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PubMed2000

Cervical carcinoma: assessment of parametrial invasion and lymph node metastasis with magnetic resonance imaging.

BACKGROUND: Clinical tumor staging of cervical carcinoma has its limitations. The purpose of this study was to stage cervical carcinoma by magnetic resonance imaging (MRI), with an emphasis on the assessment of parametrial invasion and pelvic lymph node metastasis. METHODS: MRI was performed in 51 women with tissue-proven cervical carcinoma 2 weeks prior to surgery. Images were analyzed for parametrial invasion, pelvic lymph node metastasis and tumor stage. The results were compared with the histopathologic findings after surgery in all patients. RESULTS: In assessing parametrial invasion, MRI had an accuracy of 94%. In assessing pelvic lymph node metastases, MRI was accurate in 86.3% of cases. In determining stage of disease, MRI had an accuracy of 76.5%. The accuracy of MRI in differentiating localized (< or = stage IIA) from advanced disease (> or = stage IIB) was 94.1%. CONCLUSIONS: MRI is accurate in the evaluation of parametrial invasion and lymph node metastases and in the differentiation of localized and advanced disease. MRI is beneficial in planning treatment for patients with cervical cancer.

Adult↗
PubMed2002

Hypoxia promotes lymph node metastasis in human melanoma xenografts by up-regulating the urokinase-type plasminogen activator receptor.

Clinical studies have shown that metastatic spread is associated with hypoxia in the primary tumor. The mechanism behind this association has not been identified and, in fact, it has not been established whether hypoxia induces metastasis or whether the most metastatic cell phenotypes develop the most hypoxic tumors. The present study demonstrates that hypoxia promotes spontaneous lymph node metastasis in R-18 human melanoma xenografts by up-regulating the urokinase-type plasminogen activator receptor (uPAR). Pimonidazole was used as a hypoxia marker, and hypoxia and uPAR expression were detected by immunohistochemistry. R-18 cells were capable of up-regulating uPAR under hypoxic conditions in vitro, as revealed by Western and Northern blot analyses, and uPAR-positive regions showed a high degree of colocalization with hypoxic regions in R-18 tumors. There was a strong correlation between uPAR-positive fraction and hypoxic fraction in individual tumors (P < 0.00001). Incidence of metastases, hypoxic fraction, and uPAR-positive fraction increased with the size of the primary tumor with similar kinetics. Metastatic tumors showed approximately 1.5-fold higher hypoxic fraction (P = 0.00004) and approximately 1.4-fold higher uPAR-positive fraction (P = 0.0003) than nonmetastatic tumors of the same size. Moreover, treatment with neutralizing antibody against uPAR prevented metastasis almost completely. Only 1 of 30 treated mice developed metastases, whereas 14 of 30 control mice were metastasis positive, suggesting that functional uPAR is a prerequisite for lymph node metastasis in R-18 tumors. The study reported here suggests that metastatic spread may be promoted by hypoxia in the primary tumor and identifies the plasminogen activation system as an important target for the treatment of malignant melanoma.

Animals↗
PubMed1997

Impact of minimal lymph node metastasis on long-term prognosis after radical prostatectomy.

OBJECTIVES: In the management of clinically localized prostate cancer, understanding is of major concern. There is a considerable therapeutic dilemma in those patients in whom staging lymphadenectomy prior to intended radical prostatectomy reveals lymph node metastases. METHODS: Pelvic lymph node dissection and radical retropubic prostatectomy were performed in 132 consecutive patients. Patients with extracapsular disease and/or positive lymph nodes received adjuvant radiotherapy. Median follow-up after surgery was 7 years and 2 months. To study the influence of minimal lymph node metastasis, category pN1 was further subdivided into pN1.1 and pN1.2. Involvement of the prostatic capsule was either classified as infiltration (pT3.1) or performation (pT3.2) of the capsule. RESULTS: Disease-free survival after 10 years was 58% in patients with negative nodes, 37% in category pN1.1, 25% in category pN1.2 and 10% in category pN2. Corrected overall survival was 83% for node-negative patients and 73% for category pN1.1, but it was only 33% for pN1.2 and 29% for pN2. Patients in category pT3.1 had a statistically significant better survival than those in pT3.2. CONCLUSIONS: We conclude that radical prostatectomy combined with adjuvant radiotherapy is a valuable option in prostate cancer patients with minimal lymph node metastasis. When compared to infiltration of the capsule, complete capsular perforation does adversely affect prognosis.

Adenocarcinoma↗
PubMed2004

Expression of VEGF-C and VEGF-D at the invasive edge correlates with lymph node metastasis and prognosis of patients with colorectal carcinoma.

Vascular endothelial growth factor (VEGF)-C and VEGF-D are potent lymphangiogenic factors produced by tumor and stromal cells. The purpose of this study was to determine whether expression of VEGF-C and/or VEGF-D correlates with clinicopathological features of human colorectal carcinoma. Expression of mRNAs for VEGF-C, VEGF-D, and their receptor VEGFR-3 was examined by reverse transcription-polymerase chain reaction (RT-PCR) in six colon carcinoma cell lines and in fresh endoscopic biopsy specimens from 20 patients with colorectal carcinoma. Expression of VEGF-C and VEGF-D protein was also examined immunohistochemically in 139 archival surgical specimens of human colorectal carcinoma. Of the six cell lines, one (Colo320D) constitutively expressed VEGF-C and four (Colo320D, DLD-1, km12sm, km12c) constitutively expressed VEGF-D mRNA. Expression of VEGF-D mRNA was increased under low oxygen conditions, and all six cell lines constitutively expressed VEGF-D mRNA under hypoxic conditions. Of the 139 specimens of human colorectal carcinoma, 65 (46.8%) showed intense VEGF-C immunoreactivity and 41 (29.5%) showed intense VEGF-D immunoreactivity. In 49 (75.3%) of the 65 and 20 (48.8%) of the 41 cases, heterogeneous intratumoral staining was observed for VEGF-C and VEGF-D, respectively, with the highest levels of expression at the invasive edges. VEGF-C expression correlated with the depth of tumor invasion, lymphatic involvement, venous involvement, lymph node metastasis, and liver metastasis, and VEGF-D expression correlated with the depth of tumor invasion, lymph node metastasis, and liver metastasis. No correlation was observed between VEGF-C and VEGF-D expression in tumors. The survival time of patients with VEGF-C-positive tumors was significantly shorter than that of patients with VEGF-C-negative tumors, and the survival time of patients with VEGF-D-positive tumors was significantly shorter than that of patients with VEGF-D-negative tumors. The survival time of patients with both VEGF-C- and VEGF-D-positive tumors was significantly shorter than that of patients with both VEGF-C- and VEGF-D-negative tumors. These results suggest that VEGF-C and VEGF-D may be independent and important prognostic factors in patients with human colorectal carcinoma.

Adenocarcinoma↗
PubMed1995

Lymph node metastasis of early stage carcinoma of the esophagus and of the stomach.

We undertook a comparative histologic study of early stage carcinoma of the esophagus and stomach, with tumor invasion limited to the submucosa. Here we analyze lymph node metastasis, lymphatic invasion, and vascular invasion. Our study is based on a retrospective review of 77 patients with early stage carcinoma of the esophagus and 192 patients with early stage carcinoma of the stomach treated during the period from 1973 through 1991. The incidence of lymph node metastasis and lymphatic invasion was significantly higher in intramucosal or submucosal esophageal cancer than in intramucosal or submucosal gastric cancer. However, there was no significant difference between intramucosal esophageal cancer and submucosal gastric cancer. The metastatic site of lymph nodes in esophageal cancer tended to be distant from the location of primary tumor compared with lymph nodes invaded by gastric cancer. Lymphatic invasion and vessel invasion between submucosal esophageal cancer and submucosal gastric cancer was statistically significant. From these results, we conclude that intraepithelial or intramucosal esophageal cancer is comparable to early stage carcinoma of the stomach, whereas submucosal esophageal cancer is actually an advanced lesion.

Adenocarcinoma↗
PubMed2003

Allelic loss of chromosome 2 in human oral squamous cell carcinoma: correlation with lymph node metastasis.

To evaluate the role of chromosome 2 deletions in human oral squamous cell carcinoma (SCC) progression and to define the precise location of putative tumor suppressor genes, we examined 40 primary tumors and seven lymph node metastatic tumors from 40 patients with oral SCC by the polymerase chain reaction (PCR)-loss of heterozygosity (LOH) assay, using 10 different polymorphic loci on the long arm of chromosome 2. LOH was observed in 67.5% of the patients at one or more loci on the chromosome 2q. Two commonly deleted regions with high frequency of LOH, D2S1327 region at 2q32-35 (31.6%) and D2S206 region at 2q36 (36.7%), were identified by the deletion mapping of chromosome 2q, suggesting the presence of putative tumor suppressor genes associated with oral SCC. Examination of seven metastatic tumors also revealed four commonly deleted regions, D2S436, D2S1327, D2S155, and D2S164. Of these four regions D2S1327 region has no significant increase in the frequency of LOH between in primary tumors and in metastatic tumors. However, at other three regions the frequencies were much increased in metastatic tumors, comparing the results in primary tumors. Especially, very high frequencies of LOH in metastatic tumors were detected at two regions on 2q35, 100.0% at D2S155 and 57.1% at D2S164, suggesting the significant relationship between lymph node metastasis and LOH at these two regions. Our results indicate that LOH on chromosome 2q is a common event in oncogenesis and/or progression of oral SCC, and also suggest that the LOH at 2q35 play a significant role in the lymph node metastasis.

Carcinoma, Squamous Cell↗
PubMed2005

Actinin-4 increases cell motility and promotes lymph node metastasis of colorectal cancer.

BACKGROUND & AIMS: Enhanced motility of cancer cells by remodeling of the actin cytoskeleton seems crucial in the process of cancer invasion and metastasis. We previously identified an actin-binding protein, actinin-4, as a new biomarker of cancer invasion and an indicator of prognosis for patients with breast cancer. However, its involvement in the mechanisms of cancer invasion and metastasis remains undetermined. The current study tested the role of actinin-4 in the motility and metastatic potential of colorectal cancer cells. METHODS & RESULTS: Quantitative immunofluorescence histochemistry showed that the expression level of the actinin-4 protein was increased in 73.1% (19/26) of the cases of colorectal cancer over the corresponding normal intestinal epithelium. The increased expression of actinin-4 was most significant in dedifferentiated cancer cells at the invasive front. A colorectal cancer cell clone capable of inducing actinin-4 using the tetracycline-regulatory system (designated DLD1 Tet-off ACTN-4) was established. Upon the induction of actinin-4, DLD1 Tet-off ACTN-4 cells spread filopodia and significantly increased their motility ( P = .00027); actinin-4 protein was concentrated at the leading edges of these actin-rich podia. When injected into the mesocecum of severe combined immunodeficient mice, DLD1 Tet-off ACTN4 cells, but not the control cells, metastasized into regional mesenteric lymph nodes, resembling the behavior of clinical cancers. The expression of actinin-4 in focally dedifferentiated cancer cells at the invasive front was significantly correlated with the frequency of lymph node metastasis of colorectal cancer ( P = .038). CONCLUSIONS: Actinin-4 actively increases cell motility and promotes lymph node metastasis of colorectal cancer.

Actinin↗
PubMed1997

Relationship of nonstaging pathological risk factors to lymph node metastasis and recurrence in clinical stage I endometrial carcinoma.

OBJECTIVE: To determine if DNA ploidy, hormone receptors, vascular space invasion (VSI), perivascular lymphocytes (PVL), and the oncogenes HER-2/neu, p53, and bcl-2 are independent prognostic indicators for lymph node metastasis and cancer recurrence in clinical stage I endometrial carcinoma. METHODS: Among 349 patients with clinical stage I endometrial cancer 31 patients either had lymph node metastases when surgically staged or developed recurrent cancer. Using a case-control matched-pair technique, controls were selected for each of 24 cases by matching for age, histological grade, depth of myometrial invasion, performance of node dissection, and use of adjuvant radiation therapy. In a blinded fashion a pathologist reviewed all histopathology, and all molecular tests were performed on paraffin-embedded tissue samples. Statistical analysis was performed by chi2 and McNemar's tests. RESULTS: VSI was the only histopathological factor significantly related to positive lymph nodes and cancer recurrence (P = 0.01), independent of grade and myometrial invasion. Aneuploidy, oncogene expression (p53, HER-2/neu, bcl-2), and hormone receptors were not significantly related to lymph node metastasis and cancer recurrence. CONCLUSIONS: The presence of vascular space invasion is a pathological factor independently associated with a risk of nodal metastasis and cancer recurrence in clinical stage I endometrial cancer. DNA ploidy, oncogene expression, and hormone receptor status do not have more predictive value than standard staging pathological criteria.

Aged↗
PubMed2005

[A case of advanced gastric cancer with paraaortic lymph node metastasis reaching long-term survival by TS-1 treatment].

A 62-year-old male patient with paraaortic lymph node metastasis of type 2 gastric cancer underwent distal gastrectomy with partial resection of transverse colon. MTX/5-FU sequential therapy was performed 5 times as adjuvant chemotherapy. After that TS-1 was administered on a 4-week dosing regimen with a 2-week interval between sessions. The patient regimen was discontinued temporarily because of thrombocytopenia. Therefore the schedule was changed to a 2-week dosing regimen with a 1-week interval between sessions at 2 years after operation. Paraaortic lymph node size was then checked by abdominal CT one or two times a year. The size showed no change for 3 years after operation. Then, 3 years and 3.5 years later, CT follow-up did not show paraaortic lymph node or other organ metastasis. We judged the effect of TS-1 was CR. Now the patient is disease-free at 4 years after operation.

Antimetabolites, Antineoplastic↗
PubMed1997

Down-regulated expression of CD44 variant 6 in oral squamous cell carcinomas and its relationship to regional lymph node metastasis.

The expression of the adhesion molecule CD44 variant 6 (CD44v6) was studied immunohistochemically on 38 oral squamous cell carcinomas (SCCs) and 10 biopsies of healthy oral mucosa. The relationship between the expression of CD44v6 and regional lymph node metastasis was also investigated. The expression of CD44v6 was apparently down-regulated in oral SCC, but not in normal oral mucosa. Carcinomas expressing lower levels of CD44v6 exhibited more frequent regional lymph node metastasis. The expression of CD44v6 showed no statistically significant relationship to the degree of differentiation, but tended to be down-regulated in poorly differentiated carcinoma. No significant relation was found between the expression of CD44v6 in primary and metastatic lesions.

Antibodies, Monoclonal↗
PubMedDate not supplied

Lymph node metastasis in gastric cancer in the upper third of the stomach--surgical treatment on the basis of the anatomical distribution of positive node.

BACKGROUND/AIMS: Little is known about the most appropriate surgical procedure for gastric cancer in the upper third of the stomach. The objective of this study was to determine the most appropriate surgical treatment for gastric cancer in the upper third of the stomach. METHODOLOGY: The clinicopathological characteristics of 115 node-positive gastric cancers in the upper third of the stomach were reviewed retrospectively and compared with those of 111 node-negative gastric cancers in the upper third of the stomach. RESULTS: Node-positive gastric cancers showed higher rates of peritoneal metastasis (p < 0.005), larger tumor sizes (p < 0.005), deeper tumor penetration (p < 0.005), higher rates of diffuse type in histology (p < 0.025), and more advanced histological stages (p < 0.005), than node-negative gastric cancers. Patients with node-positive gastric cancer demonstrated a poorer survival rate than those with node-negative gastric cancer (p < 0.005). Lymph node metastasis along the lower stomach was observed in cases of gastric cancer which had invaded beyond the muscularis propria of the stomach but not in those confined within the muscularis propria. No lymph node metastasis in the splenic hilum was found in association with gastric cancer when the depth was limited to the mucosa or the submucosa. CONCLUSION: The appropriate surgical procedures for the treatment of gastric cancer in the upper third of the stomach are as follows: a) proximal gastrectomy without splenectomy for gastric cancer when the depth is limited to the mucosa or the submucosa, b) proximal gastrectomy with splenectomy for gastric cancer when the depth of invasion extends to the muscularis propria, c) total gastrectomy with splenectomy for gastric cancer when the depth of invasion extends beyond the muscularis propria.

Female↗
PubMedDate not supplied

Resection of paraaortic lymph node metastasis of colon cancer with graft replacement.

The metastasis sites of colon cancer are the liver, lungs, bones, peritoneum, and lymph nodes. Lymph node recurrences, however, are seldom resected metachronously. We report here a case of en-bloc resection of paraaortic lymph node recurrence together with the invaded abdominal aorta, left kidney and ureter 4 years after curative resection of sigmoid colon cancer. Combined resection of the metastatic lymph nodes and the abdominal aorta would be an even more radical procedure and treatment for cancer because of lymphatic spread around the aorta. The slow growth of the cancer might justify this aggressive resection. This is the first report of resection of late paraaortic lymph node metastasis and simultaneous abdominal aortic graft replacement.

Adenocarcinoma↗
PubMed1992

Endorectal ultrasonography for the assessment of wall invasion and lymph node metastasis in rectal cancer.

Endorectal ultrasonography (ERUS) with a flexible-type radial scanner (Aloka Co. Ltd., Tokyo, Japan; 7.5 MHz) was applied to 120 patients with rectal cancer for the assessment of wall invasion and pararectal lymph node metastasis. Normal rectal wall was described as a five- or seven-layer structure excluding the lowest part within 3 cm from the anal verge. Loss of normal layers basically indicated the existence of cancer invasion. According to UICC classification, we divided the depth of wall invasion into four ultrasonographic levels (uT1-uT4), and results were correlated with histopathologic findings. Overall accuracy of the assessment was 92.0 percent (103/112). Overestimation occurred in 5 of 60 cases with T3 cancer (8.3 percent), and underestimation occurred in 1 of 19 cases with T2 cancer (5.3 percent) and 3 of 60 cases with T3 cancer (5 percent). Inflammatory cell infiltration was found around the cancer in a considerable number of cases. However, the assessment of wall invasion was hardly affected in our hands. Because the muscularis propria of the rectal wall was often recognized as a three-layer structure, uT2 cancer was subdivided into three subgroups of uPM1, uPM2, and uPM3. The assessment of invasion of sublayers in muscularis propria was possible in 14 of 19 cases (73.7 percent), and correct assessment was achieved in 57 percent of the cases. The ultrasonographic demonstration of pararectal lymph nodes was studied on 98 patients. No swollen lymph nodes were detected ultrasonographically in 35 of 98 cases (35.7 percent), but cancer metastasis was found histopathologically in 5 of these 35 cases (14.3 percent). The metastasis was observed more frequently in lymph nodes with a diameter of more than 5 mm (53.8 percent) and in those with a well-defined boundary and with an uneven and markedly hypoechoic pattern (72.3 percent). Although unable to detect minimal cancer foci. ERUS was considered a very useful tool for the assessment of the depth of cancer invasion in the rectal wall and pararectal lymph node metastasis.

Humans↗
PubMed1989

Relation of lymph-node metastasis to histopathologic appearance in oral cavity and oropharyngeal carcinoma: a case series and literature review.

A number of histopathologic parameters in squamous cell carcinoma of the oral cavity and oropharynx have been identified as having a statistically significant correlation with regional lymph-node metastasis. These parameters have been inconsistent and not readily reproducible. In an attempt to confirm these parameters, a retrospective analysis of 22 patients with T1 to T4 squamous cell carcinoma of the oral cavity and oropharynx was performed. Initially, these patients were managed with either wide local excision or surgical excision of the primary tumor combined with radical neck dissection. There was a minimum of 3 years of follow-up. Chi-square contingency tables and Fisher's Exact Test were used to correlate histopathologic parameters with lymph-node metastasis. Statistically significant correlations were found for tumor thickness and inflammatory infiltrate.

Adult↗
PubMed2006

Prognosis of breast cancer after supraclavicular lymph node metastasis: not a distant metastasis.

BACKGROUND: We performed this study to analyze the survival of breast cancer patients with isolated supraclavicular lymph node metastasis (SLNM) and assess whether SLNM is distant metastasis or not. METHODS: Sixty-three patients who developed an isolated SLNM among 3170 primary breast cancer patients between 1990 and 1999 were enrolled. The survival after SLNM was compared with that of 151 patients who developed local recurrences and 599 who had distant metastasis and was analyzed according to different levels and numbers of positive axillary nodes. RESULTS: Thirty-five of the 63 patients died during a median follow-up of 58.3 months. The 5-year overall survival (OS) rates after SLNM, local relapse, and distant metastasis were 33.6%, 34.9%, and 9.1%, respectively. The 5-year OS for patients with involved nodes confined to axillary level I was 74.4%, which was significantly better than that for involved nodes in level II or III or SLNM (49.2%, 52.8%, and 33.6%, respectively; P < .0001). For one to three positive axillary nodes, the 5-year OS was 83.2%, which was significantly better than that for four to nine positive nodes, more than nine positive nodes, and SLNM (62.6%, 42.3%, and 33.6%, respectively). There was no significant difference between SLNM and more than nine positive nodes. Surgical removal of the supraclavicular nodes was a significantly better prognostic factor for OS after SLNM (P = .0327). CONCLUSIONS: The 5-year OS after supraclavicular nodal metastosis, local relapse, and distant metastasis were 33.6%, 34.9%, and 9.1%, respectively. Good neck control either by surgery or chemotherapy achieved better survival.

Adult↗
PubMed2003

Insights into the mechanisms of lymph node metastasis.

The mechanisms by which malignant tumors leave the primary tumor site, invade lymphatics, and metastasize to regional lymph nodes (RLNs) are complex and interrelated. Although the phenomenon of lymph node metastasis has been recognized for over 200 years, the exact mechanisms have only recently been the subject of intense interest and sophisticated experimentation. Sentinel lymph node biopsy has rapidly entered the clinical mainstream for melanoma and breast carcinoma, and this technique has provided confirmation of the orderly anatomic progression of tumor cells from primary site to the RLNs through lymphatic capillaries and trunks. Exciting studies involving the pathophysiology of interstitial fluid pressure in tumors and the peritumoral extracellular matrix have focused on lymphatic flow and tumor microenvironment and microcirculation. Molecular techniques have led to the definition of unique markers found on lymphatic endothelial cells. These markers have enabled scientists to identify peritumoral and intratumoral lymphatics and to visualize the ingrowth of tumor cells into the lumena of lymphatic capillaries. Tumor-secreted cytokines, such as vascular endothelial growth factors (VEGF)-C and -D, bind to VEGF receptors on lymphatic endothelial cells and induce proliferation and growth of new lymphatic capillaries; this process is similar to the well-known mechanism of angiogenesis, which results from the proliferation of new blood vessel capillaries. Lymphangiogenesis is associated with an increased incidence of RLN metastasis, and it is possible that this step is essential to the metastatic process. Directional movement toward lymphatics and lymph nodes appears to follow a chemokine gradient, and it is likely that some tumor cells that express certain types of chemokine receptors are more likely to metastasize to the RLNs. In contrast, tumor cells that do not express specific receptors that are responsive to lymphatic chemokines may not metastasize. New knowledge regarding the molecules involved in these processes should enable improvements in prognostic and possibly therapeutic approaches to the management of malignant tumors.

Biomarkers, Tumor↗
PubMed1975

Studies on tumor variability. V. In vivo and in vitro investigations on H10Z tumor lymph node metastasis.

In vivo and in vitro investigations of a Syrian hamster tumor metastasis in the lymph node (H10Zm) in comparison with the primary tumor (H10Z) are performed. It is shown that the metastasis differs from the primary tumor by the prevalence of M secondary cell type characterized by globulous appearance, decreased adhesion and the presence of two long submetacentric marker chromosomes. Since a cell type with such cytogenetical characters was also found in the primary tumor as well as in a non-metastasizing tumor variant, it is suggested that the role of the induction-selection phenomenon in the occurrence of H10Z tumor metastases, i.e., new inductor agents occurred in the tumor's environment, might produce the induction of certain repressed mutant genes in M secondary cell type, bringing about certain phenotypical alterations (e.g., the decrease of the mutual cell adhesion) which could favorize the migration and selection of this cell type.

Animals↗