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Incidence of lymph node metastasis and its impact on long-term prognosis in clinically localized prostate cancer.

BACKGROUND: Pelvic lymph node dissection (PLND) is an important staging method for men with clinically localized prostate cancer. We report our experience with staging PLND and the impact of lymph node metastasis on long-term prognosis. METHODS: One hundred forty-eight consecutive patients who underwent staging PLND for clinically localized prostate cancer were retrospectively studied. Patients were evaluated for the presence and number of lymph node metastases, treatment (prostatectomy vs. radiotherapy), and endocrine therapy, and analyzed with respect to disease progression and survival. The mean follow-up period was 52.9 months (range, 2.3 to 165.8 months). RESULTS: Thirty-two patients (21.6%) had pelvic lymph node metastases, the incidence of which markedly decreased from 32.3% in 1982 to 1987 to 6.7% in 1994 to 1997. The intervals to disease progression and cancer death were significantly shorter in patients with positive lymph nodes (P < 0.001). In stage D1 disease, patients who underwent a radical prostatectomy tended to be free of progression longer than those receiving radiotherapy or conservative therapy (P = 0.0546). Other factors, such as early endocrine therapy, the extent of lymph node involvement and the Gleason score of the primary tumor did not predict disease progression or survival. CONCLUSION: These data suggest a decreasing trend in the incidence of lymph node metastasis in the PSA era. Although longer disease-free intervals were observed in radical prostatectomy-treated patients, the impact of an aggressive approach to stage D1 disease awaits further studies.

Adenocarcinoma↗

Role of expression of cell cycle inhibitor p27 and MIB-1 in predicting lymph node metastasis in male breast carcinoma.

Tumor expression of the proliferation marker (MIB-1) and the cell cycle-related protein (p27) may predict the biologic behavior of various human tumors. The purpose of this study was to evaluate the role of p27 and MIB-1 expression in predicting lymph node metastasis in male breast carcinomas (MBCs). We studied 67 patients with invasive MBC who had undergone modified radical mastectomy. Pathologic lymph node status was correlated with the p27 protein and the MIB-1 proliferation index. These factors were studied immunohistologically by standard methods. Men in this study ranged from 36 to 92 years of age (mean, 63 years); 43 (64%) were T1 lesions, and 24 (36%) were T2 lesions. Twenty-nine patients (43%) had positive nodes. p27 was expressed in 43 tumors (64%) and MIB-1 in 13 tumors (19.4%). Tumors with positive p27 showed positive lymph nodes in 10 cases (23%). In contrast, p27-negative tumors had positive lymph nodes in 18 cases (75%). Tumors positive for MIB-1 show positive lymph nodes in 11 cases (85%). However, when MIB-1 was negative, only 16 patients (30%) had positive lymph nodes. Multivariate logistic regression analysis confirmed the utility of MIB-1 overexpression in predicting lymph node metastasis ( p < 0.0006). Also, decreased p27 protein expression strongly correlates with lymph node metastasis ( p < or = 0.0001). Furthermore, when p27 was negative and MIB-1 was positive, 100% of the patients had positive lymph nodes. In contrast, when p27 was positive and MIB-1 was negative, only 12% of patients had positive lymph nodes. The reduced expression of the p27 protein and the overexpression of the MIB-1 proliferation index in this study show a significant correlation in predicting lymph nodes metastasis in MBCs.

Adult↗

[Clinicopathologic studies of 100 cases of lymph node metastasis in cardiac carcinoma].

The specimens of 100 cases of carcinoma of the gastric cardiac were studied after curative resection between 1985 and 1988. A total of 2213 lymph nodes were obtained, which were then divided into 23 group and 3 station in accordance with the Japanese staging system for esophageal and gastric carcinoma. Our data were as follow: (1) Eighty eight out of the hundred had lymph nodes metastasis, giving a metastatic rate of 88%: (2) 647 of 2213 lymph nodes were positive for metastasis. The degree of metastasis was 29.2%. The degree of metastasis of station 1,2,3 were 32%, 32.82%, and 14.65% respectively. That of group 1,2,3,4,7 and 110 were 42.5%, 32%, 36%, 11%, 39%, and 20.5% respectively. The lymph nodes of group 12, 14, 15, 16 and 17 were not involved; (3) The extent of lymph nodes metastasis of cardiac carcinoma were closely related the bulk of carcinoma, gross appearance, depth of infiltration and histological type (P less than 0.05). The authors consider that abdominal lymph node metastasis were of importance for cardiac carcinoma. The group 7 should be cleaned first. Lymph nodes dissection would be started from the level of inferior pulmonary vein and ended at the pylorus region.

Adenocarcinoma↗

Localization of Epstein-Barr virus in lymph node metastasis with nasopharyngeal carcinoma.

Epstein-Barr virus DNA was detected in 3 cases of lymph node metastasis with nasopharyngeal carcinoma, using in situ hybridization. EBV-DNA was demonstrated on the nuclei of the neoplastic cells, and was absent on those of lymphocytes. Localization of EBV-DNA in neoplastic cells was confirmed by the double-labeling method combining in situ hybridization and immunocytochemistry. Direct evidence of the presence of EBV-DNA in malignant epithelial cells from lymph node metastasis with nasopharyngeal carcinoma was clearly demonstrated in this study.

Carcinoma↗

Solitary lymph node metastasis of gastric cancer as a basis for sentinel lymph node biopsy.

BACKGROUND/AIMS: In order to examine the biology of sentinel lymph node of stomach cancer, we investigated solitary lymph node metastases that were hypothesized to represent sentinel lymph node. METHODOLOGY: In the 4,620 primary gastric cancers between 1964 and 1997, 1271 cases with a localized tumor were selected and the localization of the solitary metastases in relation to the primary tumors were studied. RESULTS: Of the 130 tumors with a single basin metastasis, only 71% of the tumors in the upper third, 75% of the middle and 80% of the lower involved the node basins in the close vicinity. In the anterior wall and the greater curvature the rates of adjacent metastasis were more than 90%, while in the posterior wall and the lesser curvature they were 76% and 43%, respectively. Metastases of the remaining cases were found at more distant basins. CONCLUSIONS: In stomach cancer sensitivity of sentinel lymph node biopsy would be very low by the exploration of the adjacent basin especially for the lesions in the lesser curvature and posterior wall.

Adenocarcinoma↗

Relationship of lymph node metastasis to primary tumor size and microscopic appearance of roentgenographically occult lung cancer.

We investigated the relationship of lymph node metastasis to primary tumor size and microscopic appearance in 92 resected specimens obtained from patients with roentgenographically occult lung cancer (ROLC) located at a site along the airway between the main bronchus and the sub-subsegmental bronchi. Most of the patients were discovered by mass screening. All were treated surgically after bronchoscopic localization of cancer. The bronchial tree of the resected specimens was serial-sectioned into 2-mm thick blocks from the margin of resection to the sub-subsegmental bronchi. Bronchial wall invasion was noted in some blocks of all the specimens. The length of longitudinal extension (LLE) was defined as the product of the thickness and the number of consecutive blocks involved, counting from the most proximal to the most distal block. LLE was used as primary tumor size. Hilar and mediastinal lymph nodes were examined in 84 patients who underwent lymph node dissection. No nodal involvement was found in 59 cancers with LLE of less than 20 mm. Of 25 cancers with LLE of 20 mm or more, six showed nodal involvement. Eleven in situ carcinomas and four cancers of the "suspicious for invasion" type showed no lymph node metastasis. We contend that no lymph node dissection is required when pulmonary resection is performed for patients with ROLC if it is in situ carcinoma, if it is of the "suspicious for invasion" type, or if the LLE is smaller than 20 mm.

Aged↗

[Magnetic resonance imaging enhanced by superparamagnetic iron oxide particles in detecting lymph node metastasis of tumors: an experimental study].

OBJECTIVE: To investigate the value of superparamagnetic iron oxide particles (SPIO) in magnetic resonance (MR) imaging for detecting lymph node metastasis of tumors. METHODS: Twelve New Zealand rabbits were used in this study, 6 of which received unilateral intra-muscular inoculation of VX2 carcinoma cells to induce lymph node metastasis of the tumor, and the other 6 served as normal control group. MR images of the lymph nodes of the rabbits were obtained before and 12 h after subcutaneous injection of SPIO, followed by image analysis in correlation with pathological examinations. RESULTS: On plain MR images, normal and metastatic lymph nodes showed similar signal characteristics. After administration of SPIO, the signal intensity of both normal lymph nodes and metastatic ones remained unchanged in spin echo (SE) T1-weighted images. On SE T2-weighted images, the signal intensity of normal lymph nodes significantly decreased heterogeneously, while that of all metastatic lymph nodes remained unchanged. In gradient recalled echo (GRE) T2-weighted images, the signal intensity of normal lymph nodes decreased significantly and homogeneously, while that of 4 rabbits in metastasis group remained unchanged, with the signal intensity in the other 2 rabbits decreased heterogeneously. CONCLUSION: SPIO-enhanced MR imaging can be applied to detect lymph node metastasis of the tumors.

Animals↗

Importance of molecular analysis in detecting cervical lymph node metastasis in head and neck squamous cell carcinoma.

BACKGROUND: Because of the impact of nodal status on treatment and survival in squamous cell carcinoma of the head and neck, accurate staging of cervical lymph nodes is critical. This article explores the value of molecular analyses in the detection of cervical lymph node metastasis. METHODS: A review of the literature was carried out and combined with our own experience regarding the role of molecular analyses in detecting cervical lymph node metastasis. RESULTS: Few studies have demonstrated the diagnostic and prognostic relevance of molecular analysis in detecting tumor cells in lymph nodes. Nodal staging was improved by the use of molecular techniques; when compared with histopathologic examination, however, the small sample size of these studies did not allow definitive conclusions. CONCLUSIONS: Molecular analysis is exquisitely sensitive in detecting very small cancer deposits within lymph nodes. It provides an oncologic basis that may be used to guide therapy and influence outcomes. It should be recommended for diagnostic use in controlled studies of patients without evidence of lymph node metastasis on routine hematoxylin-eosin-stained sections. The clinical significance of these types of metastases, however, must be determined with carefully designed and controlled prospective clinical trials.

Biomarkers, Tumor↗

The value of single versus multiple sections for detection of lymph node metastasis.

This study was undertaken to determine the value of serial sectioning of lymph nodes as an aid in optimally examining cervical specimens for metastasis. The presence or absence of lymph node metastasis in 802 lymph nodes obtained from 51 consecutive neck dissection specimens were initially determined by the routine method, examination of one section from each node. This examination revealed 40 lymph nodes with metastatic involvement. Further study of the 716 lymph nodes that were initially interpreted as free of tumor by serial sectioning added only two positive nodes. Thus, serial sectioning did not contribute significantly to the detection of lymph node metastasis.

Humans↗

[Proliferating cell nuclear antigen (PCNA) in ovarian carcinoma and its relation to lymph node metastasis and prognosis].

OBJECTIVE: To investigate expression of proliferating cell nuclear antigen (PCNA) in ovarian epithelial cancer and its relation to lymph node metastasis, second-look laparotomy (SLL) and prognosis. METHODS: Monoclonal antibody PC10 was used to stain PCNA in archival paraffin-embedded tissues. RESULTS: PC10 immunostaining was performed successfully in all 74 primary and 31 intraperitoneal metastatic tumors. The expression of PCNA was significantly elevated in 31 metastatic tumors compared with their primary tumor from the same patient (7.94 vs 6.89, P = 0.042). The expression was more marked in bilateral than in unilateral ovarian cancer but it was not associated with lymph node metastasis, clinical stage, histologic grade and subtype. In 28 patients with stage III ovarian cancer undergone SLL, the mean immunoreactive score (IRS) of PCNA of the primary tumor was significantly higher in patients with negative SLL than in those with positive SLL (7.59 vs 6.10, P = 0.03). Since chemotherapy was performed following surgical debulking, negative SLL more frequently seen in patients with high PCNA expression might suggest better chemotherapeutic sensitivity due to higher proliferation fraction of tumor cells. Univariate analysis of survival indicated that the overall survival was inversely associated with the level of PCNA expression, while multivariate analysis with Cox's model showed that independent prognostic factors were the residual tumor after primary debulking (P < 0.001) and clinical stage (P < 0.05), followed by PCNA expression (P = 0.09). CONCLUSION: The expression of PCNA may be useful in predicting prognosis, but is not correlated with lymph node metastasis.

Adult↗

Contralateral pelvic and aortic lymph node metastasis in clinical stage I epithelial ovarian cancer.

Bilateral pelvic and aortic node lymphadenectomy is recommended for clinically localized unilateral epithelial ovarian adenocarcinoma (International Federation of Gynecologists and Obstetricians stage IA). The laterality of nodal metastasis in clinical stage I disease is rarely documented in the literature. Some authors have reported that ipsilateral node dissection is adequate for staging. A patient with contralateral pelvic and aortic lymph node metastasis and clinical stage I epithelial ovarian adenocarcinoma is presented. Pathologic findings were consistent with contralateral-only lymph node metastasis. This case illustrates the importance of bilateral lymph node sampling for appropriate staging of clinically localized epithelial ovarian cancer.

Adenocarcinoma↗

Allelotype analysis of early colorectal cancers with lymph node metastasis.

Several studies have indicated that frequent allelic losses in some specific chromosomal regions occur during colorectal cancer (CRC) progression. To clarify the correlation between such allelic losses and metastatic potential, the allelotype of lymph node-positive early CRCs, which are small but extremely malignant cancers consisting of metastatically competent cells, were investigated. Nineteen paraffin-embedded specimens of early CRC (pT1 tumors according to TNM classification) with positive lymph nodes were collected. The tumor tissues were examined for loss of heterozygosity (LOH), using microsatellite markers on chromosomes 1p34-36, 8p21-22, 14q32, 18q21 and 22q12-13. The relationship between p53 protein expression and the metastatic status was also investigated by immunohistochemical staining. A group of 20 early CRCs with negative lymph nodes having a similar distribution of macroscopic appearance were used as controls. Among the 19 node-positive tumors, LOH at 8p21-22 and 18q21 was detected in 11 cases (57.9%) and 17 cases (89.4%), respectively. Allelic losses within these 2 regions in node-positive tumors were significantly more frequent than that in node-negative ones (p < 0.01). No significant correlation was found between LOH at 1p34-36, 14q32 or 22q12-13 and lymph node metastasis. p53 protein expression was not significantly associated with lymph node metastasis. Our results suggest that putative tumor suppressor genes, which may be involved in the metastatic process of CRC, are located on chromosomes 8p21-22 and 18q21. Allelic losses in these regions are possible risk factors for lymph node metastasis of early CRC.

Adult↗

Distribution of lymph node metastasis in T1 sigmoid colon carcinoma: should we ligate the inferior mesenteric artery?

OBJECTIVE: In standard oncological sigmoid colectomy, the inferior mesenteric artery is ligated either at its origin or at the level of the left colic artery. However, in patients with early-stage carcinoma, the distribution of metastatic nodes may be limited. The aim of this study was to clarify the prevalence and distribution of lymph node metastasis in T1 sigmoid colon carcinoma and to determine the adequate range of lymph node dissection. MATERIALS AND METHODS: The study included 121 consecutive patients treated for T1 sigmoid colon carcinoma. Clinicopathologic factors associated with nodal metastasis and the distribution of metastatic nodes were analyzed. RESULTS: Of 121 patients, 12 (10%) had nodal involvement. The depth of invasion and the presence of lymphatic and vascular invasion were significantly associated with nodal metastasis. Of these 12 patients, 11 (92%) had lymph node metastasis confined to pericolic nodes. Nodes along the sigmoidal artery were involved in one patient. There was no involved node along the superior rectal artery or at the root of the inferior mesenteric artery. CONCLUSIONS: Lymph node dissection for T1 sigmoid colon carcinoma should be limited to the root of the sigmoidal artery, and the inferior mesenteric artery should be preserved.

Adenocarcinoma↗

Patterns of lymph node metastasis in carcinoma of the ampulla of Vater.

BACKGROUND/AIMS: Identification of lymph node metastasis may guide surgical therapy. The aim of this study was to clarify the lymphatic spread in ampullary carcinoma in relation to local tumor extent (pT category in the pTNM classification). METHODOLOGY: The distribution and number of lymph node metastases were histologically examined in 35 patients with ampullary carcinoma. RESULTS: Lymph node metastases were present in 10 of 15 patients (67%) with pT2 tumor and in 10 of 11 (91%) with pT3 tumor. Nodal involvement was not identified in 9 patients with pT1 tumor. The incidence of node-positive patients was higher in pT2 and pT3 tumors than in pT1 tumors (P < 0.01). The total number of positive nodes per node-positive patient was greater in pT3 tumors than in pT2 tumors (mean 3.50 vs. 1.30, P < 0.001). All node-positive patients had metastasis to the posterior pancreaticoduodenal node. The number of positive nodes per node-positive patient in both the posterior pancreaticoduodenal and the superior mesenteric region was greater in pT3 tumors than in pT2 tumors (P < 0.01 and P < 0.05). CONCLUSIONS: With increasing pT category in ampullary carcinoma, lymphatic spread extended from the posterior pancreaticoduodenal region to the superior mesenteric nodes.

Aged↗

Serum levels of squamous cell carcinoma antigen as a predictor of inguinofemoral lymph node metastasis in patients with vulvar cancer.

OBJECTIVE: To evaluate the predictive value of preoperatively determined squamous cell carcinoma antigen (SCC-Ag) serum levels for the risk of inguinofemoral lymph node metastasis. STUDY DESIGN: In this retrospective trial, preoperative serum levels of SCC-Ag in 29 patients with invasive squamous cell vulvar cancer (pT1 + 2) were evaluated and compared with nodal status. RESULTS: Twenty patients had negative inguinofemoral nodes, whereas in nine an inguinofemoral lymph node metastasis could be observed. The median SCC-Ag in women with negative nodes was 1.3 micrograms/L (0.2-11.5) and with positive nodes, 2.7 micrograms/L (0.4-9.1) (P = .35). CONCLUSION: Measurement of the serum level of SCC-Ag cannot be used for preoperative evaluation of the risk of lymph node metastasis in patients with clinically localized tumors since there is a significant overlap between both cohorts.

Adult↗

Novel animal model of lymph node metastasis by intrauterine inoculation of the actively metastatic subline PL3 separated from rat Walker 256 tumor cells.

To investigate the cellular mechanism of lymph node metastasis by tumor cells through the lymphatic vessels in the uterine corpus, we selected an active metastatic subline (PL3) from rat Walker 256 tumor cells and used it to develop a novel experimental model of lymph node metastasis induced by intrauterine inoculation of the tumor cells. Light- and electron-microscopic examinations revealed that the inoculated PL3 cells could actively infiltrate the endometrium from the uterine cavity and form a primary lesion in the uterine corpus. A few PL3 cells in the myometrium were found in the lumen of the peripheral lymphatic vessels on day 7 after inoculation. The regional lymph nodes around the uterus were then invaded by the migrated PL3 cells, and finally (after 3 weeks), most of the parenchyma of the nodes was replaced by metastasized tumor cells. By flow-cytometric analysis, the metastatic PL3 cells expressed CD44, like Walker 256 cells, but lacked integrin alphaL- and alpha4-chains. However, expression of ICAM-1 was considerably down-regulated in the PL3 cells compared to the parent cells. More aggressive invasion was shown by the PL3 cells compared to the parent cells in the in vitro invasion assay. These findings suggest that this experimental model and the separated PL3 cells are suitable for thorough investigations of the unidentified metastatic process and the related cellular behavior involved in the onset of lymphatic invasion by the primary lesion. Furthermore, our model more closely reproduces the clinical conditions related to lymph node metastasis of malignant carcinomas through the lymphatic vessels than does any previously reported animal model.

Animals↗

[Clinical investigation of lymph node metastasis in carcinoma of the hypopharynx].

Carcinoma of the hypopharynx has a great tendency to metastasize to the neck. In addition it often metastasizes to the upper retropharyngeal lymph nodes (Rouviere's lymph nodes) and to the paratracheal lymph nodes. In this study, in order to determine the pattern of lymph node metastasis, 112 patients with carcinoma of the hypopharynx who had undergone bilateral radical neck dissection, bilateral paratracheal dissection, bilateral dissection of retropharyngeal nodes as an initial treatment between January 1982 and June 1997 in the Kurume University Hospital, were retrospectively reviewed in detail. Special attention was paid to retropharyngeal nodes and paratracheal lymph nodes. In N0 cases neck metastases were seen in more than one-quarter of the patients. Metastasis to retropharyngeal lymph nodes and to the paratracheal lymph nodes was seen in 5.4% and 12.5% of the patients, respectively. The frequency of metastasis to paratracheal lymph nodes had a significantly close relationship with that to the upper and lower jugular lymph nodes. The frequency of metastasis to retropharyngeal lymph nodes also had significantly close relationship with that to paratracheal lymph nodes, while having no relationship with that to other neck lymph nodes. These results suggest the following: 1) In patients with T1 or T2 PS type carcinoma of the hypopharynx, in which the lesion is confined unilaterally and is presumed to have been successfully treated by laser surgery prior to radiotherapy, unilateral neck dissection alone will be sufficient. In all the other patients with carcinoma of the hypopharynx bilateral neck dissection must be performed. 2) In all patients retropharyngeal lymph nodes and paratracheal lymph nodes should be dissected as much as possible and postoperative irradiation to both areas will be necessary.

Female↗

Expression analysis of vascular endothelial growth factors and their relationships to lymph node metastasis in human colorectal cancer.

This study was undertaken to determine whether expressions of the vascular endothelial growth factor (VEGF) family (VEGF-A, VEGF-B, VEGF-C, and VEGF-D) are correlated with clinicopathological parameters, with particular reference to lymph node metastasis in colorectal cancer. Total RNA was isolated from 82 surgical specimens of colorectal cancer and matched to normal mucosa with (n = 41) or without (n = 41) lymph node metastasis. The mRNA expression of each VEGF family member was quantified by real-time quantitative (RTQ) RT-PCR assay. VEGF-B and VEGF-C mRNA were significantly higher both in the tumors with lymph node metastasis (p = 0.027 and p = 0.024, respectively) and in tumors with lymphatic invasion (p = 0.042 and p = 0.005, respectively). In contrast, VEGF-D mRNA was down-regulated in tumors with lymphatic involvement (p = 0.047). Among the other clinicopathological factors, we noted that VEGF-A mRNA was higher in tumors with liver metastasis than in those without (p = 0.018) and was higher in tumors with venous invasion than in those without (p = 0.007). The results of this study demonstrate that high levels of VEGF-B, C and low levels of VEGF-D mRNA expression are associated with lymph node metastasis and lymphatic involvement. These results suggest that a balance among VEGF-B, VEGF-C, and VEGF-D might contribute to the lymphangiogenic process and metastasis in colorectal cancer.

Aged↗