Poor Prognosis of Advanced Gastric Cancer with Metastatic Suprapancreatic Lymph Nodes

Background

Whether gastrectomy with D2 lymphadenectomy improves survival of patients with advanced gastric cancer (AGC) remains controversial. Few studies have described the pathological features of AGC with metastatic suprapancreatic lymph nodes (LN), which are the target of D2 lymphadenectomy. This study therefore aims to clarify the prognosis and clinical pathological features including the number and location of metastatic LN in AGC with metastatic suprapancreatic LN.

Methods

406 patients with AGC, who underwent gastrectomy with D2 lymphadenectomy from 1982 to 2007 at Oita University, were reviewed retrospectively with regard to presence or absence of metastatic suprapancreatic LN. The pathological factors associated with AGC with metastatic suprapancreatic LN were examined by univariate and multivariate analysis.

Results

Of 362 patients with AGC, 78 had suprapancreatic LN metastasis (21.5 %), differing significantly in terms of presence of vascular invasion and having a larger number of metastatic perigastric LN in comparison with only metastatic perigastric LN on univariate analysis. According to multivariate analysis, they were associated with presence of vascular invasion and a large number of total metastatic LN (more than two; N2≤). The overall 5-year survival rate of the AGC with perigastric LN metastasis (station 1–7) group was 37.9 % and of the AGC with suprapancreatic LN metastasis group was 12.8 %. There were significant differences in each group (P < 0.05).

Conclusions

Patients with AGC with metastatic suprapancreatic LN had a large number of total metastatic LN and poor prognosis, suggesting that it may be a systemic disease.     

Morphological Distribution of Metastatic Foci in Sentinel Lymph Nodes with Gastric Cancer

Background The TNM classification defines micrometastasis (MM) and isolated tumor cells (ITC) in lymph nodes (LN). Sentinel node (SN) navigation surgery has been introduced in gastrointestinal cancer. Few reports have examined the morphological distribution of MM and ITC of SN in gastric cancer. The purpose of this study was to clarify the clinical significance of the morphological distribution of cancer cells in SNs according to metastasis (MA), MM, and ITC. Methods All dissected LNs obtained from 160 consecutive patients with mapped SNs arising from cT1–2 N0 tumors were examined. Metastasis in these LNs was examined by histology and cytokeratin staining. The distribution of MA, MM, and ITC was classified as marginal sinus (MS), intermediate sinus (IS), parenchymal (PA), and diffuse types (DF). Results Nodal metastases were detected in 65 SNs from 30 patients and MA, MM, and ITC accounted for 53.9%, 21.5%, and 24.6%, respectively. MS, IS, PA, and DF accounted for 57%, 6%, 17%, and 20.0%, respectively. Patients with metastasis of non-MS had more nodal metastasis in non-SNs (P = .025) and had nodal metastasis in second tier (P = .009), compared with the patients with metastasis of MS. The incidence of metastasis in non-MS was higher in tumors larger than 40 mm than those smaller than 40 mm (P = .011). Conclusion When performing SN navigation surgery in gastric cancer, we should keep in mind that the patients with tumor larger than 40 mm in size and nodal metastasis of non-MS may have non-SN metastasis and nodal metastasis in second tier.     

A New pN Staging System Based on Both the Number and Anatomic Location of Metastatic Lymph Nodes in Gastric Cancer

Background

Our aim was to establish a new pN staging system for gastric cancer based on the number and location of metastatic lymph nodes (MLNs) and to compare it with other systems.

Methods

We retrospectively analyzed the prognostic data of 521 gastric cancer patients who underwent curative resection. Survival analyses were used to establish a pN staging system that considers both the number and location of MLNs and to compare discriminatory ability and monotonicity of gradients (linear trend χ ² score), homogeneity ability (likelihood ratio test), and prognostic stratification ability (Akaike information criterion) between Japanese Gastric Cancer Association (JGCA) and Union for International Cancer Control (UICC) systems.

Results

Cut-point survival analysis divided pN⁺ patients into two groups: Nxn_1~6 and Nxn_≥7. N0, N1, N2, and N3 (the previous classifications) were replaced by N0, N1n_1~6, N2n_1~6, and N1n_≥7 + N2n_≥7 + N3n_1~6 + N3n_≥7, respectively. Compared with two widely used staging systems, the new system had the highest likelihood ratio test [106.06 (new) vs 95.09 (JGCA) vs 94.33 (UICC)] and linear trend χ ² scores [102.30 (new) vs 89.12 (JGCA) vs 86.97(UICC)] and the lowest Akaike information criterion (AIC) score [2,283.88 (new) vs 2,285.31 (JGCA) vs 2,299.88 (UICC)].

Conclusion

A new pN staging system based on the number and location of MLNs is an efficient prognostic indicator of the survival of patients with gastric cancer following radical surgery.     

Detection of Metastatic Lymph Nodes Using 5-Aminolevulinic Acid in Patients with Gastric Cancer

Background

Precise diagnosis of lymph node metastases is essential to select therapeutic strategy for patients with gastric cancer, and rapid intraoperative diagnosis is useful for performing less invasive surgery. In this study, we focused on a known photosensitizer, 5-aminolevulinic acid (5-ALA), and examined the feasibility of 5-ALA-induced protoporphyrin IX (PpIX) fluorescence to detect metastatic foci in excised lymph nodes of patients with gastric cancer.

Methods

A total of 144 lymph nodes obtained from 14 gastric cancer patients were examined. The patients were administered 5-ALA orally before surgery. Excised lymph nodes were cut in half and observed by fluorescence microscopy. The diagnostic results were compared to those of the routine histopathological examination.

Results

Observed red fluorescence of PpIX was identical to the metastatic focus, with 84 % accuracy. Twelve non-metastatic lymph nodes showed unexpected PpIX accumulation to lymphoid follicles, but these could be discriminated based on their characteristic fluorescence patterns. With incorporation of this morphological consideration, this method demonstrated good diagnostic power with 92.4 % accuracy. On the quantitative analysis using the signal intensity ratio of red to the sum of red, green, and blue (R/(R + G + B) ratio) as an index corresponding to red fluorescence of PpIX, metastatic lymph nodes showed significantly higher value than non-metastatic lymph nodes (p < 0.0001). The area under the curve was calculated as 0.832 throughout Receiver operating characteristic analysis.

Conclusions

Our results demonstrated that 5-ALA-induced fluorescence diagnosis is a simple and safe method and is a potential candidate for a novel rapid intraoperative diagnostic method applicable to clinical practice.     

胃癌第6组及其亚组淋巴结转移率和转移度的初步研究

目的检测胃幽门下(第6组)及其亚组淋巴结转移情况,以探讨临床合理清扫第6组淋巴结的价值。方法回顾性分析2006年1月至2009年12月期间我院80例接受根治性手术且有完整第6组及其3个亚组淋巴结送检资料的胃癌患者的临床病理资料,以胃网膜右静脉为参照将第6组淋巴结分为第6a、6b和6c亚组,计算第6组及其亚组淋巴结转移率和转移度,并对其淋巴结转移情况与胃癌临床病理特征和其他组(第7、8a和9组)淋巴结转移情况的关系进行logistic回归分析。结果 80例胃癌患者中第6组淋巴结转移率为41.3%(33/80),转移度为26.0%(108/415)。第6a亚组淋巴结转移率为7.5%(6/80),明显低于第6b亚组(16.3%,13/80)和第6c亚组(36.3%,29/80),P<0.001;第6a、6b和6c亚组淋巴结转移度分别为25.0%(8/32)、17.6%(13/74)和28.2%(87/309),差异无统计学意义(P=0.292)。第6a亚组阳性淋巴结与T分期(P=0.042)和N分期(P=0.006)有关;第6b亚组阳性淋巴结与N分期(P=0.002)和TNM分期(P=0.013)有关;第6c亚组阳性淋巴结与肿瘤分化程度(P=0.008)、T分期(P=0.003)、N分期(P=0.000)和TNM分期(P=0.000)有关。logistic回归分析显示:第6组淋巴结转移情况与第8a组淋巴结转移(P=0.023)和N分期(P=0.002)均有关;第6a亚组淋巴结转移与第8a组淋巴结转移有关(P=0.018);第6b亚组淋巴结转移与N分期有关(P=0.005);第6c亚组淋巴结转移与第8a组淋巴结转移(P=0.016)和N分期(P=0.004)均有关。结论胃癌手术中要彻底清扫第6组淋巴结,尤其要重视第6a和6b亚组淋巴结的清扫。     

胃癌淋巴结转移的CT分组定位诊断法

目的：评价CT对胃癌淋巴结转移的诊断价值以及临床应用价值。方法：采用分组定位诊断方法，通过识别CT上作为标志的血管、脏器以确定各组淋巴结所在位置，将CT观察结果与手术所见和病理检查结果相比较，得出CT对各组淋巴结诊断的准确性、特异性、敏感性。结果：CT检查胃癌转移淋巴结准确率较高的为第3、7、9、1、16组等，敏感性较高的为第3、1、7、9、16组等，特异性较高的为第3、7、9、12、1、16组等。结论：分组定位诊断法全面评价了CT对胃癌各组淋巴结转移的诊断性能，将此方法的特点与临床病理、淋巴结转移规律相结合，对提高术前分期准确性、选择合理的治疗方法具有一定价值。     

Outcome of Patients With Proximal Gastric Cancer Depends on Extent of Resection and Number of Resected Lymph Nodes

Background: Studies have shown that the survival of patients with gastric adenocarcinoma is related to the number of regional lymph nodes with metastases. The probability of identifying node-positive cancers increases with the number of lymph nodes resected and examined. It has been recommended that at least 15 lymph nodes be removed and examined for adequate staging. Prospective randomized studies have shown the lymph node yield is much greater with the D2 resection than the D1. This study evaluated the relative contribution of both the number of resected lymph nodes and the extent of gastric resection (D1/D2) on the outcome of patients with proximal gastric cancer.Methods: The medical records of 114 patients with adenocarcinoma of the proximal stomach, who underwent a curative gastric resection, were reviewed. Patients were stratified into four groups, i.e., two groups, D1/D1.5 and D2/D2.5, based on the extent of resection, and two groups based on the number of lymph nodes removed, fewer than 15 lymph nodes and 15 or more lymph nodes. Survival was determined by the method of Kaplan-Meier and differences compared by the log-rank test. Multivariate analysis was performed by using the Cox model.Results: The number of resected lymph nodes had no effect on the survival of the group as a whole. A significant improvement in survival was noted for patients with a D2 or greater resection. The median survival of patients with 15 or more lymph nodes resected improved from 25 months to 42 months when treated with an extended resection, (D2 or D2.5). Resection of 15 or more lymph nodes alone, or combined with an extended resection, resulted in a statistically significant improvement in survival for patients in American Joint Committee on Cancer Staging (AJCC) stage II.Conclusions: Both resection of 15 or more lymph nodes and extended lymphadenectomy contributed to the survival advantage observed in patients with AJCC stage II gastric cancer. The D2 gastric resection prolonged the median survival time and improved the 5-year survival rate for patients with 15 or more resected lymph nodes.Presented at the 52nd Annual Meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

次级淋巴组织趋化因子在胃癌淋巴结转移中的作用

目的：研究次级淋巴组织趋化因子（secondary lymphoid tissue chemokine,SLC)在胃癌淋巴结中的表达，以进一步阐明胃癌淋巴转移的机制。方法：用逆转录聚合酶链反应（RT－PCR）测定29例胃癌组织淋巴结中SLC mRNA的表达。结果：胃癌转移淋巴结中SLC mRNA的表达均显著低于相应的正常胃黏模组织，但其表达与病人的临床病理特征并不相关。结论：在胃癌转移淋巴结中，SLC的表达明显受抑，后者可能在胃癌的淋巴结转移中起了重要作用，提高淋巴结中SLC的表达可能成为控制胃癌转移和复发的又一关键途径。     

Adjustment of N Stages of Gastric Cancer by the Ratio Between the Metastatic and Examined Lymph Nodes

Background  The present study attempted to determine whether N stage could be adjusted for the differences in survival rates based on the ratio between the examined and metastatic lymph nodes (LN ratio). Methods  Five hundred and twenty-nine patients with both >15 lymph nodes examined and ≥ N1 after R0 resection were enrolled in the present study. To determine the cutoff LN ratio, the ratios at each N stage were compared at intervals of 10% with the log-rank test of Kaplan–Meier estimates of the survival curves. Results  The 5-year survival rate of patients with N1 was 71.7%. Those of N2 patients with LN ratio of <60% (n = 116) and ≥60% (n = 3) were 37.0% and 0%, respectively. Those of N3 patients with LN ratio of <30% (n = 32), between 30% and 60% (n = 67), and ≥60% (n = 26) were 31.0%, 16.3%, and 0%, respectively. Thus, adjusted N2 was obtained from the sum of N2 < 60% and N3 < 30%. N3 with an LN ratio between 30% and 60% was regarded as adjusted N3. N2 and N3 patients with an LN ratio of ≥60% were regarded as adjusted T4. The 5-year survival rate in patients with adjusted N2, N3, and N4 were 35.7%, 16.3%, and 0%, respectively. Multivariate analysis showed adjusted N stage and tumor depth were significant independent prognostic factors. Conclusions  The results of this study suggest that, since stage migration can be induced in the N staging system, such stage migration can be adjusted by the LN ratio based on the survival rate.     

The Prognosis of Patients Operated on for Gastric Cancer in Relation to the Percentage of Lymph Nodes Invaded by Tumour

Introduction : In evaluating the type of gastrectomy and lymphadenectomy for gastric cancer, adequate prognosis has been dependant on the retrieval of at least 15 lymph nodes. We propose an alternative method in which the prognostic value is evaluated, according to whether or not more than 20% of the retrieved lymph nodes are invaded by tumour.

Materials & Methods : Sixty-five patients (36 men, 29 women) with a median age of 69 years (mean age 68.9 ± 12.1 years) were evaluated, who were operated upon between 1985 and 1999 for gastric cancer by gastrectomy with either D1 or D2 lymphadenectomy.

Results : The average number of retrieved lymph nodes was 10.4 ± 8.6. In 51 patients (78.5%) less than 15 and in 14 patients (21.5%) 15 or more lymph nodes were retrieved, according to the TNM guidelines. In our study, there is a statistically significant difference in prognosis between patients with less than 20% and those with more than 20% of the retrieved lymph nodes invaded by tumour, irrespective of the total number of lymph nodes resected. Conclusion : Gastric cancer patients in whom less than 20% of the retrieved lymph nodes are invaded, have a significantly better prognosis compared with patients in whom 20% or more of the lymph nodes retrieved are invaded by tumour, irrespective of the total number of retrieved lymph nodes.     

淋巴结转移率对结直肠癌患者预后的影响

为探讨淋巴结转移率（rN）对结直肠癌患者预后的影响,回顾分析362例结直肠癌患者的临床病理资料和随访情况,分析rN与结直肠癌患者预后的关系。结果显示,患者3年、5年生存率与rN分期有关,P〈O．05。结果表明,rN分期可帮助评估结直肠癌患者的预后。     

胸段食管鳞癌淋巴结合理廓清范围的探讨

目的通过分析胸段食管鳞癌淋巴结转移方式、转移规律及其与相关病理因素的关系,探讨淋巴结合理廓清范围。方法对117例胸段食管鳞癌患者行食管癌手术中摘除有癌转移的淋巴结155枚,采用logistic回归分析临床病理因素与淋巴结转移的关系。结果胸段食管鳞癌患者无论肿瘤病理类型和临床状态如何,均有淋巴结转移。肿瘤分化程度和浸润深度对淋巴结转移率有明显的影响,肿瘤分化越低,浸润深度越深,淋巴结转移率越高。纵隔淋巴结转移多位于隆突下和癌旁,腹腔淋巴结转移多发生于胃左血管旁及胃小弯处。结论对胸段食管鳞癌应行常规胸、腹两野淋巴结清扫,尤其对T3和T4的患者,对有颈部淋巴结转移的患者应行颈、胸、腹三野淋巴结清扫;手术中对颈部可疑淋巴结转移的患者可行活组织冰冻病理检查。尽可能达到根治,提高手术疗效。     

The Microanatomic Location of Metastatic Breast Cancer in Sentinel Lymph Nodes Predicts Nonsentinel Lymph Node Involvement

Background The majority of sentinel node (SN) positive breast cancer patients do not have additional non-SN involvement and may not benefit from axillary lymph node dissection (ALND). Previous studies in melanoma have suggested that microanatomic localization of SN metastases may predict non-SN involvement. The present study was designed to assess whether these criteria might also be used to be more restrictive in selecting breast cancer patients who would benefit from an ALND. Methods A consecutive series of 357 patients with invasive breast cancer and a tumor-positive axillary SN, followed by an ALND, was reviewed. Microanatomic SN tumor features (subcapsular, combined subcapsular and parenchymal, parenchymal, extensive localization, multifocality, and the penetrative depth from the SN capsule) were evaluated for their predictive value for non-SN involvement. Results Non-SN metastases were found in 136/357 cases (38%). Microanatomic location and penetrative depth of SN metastases were significant predictors for non-SN involvement (<0.001); limited penetrative depth was associated with a low frequency of non-SN involvement with a minimal of 10%. Conclusions Microanatomic location and penetrative depth of breast cancer SN metastases predict non-SN involvement. However, based on these features no subgroup of patients could be selected with less than 10% non-SN involvement.