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Adjuvant small field pelvic radiation for patients with high risk, stage IB lymph node negative cervix carcinoma after radical hysterectomy and pelvic lymph node dissection. A pilot study.

BACKGROUND: After radical hysterectomy and pelvic lymph node dissection, an identifiable subgroup of patients with International Federation of Gynecology and Obstetrics Stage IB lymph node negative cervix carcinoma remains at high risk of pelvic recurrence. This study attempted to determine whether postoperative small field of pelvic radiation can improve the disease free survival (DFS) of this high risk group of patients without producing significant morbidity. METHODS: Between 1991 and 1995, after radical surgery, 25 patients with Stage IB lymph node negative cervix carcinoma were considered to be at high risk of pelvic recurrence on the basis of tumor dimension, depth of stromal invasion, and the presence of lymph-vascular space invasion. All had a score >/= 120 as determined by the Gynecologic Oncology Group (GOG) study. These patients received 50.4 gray of adjuvant radiation to a small central pelvic field and were followed prospectively. A Kaplan-Meier 5-year DFS curve was generated. A log rank analysis produced an estimated log rank P value (est P value) by comparing the 5-year DFS of the patients in the current study with the 5-year DFS of the corresponding high risk group of the GOG study (observation only). The morbidity of small field pelvic radiation was recorded. RESULTS: Among the 25 patients who received small field pelvic radiation, the mean GOG score was 166 (range, 120-263) and the mean follow-up was 32 months (range, 12-64 months). There was 1 recurrence (4%) recorded at 16 months. The log rank analysis demonstrated a significant improvement in the 5-year DFS for the group who received adjuvant small field pelvic radiation (est P value = 0.005) when compared with the DFS of the high risk GOG patients who were observed postoperatively. Four cases of minor morbidity were recorded: lymphedema (three cases) and mild rectal incontinence (one case). No major morbidity was reported. CONCLUSIONS: With low morbidity, adjuvant small field pelvic radiation appears to improve significantly the 5-year DFS of patients with high risk, lymph node negative Stage IB cervical carcinoma. However, this pilot study requires verification.

Adult↗

[Efficacy of elective lymph node dissection in malignant melanoma of the extremities and trunk. An analysis in view of the sentinel lymph node biopsy].

Elective lymph node dissection (ELND) is increasingly displaced by the Sentinel-lymph node biopsy. In this view we analyzed the efficacy of ELND in the treatment of malignant melanoma of the extremities and the trunc. Between 1979 and 1998 we performed a lymph node dissection in 834 patients (336 male, 498 female; average age 52 years). The analysis of the prospectively collected data was based on those 650 patients in whom an ELND was performed for UICC-stage I (T2) to stage III melanoma. The 5-year survival rate was 75% for all 650 patients. It was 87% for patients suffering from stage I-disease (T2-n = 65), 86% for those with stage II-disease (n = 354) and 47% in case of stage III-disease (n = 231) respectively. In 7 of the 73 patients undergoing ELND for a T2-tumor, in 56 of the 424 patients suffering from T3-tumor and in 38 of the 153 patients with a T4-tumor clinically obvious lymph node metastases had been detected by ELND. Discerning our results, we could demonstrate that a few of our patients profited from ELND, namely the patients in those clinically obvious metastases could be detected and survival could be achieved, i.e. 29 of all 650 electively dissected patients (2 of 7 T2N1-patients, 18 of 56 T3N1-patients and 9 of 38 T4N1-patients). We regard this benefit as an argument not to abandon the histological evaluation of the regional lymph nodes. However, because of the limited efficacy of elective lymphadenectomy, ELND should be displaced by the less invasive Sentinel-lymph node biopsy.

Adolescent↗

Results of extended lymph node dissection for gastric cancer cases with N2 lymph node metastasis.

The therapeutic value of extended lymph node dissection (D2) for gastric cancer remains controversial. Limited lymph node dissection, however, leaves cancer cells in the second tier of nodes (N2) in patients with N2 metastasis. This retrospective study was, therefore, undertaken to clarify which patients would be most likely to benefit from D2 dissection, even with N2 metastasis. Two groups, N2 cases with (n = 40) and without (n = 24) the development of recurrence after curative surgery, were compared. Borrmann type IV and serosal invasion were significantly related to recurrence. The number of metastatic nodes did not differ significantly between the two groups. All (7/7) of the Borrmann type IV cases with N2 metastasis developed recurrence and died. However, one quarter (7/30) of the cases with serosal invasion and N2 metastasis showed no sign of recurrence. D2 dissection is a surgical treatment which offers the potential to cure gastric cancers, other than Borrmann type IV tumor, with N2 metastasis.

Female↗

Paradigm shift of staging and treatment for early breast cancer in the sentinel lymph node era.

Lymph node status is the most reliable prognostic indicator for the clinical outcome of patients with most solid cancers. Because it is the first node draining the primary cancer, the sentinel lymph node (SLN) is most likely to harbor metastatic cancer cells. The tumor size of primary breast cancer is highly correlated with SLN metastasis. If the SLN is negative, the negative predictive value of the remaining nodal basin exceeds 95%. It appears that even using different techniques from different institutions, the successful rate to harvest the SLN is more than 95%. The false-negative rate is about 5-10% in most series. Breast cancer patients with early detection and a negative SLN have a significantly improved survival rate. The SLN data in breast cancer is so convincing that SLN information has been incorporated into the new American Joint Committee on Cancer (AJCC) classification of breast cancer. The therapeutic value of additional lymph node dissection after a positive SLN for breast cancer is still controversial. Follow-up data from breast cancer patients is somewhat limited, but available information shows that patients with negative SLNs fare much better. In summary, several important patterns of metastasis can be established based on the current SLN experience: 1) The earlier the breast cancer is found, the less the metastatic potential. 2) In most cases, breast cancer follows an orderly progression of metastasis to the SLN. 3) A small subgroup of patients may develop systemic dissemination without SLN involvement. Since metastatic cancer is usually incurable, it is important for oncologists to detect and resect an early breast cancer without delay. The challenge in the future will be to dissect these different patterns of metastasis based on molecular or genetic markers. Such information will be critical to select high-risk patients for adjuvant therapy.

Biomarkers, Tumor↗

[Regional neck lymph nodes and primary tumors. 1. Neck lymph node metastases].

The metastasis are situated in the primary regional lymphnodes. Preoperative palpation of the neck gives unreliable results. The extent of the primary tumor has no correlation to the occurence of metastasis. When the tumor is localized in the supraglottic, transglottic or in the tongue base region the frequency of metastasis in lymph nodes is approximately equal; more than half of them have metastasis. When the tumor is localised in sinus piriformis or in the marginal region a still higher frequency of metastasis is found.

Head and Neck Neoplasms↗

Erythrophagocytosis of the lymph node macrophages caused by autotransplantation of the splenic tissue into the lymph nodes of rat.

The rat splenic tissue, autotransplanted into the mesenteric lymph node, regenerated about three months. The recipient lymph node became reddish because of the increase of erythrocytes in the lymphatic sinuses and medullary cords. The macrophages in the lymphatic sinus showed an active erythrophagocytosis. In electron microscopy, these macrophages contained the graded degradation of erythrocytes and closely contacted with lymphocytes. These observations represent the splenic autotransplants in the lymph node changes the recipient lymph node into the hemolymph node, and the lymph node macrophages do not recognize the self-erythrocytes as self-ones.

Animals↗

Added value of the presence of blue nodes or hot nodes in sentinel lymph node biopsy of breast cancer.

BACKGROUND: Combined use of blue dye and radiocolloid is considered to be useful for sentinel lymph node (SLN) biopsy of breast cancer. Whether both techniques together is superior to either alone was analyzed. PATIENTS AND METHODS: A consecutive series of 308 cases of breast cancer who underwent SLN biopsy using the combination technique was used. The frequency of a blue node or hot node was analyzed in all cases and only node-positive cases. Furthermore, the frequency of a blue node and hot node together, or either alone, and the highest radiocount of the SLNs in each case were examined for correlation with 8 clinicopathologic features. Three types of SLN containing both blue dye and radioactivity (blue-hot node), blue dye alone (blue-only node) and radioactivity alone (hot-only node), and the SLN radiocounts were analyzed for correlation with metastatic tumor. RESULTS: Of 308 cases, a blue node was present in 298 (97%), a hot node in 295 (96%), and either a blue or hot node in 306 (99%). The presence of a blue node or hot node was similarly affected by previous surgical biopsy and body mass index (BMI), and the presence of a hot node was also affected by age and tumor location. However, the presence of either a blue node or hot node was not affected by any of these characteristics. Of 77 node-positive cases, 8 (10%), 15 (19%) and 6 (8%) were considered to be node-negative based on blue node, hot node and either blue node or hot node positivity, respectively. The frequency of positivity for SLN metastasis decreased in order from blue-hot, blue-only to hot-only nodes. Of 62 cases with metastatic hot nodes, six (10%) were negative when the hottest node was examined, but the second-hottest node was positive. CONCLUSIONS: The added value of the presence of blue node or hot node was confirmed in the SLN biopsy using the combination technique, which suggests that all blue nodes and hot nodes need to be harvested.

Adult↗

Predictors of tumour involvement in remaining axillary lymph nodes of breast cancer patients with positive sentinel lymph node.

AIMS: To characterize the various clinicopathologic features in cases of breast cancer with positive sentinel lymph nodes (SLNs), in order to determine factors that might help in predicting the involvement of the non-SLNs. METHODS: A retrospective database review was performed of 726 breast cancer patients with stage 0-II, in whom SLNs were successfully identified. One hundred eighty-five of these patients showed positive SLNs, and subsequently underwent axillary lymph node dissection (ALND). These cases were divided into two groups based on the presence or absence of metastases in the non-SLNs, i.e. positive non-SLNs (NSLN+; 81 cases) and negative non-SLNs (NSLN-; 104 cases). RESULTS: Multivariate analysis revealed that a larger size of the primary tumour (>2.0cm), presence of lymphatic invasion, larger size of the largest SLN metastasis (>2mm), and a 100% metastatic rate in the SLNs (number of positive SLNs/number of harvested SLNs) were significantly associated with NSLN+. Among the cases in which all the four factors were present, 73% (30/41) were found to have NSLN+. CONCLUSION: We found four independent predictors in relation to non-SLN metastasis. Although these factors might be useful for determining the need of additional ALND, it would seem that even the presence of all of these four factors in combination may be insufficient to safely omit ALND. Thus, until further evidence is accumulated from the results of large clinical trials, ALND would still be recommended for patients with SLN metastasis.

Axilla↗

Factors predictive of tumor-positive nonsentinel lymph nodes after tumor-positive sentinel lymph node dissection for melanoma.

PURPOSE: Approximately 20% of sentinel node (SN) positive melanoma patients have additional non-SN (NSN) metastasis. The rationale for this study was to identify the factors associated with additional nodal disease, as a method to determine which patients may most benefit from completion lymph node dissection (CLND). PATIENTS AND METHODS: During 1990 to 2002, 1,599 patients have undergone SN biopsy at our institute. 19.5% underwent CLND for tumor-positive SN. One hundred ninety-one of these patients had clinicopathologic information available for review. Univariate analyses used chi2 test, Wilcoxson rank sum test, and chi2 test for trend. Multivariate analyses used logistic regression and Wald test. RESULTS: Forty-six (24%) patients had tumor-positive NSN. Univariate analyses showed that primary thickness (Breslow and Clark), primary site, SN tumor size, and number of tumor-positive SNs were significantly associated with tumor-positive NSN. Multivariate analysis (167 patients), confirmed that Breslow and SN tumor size were independently predictive. Sex, histology, ulceration, mitotic index, and SN basin location were not predictive. Risk stratification by the number of prognostic factors present (Breslow > or = 3 mm and SN tumor size > or = 2 mm) showed that probability of finding tumor-positive NSN was 12.3% in the low-risk group (0 factors), 30.9% in the intermediate-risk group (1 factor), and 41.9% in the high-risk group (2 factors). CONCLUSION: Thicker primary and larger SN tumor size are factors that correlate best with tumor-positive NSN. Although none of these factors are absolutely predictive of residual nodal disease, these factors must be strongly considered if the SN contains metastasis, as they provide enhanced risk assessment for NSN tumor-positivity.

Adolescent↗

The prognostic significance of the percentage of positive/dissected axillary lymph nodes in breast cancer recurrence and survival in patients with one to three positive axillary lymph nodes.

BACKGROUND: Adjuvant therapy for women with T1-T2 breast carcinoma and 1-3 positive lymph nodes is controversial due to discrepancies in reported baseline locoregional recurrence (LRR) risks. This inconsistency has been attributed to variations in lymph node staging techniques, which have yielded different numbers of dissected lymph nodes. The current study evaluated the prognostic impact of the percentage of positive/dissected lymph nodes on recurrence and survival in women with one to three positive lymph nodes. METHODS: The study cohort was comprised of 542 women with pathologic T1-T2 breast carcinoma who had 1-3 positive lymph nodes and who had undergone mastectomy and received adjuvant systemic therapy without radiotherapy. Ten-year Kaplan-Meier (KM) LRR, distant recurrence (DR), and overall survival (OS) rates stratified by the number of positive lymph nodes, the number of dissected lymph nodes, and the percentage of positive lymph nodes were examined using different cut-off levels. Multivariate analysis was performed to evaluate the prognostic significance of the percentage of positive lymph nodes in disease recurrence and survival. RESULTS: The median follow-up was 7.5 years. LRR, DR, and OS rates correlated significantly with the number of positive lymph nodes and the percentage of positive lymph nodes, but not with the number of dissected lymph nodes. The cut-off level at which the most significant difference in LRR was observed was 25% positive lymph nodes (the 10-year KM LRR rates were 13.9% and 36.7% in women with < or = 25% and > 25% positive lymph nodes, respectively; P < 0.0001). Higher DR rates and lower OS rates were observed among patients who had > 25% positive lymph nodes compared with patients who had < or = 25% positive lymph nodes (DR: 53.0% vs. 30.3%, respectively; P < 0.0001; OS: 43.4% vs. 62.6%, respectively; P < 0.0001). In the multivariate analysis, the percentage of positive lymph nodes and the histologic grade were significant, independent factors associated with LRR, DR, and OS. CONCLUSIONS: The presence of > 25% positive lymph nodes was an adverse prognostic factor in patients with 1-3 positive nodes and may be used to identify patients at high risks of postmastectomy locoregional and distant recurrence who may benefit with adjuvant radiotherapy and more aggressive systemic therapy regimens.

Adult↗

Computer simulations of lymph node metastasis for optimizing the pathologic examination of sentinel lymph nodes in patients with breast carcinoma.

BACKGROUND: Many empiric protocols are used to detect metastases in sentinel lymph nodes (SLNs), but comparison of the efficacy of these methods is impractical because tissue is lost in processing, making reassessment with another policy difficult. Consequently, performance indicators of this test are largely unknown. DESIGN: The authors retrospectively examined 112 SLNs removed from 89 patients with breast carcinoma treated at the authors' institution and used the histologic data to devise a mathematic model of a SLN with Matlab modeling software. The authors simulated examination of this computer-generated (virtual) lymph node according to several macroscopic and histologic sampling protocols and for each protocol assessed the probability of detecting micrometastases of specified sizes. The authors used published costing figures to estimate the cost of the policies. RESULTS: Direct comparison of 6 sectioning strategies currently in use by pathology laboratories showed the chances of detecting a 500-microm metastasis ranged from 20% to 75%. Four of the 6 protocols had a less than 30% chance of detecting metastases of this size. The detection rate of smaller metastases was poorer. Cost was not a good discriminator because some policies were more efficient than others. CONCLUSIONS: The detection of metastases is highly dependent on the methods used to look for them. The authors' simulations suggest that commonly used methods of examining lymph nodes have high false-negative rates, particularly for small metastases. There is an urgent need for pathologists and clinicians to agree on the minimum size of SLN metastases that will be sought by histology and set standard methods for examining these lymph nodes.

Breast Neoplasms↗

A study of modified lymphatics in the deep cortex of ruminant lymph nodes.

Ruminant lymph nodes, except when very small, were found to have a system of smooth-walled channels in the periphery of the 'deep cortical units' defined by Bélisle & Sainte-Marie (1981 a,b). Each channel originated with many 'blind' branches in the subnodular layer of the cortex and ended by joining a medullary sinus. The wall consisted of a continuous endothelial lining, a sometimes thin or discontinuous basement membrane without a basal lamina, and at least one layer of flattened reticular fibroblasts. The endothelium was higher than in most typical lymphatics, with a cytoplasmic fine structure similar to that of sinus-lining cells in the medullary sinuses. The intercellular junctions were generally long and elaborate. The lumen often contained opaque material, especially in the branches, as for initial lymphatics, as well as a few lymphocytes and an occasional nonlymphoid cell, but sinus macrophages were never seen. In some lymph nodes the lumen was crowded with lymphocytes. When small ferripolymaltose particles arrived in the node with the afferent lymph, many of them rapidly passed through the outer cortex and reached the lumen of the smooth-walled channels by way of the intercellular junctions of the endothelium. When colloidal carbon was introduced the same way, some of it also reached the channels where it accumulated in the basement membrane and in vesicles and vacuoles of the endothelium. These channels are interpreted as initial lymphatics of the same type as in other lymphoid organs rather than lymph node sinuses. They seem to play an important role for the exit of lymphocytes from the nodes and also for the passage of particulate material, including antigens, through those areas where recirculating lymphocytes arrive in the cortex.

Animals↗

Survival outcomes in node-negative breast cancer patients evaluated with complete axillary node dissection versus sentinel lymph node biopsy.

BACKGROUND: Sentinel lymph node (SLN) biopsy combined with microstaging-associated immunohistochemical staining for cytokeratin more accurately assigns patients to their corresponding diagnostic stage. The purpose of this study was to compare the survival outcomes of node-negative patients who received an SLN biopsy with historical control data of node-negative patients who received routine complete axillary lymph node dissection (CALND) in the pre-SLN biopsy era. METHODS: Under institutional review board approval, 2458 node-negative invasive breast cancer patients between the ages of 25 and 94 years (mean, 60 years) were treated at our institution from January 1986 to May 2004. Of these 2458 patients, 604 (25%) were evaluated with CALND, whereas 1854 (75%) were evaluated with SLN biopsy. All were treated according to the current stage-specific guidelines. Kaplan-Meier graphs of overall survival and disease-free survival were constructed for each group of patients, and the two groups were compared by using the log-rank test. RESULTS: Overall survival and disease-free survival for the CALND and SLN biopsy groups did not differ significantly (P = .98). The average number of lymph nodes extracted in the pre-SLN biopsy group was 18, whereas the average number of SLNs extracted in the post-SLN biopsy group was 3. CONCLUSIONS: The survival rate among node-negative breast cancer patients who received an SLN biopsy alone has proven to have no significant difference (P = .98) from the survival rate among node-negative patients who received a CALND. SLN biopsy alone should replace CALND as the primary tool for axillary staging of breast cancer in node-negative patients.

Adult↗

[Reasonable lymph node dissection for T2 or T3 midthoracic esophageal cancer with cervical lymph-node metastasis].

In order to determine the reasonable lymph node dissection for T2 or T3 midthoracic esophageal cancer with cervical lymph node metastasis, a retrospective study was carried out on 106 patients receiving resection between 1983 and 1996. Metastasis to cervical lymph node was obtained in 27.4% (29/106) of patients with T2 or T3 midthoracic esophageal cancer. Within 29 patients, metastasis in cervical node only, in two fields and in three fields occupied 17.2%, 41.4% and 41.4%, respectively. And according to the histologic examination of dissected lymph nodes, metastatic sites spreaded from neck to perigastric region. Five-year survival rate of 23 patients receiving curative operation was 33.0%, and that of 13 patients excluding 3-field metastasis was 51.9%. But the main sites of nodal recurrence were cervical or superior mediastinal nodes along the bilateral recurrent laryngeal nerves, and the rate of nodal recurrence was 47.8%. These results of actual state of lymph node metastasis and prognostic benefit of aggressive dissection suggest that 3-field lymph node dissection is mandatory for T2 or T3 midthoracic esophageal cancer with cervical lymph node metastasis. And we should endeavor to upgrade the precise dissection in order to decrease the nodal recurrence.

Esophageal Neoplasms↗

The size of regional lymph nodes does not correlate with the presence or absence of metastasis in lymph nodes in rectal cancer.

We evaluated the relationship between the size of regional lymph nodes and the presence of metastasis in them in rectal cancer. Of 1,064 lymph nodes in 46 specimens, 133 (13%) were found to have metastases. A half of the positive nodes and most of the negative ones were less than 5 mm in diameter. Therefore, we must find lymph nodes smaller than 5 mm in diameter for assessment of lymph node metastasis. Although positive nodes were larger than negative ones, there was no significant difference. However, when comparing the size of lymph nodes in relation to their location, the epi- and pararectal lymph nodes larger than 10 mm in diameter were highly suggestive of metastases, but the size of the lymph node was not a reliable indicator of lymph node metastases in other situations.

Humans↗