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S-classification of sentinel lymph node biopsy predicts the results of complete regional lymph node dissection.

The purpose of this study was to identify melanoma patients with positive sentinel lymph nodes (SLNs) at increased risk for further metastases in this specific lymph node basin. A series of consecutive patients with primary malignant melanoma stage I and II were evaluated retrospectively. The results of SLN biopsy in 26 patients with positive SLNs were compared with those of complete regional lymph node dissection (RLND) using the recently published S-classification of SLNs. The results of S-classification of SLNs were correlated with the outcome of complete RLND. There was a significant correlation between the S stage of positive SLNs and the results of complete RLND (P=0.02). Only patients with SIII stage (n=4) SLNs were found to have further metastases in the residual lymph node basin. The present study indicates that patients with SI stage and SII stage SLNs rarely have further metastases in the specific lymph node basin.

Adult↗

Vascular endothelial growth factor-C and vascular endothelial growth factor-d messenger RNA expression in breast cancer: association with lymph node metastasis.

Lymph node metastasis is a major prognostic factor for patients with breast cancer. Vascular endothelial growth factors (VEGF)-C and VEGF-D are capable of stimulating lymphangiogenesis, and VEGF-C enhances lymphatic metastasis. The aim of the present study was to determine whether VEGF-C and VEGF-D messenger RNA (mRNA) expression is correlated with lymphatic invasion and lymph node metastasis in patients with breast cancer. Total RNAs were isolated from 33 surgical specimens of breast cancer tissue and 7 samples of normal breast tissue. VEGF-C and VEGF-D mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction analysis. There was no correlation between VEGF-C mRNA expression and lymphatic invasion or lymph node metastasis. However, VEGF-D mRNA expression was decreased in cancer tissue, and it was inversely correlated with lymphatic invasion and the number of metastatic lymph nodes. An increased VEGF-C/VEGF-D ratio was also correlated with lymph node metastasis and the number of metastatic lymph nodes. Our results suggest that a decrease in VEGF-D mRNA or an increase in the VEGF-C/VEGF-D ratio may have an association with tumorigenesis and/or lymph node metastasis in breast cancer.

Adult↗

Topography of the major superficial lymph nodes and their efferent lymph pathways in the koala (Phascolarctos cinereus).

The koala has an inguinoaxillary lymph trunk on either side of the ventral midline, and this carries efferent lymph from the superficial inguinal lymph node directly to the deep axillary lymph node. The superficial lymph nodes are large and soft compared with those of the domestic species, and each lymph centre usually contains only one or two large lymph nodes. Koalas have a rostral mandibular lymph node which has not been described in other species, but lack popliteal and subiliac lymph nodes. The superficial lymph nodes which are readily palpable in the live koala are the facial, rostral mandibular, mandibular, superficial axillary and superficial inguinal. All superficial lymph pathways terminate at the confluence of the common jugular and subclavian veins.

Animals↗

[advantages and disadvantages of three regional lymph node dissection of thoracic esophageal carcinoma and the lymph node dissection by thoraco-abdomino-midsternal approach].

The 117 cases of two regional (thoraco-abdominal) lymph node dissection were compared to the 56 cases of three regional (with neck area in addition) lymph node dissection for esophageal carcinoma. As for operative death and postoperative complications, there were no difference between these two groups. The prognosis of three regional dissecting group was better than that of two regional dissecting group concerning about the cases that lymph node metastases were less than 1 or 2, the depth of invasion was limited to just near adventitia (a1) and the locations were in upper or midthoracic esophagus. But also the rate of postoperative recurrence to the neck and uppermediastinal lymph nodes were high in spite of three regional dissection. Putting together with all cases, significant improvement of prognosis were not obtained in the three regional group compared to two regional group. So we thought the usual three regional lymph node dissection might not be sufficient. Recently we added midsternotomy and made the lymph node dissection in neck-thoracic junction more complete. This procedure did not make the operative death and postoperative complications increase and the improvement of prognosis was expected by it.

Abdomen↗

Cervical lymph nodes play the role of regional lymph nodes in brain tumour immunity in rats.

Recent physiological and anatomical studies have demonstrated that a major fraction of brain interstitial and cerebrospinal fluid drains into cervical lymph nodes (CLN) in a number of experimental animals. To investigate the role of CLN in brain tumour immunity, temporal profiles of MHC class II molecule expression and T lymphocyte subsets in brain tumours, CLN and other lymphoid tissues were analysed by immunocytochemistry. A total of 64 Wistar rats weighing 250 g were used. Two weeks after the transplantation of C6 glioma cells (10(6) cells/1 microl) into a rat brain, expression of MHC class II molecules was induced in the brain and all systemic lymphoid tissues examined. However, the subsequent appearance of CD4 or CD8 positive cells was strictly confined to CLN, and coincided with the infiltration of such cells into the brain tumour 2 weeks after transplantation. In the group of animals in which cervical lymphadenectomy was followed by intracerebral transplantation of C6 glioma cells, infiltration of CD4 or CD8 positive cells into the brain tumour was delayed until 3 weeks after the transplantation, and the production of such cells was by the spleen. These results suggest that CLN act as regional lymph nodes in brain tumour immunity.

Animals↗

The use of sonography in differentiating cervical lymphomatous lymph nodes from cervical metastatic lymph nodes.

Lymphoma and metastases are common causes of cervical lymphadenopathy. Clinical examination alone is unable to differentiate the two. Ultrasound (US) with its high sensitivity and specificity when combined with a find needle aspiration cytology (FNAC) is therefore the ideal initial investigation. We present the spectrum of findings in 19 patients with non Hodgkins lymphoma (NHL), 15 patients with pharyngeal, laryngeal and oesophageal (PLO) carcinomas, 22 patients with oral cavity tumours and 12 patients with infraclavicular carcinomas. The US features found consistently useful in differentiating NHL from other metastases were the distribution of the nodes, distal enhancement and lack of intranodal necrosis. Other US features of abnormal nodes helped identify abnormality but did not help in differentiation.

Adolescent↗

Assessment of metastases to aortic and pelvic lymph nodes in epithelial ovarian carcinoma. A proposal for essential sites for lymph node biopsy.

BACKGROUND: In staging epithelial ovarian carcinoma, it is necessary to assess the presence of lymph node metastases. However, the essential sites of selective lymph node biopsy have yet to be determined. METHODS: The distribution of metastatic aortic and pelvic lymph nodes was studied in 48 patients with positive lymph nodes of 110 patients with ovarian carcinoma who underwent systematic lymphadenectomy of the aortic and pelvic regions extending to the level of the renal vessels. For purpose of analysis, the lymph nodes were classified into five subgroups: the aortic lymph nodes above the inferior mesenteric artery (A1), the aortic lymph nodes below the inferior mesenteric artery (A2), the common iliac and sacral lymph nodes (P1), the internal and external iliac and obturator lymph nodes (P2), and the suprainguinal (the lowest external iliac) lymph nodes (P3). RESULTS: The incidence of metastases to A1, A2, P1, P2, and P3 was 79%, 71%, 46%, 77%, and 40%, respectively. Provided that 2 of the 5 lymph node subgroups were selected for biopsy, the combination of A1 and P2 gave the best results in sensitivity (94% [45 of 48 patients]) and negative (95% [62 of 65 patients]) predictive value for detection of lymph node metastases. CONCLUSIONS: These data indicate that aortic lymph nodes above the inferior mesenteric artery and the internal and external iliac and obturator lymph nodes are essential sites for selective lymph node biopsy in staging epithelial ovarian carcinoma.

Adult↗

Microvessel density predicts the radiosensitivity of metastatic head and neck squamous cell carcinoma in cervical lymph nodes.

Cervical lymph node metastasis is the most common recurrence pattern of head and neck squamous cell carcinoma (HNSCC), and it is usually treated with radiation therapy and/or neck dissection. There has long been a desire for markers useful in predicting radiosensitivity to enable assignment of patients with recurrent head and neck cancer to clinical trials to improve their survival rates and quality of life. A total of 43 cases of HNSCC treated with whole or elective neck irradiation (total dose, 26-70 Gy; median, 60 Gy) for recurrent metastatic SCC in neck lymph nodes after neck dissection between 1992 and 1999 were the subject of this study. The relationship between radiosensitivity and clinicopathological and histopathological factors, including the Ki-67-labeling index for cell proliferation, p53 immunoreactivity and microvessel density (MVD), in surgical neck lymph node specimens were investigated by univariate and multivariate analysis. Of the 43 patients, 31 had recurrent tumors in neck lymph nodes after radiotherapy. Univariate analysis revealed significant associations between radiosensitivity and both high grade of keratinization (p=0.033) and low MVD (p=0.004), and marginally significant associations between radiosensitivity and grade of differentiation of the cancer in the lymph nodes (p=0.070). Multivariate analysis showed that only MVD had predictive value (p=0.016). Tumors with a high MVD possessed a significantly better neck control rate than tumors with a low MVD (p=0.004) by Kaplan-Meier analysis. MVD can be used as a good predictive marker for radiosensitivity of metastatic HNSCCs in cervical lymph nodes after neck dissection.

Aged↗

Lymph-node revealing solution: a new method for detecting minute lymph nodes in cystectomy specimens.

OBJECTIVE: To describe the use of a new lymph-node revealing solution (LNRS) for detecting lymph node involvement in total cystectomy specimens from patients with locally confined invasive transitional cell carcinoma (TCC) of the bladder, and to compare the results obtained with those using the conventional method (palpation and sectioning perivesical fat) that may fail to detect very small lymph nodes. MATERIALS AND METHODS: Of 12 cystectomy specimens obtained from patients with TCC, six in which 0-3 metastatic nodes were identified by the conventional method were further investigated using LNRS. The revealing solution comprised 95% ethanol, diethyl ether, glacial acetic acid and buffered formalin (65:20:5:10 v/v) prepared under a fume-hood. After evaluation using the conventional method, the specimens were immersed for 6-12 h in the solution, washed under running tap water and the adipose tissue sectioned at intervals of 2-3 mm. Lymph nodes were identified as white, chalky nodules against the background of yellow fat. The number of the lymph nodes identified by conventional and the LNRS methods was recorded and classified according the TNM system. RESULT: Twenty-two lymph nodes were detected by the conventional method, of which four were positive for tumour metastasis. Using the LNRS, an additional 21 nodes were identified among which 12 were positive. The mean size of the lymph nodes detected by the conventional and LNRS methods was 7.96 mm and 3.81 mm, respectively. The stage of three patients was increased (Nx to N2, N0 to N2 and N1 to N2) and therefore two of these patients received adjuvant chemotherapy. CONCLUSIONS: LNRS significantly enhanced the yield of normal and metastatic nodes of cystectomy specimens and may identify smaller nodes. The LNRS method allows a more accurate staging with better assessment of the prognosis and need for adjuvant therapy.

Carcinoma, Transitional Cell↗

An axilla scoring system to predict non-sentinel lymph node status in breast cancer patients with sentinel lymph node involvement.

BACKGROUND: Axillary lymph node dissection (ALND) is the current standard of care for breast cancer patients with sentinel lymph node (SN) involvement. However, the SN is the only involved axillary node in a significant proportion of these patients. Here we examined factors predictive of non-SN involvement in patients with a metastatic SN, in order to develop a scoring system for predicting non-SN involvement. MATERIALS AND METHODS: This study was based on a prospective database of 337 patients who underwent SN biopsy for breast cancer, of whom 81 (24%) were SN-positive; we examined factors predictive of non SN involvement in the 71 of these 81 women who underwent complementary ALND. All clinical and histological criteria were recorded and analysed according to non-SN status, by using Chi-2 analysis, Student's t-test, and multivariate logistic regression. RESULTS: Univariate analysis showed a significant association between non-SN involvement and histological primary tumor size (p=0.0001), SN macrometastasis (p=0.01), the method used to detect SN metastasis (H&E versus immunohistochemistry) (p=0.03), the number of positive SNs (p=0.049), the proportion of involved SNs among all identified SNs (p=0.0001) and lymphovascular invasion (p=0.006). Histological primary tumor size (p=0.006), SN macrometastasis (p=0.02) and the proportion of involved SNs among all identified SNs (p=0.03) remained significantly associated with non-SN status in multivariate analysis. Based on the multivariate analysis, we developed an axilla scoring system (range 0-7) to predict the likelihood of non-SN metastasis in breast cancer patients with SN involvement. CONCLUSION: In patients with invasive breast cancer and a positive SN, histological primary tumor size, the size of SN metastases, and the proportion of involved SNs among all identified SNs were independently predictive of non-SN involvement.

Adult↗

Risk factors for patients with pelvic lymph node metastases following radical cystectomy with en bloc pelvic lymphadenectomy: concept of lymph node density.

PURPOSE: We evaluated the clinical outcomes and risk factors for progression in a large cohort of patients with lymph node metastases following en bloc radical cystectomy and bilateral pelvic lymphadenectomy. MATERIALS AND METHODS: From July 1971 through December 1997, 1,054 patients underwent radical cystectomy and bilateral pelvic-iliac lymphadenectomy for high grade, invasive transitional cell carcinoma of the bladder. Of these patients 244 (23%) with a median age of 66 years (range 36 to 90) had pathological lymph node metastases. Overall 139 of the 244 patients (57%) received some form of chemotherapy. At a median followup of greater than 10 years (range 0 to 28) outcomes data were analyzed in univariate analysis according to tumor grade, carcinoma in situ, primary bladder tumor stage, pathological subgroups, total number of lymph nodes removed and involved with tumor, and lymph node density (total number of positive lymph nodes/total number removed). In addition, the form of urinary diversion and the administration of chemotherapy were also evaluated. Multivariate analysis was then performed to analyze these variables independently. RESULTS: The incidence of positive lymph nodes increased with higher p stage and pathological subgroups. Of 669 patients 75 (11%) with organ confined primary tumors and 169 of 385 (44%) with extravesical tumor extension had involved lymph nodes. The median number of lymph nodes removed in the 244 lymph node positive cases was 30 (range 1 to 96), while the median number of positive lymph nodes was 2 (range 1 to 63). Overall recurrence-free survival at 5 and 10 years for the 244 patients with lymph node positive disease was 35% and 34%, respectively. Patients with lymph node positive disease and an organ confined primary bladder tumor had significantly improved 10-year recurrence-free survival compared with those with extravesical tumor extension (44% vs 30%, p = 0.003). The total number of lymph nodes removed at surgery was also prognostic. Patients with 15 or less lymph nodes removed had 25% 10-year recurrence-free survival compared with 36% when greater than 15 lymph nodes were removed. Recurrence-free survival at 10 years for patients with 8 or less positive lymph nodes was significantly higher than in those with greater than 8 positive lymph nodes (40% vs 10%, p <0.001). The novel concept of lymph node density was also a significant prognostic factor. Patients with a lymph node density of 20% or less had 43% 10-year recurrence-free survival compared with only 17% survival at 10 years when lymph node density was greater than 20% (p <0.001). On multivariate analysis the total number of lymph nodes involved, pathological subgroups of the primary bladder tumor, lymph node density and adjuvant chemotherapy remained significant and independent risk factors for recurrence-free and overall survival. CONCLUSIONS: Patients with lymph node tumor involvement following radical cystectomy may be stratified into high risk groups based on the primary bladder tumor, pathological subgroup, number of lymph nodes removed and total number of lymph nodes involved. Lymph node density, which is a novel prognostic indicator, may better stratify lymph node positive cases because this concept collectively accounts for the total number of positive lymph nodes (tumor burden) and the total number of lymph nodes removed (extent of lymphadenectomy). Future staging systems and the application of adjuvant therapies in clinical trials should consider applying lymph node density to help standardize this high risk group of patients following radical cystectomy.

Adult↗

Sentinel lymph node biopsy in melanoma patients with clinically negative regional lymph nodes--one institution's experience.

The purpose of this prospective study of sentinel lymph node (SLN) biopsy in a large series of melanoma patients with clinically negative regional lymph nodes from one cancer centre was to analyse the reliability of the procedure, the pattern of failures during follow-up and the factors affecting the clinical outcome of patients. Between April 1995 and November 2001, 726 consecutive patients with primary cutaneous malignant melanoma underwent SLN biopsy with preoperative lymphoscintigraphy. The vital blue dye technique was used in 170 patients, and the blue dye technique combined with intraoperative lymphoscintigraphy in 556 patients. The primary melanoma sites were head and neck in nine patients, the extremities in 419 patients, and the trunk in 298 patients. The median Breslow thickness was 3.0 mm. All patients were followed closely, the median follow-up time being 34 months. The sentinel node(s) were successfully identified in 96% of patients. Intraoperative lymphoscintigraphy combined with the blue dye technique improved the SLN identification rate (technical success in 97.3% of cases) compared with the blue dye technique alone (technical success in 91.6%). The rate of failed SLN procedures was significantly (P = 0.007) lower in inguinal basins (3.1%) compared with axillary basins (7.9%). SLN metastases were detected in 147 patients (20.2%). The presence of SLN metastases correlated significantly with primary tumour thickness and ulceration (P < 0.001). The false-negative SLN biopsy rate was 4.66% (27 out of 579 SLN-negative patients). All but two node-positive patients underwent complete lymphadenectomy. Lymph nodes other than SLNs were found to contain metastases in 26.9% of patients (39 out of 145). The 5 year overall survival (OS) rate was 84% for SLN-negative patients and 40% for SLN-positive patients. Five variables showed a strong, statistically significant negative independent prognostic association with OS: positive SLN status (P = 0.000001), primary melanoma thickness > 4 mm (P = 0.0009), male gender (P = 0.001), more than one lymph node involvement (P = 0.02) and lymph node extracapsular extension (P = 0.03). SLN biopsy is currently a valuable and effective diagnostic procedure for the precise staging of patients with clinically N0 cutaneous melanoma. So far SLN biopsy seems to be the only accessible method for consciously oriented detection of nodal micrometastases in melanoma that would otherwise go undetected. SLN status is the most important factor proven to distinguish high and low risk melanoma patients.

Adolescent↗