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Proportion of ground-glass opacity on high-resolution computed tomography in clinical T1 N0 M0 adenocarcinoma of the lung: A predictor of lymph node metastasis.

OBJECTIVE: In patients with clinical T1 N0 M0 lung adenocarcinoma, we investigated whether the proportion of ground-glass opacity area measured on high-resolution computed tomography was valuable for predicting the existence of lymph node metastasis, lymphatic invasion, or vascular invasion. METHODS: Between 1994 and 1999, 111 patients with clinical stage IA adenocarcinoma underwent surgical resection of the lung at our hospital. Of these, 96 patients received high-resolution computed tomography of the chest, and they constituted the study population. The tumors were semiquantitatively classified into 5 groups on the basis of the proportion of ground-glass opacity area to whole tumor shadow on high-resolution computed tomography: group I, 0%; group II, 1% to 25%; group III, 26% to 50%; group IV, 51% to 75%; and group V, 76% to 100%. Correlations of computed tomographic findings, pathologic results of lymph node metastasis and lymphatic and vascular invasion, and the histologic subtype according to the new World Health Organization classification were examined. We also investigated the characteristics of the patients with ground-glass opacity areas on high-resolution computed tomography and their value for predicting lymph node metastasis. RESULTS: Among the 96 patients, 15 (15.6%) had mediastinal lymph node metastases, and 3 (3.1%) had hilar node metastases. Regarding the proportion of the ground-glass opacity area of the tumors, 15 (15.6%) tumors were classified as group V, 11 (11.5%) as group IV, 9 (9.3%) as group III, 22 (22.9%) as group II, and 39 (40.6%) as group I, respectively. Of the 18 patients with lymph node metastases, no patients were found in groups IV and V, 2 (22.2%) were found in group III, 4 (18.2%) were found in group II, and 12 (30.8%) were found in group I (trend P =. 003), respectively. Twenty-six patients classified into groups IV and V also showed neither lymphatic invasion nor recurrence. All the smaller tumors (< or =2.0 cm) in group IV or V were histologically proved to be bronchioloalveolar carcinoma. Adjusted for smoking status and other characteristics, patients without ground-glass opacity on high-resolution computed tomography had a significantly increased risk of concurrent lymph node metastasis compared with those with ground-glass opacity. CONCLUSION: In patients with clinical T1 N0 M0 adenocarcinoma, the proportion of ground-glass opacity area on thin-section computed tomography scans was a strong predictor for tumor aggressiveness and thus could be a useful index for planning limited surgical resection for these patients.

Adenocarcinoma↗

Ultrasound diagnosis of lymph node metastasis in head and neck cancer.

The role of ultrasonic (US) examination in the detection of cervical lymph node metastasis from head and neck cancer has been evaluated. The subjects were 57 patients with carcinoma of the oral cavity, maxillary sinus or oropharynx who underwent radical neck dissection. The preoperative US and postoperative histopathological findings were compared in 181 lymph nodes (LNs) of 5 mm or more in diameter. LNs were evaluated by US with reference to their size, shape, boundary and internal echoes. The histologically positive rate was higher for larger LNs on US scans: 96% (44/46) of LNs of 15 mm or more were positive. On the other hand, 95% (18/19) of the flat LNs were negative. The positive rate was higher for well delineated than poorly delineated LNs, but similar among the homogeneous, heterogeneous and reflective core patterns of internal echoes. No LNs were detected by US in six of the 57 patients, of which four were true negative and the other two false negative. In the two false negative patients, histopathological examination showed a total of four LNs with two showing extensive extranodal spread of tumour and fibrosis of the surrounding tissue due to previous radiotherapy. Whether LNs are metastatic or not is difficult to determine directly by US. However, the positive rate can be enhanced by evaluation of the size, shape and boundary of the LN. US is indispensable for diagnosing cervical lymph node metastasis in patients with malignant head and neck tumours.

Head and Neck Neoplasms↗

[Screening of differential expression genes between primary breast cancer and its lymph node metastasis using single primer amplification of cDNA for microarray].

OBJECTIVE: To screen genes related to breast cancer metastasis by comparing difference of expression profile between primary breast cancer and its lymph node metastasis. METHODS: The cell total RNA was extracted from 10 breast cancer specimens, including the primary cancer and metastatic cancer tissues of axillary lymph nodes resected during operation. Single primer amplification (SPA) was used to prepare fluorescence-labeled targets and then Oligo microarray concluding 21 000 human functional genes was used to screen out 1.5 fold or more differential expression genes in at least 5 pairs of samples. The screened-out genes were identified by real-time PCR. RESULTS: Preparing targets by using SPA reduced the initial RNA to 0.25 microg, with 57 genes screened out, the expression of 19 of which were up-regulated and the expression of 38 of which were down-regulated in the metastatic tissues. Eight differentially expressed genes were related to cell migration and adhesion, 14 to signal transduction, and 14 to cell growth or metabolism. Real-time PCR showed that the fibronectin (FN) mRNA expression in the lymph node metastasis was only 1/3.6 of that in the matched primary breast cancer in 30 cases (t = -3.188, P = 0.003). CONCLUSION: SPA is a sensitive method for preparing targets. Genes related to cell migration and adhesion, signal transduction, and cell growth or metabolism, which are associated with the biology process of metastasis have been screened out. FN as a potent marker may contribute to diagnosis of metastasis and prognosis for breast cancer patients.

Adult↗

Chemosensitivity of breast cancer lymph node metastasis compared to the primary tumor from individual patients tested in the histoculture drug response assay.

Lymph node metastasis is often the first indication of the aggressiveness of breast cancer. Effective chemotherapy in breast cancer depends on targeting the metastatic component of the disease. In order to optimize chemotherapy in the metastatic target of breast cancer, the histoculture drug response assay (HDRA) was performed on surgical specimens of primary tumor and axillary lymph node metastasis from 30 breast cancer patients. The surgical specimens were cut into approximately 10 mg pieces, and placed onto the collagen gel sponges in the medium containing previously-determined cutoff concentrations of doxorubicin (DXR), 5-fluorouracil (5-FU), cisplatin (DDP), and mitomycin C (MMC). After incubation for 7 days, the chemosensitivity of the tumor fragments was evaluated with the 3-(4,5-dimethythiazol2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) endpoint. The lymph node metastases were more resistant than the primary tumor for DXR, 5-FU, and MMC (p < 0.05) but not for CDDP. The data suggest that both primary tumor and metastases from individual patients should be tested in the HDRA to enhance clinical efficacy of chemotherapy.

Antineoplastic Agents↗

The relationship of primary tumor thickness in carcinoma of the tongue to subsequent lymph node metastasis.

OBJECTIVES: To study whether primary tumor thickness of stage I/II tongue carcinoma provides information about subsequent lymph node metastasis. METHODS: Twenty consecutive patients with T1N0M0 or T2N0M0 tongue carcinoma were studied. Primary tumor thickness was measured with post-contrast helical computed tomography or intra-oral sonography. Cervical lymph nodes were evaluated periodically with sonography at intervals of 2-4 weeks. Sensitivity, specificity and accuracy for subsequent metastasis was calculated. RESULTS: Positive sonographic findings appeared in nine nodes of nine patients during this follow-up period. Eleven patients underwent neck dissections, and nine had histopathologically positive nodes. Nine patients had no sonographic findings of metastasis during a minimum follow-up period of 20 months. Primary tumor thickness varied from 3-16 mm. Using 5 mm as a cut-off thickness, the sensitivity, specificity and accuracy for subsequent lymph node metastasis were 64, 100 and 75% respectively. CONCLUSIONS: Patients with stage I/II tongue carcinoma which is more than 5 mm thick are more likely to develop lymph node metastasis.

Carcinoma, Squamous Cell↗

Bcl-2 expression is associated with lymph node metastasis in human ductal breast carcinoma.

The Bcl-2 proto-oncogene product blocks apoptosis. We retrospectively studied Bcl-2 expression in 124 primary tumors from patients diagnosed with T1 (2 cm or less) breast carcinoma with (T1N1) or without (T1N0) lymph-node metastasis. Bcl-2 protein was detected by immunohistochemistry on paraffin-embedded tissue sections. Multivariate logistic regression modeling was used to estimate prevalence odds ratios for lymph-node metastasis. Bcl-2 was widely expressed among T1 tumors showing a strong positive relationship with estrogen (ER)- and progesterone (PR)-receptor-positive tumors. However, a significant inverse correlation was seen between Bcl-2 expression and histological grade, Bcl-2 being absent in the majority of T1 undifferentiated tumors (grade-III carcinomas). Furthermore, Bcl-2 was more frequently expressed in T1N1 cases (72.2%) than in T1N0 specimens (45.7%). The odds for lymph-node metastasis in the Bcl-2-positive group was 3.6 times larger than that in the Bcl-2-negative group. The co-expression of PR significantly modified the effect of Bcl-2 on the odds for lymph-node metastasis, suggesting the existence of a synergistic interaction between the 2 parameters. We studied the percentage of dead cells in primary tumors by in situ DNA fragmentation (FDNA), and found an inverse correlation between Bcl-2 expression and FDNA. This supported the hypothesis that Bcl-2 extends cell survival. In conclusion, our study provides evidence that Bcl-2 expression is involved in breast-cancer progression, at least in a subset of well-differentiated and PR-positive tumors.

Adult↗

Vascular endothelial growth factor C promotes lymph node metastasis in a rectal cancer orthotopic model.

PURPOSE: Vascular endothelial growth factor C (VEGF-C), a novel member of the vascular endothelial growth factor family, is a relatively specific lymphangiogenic growth factor. It has been suggested that increased expression of VEGF-C in primary tumors is correlated with lymph node metastasis. We conducted this study to determine whether VEGF-C directly affects lymphangiogenesis and lymph node metastasis in colorectal cancer. METHODS: For an accurate analysis and clear visualization of metastases, the rectal cancer cell line, DLD1, was engineered to stably express green fluorescent protein (GFP) (DLD1/GFP). We implanted DLD1/GFP cells overexpressing VEGF-C orthotopically into the rectal walls of nude mice. RESULTS: Lymph node metastasis was confirmed in all (100%) of the mice bearing DLD1/GFP-VEGF-C tumors, but in only 25% of the mice bearing control tumors. There were more lymph node metastases per mouse in the mice bearing DLD1/GFP-VEGF-C tumors than in the mice bearing control tumors. There were no differences in cell growth and motility in vitro or in the resulting tumor volume from the implanted cells between the two groups. Immunohistochemical staining revealed that VEGF-C induced the growth of lymphatic vessels, which were enlarged in the tumor periphery and contained tumor cell emboli. CONCLUSION: These results suggest that VEGF-C-induced lymphangiogenesis mediates tumor spread and the formation of lymph node metastasis.

Animals↗

Lymphatic mapping and sentinel node identification as related to the primary sites of lymph node metastasis in early stage ovarian cancer.

OBJECTIVE: We evaluated the primary sites of lymph node (LN) metastasis in patients during the early stage of ovarian cancer. METHODS: Study 1: patients with clinical stage I and II common epithelial ovarian carcinoma (n = 150) underwent systematic retroperitoneal LN dissection of the pelvic and paraaortic areas. The relationship between the incidence and location of LN metastasis and clinical and histological characteristics was examined. Study 2: we studied 11 women with endometrial or fallopian tube tumors. At laparotomy, activated charcoal solution was injected into the unilateral cortex of the ovary. Ten minutes later, the retroperitoneal spaces were opened and charcoal uptake within the pelvic lymph node (PLN) and paraaortic node (PAN) as far as the level of renal vein was examined. RESULTS: Study 1: The incidence of LN metastasis by stage was 6.5% (8/123) in stage I and 40.7% (11/27) in stage II. Among 19 patients with LN metastasis, 14 had only PAN, 2 had only pelvic LN, and 3 had both PAN and PLN metastases. Metastasis was limited to the ipsilateral side in 12 (63%) patients, but was bilateral in 5 (26%) and contralateral to the neoplastic ovary in 2 (11%). Positive peritoneal cytology was significantly (P < 0.05) correlated with lymph node metastasis. Study 2: Lymphatic channels along the ovarian vessels were identified in all injected ovaries. Charcoal was deposited in the LN of all patients. The locations of these nodes included PAN in all patients, common iliac node in three, and external iliac node in one. CONCLUSION: PAN is the primary site of LN metastasis in ovarian cancer. Bilateral PAN dissections are necessary to determine the extent of tumors even in stage I ovarian carcinoma.

Adult↗

[Surgical treatment of carcinoma of the cardia with special references to mediastinal extension and lymph node metastasis].

We retrospectively analyzed the clinicopathological findings in 141 patients with advanced cardiac cancer. According to histological type, 117 patients had an adenocarcinoma and 24 patients a squamous cell carcinoma. Curative resection was performed in 114 patients, whereas the remaining 27 patients underwent palliative resection. Preoperative endoscopic ultrasonography and abdominal ultrasound were useful for the diagnosis of esophageal invasion and lymph node metastases. Particularly, the classification of paraaortic lymph node metastasis by ultrasound was important in deciding on the surgical method. Mediastinal lymph node metastases were found histologically in 19 of 68 patients. The survival of patients with mediastinal lymph node metastasis was poor. However, among them, a favorable outcome was expected for patients with few involved nodes and if only perigastric node involvement in abdominal nodes was found. Paraaortic lymph node metastasis was found histologically in 15 of 48 patients (27.9%). Two of 35-year survivors had 5 or fewer lymph node metastases, and showed only perigastric and paraaortic node involvement. It is equally important that tumor extension and lymph node metastases in the mediastinum and abdomen should be determined in the surgical treatment of advanced carcinoma of the cardia.

Adenocarcinoma↗

[Ratio of lymph node metastasis in gastric carcinoma after D2 gastrectomy].

The classification of lymph node metastasis in patients with gastric carcinoma is controversial. In the past, all systems used for this disease defined N classification by the location of lymph node metastases relatively to the primary tumor. In the 1997, the UICC and AJCC redefined the pathologic nodal status on the basis of the number of involved nodes rather than their location. More recently, the ratio between the number of metastatic and the total examined lymph nodes has been proposed as a new quantitative staging system. Aim of our study was to clarify the outcome of the ratio of the metastatic lymph nodes (RML) in a monoinstitutional series of 164 patient with primary gastric cancer who underwent gastrectomy with D2 lymph node dissection. Our data showed that ratio of metastatic lymph nodes is a simple, convenient, and reproducible staging system with an ability to predict surgical results and it is an independent prognostic factor after D2-gastrectomy.

Gastrectomy↗

Prognostic factors in patients with squamous oesophageal cancer associated with solitary lymph node metastasis after oesophagectomy and extended lymphadenectomy.

It is not fully understood whether oesophageal cancer, associated with solitary lymph node metastasis, is still a local disease or already a systemic one. Among 283 patients with squamous oesophageal cancer who underwent oesophagectomy and 3-field lymphadenectomy, 37 patients had single metastasized nodes. Clinicopathologic factors, following Japanese Guideline for the Clinical and Pathological studies on Carcinoma of the Esophagus, related to survival and pre-operative predictability of nodal involvement was studied. Five-year survival was 48%. Initial pattern of recurrence was mostly haematogenous. Among the factors related to survival, grade of lymph node metastasis (pN1 vs. pN2, pN3, p=0.006) was more closely related than depth of invasion (pT1, pT2 vs. pT3, pT4, p=0.037). Five-year survival was 71.7% for pN1 patients, whereas it was 22% for pN2 or pN3 patients. Of the metastasized nodes 65% were <10 mm, and 27% was <5 mm in the maximum diameter. Oesophageal cancer is still a local disease in half of the patients with a solitary metastasized node. For these patients, dissection along the recurrent laryngeal nerve is necessary to retrieve the node possibly metastasized.

Aged↗

Correlation of proliferative markers (Ki-67 and PCNA) with survival and lymph node metastasis in oral squamous cell carcinoma: a clinical and histopathological analysis of 113 patients.

The purposes of this study were to examine the correlations between proliferation markers and survival rate in oral squamous cell carcinoma (OSCC) patients, and to evaluate the efficacy of proliferation markers in predicting lymph node metastasis. The patients' age, gender, T score, clinical stage, PCNA and Ki-67 index were analysed. Univariate analysis showed that T score had a significant influence on survival, and stage 4 group had a significantly lower survival rate. Lymph node metastasis was also a significant predictor of survival. Using a cut-off point of 25%, those patients with lower Ki-67 scores had survival advantage over those with higher Ki-67 scores. PCNA did not show any differences in survival with a cut-off point of 50%. Ki-67 and PCNA were significantly higher in the primary tumours associated with lymph node metastasis (pN+) than in those without lymph node metastasis (pN0). Multivariate analysis showed that clinical stage and Ki-67 were independent prognostic factors for survival in OSCC patients. From this result, it can be postulated that the cancer staging based on the TNM stage was a powerful prognostic variable and Ki-67 had a significant effect on the cumulative survival rate.

Adolescent↗

[The value of 99mTc-DX105 cervical lymphatic imaging in detecting cervical lymph node metastasis of laryngeal and hypopharyngeal carcinoma].

OBJECTIVE: To study the value of single photon emission-computed tomography (SPECT) lymphatic imaging by percutaneous injection of 99mTc-DX105 in detecting cervical lymph node metastasis of laryngeal and hypopharyngeal carcinoma. METHOD: One-three days before the operation, 185MBq 99mTc-DX105 was injected via bilateral mastoids portion percutaneously in each of 30 patients with laryngeal and hypopharyngeal carcinoma, and thus SPECT lymphatic imaging was conducted. Then, the diagnostic result was compared with those of pathological examination of neck dissection specimens. RESULT: In SPECT lymphatic imaging of 53 sides neck of 30 patients, 24 sides cervical lymph node were positive, and 3 sides were false positive; 29 sides cervical lymph node were negative, and 1 side was false negative, Sensitivity, specificity and accuracy of SPECT lymphatic imaging were 95.5% (21/22), 90.3% (28/31) and 92.5% (49/53) respectively. Among the 8 sides cervical lymph node metastasis which were false negative by clinical palpation, 7 sides were positive by SPECT lymphatic imaging. CONCLUSION: It is suggested that SPECT lymphatic imaging by percutaneous injection of 99mTc-DX105 in detecting cervical lymph node metastasis of laryngeal and hypopharyngeal carcinoma is pretty valuable for guiding clinical neck node dissection.

Adult↗

Fluorine 18-tagged fluorodeoxyglucose positron emission tomographic scanning to predict lymph node metastasis, invasiveness, or both, in clinical T1 N0 M0 lung adenocarcinoma.

OBJECTIVE: We sought to predict lymph node metastasis and tumor invasiveness in clinical T1 N0 M0 lung adenocarcinomas, and we measured fluorodeoxyglucose uptake on positron emission tomography. METHODS: Fluorodeoxyglucose positron emission tomography was performed on 44 patients with adenocarcinomas of 1 to 3 cm in size clinically staged as T1 N0 M0 before major lung resection with lymph node dissection. Fluorodeoxyglucose uptake was evaluated by using the contrast ratio between the tumor and contralateral healthy lung tissue. Lymphatic and vascular invasion within tumors, pleural involvement, and grade of histologic differentiation were examined. RESULTS: The pathologic tumor stage was T1 N0 M0 in 36 patients, and a more advanced stage was found in 8 patients. Although all 22 adenocarcinomas with a contrast ratio of less than 0.5 in fluorodeoxyglucose uptake were pathologic T1 N0 M0 tumors, 8 (36%) of 22 with a contrast ratio of 0.5 or greater were of a more advanced stage than T1 N0 M0, with the difference being significant (P =.002). Adenocarcinomas with a contrast ratio of less than 0.5 showed less lymphatic and vascular invasion and less pleural involvement than those with a contrast ratio of 0.5 or greater (P =.006, P =.004, and P =.02, respectively). The grade of histologic differentiation was well differentiated in 19 of 22 adenocarcinomas with a contrast ratio of less than 0.5 (86%), which was a greater frequency than the 4 (18%) of 22 adenocarcinomas with a contrast ratio of 0.5 or greater (P <.001). CONCLUSION: Clinical T1 N0 M0 lung adenocarcinomas with a contrast ratio of less than 0.5 usually did not have lymph node metastasis, had less tumor involvement of vessels or pleura, and were more frequently well differentiated than those with a contrast ratio of 0.5 or greater. Limited lung resection could be indicated, lymph node dissection or mediastinoscopy could be reduced, or both in this type of adenocarcinoma.

Adenocarcinoma↗

The role of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET) in the diagnosis of recurrence and lymph node metastasis of cervical cancer.

The usefulness of positron emission tomography with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG-PET) in diagnosing recurrence and lymph node metastasis of uterine cervical cancer was evaluated as a preliminary study. The FDG uptake of 13 cervical cancer patients, including 4 patients with recurrence, was evaluated. The FDG uptake of the cervices of 5 patients who underwent PET studies for non-cervical tumors were used as control. In 2 patients who had undergone radical hysterectomy, we compared the diagnosis of lymph node metastasis based on FDG-PET and magnetic resonance imaging. The FDG uptake in the 9 primary cervical cancers was greater than that in normal cervices (p=0.025). Examination of the 4 recurrent tumors revealed a higher FDG uptake than that in normal cervices (p=0.0022). Metastatic lesions in lymph nodes showed an accumulation of FDG on the PET scan. In conclusion, FDG-PET may be an effective diagnostic tool for detecting recurrence and lymph node metastasis of uterine cervical cancers.

Adult↗

[The expression difference of VEGF, PDGF/dThdPase and MVD on primary hypopharyngeal carcinoma and metastasis lymph nodes].

OBJECTIVE: To evaluate the difference of angiogenic factors PDGF/dThdPase,VEGF expression and microvessel density (MVD) in primary hypopharyngeal tumor and metastasis lymph nodes. METHOD: The author studied immunohistochemically a series of 48 primary hypopharyngeal carcinoma patients and metastasis lymph nodes were calculated. RESULT: The percentage of VEGF was 25.38% in primary tumor and 21.52% in lymph nodes. No significant difference was found. The percentage of PDGF/dThdPase was 29.59% in primary tumor and and 21.2% in lymph nodes. This showed significent difference. VEGF showed significent difference between live and death group(P < 0.05) and among differentiation group (P < 0.05). MVD showed significant difference between live and death group, early and late stage group, and T1-2 and T3-4 group (P < 0.05). There were statistically significant correlations between the score of PDGF/ dThdPase, or VEGF and the score of MVD respectively. CONCLUSION: The present study suggests that there was a correlation between VEGF or PDGF and MVD. VEGF and MVD were possible to be prognostic discriminators in hypopharyngeal carcinoma. PDGF expression in lymph nodes was significant higher than in primary tumors, and MVD expression in primary tumor was significant higher than in lymph nodes.

Adult↗