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Predictive factors of lymph node metastasis in patients with undifferentiated early gastric cancers.

BACKGROUND: For intramucosal differentiated early gastric cancer that has little risk of lymph node metastasis, local treatment such as endoscopic mucosal resection has been generally accepted as an adequate treatment. We studied clinicopathological characteristics of undifferentiated early gastric cancer at our institution to identify the predictive factors for lymph node metastasis and qualify lesions that should be referred for gastrectomy and not endoscopic mucosal resection. METHODS: We retrospectively analyzed the clinicopathological features (patient age and gender, tumor size, location, macroscopic type and histological type, presence of ulceration, depth of tumor invasion, and lymphatic-vascular involvement) in 332 patients with undifferentiated early gastric cancer who underwent gastrectomy with regional lymph node dissection. RESULTS: Lymph node metastasis was observed in 45 patients (14%). Univariate analysis revealed that depth of tumor invasion (submucosa), tumor size (>30 mm), and lymphatic-vascular involvement (positive) were associated with lymph node metastasis. Only lymphatic-vascular involvement (positive) was found to have a significant association (odds ratio, 7.4; 95% confidence interval, 2.9-19.0) by multivariate analysis. CONCLUSIONS: Lymphatic-vascular involvement was the only independent predictive risk factor for lymph node metastasis. This pathologic factor was not useful for identifying patients at high risk of lymph node metastasis who should be offered gastrectomy rather than endoscopic mucosal resection.

Adult↗

Relationship between existence of lymphatic invasion in peritumoral breast tissue and presence of axillary lymph node metastasis in invasive ductal carcinoma of the breast.

Specimens obtained from 92 patients with invasive ductal carcinoma of the breast by quadrantectomy and axillary lymph node dissection were examined to evaluate the relationship between existence of lymphatic invasion in peritumoral breast tissue and presence of axillary lymph node metastasis. The number of lymphatic invasions was classified into 4 groups (ly0-3) by counting the number of peritumoral lymphatic invasions. In addition, immunohistochemistry for cytokeratin was performed to locate micrometastasis in the dissected lymph nodes. Thirty-seven (40.2%) of 92 cases had foci of lymphatic invasion and 29 (31.5%) cases revealed lymph node metastasis on initial routine examination. The rate of diagnosis of lymph node metastasis assessed by the existence of lymphatic invasion had an accuracy of 84.8%, a sensitivity of 89.7% and a specificity of 82.5%. On the other hand, all 3 cases (4.8%) with micrometastasis detected by immunohistochemistry for cytokeratin, showed lymphatic invasion. The rate of diagnosis after detection of micrometastasis increased and exhibited 88.0% accuracy. In addition, the rate of prediction of lymph node metastasis in cases with tumor larger than 15 mm was also high, and its accuracy was 88.2%. These results suggest that the assessment of peritumoral lymphatic invasion is very useful for predicting the presence of axillary lymph node metastasis including micrometastasis. They also suggest that excision specimens should be examined for lymphatic invasion, and that the results of the examination might be necessary to pick up false-negative cases and those at high risk for lymph node metastasis among patients who have not undergone lymph node dissection based on the result of sentinel lymph node biopsy.

Adult↗

Lymph node metastasis of early gastric cancer with submucosal invasion.

BACKGROUND: A clinicopathological study of early gastric cancer with submucosal invasion was carried out in relation to lymph node metastasis. METHODS: A retrospective study was conducted of 245 patients with submucosal gastric cancer treated by gastrectomy combined with D2 lymph node resection between 1985 and 1994 in a university hospital. RESULTS: Lymph node metastasis was observed in 34 patients (14 per cent). The mortality rate due to recurrence in patients with lymph node metastasis (three of 34) was significantly higher than in those without lymph node metastasis (five (2 per cent) of 211) (chi2 = 3.95, 1 d.f., P < 0.05). Tumour size, depth of invasion, lymphatic involvement of cancer cells and preoperative diagnosis of advanced cancer correlated significantly with the presence of lymph node metastasis. When the submucosal carcinomas were classified into three categories according to depth of invasion by dividing the submucosal (sm) layer into three equal parts, sm1, sm2 and sm3, the incidence of lymph node metastasis increased from 2 per cent to 12 and 20 per cent respectively. CONCLUSION: When the pathological report reveals sm1 invasion after laparoscopic or endoscopic surgery, reoperation should not be necessary because sm1-carcinomas with diameters of less than 2 cm do not usually metastasize to the lymph nodes.

Adult↗

Indications for pylorus-preserving gastrectomy for gastric cancer based on lymph node metastasis.

BACKGROUND/AIMS: It is necessary to study the relation between lymph node metastasis in the suprapyloric or lesser curvature regions and clinicopathologic findings in order to determine the indications for pylorus-preserving gastrectomy. METHODOLOGY: We reviewed all pertinent data from the cases of 109 patients with gastric cancer located mainly in the middle third of the stomach focusing particularly on status of lymph node metastasis and clinicopathologic findings. All patients had been treated by conventional gastrectomy with regional lymph node dissection (D2 or D3). RESULTS: Lymph node metastases were found in the lesser curvature or suprapyloric regions in 18 patients. Primary tumors were located in the lesser curvature side in 15 of these 18 patients and in the greater curvature side in only 3. Primary tumors in the greater curvature side with involvement in the lesser curvature or suprapyloric lymph nodes were greater than 4.0 cm in diameter, whereas primary tumors in the lesser curvature side with such metastasis were greater than 1.3 cm. CONCLUSIONS: Indications for pylorus-preserving gastrectomy with preserving of the pyloric branch of the vagal nerve perhaps can be expanded to middle stomach cancer located in the greater curvature side that is less than 4.0 cm in diameter.

Adenocarcinoma↗

Lymph node metastasis in stage I epithelial ovarian cancer.

OBJECTIVES: A relatively high incidence of para-aortic and pelvic lymph node metastasis is found in epithelial ovarian cancer. This paper investigates the clinicomorphological features of intra-abdominal stage I epithelial ovarian cancer that may predict the occurrence of lymph node metastasis and the prognosis of patients in whom lymph node metastases are identified. METHODS: From November 1988 to December 1997 we performed systematic para-aortic and pelvic lymphadenectomy as primary surgery in 47 patients with intra-abdominal stage I epithelial ovarian cancer. The incidence of lymph node metastasis in these patients and the clinicomorphological features of the patients with lymph node involvement were examined. RESULTS: Five patients (10.6%) were metastasis positive (IC: four; IA: one), of whom four had serous adenocarcinoma. Serous adenocarcinoma was associated with a significantly higher incidence of metastases than other histological types (P < 0.05). The number of positive lymph nodes was one in four patients and two in one patient, and the metastatic sites ranged from the para-aortic to the suprainguinal lymph nodes. All five metastasis-positive patients were alive and disease free at the time of this report (survival 28-85 months: median 59 months). CONCLUSION: This clinical study suggests that serous adenocarcinoma carries a high risk of lymph node metastasis, requiring systematic lymphadenectomy for accurate staging in intra-abdominal stage I epithelial ovarian cancer.

Adenocarcinoma↗

[A case report of gastric carcinoma with complete remission of paraaortic lymph node metastasis by 5'-DFUR and MMC administration after resection of primary tumor].

A 53-year-old man was referred to our hospital with Borrmann type 2 advanced gastric cancer with a Virchow's node metastasis. A CT scan revealed a paraaortic lymph node metastasis. Because the tumor was diagnosed as being a poor candidate for curative resection, only a total gastrectomy was done. After surgery, administration of 5'-DFUR and MMC was begun. As a result, the paraaortic lymph node metastasis disappeared and the Virchow's node metastasis was reduced. The patient is well with no sign of recurrence 20 months after the operation.

Antineoplastic Combined Chemotherapy Protocols↗

Inhibition of lymph node metastasis by an anti-angiogenic agent, TNP-470.

We assessed the inhibitory action of TNP-470 on lymph node metastasis in a metastatic model system using athymic nude mice. Mice were injected subcutaneously with 5 x 10(6) HT-1080 cells in the right groin. TNP-470 (10, 30 and 100 mg kg-1) was injected subcutaneously nine times in total every other day from the 7th day after tumour inoculation. Axillar and inguinal lymph nodes were dissected, and DNA was extracted 5 weeks after tumour inoculation. Specific detection of a human beta-globin-related sequence in metastasized human tumour cells in nude mice was done by the polymerase chain reaction (PCR) technique and analysed by Southern blotting. Anti-tumour effects on primary sites were seen only in the 100 mg kg-1 treatment group. Lymph node metastasis of transplanted HT-1080 cells was seen in all mice of the no treatment group (5/5). On the other hand, incidences of lymph node metastasis in treated mice were 2/4 mice (100 mg kg-1, 2/5 mice (30 mg kg-1) and 4/5 mice (10 mg kg-1). The inhibition ratios of lymph node metastasis were 82.3% at 10 mg kg-1, 97.2% at 30 mg kg-1 and 97.5% at 100 mg kg-1 respectively. This agent may be useful to inhibit lymph node metastasis.

Animals↗

Evaluation of prognostic significance in extracapsular spread of lymph node metastasis in patients with gastric cancer.

BACKGROUND: Extracapsular spread of lymph node metastasis has been shown as a negative prognostic factor in cancers of several other organs. This study was performed to clarify the prognostic significance of extracapsular spread in patients receiving curative resection for gastric cancer. METHODS: Extracapsular spread was defined as infiltration of cancer cells beyond the capsule of the metastatic lymph node. Four hundred and two patients who underwent curative gastrectomy were evaluated. Eight potential prognostic factors, including the International Union Against Cancer (Union International Contra la Cancrum; [UICC]) N stage and nodal status classified by the presence of lymph node metastasis or extracapsular spread, were examined. RESULTS: Three survival curves grouped by nodal status differed significantly, and prognosis of patients with extracapsular spread was significantly worse than for the other groups. Both UICC N stage ( P < .001) and nodal status ( P < .001) were significant prognostic factors by multivariate analysis. UICC N stages were subcategorized by nodal status, and survival was shown to be significantly worse in patients with extracapsular spread in the UICC N1 group ( P = .04). CONCLUSIONS: Extracapsular spread was a significant negative prognostic indicator on multivariate analysis, and may be useful in combination with UICC N stage. Extracapsular spread was regarded as an important indicator to refine the nodal staging system in gastric cancer.

Adult↗

Serum soluble interleukin-2 receptor as a predictor of lymph node metastasis in early gastric cancer.

BACKGROUND: In the present study, we investigated the clinical significance of serum soluble IL-2R as a predictor of lymph node metastasis in patients with early gastric cancer. PATIENTS AND METHODS: Seventy-four patients with early gastric cancer were enrolled in this study. Levels of serum soluble IL-2R were measured by an enzyme-linked immunosorbent assay. RESULT: Significant differences in serum soluble IL-2R between the control group and cases of T1 were not recognized. On the other hand, levels of serum soluble IL-2R in 74 patients with early gastric cancer (T1) were significantly lower than those of T2, T3, and T4 (p < 0.05). There were no significant differences in serum soluble IL-2R between cases of mucosal and submucosal invasion (379 +/- 42 vs. 382 +/- 35 U/ml). Six of 35 patients with submucosal invasion (17.1%) had lymph node metastasis, but none of the 39 patients with mucosal invasion. In the 6 cases showing lymph node metastasis, the macroscopic types were IIc + Ul(+) in 4, and IIc + IIa and IIc + IIb in 1, respectively. Histopathologically, there were 5 poorly and 1 moderately differentiated adenocarcinomas. In 6 cases with lymph node metastasis, serum soluble IL-2R levels were significantly higher than in those without lymph node metastasis (556.8 +/- 73 vs. 329 +/- 22 U/ml, respectively, mean +/- SEM, p < 0.05). Five of these 6 cases demonstrated statistically significantly increased levels of serum soluble IL-2R (sensitivity 83%, specificity 63%), suggesting serum soluble IL-2R as a predictor of lymph node metastasis in early gastric cancer (p < 0.05). CONCLUSION: According to these data, in patients of early gastric cancer with increased levels of serum soluble IL-2R, endoscopic mucosal resection or minimal invasive gastrectomy without dissection of regional lymph nodes should be avoided, since there is a high risk of lymph node metastasis.

Adult↗

Predictive factors for lymph node metastasis in T1 stage colorectal carcinomas.

PURPOSE: Selective endoscopic resection may cure early colorectal cancer (T1), but the management is controversial. There is concern about the small risk of lymph node metastasis, which will not be treated by endoscopic resection alone. The authors sought predictive markers of lymph node metastasis to assist patient management. METHODS: The authors retrospectively analyzed consecutive cases of T1 stage colorectal cancer resected using endoscopic 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 (> or = 2,000 microm) 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 endoscopic resection.

Aged↗

[Angiographic evaluation of lymph node metastasis in gastric cancer].

Areas of lymph distribution and groups of lymph nodes of the stomach are related to the areas of blood vessel distribution. Angiography is one of the methods to diagnose gastroserous disorders. Out of 164 metastatic lymph nodes in 50 cases of (n+) gastric cancer, the metastasis was recognized macroscopically and histologically in 111 lymph nodes (N. group), and histological metastasis findings was recognized in 53 cases (n group). Mapping of gastric lymph nodes and surrounding blood vessels was performed and preoperative angiograms were evaluated retrospectively in view of the positive lymph nodes. The positive diagnostic ratio of all lymph nodes was expressed as a percent for all metastatic lymph nodes and individual metastatic nodes were evaluated in terms of group, n-number, tumor location, depth of invasion, histologic type of the primary lesion, invasion to intra-serous wall lymph nodes and etc. Conventional diagnosis of the metastatic lymph nodes was made based on the compression and rigidity of the vessels in the angiogram with little correlation with other angiographical findings. In the present study, however, the correlation was clarified and positive lymph node metastasis could be proved by angiogram prior to surgery with considerable accuracy.

Adenocarcinoma↗

Lymph node metastasis and prognosis in small peripheral non-small-cell lung cancers.

OBJECTIVE: The lymph node dissection and curative resection for small peripheral non-small-cell lung cancers, it is essential to know the incidence and distribution of lymph node metastasis to confirm the pathological stage. METHODS: Between January 1984 and August 1996, lobectomy with systemic mediastinal dissection (standard lobectomy) was conducted in 49 patients with small peripheral non-small-cell lung cancers (2.0 cm or less in diameter), and limited resection was conducted in 15 with cardiopulmonary insufficiency. RESULTS: Lymph node metastasis was confirmed histologically in 14 patients undergoing standard lobectomy (28.6%). The incidence of lymph node metastasis was high in tumors with pleural (p2) or subpleural (p1) involvement (63.6%) (7/14). The 5-year survival between standard lobectomy and limited resection patients (83% vs. 71%) was not statistically significant. In patients undergoing standard lobectomy, survival in those with node-negative disease was better than in those with node-positive disease (94% vs. 44%, p < 0.01). CONCLUSIONS: Lymph node involvement, especially in tumors with pleural involvement, is not uncommon, even when tumors are 2.0 cm or less in diameter. Systemic hilar and mediastinal dissection is therefore required for disease staging and treatment.

Aged↗

Diagnostic efficacy of the preoperative lymphoscintigraphy, Ga-67 scintigraphy and computed tomography for detection of lymph node metastasis in cases with ovarian or endometrial carcinoma.

BACKGROUND: To investigate the diagnostic efficacy of preoperative lymphoscintigraphy (LS), Ga-67 scintigraphy (GS) and computed tomography (CT) for detection of lymph node metastasis in patients with endometrial or ovarian carcinoma. METHODS: The results of preoperative LS, GS and CT used to detect lymph node metastasis were compared to the postoperative histopathological results of lymph node dissection materials of a total of 37 patients, including 16 patients with endometrial and 21 patients with ovarian carcinomas. The diagnostic efficacy of these methods for detecting lymph node metastasis were calculated. RESULTS: When the results of all of the patients were taken into account, the preoperative LS, GS and CT were found to have sensitivities of 50%, 20% and 40% and specificities of 51.8%, 96.3%, and 92.6%, respectively, for detection of pelvic lymph node metastasis. The same methods had sensitivities of 27.3%, 27.3% and 72.7% and specificities of 88.5%, 88.5%, 84.6%, respectively, for detecting para-aortic lymph node metastasis in all patients. CONCLUSION: These data suggested that although LS, GS and CT had relatively high specificity, low sensitivity of these imaging methods precluded their routine preoperative use for diagnosis of lymph node metastasis of ovarian or endometrial carcinoma.

Adolescent↗

Lymph node metastasis in patients with adenocarcinoma of gastric cardia.

BACKGROUND AND METHODS: Prospectively, a consecutive series of 42 patients undergoing extended radical total gastrectomies (R 3/4 lymph node dissection) for adenocarcinoma of the gastric cardia from January 1988 to June 1991 were studied. The aims of this study were to evaluate the status of lymph node metastasis and the relationship between the frequency of nodal involvement and the extent of the primary tumor invasion. The Japanese criteria was used for postoperative staging. RESULTS: The incidence of operative morbidity and mortality in the series were 40.5% and 9.5%, respectively. Twenty-two (52%) of the patients had lymph node metastasis. For those patients, the most common sites of nodal involvement were the lesser curvature (72.7%), pericardiac (68.2%), left gastric artery (45.5%), left greater curvature (31.8%), splenic artery (31.8%), and the hilum (22.7%), inferior paraesophageal (18.2%), and diaphragmatic (18.2%) regions. Only one skip lymph node metastasis was discovered. In addition, no lymph node metastasis was found in the following areas: hepatoduodenal ligaments, mesenteric root, right paraadrenal, and subcardial lymph nodes. CONCLUSIONS: The study's results demonstrate that there seemed to a correlation among the status of lymph node metastasis, tumor size, and the depth of tumor invasion. However, the depth of tumor invasion appears to be a more important factor than tumor size in influencing the status of lymph node metastasis. The local recurrence rate was 2.4%. Consequently, the authors recommend that for the tumor with mucosal invasion only, a relatively conservative lymphadenectomy may be sufficient, but for tumors that invade beyond the mucosal region, radical lymphadenectomy may be helpful in preventing local recurrence.

Adenocarcinoma↗

Frequency of nonsentinel lymph node metastasis in melanoma.

BACKGROUND: Completion lymph node dissection (CLND) may not be necessary for some patients because nodal metastasis is rarely detected beyond the sentinel lymph nodes (SLNs). This analysis was performed to determine, among patients with positive SLNs, the rate of nodal metastasis found in nonsentinel nodes (NSNs). METHODS: This analysis includes patients with positive sentinel nodes, detected by hematoxylin and eosin (H&E) staining or immunohistochemistry (IHC), who then underwent CLND. RESULTS: This analysis included 274 patients with at least one positive SLN who underwent CLND of 282 involved regional nodal basins. Of the 282 SLN-positive nodal basins, 45 (16%) were found to have positive NSNs in the CLND specimen. Breslow thickness, Clark level, presence of ulceration, histological subtype, presence of vertical growth phase, evidence of regression, presence of lymphovascular invasion, number of positive SLNs, age, sex, and presence of multiple draining nodal basins were not predictive of positive nodes in the CLND specimen. Patients with SLN metastases detected only by IHC had an equal likelihood of having positive NSNs as those patients with positive SLNs on H&E examination. CONCLUSIONS: No patient population could be identified with minimal risk of non-SLN metastasis. When a positive SLN is identified on either H&E staining or IHC, CLND should be performed routinely.

Adult↗

Flow cytometric analysis of squamous cell carcinomas of the oral cavity in relation to lymph node metastasis.

Nuclear DNA content and cell kinetics were studied in 40 squamous cell carcinomas of the oral cavity by flow cytometry to evaluate the diagnostic significance of the method in predicting lymph node metastasis. The presence of lymph node metastasis was confirmed histologically in 20 carcinomas. The incidence of metastasis was 36% in group A (22 carcinomas of the tongue and floor of the mouth) and 67% in group B (18 carcinomas of the alveolus and gingiva). On flow cytometric analysis, DNA aneuploidy was observed in 23 tumors (58%). The incidence of lymph node metastasis in the aneuploid tumors was 70%, which was significantly higher than the 24% for the diploid tumors. This also was the case for both of the subgroups. The incidence of aneuploidy and the DNA index for tumors with metastasis were 80% and 1.58, respectively. These values were significantly higher than the 35% and 1.16 for tumors without metastasis, but there were no significant differences in the S phase and G2M phase fractions between the tumors with and without metastasis. The incidence of aneuploidy in tumors with metastasis was also higher in group A (75% versus 36%) and group B (83% versus 33%). In terms of histologic differentiation, the incidence of metastasis and aneuploidy increased as the degree of differentiation decreased. Similar relationships were found between the histologic grade of malignancy and the incidence of metastasis and aneuploidy. The results indicate that nuclear DNA content analysis by flow cytometry is useful as a supplement to clinical and histologic evaluation in predicting the tendency of squamous cell carcinomas of the oral cavity to metastasize to regional lymph nodes.

Adult↗

Quantification of vascular endothelial growth factor-C and its receptor-3 messenger RNA with real-time quantitative polymerase chain reaction as a predictor of lymph node metastasis in human colorectal cancer.

BACKGROUND: This study was undertaken to determine whether vascular endothelial growth factor-C (VEGF-C) and the expression of its receptor VEGF receptor-3 (VEGFR-3) are correlated with lymph node metastasis in human colorectal cancer and whether their expression levels might be used to predict lymph node metastasis. METHODS: Fifty-three surgical specimens of colorectal cancer with (n = 24) or without (n = 29) lymph node metastasis were studied. The messenger RNA (mRNA) expression of VEGF-C and VEGFR-3 was quantified with a new method for kinetic quantitative polymerase chain reaction (PCR), real-time quantitative (RTQ) reverse transcriptase-PCR. In addition, their protein expressions were assessed immunohistochemically. RESULTS: The VEGF-C mRNA level in primary tumors correlated with VEGF-C protein expression, lymph node metastasis, and lymphatic invasion. Sixteen of 24 patients with lymph node metastasis showed VEGF-C mRNA overexpression. Morphologically, VEGF-C protein expression in primary tumors showed a statistically significant relationship with lymph node metastasis and lymphatic invasion. CONCLUSION: Real-time quantitative reverse transcriptase-PCR is a sensitive method for detection and quantification of VEGF-C and VEGFR-3 mRNA expression. Furthermore, the expression levels of VEGF-C mRNA and protein in colorectal cancer are correlated with lymph node metastasis and lymphatic invasion.

Aged↗

Epithelioid sarcoma: an analysis of 22 cases indicating the prognostic significance of vascular invasion and regional lymph node metastasis.

Twenty-two cases of epithelioid sarcoma seen and/or treated at Memorial Hospital are presented. With the exception of one tumor which occurred in the neck, all the sarcomas arose in the upper (15 cases) or lower extremities (6 cases). Ten originated in the hand. At the time of initial treatment, 14/22 patients were between 20 and 40 years of age. The tumor most commonly presented as a nodular lesion and involved dermis, subcutaneous tissue, fascia and tendons, and when it recurred (13 cases) it tended to grow proximally along tendons and fascial planes. Of special interest was the finding of vascular invasion in surgical specimens removed from 5 patients. Four of these represented recurrent tumor, and in two cases the vascular invasion was massive. Two of these patients also demonstrated tumor emboli in pulmonary vessels and cardiac involvement at autopsy. Metastasis to regional lymph nodes occurred in eight cases (42%). Follow-up ranging from 2 to 34 years (average of 8 years) was obtained for 19 cases (86%). Eleven patients are alive with disease or died as a result of their sarcoma (58% of the follow-up group). Adverse prognostic factors included recurrence after initial local excision, vascular invasion and lymph node metastasis. All of the patients with intravenous extension of tumor and 6 of 8 patients with lymph node involvement died with pulmonary metastases. Our data suggest that cure may best be achieved by amputation or by an exceptionally wide en bloc excision as early as possible, depending upon the location and extent of the original tumor.

Adolescent↗