独立性危险因素。结论 胃黏膜下层癌淋巴结转移与肿瘤组织学类型、大小、部位及脉管内癌栓等因素有关。临床上应参考上述临床病理因素判断淋巴结转移风险,制定合适的治疗方案。     

Solitary Lymph Node Metastasis in Gastric Cancer

The feasibility and diagnostic reliability of sentinel node (SN) biopsy for gastric cancer are still controversial. We studied the clinicopathological features and localization of solitary lymph node metastasis (SLM) in gastric cancer to provide useful information for use of the SN concept in gastric cancer. From 2000 to 2004, 3,267 patients with gastric cancer underwent D2 radical gastrectomy. The clinicopathological features of 195 patients with histologically proven SLM and the distribution of metastasized nodes were assessed. The incidence of SLM was 6.0% in all cases. Compared with the node-negative patients, significant differences were observed in age, tumor size, depth of invasion, and surgical type. The cumulative 5-year survival rate of patients with SLM was 80.5%, which was significantly lower than 90.2% for node-negative patients (P < 0.001). Of patients with SLM, 82.6% had it in the perigastric node area (N1), and the other 17.4% patients had skip metastasis in the N2-N3 nodes. Perigastric nodes were the most common first sites of drainage from the tumor, making them the main targets of the operative SN mapping procedure. Due to the higher than expected incidence of skip metastasis in gastric cancer, D2 lymphadenectomy should be performed until the reliability of SN navigation surgery is validated in multicenter prospective clinical trials.     

Prognostic Significance of the Metastatic Lymph Node Ratio in Gastric Cancer Patients

Background  

Lymph node metastasis is considered one of the most important prognostic factors in gastric cancer. However, the optimal system for accurate staging of lymph node metastasis for patients with gastric cancer remains controversial. This study was designed to investigate the prognostic significance of the metastatic lymph node ratio (MLR), which is calculated by dividing the number of metastatic lymph nodes by the total number of nodes harvested from patients with gastric cancer.     

Predictors to Assess Non‐Sentinel Lymph Node Status in Breast Cancer Patients with Sentinel Lymph Node Metastasis

Abstract: The next step of sentinel lymph node biopsy (SLNB) in breast cancer is to determine which patients need axillary lymph node dissection (ALND) following a positive SLNB. A prospective database of 239 patients who underwent SLNB followed by complete ALND at Keio University Hospital from January 2001 to June 2005 was reviewed. A total of 131 patients with one or more positive sentinel lymph nodes (SLNs) were further analyzed. A univariate analysis showed a significant correlation between non‐SLN involvement and lymphatic invasion, vascular invasion, number of tumor‐involved SLNs, radioactivity of SLNs, and size of SLN metastasis (p = 0.0002, p = 0.004, p = 0.006, p = 0.04, p = 0.03, respectively). By multivariate analysis, lymphatic invasion and the number of tumor‐involved SLNs remained significant predictors of non‐SLN involvement. In breast cancer patients with a positive SLN, lymphatic invasion and the number of tumor‐involved SLNs were both independent predictors of non‐SLN involvement.     

胃癌淋巴结转移研究的进展与新规定

近年，胃癌外科治疗取得较大进步，这些成绩与其外科基础研究不断深入相伴而行，相辅相成。本文仅就目前胃癌淋巴结转移的数点研究，结合作者经验体会简述如下。胃癌部位划分与淋巴结站属的新规定过去，日本胃癌处理规约将胃分为3大部，其名称及代号为贲门部（C）、中部（M）、窦部（A），再分为5个区[1]。新规约改为上部（U）、中部（M）和下部（L），分为6个区，即①LMU/MUL/MLU/UML；②LD/L；③LM/M/ML；④MU/UM；⑤U；⑥E+。将“L”和“U”单独提出，各部区所属淋巴结亦有一定变动。将每区的D2清除术作为标准根治的清除术…     

腹腔镜胃癌根治术的现状与前景

胃癌是常见的消化道恶性肿瘤之一,在我国早期胃癌所占比例很小,约90%的病例确诊时已为进展期胃癌。随着内镜、B超、超声内镜等诊疗技术的发展,早期胃癌的诊出率逐渐增多,日本约50%的胃癌为早期胃癌。胃癌的微创治疗包括内镜下胃黏膜切除术、腹腔镜胃腔内黏膜切除术、腹腔镜胃楔形切除术,腹腔镜胃癌根治术也随之得到了较大的发展。1993年Ohgami报道了腹腔镜胃楔形切除术,1994年Ohashi报道了腹腔镜胃腔内黏膜切除术用于治疗无淋巴结转移风险的早期胃癌患者,取得了较好的临床疗效,但由于这两种手术方式均不对胃周淋巴结进行清扫,其应用范围比…