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Number of lymph node metastases is better predictor of prognosis than level of lymph node metastasis in patients with node-positive colon cancer.

BACKGROUND: Lymph node metastasis is the most important prognostic factor for colon cancer patients. Survival is also related to the number and level of positive lymph nodes (PLNs). Definitions of degree of PLNs for colon cancer differ greatly between the number and level of PLNs. STUDY DESIGN: The aim of this study is to compare number and level of PLNs to see which is a better predictor of prognosis for node-positive colon cancer. One hundred eighteen patients underwent histologically curative resection for node-positive colon cancer. We calculated the cumulative 5-year survival rates and examined prognostic factors for multivariate analysis based on the number and level of PLNs and additional factors. The number of PLNs was classified as either one to three PLNs or more than four PLNs, and level of PLNs was classified as either Level I (pericolic lymph node metastasis) or Level II (lymph node metastasis along the major named vessel supplying the tumor, and that around the origin of a main artery). RESULTS: Cumulative 5-year survival rates were statistically different between the 1 to 3 PLNs group and the more than 4 PLNs group, but not significantly different between Level I group and Level II group. Multivariate analysis showed that number, not level, of PLNs was an independent prognostic factor. CONCLUSIONS: In node-positive colon cancer, number of PLNs predicted prognosis better than level of PLNs.

Adult↗

Minimal risk of macrometastases in the non-sentinel axillary lymph nodes in breast cancer patients with micrometastatic sentinel lymph nodes and preoperatively ultrasonically uninvolved axillary lymph nodes.

Micrometastases in the sentinel lymph node (SLN) carry a considerable risk of macrometastases in the non-sentinel lymph nodes (NSLN), resulting in axillary lymph node dissection (ALND). Preoperative ultrasound (US) examination of the axillary lymph nodes combined with a fine-needle aspiration biopsy (FNAB) has been proved to discover metastases in the axillary lymph nodes. The aim of our study was to assess the risk of macrometastases in NSLN in patients with micrometastatic SLN after a preoperative US examination of the axillary lymph nodes. The study included 36 patients in whom, after preoperative axillary US, micrometastases in the SLN were revealed and ALND was subsequently performed. At final histopathology, no macrometastases were discovered in the NSLN. In four patients, additional micrometastases were discovered in the NSLN. In conclusion, the risk of macrometastases in the NSLN in patients with preoperatively ultrasonically uninvolved axillary lymph nodes is minimal.

Adult↗

[Lymph node mapping and axillary sentinel lymph node biopsy in 243 invasive breast cancers with no palpable nodes. The south Lyon hospital center experience].

STUDY AIM: To evaluate the effect of intraoperative lymph node mapping and sentinel lymph node dissection (SLND) on the axillary staging of patients with N0 breast carcinoma. Two techniques were used: blue dye alone (Evans Blue and Patent Blue) and combined technique (blue dye and isotope). METHODS: The incidence of axillary node metastasis in axillary lymph node dissection (ALND) and SLND was compared prospectively. Multiple sections of each SLN were examined by HPS staining and immunohistochemical techniques. Two sections of each non sentinel node in ALND specimens were examined by routine HPS staining. RESULTS: 243 patients underwent ALND after SLN biopsy. The SLN detection rate was 225/243 cases (92.59%): 89.94% with blue dye alone and 100% with the combined technique. The false-negative rate was less than 2%. CONCLUSION: SN biopsy is an accurate staging technique for N0 breast cancer. SLN biopsy with multiple sections and immunohistochemical staining of the SLN can identify significantly more patients with lymph node metastases than ALND with routine HPS staining.

Biopsy↗

T and B lymphocyte populations in human normal lymph node, regional tumour lymph node and inflammatory lymph node.

We have determined the T and B lymphocyte subpopulations in normal human lymph nodes. The lymphocyte profile was the same irrespective of the anatomical distribution and was similar to that found in peripheral blood with identical T and B cell values but with a lower Fc and a higher C3-receptor-bearing lymphocyte subpopulation. This pattern showed a marked change in the regional nodes of patients with mammary carcinoma and nodes draining a variety of other solid tumours, with a fall in T and pronounced elevation of B, Fc and C3 cells but with a persistence of C3 predominance. The lymphocyte profile found in tonsils and nodes draining inflammatory foci was a similar but further exaggeration of the tumour node pattern, with reversal of T and B cell ratios. The T and B lymphocyte percentages in the peripheral blood of patients with clinically localized breast cancer are identical to those of the healthy controls. Different Fc/C3 subsets exist in peripheral blood and lymphoid structures and probably represent a differential functional heterogeneity. Proximity of tumour to the draining node modified this profile.

B-Lymphocytes↗

Significance of preoperative lymphoscintigraphy and thin-slice computed tomography on sentinel node assessment: metastatic sentinel node in a lateral paramammary lesion out of axillary nodes from breast cancer.

Sentinel node status was evaluated using preoperative lymphoscintigraphy in a 43-year-old woman who presented with an invasive ductal carcinoma in the lower outer quadrant of the right breast. Two strong hot nodules were visualized in the affected axillary basin on an early image, and a faint accumulation of radioactive tracer was lying between the cancer in the right lower outer quadrant and the axillary hot nodules on the lymphoscintigram taken at 90 min. The faint accumulation was considered to represent a small paramammary node on thin-slice computed tomography (CT) and was confirmed by node biopsy to be a sentinel node grossly involved with tumor cells. Immediate axillary dissection and adjuvant chemotherapy was subsequently performed. Careful evaluation using lymphoscintigraphy and thin-slice CT may be associated with increased localization of true sentinel nodes.

Adult↗

Sinus node echoes and concealed concealed conduction: additional sinus node phenomena confirmed in man by direct sinus node electrography.

Direct sinus node electrography has been previously used to assess several aspects of sinus node physiology: sinus node pauses, overdrive suppression, sinoatrial entrance block. This report presents data in which sinus node electrograms confirm two additional physiologic phenomena in man: concealed conduction in the sinoatrial junction and sinus node reentry. These findings verify the presence of previously suspected phenomena by careful deductive analysis of electrocardiographic and electrographic tracings.

Adult↗

Morphology of draining lymph nodes after local immune stimulation with C. parvum: comparison of pelvic nodes in carcinoma of cervix and popliteal and inguinal nodes of guinea-pig.

Morphological changes are described in pelvic lymph nodes excised 10 days after C. parvum (CP) treatment of patients with cervical carcinoma. Guinea-pig popliteal and inguinal lymph nodes were investigated from Days 1 to 10 after an injection of 70 micrograms CP into the footpad. Eosinophils were detected from the first few hours after stimulation, initially in the marginal sinus, then in the medullary sinuses and subsequently in the efferent lymphatics. From Day 2 to Day 6, histiocyte accumulations with the appearance of epithelioid cells were found mainly in subcapsular and interfollicular areas, and small granulomas were also seen in the paracortex. The granuloma formation in the lymph node was considered as an indication of the activation of histiocytes. Besides small granulomas in the paracortex, activated interdigitating cells, surrounded by scattered lymphoblasts and eosinophils, were also present. We considered this lymphoblastic response and eosinophilic accumulation as likely to be due to blastogenic factor and eosinophil stimulation promotor. Eight to 10 days after CP stimulation, the macrophage lymphoblast eosinophil response was replaced by a B-cell reaction: germinal-centre activation and medullary plasma cells. Such a B-cell reaction was also found in the human pelvic nodes removed at operation, but this reaction could not be attributed to CP treatment alone, since cervical-carcinoma patients not treated with CP also showed such reactions. In contrast, pelvic lymph nodes removed at necropsy from females killed in traffic accidents showed no predominance of either B- or T-cell stimulation.

Animals↗

Killer cell (K) activity in human normal lymph node, regional tumour lymph node and inflammatory lymph node.

Human normal lymph nodes, irrespective of their anatomical site of origin, have a low K cell activity, which may not be detected except with the appropriate target cell and at high lymphocyte to target cell ratios (100:1). This very low killer cell activity is also found in all the homolateral axillary nodes of patients with clinical stage I and II carcinoma of the breast and in the regional draining nodes of a variety of solid tumours, whether small and localized or large and with extensive spread. In all cases proximity to the tumour and obious hyperplastic changes in the nodes have no modifying effect. This pattern of minimal reactivity is similarly found with tonsillar lymphocytes and with nodes draining inflammatory foci. The Fc and C3 receptors on surface membranes are dectected with ease, and pretreatment of lymphocytes by incubation, washing and enzymatic treatment fail to alter their reactivity, thus excluding effector cell inhibition by immune complexes. The killer cell activity of lymphocytes from the blood of breast tumor patients is similar to the activity of lymphocytes from healthy controls.

Binding Sites↗

Sentinel lymph node dissection provides axillary control equal to complete axillary node dissection in breast cancer patients with lobular histology and a negative sentinel node.

OBJECTIVE: Invasive lobular carcinoma (ILC) presents special challenges to treating physicians because of the diffuse infiltrative growth pattern. As sentinel lymph node dissection (SLND) is rapidly replacing axillary lymph node dissection (ALND) in the management of patients with early-stage breast cancer, we sought to evaluate the safety of SLND in providing axillary control in breast cancer patients with lobular histology and a negative sentinel node. METHODS: We identified 239 patients with T1-2,N0,M0 lobular breast cancer from the prospective databases of 2 institutions; all were treated between March 1994 and December 2003. RESULTS: A total of 202 patients had SLND and 37 had SLND followed by ALND. There was no significant difference between the 2 groups with respect to tumor size, presence of lymphovascular invasion, estrogen receptor (ER)/progesterone receptor (PR) and HER-2/neu status, type of breast surgery, margin status, or nuclear grade. Use of chemotherapy, radiation, and hormonal therapy was not significantly different between groups. At a median follow-up of 48 months in the ALND group and 26 months in the SLND group (range 6 to 80 months), none of the 202 patients in the SLND group had experienced an axillary recurrence, while 2 (5.4%) of the 37 patients who underwent ALND had experienced an axillary recurrence. CONCLUSIONS: SLND provided axillary control equivalent to that of ALND for patients with lobular breast cancer. SLND alone appears to be adequate axillary management of patients with lobular breast cancer and a negative sentinel node.

Axilla↗

Probability of axillary lymph node metastasis when sentinel lymph node biopsy is negative in women with clinically node negative breast cancer: a Bayesian approach.

BACKGROUND: Although sentinel lymph node biopsy(SLNB)is highly accurate in predicting axillary nodal status in patients with breast cancer, it has been shown that the procedure is associated with a few false negative results. The risk of leaving metastatic nodes behind in the axillary basin when SLNB is negative should be estimated for an individual patient if SLNB is performed to avoid conventional axillary lymph node dissection(ALND). METHODS: A retrospective analysis of 512 women with T1-3N0M0 breast cancer was conducted to derive a prevalence of nodal metastasis by T category as a pre-test(i.e., before SLNB)probability and to examine potential confounders on the relationship between T category and axillary nodal involvement. Probability of nodal metastasis when SLNB was negative was estimated by means of Bayes' theorem which incorporated the pre-test probability and sensitivity and specificity of SLNB. RESULTS: Axillary nodal metastasis was observed in 6.1% of T1a-b, 25.1% of T1c, 28.7% of T2, 35.0% of T3 tumors. Point estimates for the probability of nodal involvement when SLNB was negative ranged from 0.3-1.3% for T1a-b, 1.6-6.3% for T1c, 2.0-7.5% for T2, and 2.6-9.7% for T3 tumors with representative sensitivities of 80%, 85%, 90% and 95%, respectively. The risk may be higher when the tumor involves the upper outer quadrant of the breast, while it may be lower for an underweight woman. CONCLUSIONS: The probability of axillary lymph node metastasis when SLNB is negative can be estimated using a Bayesian approach. Presenting the probability to the patient may guide the decision of surgery without conventional ALND.

Adult↗

Type of lymph node involvement influences survival rates in T1N1M0 non-small cell lung carcinoma. Lymph node involvement by direct extension compared with lobar and hilar node metastases.

Stage II non-small cell lung cancer represents a group of patients with varying 5-year survival rates. Of 2,009 patients, we reviewed 58 patients with pT1N1M0 disease operated on from 1977 through 1994. The N1 status was refined into lymph node involvement by direct extension and/or involvement by metastases (lobar or hilar). The cumulative 5-year survival of all hospital survivors (n = 57) was 45.7%. The 5-year survival of patients with N1 direct extension was superior to survival of patients with N1 metastases (68.6% vs 31.2%; p = 0.0038). Survival of patients with N1 direct extension was better then survival of patients with N1 hilar metastases (p = 0.0006), but did not differ from survival of patients with lobar metastases. Survival was not related to histologic features, sex, and type of resection. Recurrence of malignancy occurred less in patients with N1 direct extension. In patients with N1 hilar nodes, the most common pattern was distant metastases. Survival differs according to the type of lymph node involvement: "direct extension" seems to be an early stage of the disease, while lymph node metastases represent a more advanced form.

Adult↗

Cutaneous melanoma: therapeutic lymph node and elective lymph node dissections, lymphatic mapping, and sentinel lymph node biopsy.

Early clinical observation in cancer patients suggested that tumors spread in a methodical, stepwise fashion from the primary site, to the regional lymphatics, and only then to distant locations. Based on these observations, the regional lymphatics were believed to be mechanical barriers, at least temporarily preventing the widespread dissemination of tumor. Despite evidence now available disputing its validity, this barrier theory has guided the surgical management of the regional lymphatics in cancer patients for more than a century, influencing the use of such surgical modalities as therapeutic lymph node dissection, elective lymph node dissection, and most recently lymphatic mapping and sentinel lymph node biopsy. No published randomized controlled trial exists that demonstrates improved overall patient survival for cancer of any type, including melanoma, after surgical excision of regional lymphatics. This article will review the biology of lymphatics as it relates to regional tumor metastasis, and based on available information, offer practical recommendations for the clinical dermatologist and their patients who have cutaneous melanoma.

Animals↗

Lymph node mapping and sentinel lymph node biopsy for evaluation of axillary lymph node status in early invasive breast cancer. Our experience.

The Authors show their preliminary experience with the sentinel lymph node biopsy (SLNB) in clinical early invasive breast cancer (T1N0). During a period of 15 months, forty-two patients were submitted to SLNB upon Tc99-colloid albumin injection and SLN identification by lymphoscintigraphy. The middle number of lymph nodes found in the SLNB was 1 (1-3), whereas the middle number of lymph nodes identified in level I/II ALND specimens was 15. The SLN was identified with success in all cases (100%). The axilla was positive for metastasis in 4/42 cases. The SLN was positive in all four cases in which nodal metastasis was identified. The negative predictive value of SLN was 100%. The SLN was the only site of metastasis in 3/4 cases. The SLN pathological status accurately reflected the lymphatic basin status, but further investigation is needed to define the optimal timing of colloid injection and method of examination of the SLN.

Adult↗

Sentinel lymph node biopsy alone without axillary lymph node dissection--follow up of sentinel lymph node negative breast cancer patients.

AIMS: To evaluate the rate of axillary recurrences in sentinel lymph node (SLN) negative breast cancer patients after sentinel lymph node biopsy (SLNB) alone without further axillary lymph node dissection (ALND). METHODS: Between May 1999 and February 2001 all patients who had primary invasive breast cancer and were SLN negative were eligible for this prospective study. SLNB was performed by using the combined method with radioactive tracer and blue dye. SLNs were examined by frozen section, standard H/E staining and immunohistochemistry staining. SLN negative patients did not receive further ALND. Follow-up was done three-monthly with clinical controls, blood samples and ultrasound of the breast and axilla. An annual mammogram was performed. RESULTS: 116 patients with T1 or T2 invasive breast cancer were included in this trial. All 116 patients had negative SLNs in frozen sections, in H/E staining and in immunohistochemistry staining. The mean number of removed SLNs was 2.03+/-1.22. Mean tumor size was 17.15+/-7.62 mm. Postmenopausal patients totalled 79.3 and 20.7% of patients were premenopausal. No local or axillary recurrences occurred at a mean duration of follow-up of 22.12+/-6.38 months. CONCLUSION: The absence of axillary recurrences after SLNB without ALND in SLN negative breast cancer patients supports the hypothesis that SLNB is accurate and safe while providing less surgical morbidity. Short term results are very promising. SLNB without ALND in SLN negative patients is an excellent procedure for axillary staging in a cohort of breast cancer patients with small tumors.

Adult↗

Failure to remove true sentinel nodes can cause failure of the sentinel node biopsy technique: evidence from antimony concentrations in false-negative sentinel nodes from melanoma patients.

We have recently found that antimony (originating from the technetium 99m antimony trisulfide colloid, used for preoperative lymphoscintigraphy) can be measured in tissue sections from archival paraffin blocks of sentinel nodes (SNs) by means of inductively coupled plasma mass spectrometry (ICP-MS) to confirm that removed nodes are true SNs. We performed a retrospective analysis of antimony concentrations in all our false-negative (FN) SNs to determine whether errors in lymphadenectomy (i.e., failure to remove true SNs) may be a cause of FN SN biopsies (SNBs). Among 27 patients with an FN SNB, metastases were found on histopathologic review of the original slides or additional sections in 7 of 23 patients for which they were available; however, antimony concentrations were low in 5 of 20 presumptive SNs. Our results suggest that an FN SNB can occur because of failure to remove the true SN as well as histopathologic misdiagnosis.

Antimony↗

Cost-analysis of staging methods for lymph nodes in patients with prostate cancer: MRI with a lymph node-specific contrast agent compared to pelvic lymph node dissection or CT.

The aim of this study was to compare the costs of three strategies in patients with prostate cancer in a specific setting: firstly, a strategy including MR lymphography (MRL) in which pelvic lymph node dissection (PLND) is foregone in case of a negative result. The second strategy involves computed tomography (CT) followed by a biopsy or PLND. The third strategy consists of PLND without imaging beforehand. A decision analytic model was constructed. This model represented the diagnostic process for patients with prostate cancer and intermediate or high risk for nodal metastases, comparing the costs of the three strategies. Cost analysis was done from the health care perspective. The model indicated that the expected costs for the MRL strategy were 2,527 euro. The expected costs for the strategy using CT were 3,837 euro and for PLND 3,994 euro. These results show that potential savings performing MRL instead of CT were 1,310 euro and 1,467 euro for PLND. Sensitivity analyses show that variation in costs of PLND was most influential on the costs of all strategies. However, the overall savings pattern did not alter. Average costs of MRL staging in our institution are less than for CT and PLND in staging lymph nodes of patients with prostate cancer and who are intermediate or high risk for nodal metastases.

Biomarkers, Tumor↗

Nonsentinel node metastases in breast cancer patients with isolated tumor cells in the sentinel node: implications for completion axillary node dissection.

BACKGROUND: Controversy exists regarding axillary dissection (ALND) for sentinel node (SLN) metastases detected as isolated tumor cells (ITC). We hypothesized that the number of positive non-SLNs is low and ALND is unnecessary for most patients with ITC. METHODS: From 1995 to 1999, 634 breast cancer patients underwent SLND. SLNs were examined using immunohistochemistry if hematoxylin and eosin was negative. ALND was recommended for ITC-positive SLNs. RESULTS: Seventy-eight patients (12.3%) with ITC-positive SLNs were offered ALND. Sixty-one consented, whereas 17 refused. Fifty-eight (95.1%) had negative non-SLNs. Three (4.9%) had non-SLN metastases. One patient (1.6%) had macrometastatic disease, whereas 2 (3.3%) had micrometastases. No ITC-only-positive SLN patient experienced axillary recurrence. CONCLUSIONS: When ALND was performed for ITC, 1.6% of non-SLNs harbored macrometastases and 3.3% had micrometastases. When ALND was not performed, axillary recurrence was not seen. The low risk of non-SLN disease in this study fails to support the routine use of ALND for ITC-positive SLNs.

Adult↗

Accuracy of the extent of axillary nodal positivity related to primary tumor size, number of involved nodes, and number of nodes examined.

PURPOSE: While a number of studies have evaluated the minimum number of axillary nodes that need to be examined to accurately determine nodal positivity or negativity, there is little information on the number of nodes which must be examined to determine the extent of nodal positivity. This study attempts to determine for patients with 1-3 positive nodes the probability that the number of positive nodes reported is the true number of positive nodes as well as the probability that 4 or more nodes could be positive based on primary tumor size and number of nodes examined. MATERIALS AND METHODS: From 1979 to 1998, 1652 women with Stages I-II invasive breast cancer underwent an axillary dissection as part of their breast conservation therapy and had more than 10 lymph nodes examined. The mean and median number of nodes identified in the dissection was 19 and 17 (range, 11-75). The median age was 55 years. A total of 1155 women had T1 tumors and 497 had T2 tumors. Of the 459 node-positive women, 72% had 1-3 positive nodes, 18% had 4-9 positive nodes, and 10% had 10 or more positive nodes. A mathematical model based on tumor size and number of nodes examined was created using the hypergeometric distribution and Bayes Theorem. The resulting model was used to estimate the accuracy of the reported number of positive nodes and the probability of 4 or more positive nodes based on various observed sampling combinations. RESULTS: For patients with T1 tumors and 1, 2, or 3 positive nodes, the minimum number of nodes examined needed for a 90% probability of accuracy is 19, 20, and 20. For T2 tumors and 1, 2, or 3 positive nodes, a minimum of 20 nodes is required. The probability of 4 or more positive nodes increases as tumor size and the number of reported positive nodes increase and as the number of examined nodes decreases. For a 10% or less probability of 4 or more positive nodes, a patient with a T1 tumor and 1, 2, or 3 observed positive nodes would require a minimum of 8, 15, and 20 nodes removed. For a T2 tumor and 1, 2, or 3 observed positive nodes, the corresponding numbers are 10, 16, and 20. CONCLUSION: The accuracy of the extent of axillary nodal positivity is influenced by the number of observed positive nodes, tumor size, and the number of nodes examined. Underestimation of the number of positive nodes will result in errors in the assessment of an individual's risk for locoregional recurrence, distant disease, and breast cancer death and will adversely impact on treatment recommendations. This model provides the clinician with a means for assessing the accuracy of the number of positive nodes reported in patients with 1-3 positive nodes.

Adult↗