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Occult axillary lymph node metastases discovered by serial section in node-negative breast cancer.

Serial sectioning of the axillary lymph nodes from lymph node-negative breast cancer patients is presented. All patients were admitted between 1997-1998 and underwent mastectomy and axillary node dissection. The histological examination revealed micrometastases in 5 (10%) of 50 breast cancer subjects. The detection of these micrometastases in lymph nodes may identify a high-risk node-negative population. The time and money that was spent to detect the micrometastases was too high to perform it in every case. The clinician should be aware of the occult micrometastases in node-negative cases.

Axilla↗

[Role of lymph nodes in rectal carcinoma].

The significance of the lymph nodes for the therapy and the prognostics of the rectal cancer are reviewed. Not only the depth of penetrations, but the probability of lymph node involvement (in our series tumors staged T1 had in 12% positive lymph nodes, T2 in 20% respectively, T3 in 37% and T4 in 80%) determine the possible surgical treatment. The available data of different techniques in lymphadenectomy and lymph node staging are compared and discussed. The aim of this paper is to give the oncologically interested the opportunity to pursue the actual questions and to inform themselves about the current standards in regard to the lymphatics in rectal cancer.

Humans↗

Thin-section CT evaluation and pathologic correlation of therapeutic effect of neoadjuvant chemotherapy for axillary lymph nodes of clinically node-positive breast cancer patients.

In breast cancer patients, the number of surgically resected metastatic axillary lymph nodes has been considered to correlate closely with patient prognosis. Therefore, if metastatic lymph nodes could be controlled by neoadjuvant chemotherapy pre-operatively, we would be able to select a more appropriate regimen of post-operative chemotherapy for the individual patient and expect prognostic advantages of each patient with node-positive breast cancer. In this study, we aimed to evaluate the therapeutic effect of neoadjuvant chemotherapy for metastatic lymph nodes of node-positive breast cancer patients, using thin-section (5 mm) helical CT (prone-position) with bolus injection of contrast agent. Between April 1994 and March 2002, 49 patients with node-positive breast cancer who had undergone thin-section CT study both before and following neoadjuvant chemotherapy enrolled in the study. The mean age of the patients was 48.9 years and all were female. Concerning metastatic lymph nodes status, 45 patients were classified as N1, 2 patients as N2, and another 2 as N3. In the evaluation, if at least one lymph node of >5 mm in the short diameter was detected on the CT study, the case was classified as node-positive. For lymph nodes of >1 cm in short diameter, fine-needle aspiration biopsy guided by ultrasonography was performed in order to obtain pathological confirmation of the existence of cancer metastasis. The diagnostic results of the CT study were compared with the pathologic findings of the resected specimen operatively. The neoadjuvant chemotherapy consisted of 3 to 4 times of CAF chemotherapy and an anti-estrogen agent, and intra-arterial infusion chemotherapy was also performed in patients with lymph node status of N2 or N3. The axillary status of 15 (30.6%) out of the 49 patients was evaluated as N0 after neoadjuvant chemotherapy, and 14 out of the 15 patients were confirmed as node-negative based on the pathological results. Therefore, the diagnostic accuracy of the second CT study performed following the neoadjuvant chemotherapy was 85.7%, with a sensitivity of 96.6%, a specificity of 70.0%, a positive predictive value of 82.4%, and a negative predictive value of 93.3%. The results described above demonstrate that such a sophisticated and precise CT study performed following neoadjuvant chemotherapy and evaluating the therapeutic effect on metastatic lymph nodes following the neoadjuvant chemotherapy can help to determine an appropriate regimen of post-operative chemotherapy and be of prognostic advantage in patients with node-positive breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Occult lymph node metastases in supraglottic cancers of the larynx.

Occult cervical lymph node metastases may often be associated with cancers of the supraglottic larynx. The aims of this investigation were: (1) to determine the incidence of occult lymph node metastases in patients with cancer of the larynx; (2) to assess whether the presence of such metastases was related to the extent of the primary tumor (T) and its grading (G); and (3) to discuss which therapeutic approach should be followed in treating clinically occult lymph node metastases. Our investigation included 97 patients who underwent supraglottic horizontal laryngectomy and elective cervical lymph node dissection. The incidence of occult lymph node metastases in the series considered was 27%. Based on the preoperative staging of the tumor, 14% of the cases had metastatically involved lymph nodes in the T1 tumors, 21% in the T2 tumors, 35% in the T3, and 75% in the T4. In the statistical analysis, a significant difference was shown to exist when T1 + T2 and T3 + T4 (P = 0.04) were compared. In terms of grading, occult metastases were found in 16% of the G1 tumors, 27% of the G2, and 42% of the G3. The statistical analysis demonstrated a significant difference between G1 and G3. In brief, the incidence of occult metastases was higher for the less differentiated tumors and for the ones with a higher T value; the effects of both factors are combined thereby increasing the rate of occult metastases (P = 0.05).

Adult↗

Dynamic lymphoscintigraphy and image fusion of SPECT and pelvic CT-scans allow mapping of aberrant pelvic sentinel lymph nodes in malignant melanoma.

To date, there are no reliable criteria to identify those patients with melanoma-infiltrated sentinel lymph nodes (SLNs) of the groin who might benefit from an extended lymphadenectomy, including the pelvic lymph nodes. We hypothesised that there are pelvic lymph nodes that receive lymph directly from the primary tumour, thus being at an increased risk for metastasis. In order to determine the frequency of radioactively labelled pelvic lymph nodes and the kinetics of their appearance, we introduce here a combination of dynamic lymphoscintigraphy, single photon emission computed tomography (SPECT) and image fusion of SPECT and pelvic Computed Tomography (CT)-scans. By dynamic lymphoscintigraphy and intraoperative gamma probe detection, superficially located inguinal SLNs (median 2 nodes) could be identified in all of the 51 patients included in this analysis. The histological search for micrometastases was positive in 16 patients (median Breslow thickness of the primary melanoma 2.5 mm). In 29 patients, SPECT and the image fusion technique were additionally performed. Radioactively labelled pelvic lymph nodes were detected in 20 individuals, 6 of them presenting aberrant pelvic SLNs that, on dynamic lymphoscintigraphy, had appeared simultaneously with the superficial SLN(s). Of the 6 patients in whom radioactive pelvic lymph nodes were excised together with the superficial SLN(s), only one had positive superficial SLNs. In this patient, the aberrant pelvic SLN proved to be tumour-positive. In 9 patients, there was no radiotracer uptake in the pelvic lymph nodes at all. Image fusion of SPECT and pelvic CT-scans is an excellent tool to localise exactly the pelvic tumour-draining nodes. The significance of radioactively labelled pelvic lymph nodes for the probability of pelvic metastases should be analysed further.

Adult↗

Impact of EUS-guided fine-needle aspiration on lymph node staging in patients with esophageal carcinoma.

BACKGROUND: Preoperative identification of lymph node metastases associated with esophageal carcinoma may influence treatment. EUS is the most accurate method for locoregional staging of these tumors. The impact of EUS-guided fine-needle aspiration (EUS-FNA) on lymph node staging in esophageal carcinoma is unclear. METHODS: From May 1996 to May 1999, 74 patients with esophageal carcinoma underwent preoperative EUS. After October 1998 EUS-guided FNA was performed on nonperitumoral lymph nodes greater than 5 mm in width. The results of EUS with and without FNA were retrospectively reviewed and compared. Final diagnosis was based on surgical results or EUS-guided FNA malignant cytology. Ten of the 74 patients had to be excluded for lack of lymph node stage confirmation. Final diagnosis was obtained in the remaining 64 patients (33 from the EUS only group and 31 from the EUS-FNA group). RESULTS: The results of EUS versus EUS-FNA for lymph node staging were sensitivity 63% versus 93% (p = 0.01), specificity 81% versus 100% (not significant), and accuracy 70% versus 93% (p = 0.02), respectively. Complications comprised 1 patient who developed self-limited bleeding after dilation that did not preclude completion of the EUS (1%, 95% CI [0%, 7%]). CONCLUSIONS: EUS-FNA is more sensitive and accurate than EUS alone for preoperative staging of locoregional and celiac lymph nodes associated with esophageal carcinoma. EUS-FNA of nonperitumoral lymph nodes in patients with esophageal carcinoma is safe and should be routinely performed when treatment decisions will be affected by nodal stage.

Adenocarcinoma↗

Predictive value of cathepsin D and Ki-67 expression at the deepest penetration site for lymph node metastases in gastric cancer.

To search for reliable predictors for lymph node metastasis, we immunohistochemically analyzed surgically resected gastric cancer specimens that showed invasion of submucosa (sm) and muscularis propria (mp) of the tumor. The analysis investigated cathepsin D and Ki-67 expression in 136 specimens that were divided into an sm1/sm2 group and an sm3/mp group. In sm1/sm2 group, the incidence of lymph node metastases was significantly higher in tumors with high Ki-67 labeling index (LI) (44%) than in those with low Ki-67 LI (0%). In sm3/mp group, the incidence of lymph node metastases was significantly higher in cathepsin D-positive (56%) and high Ki-67 LI tumors (64%) than in cathepsin D-negative (33%) and low Ki-67 LI (33%). Combined analysis of cathesin D expression and Ki-67 LI correlated strongly with lymph node metastases. No lesions with cathepsin D-negative expression and low Ki-67 LI had lymph node metastases in either group. Cathepsin D and Ki-67 expression may be useful predictors for lymph node metastases in gastric cancer with sm and mp invasion. As predictors, they can identify lesions without lymph node metastases and indicate lesions not needing additional treatment after endoscopic mucosal resection and laparoscopic gastrectomy.

Adult↗

Reliability of sentinel lymph node biopsy with squamous cell carcinoma of the oral cavity.

OBJECTIVES: Although sentinel lymph node biopsy (SLNB) may reduce surgery-related complications related to unnecessary lymph node dissection and is now widely used for many patients with cutaneous melanoma and breast cancer, its use for oral cancer patients remains controversial. One of the main reasons for the reluctance to initiate SLNB for oral cancer is that the frequency of skip metastasis has not been clarified. The objectives of this study are to examine the frequency of skip metastasis and to evaluate SLNB for oral cancer. STUDY DESIGN: To shed light on these concerns, we first conducted a retrospective study of 296 patients with squamous cell carcinoma of the oral cavity who underwent neck dissection. Next, the accuracy of lymph node biopsy with and without detecting sentinel lymph node was examined. RESULTS: Ten patients showed skip neck metastasis in the level III-V region without level I-II involvement. Of these patients, 7 underwent neck dissection when their initially N0 neck progressed to N+, 2 underwent neck dissection when local recurrence occurred, and only 1 underwent surgery as an initial therapy. Most patients who underwent neck dissection as the initial therapy showed skip metastasis. Intraoperative lymph node biopsy without any attempt to detect sentinel lymph nodes by means of blue dye or lymphoscintigraphy was performed on 68 patients with oral cancer. Sixty-one (90%) were diagnosed correctly, whereas 7 diagnosed as N- actually had neck metastasis. SLNB with blue dye was performed on 21 patients. In 17 of them, sentinel lymph node was easily detected, resulting in a correct diagnosis for 16 patients (94%), while 1 with a false negative result actually had micrometastasis. CONCLUSION: These findings seem to suggest that SLNB is useful and can be applied to patients with oral cancer who undergo surgery as the initial therapy.

Adult↗

Immune response of regional lymph nodes in patients with lung cancer.

To clarify immune response of regional lymph nodes in 30 patients with lung cancer, the T cell population, phytohemagglutinin (PHA) and Concanavalin A (ConA) stimulation and the T cell subpopulation bearing Ig-G Fc receptors (Tg cells) were tested concerning the clinical stage, histology and the lymph nodes locations. The T cell population, and PHA and ConA response rates in lymph nodes of stage I patients were grossly the same as those of benign lung diseases, but were statistically higher than those of stage III patients (p less than 0.025, p less than 0.005). Among the three histological types of lung cancer, regional lymph nodes of adenocarcinoma had the greatest T cell populations, and PHA and ConA responses. Concerning the location of lymph nodes, the closer the lymph nodes was to the tumor, the greater was its T cell population, and vice versa. However there was no difference in PHA and ConA responses. All lung cancer patients revealed a significant increase of Tg cells in regional lymph nodes and in their peripheral blood lymphocytes compared with peripheral blood lymphocytes in normal subjects (p less than 0.005).

Adenocarcinoma↗

The prognostic value of membrane markers and morphometric characteristics of lymphoid cells in blood and lymph nodes from patients with mycosis fungoides.

For 26 patients with mycosis fungoides (MF), the type and extent of the skin lesions, the percentage of cerebriform mononuclear cells (CMC), and T and B lymphocytes in the peripheral blood and lymph nodes were correlated with MF involvement of regional lymph nodes, the clinical course, and response to therapy. Skin tumors and an involvement of more than 25% of the skin correlated well with lymph node involvement. Normal percentages (2--18%) of CMC in the peripheral blood were found for MF patients without lymph node involvement when compared with those found for patients with benign erythroderma and healthy donors. Elevated circulating CMC percentages (greater than 20%) were observed in 9 of 11 MF patients with lymph node involvement. In the lymph node cell suspensions from nine of ten MF patients with lymph node involvement, increased CMC values were found (greater than 15%), whereas two of three MF patients without lymph node involvement showed percentages comparable (4% and 7%, respectively) with those of the control lymph nodes. In the peripheral blood of patients with MF, decreased percentages of T cells (less than or equal to 55%) were found predominantly for patients with lymph node involvement, whereas normal percentages were noted for most of the patients without lymph node involvement. No consistent differences in the percentage of T and B cells in the lymph node cell suspensions were found between MF patients with and without lymph node involvement. Patients with lymph node involvement showed in general a partial response to therapy with an unfavorable clinical course in contrast to patients without lymph node involvement. Increased percentages of CMC (greater than 20%) and decreased percentages of T cells (less than or equal to 55%) in the peripheral blood, the presence of skin tumors, and involvement of more than 25% of the skin are prognostically unfavorable signs for patients with mycosis fungoides.

Aged↗

Prediction of nonsentinel lymph node status in melanoma.

BACKGROUND: Most melanoma patients with a positive sentinel lymph node dissection (SLND) undergo a completion lymph node dissection (CLND) that does not yield additional positive nonsentinel lymph nodes (NSLN). This study was designed to determine if NSLN status can be predicted using patient, primary tumor, and sentinel lymph node (SLN) characteristics. METHODS: The study population includes melanoma patients who had a positive SLND and subsequently underwent CLND retrieved from our prospective institutional melanoma database. The primary tumor and SLN pathologies were prospectively determined. An Size/Ulceration (SU) score was derived by assigning 1 point for primary tumor ulceration and 1 point for SLN tumor size >2 mm. RESULTS: Ninety-eight patients had a positive SLND and underwent CLND. Sixteen of these patients had a positive NSLN. On univariate analysis, primary tumor characteristics (thickness, ulceration, no regression), SLN metastasis characteristics (size >2 mm, location nonsubcapsular), and SU score were all significantly associated with positive NSLN status. However, on multivariate analysis, only the SU score was a significant independent predictor of NSLN status. No patient with an SU score of 0 had a positive NSLN. CONCLUSIONS: The SU score is predictive of NSLN status in patients with a positive SLND. Patients with an SU score of 0 are very unlikely to have positive NSLNs at CLND.

Female↗

The entry of T and B lymphocytes into rat popliteal lymph nodes undergoing a graft-versus-host reaction.

The entry of radiolabeled blood-borne T and B lymphocytes into resting popliteal lymph nodes and popliteal lymph nodes stimulated with semiallogeneic lymphocytes was investigated in rats. Thoracic duct lymphocytes separated into T- and B-lymphocyte populations on nylon-wool columns were radiolabeled with 51chromium and equal numbers of T or B lymphocytes were injected intravenously. While the ratio of T and B lymphocytes in the blood is approximately 3:1 it was found that the ratio of T to B lymphocytes migrating into lymph nodes was approximately 9 T to 1 B lymphocyte in both resting and antigenically stimulated lymph nodes. Since the ratio of T to B lymphocytes in thoracic duct lymph is similar to that of blood, there is a disparity between the number of T cells entering and leaving lymph nodes. These results suggest that some T lymphocytes may return to the blood directly and/or there is increased T lymphocyte death in lymph nodes.

Animals↗

Paraaortic lymph node biopsy: a twenty-year study.

OBJECTIVES: Paraaortic lymph node biopsy is a controversial but proved technique to determine the extent of spread of cancers from the uterine cervix or endometrium. This article explores the following questions. Does the presence of positive paraaortic lymph nodes result in modification of the patient's therapy? Does the evidence gained from a paraaortic lymph note biopsy improve patient survival? STUDY DESIGN: Five hundred sixty-eight patients had paraaortic lymph node sampling in conjunction with another operative procedure between 1976 and 1995. Five hundred seven (89.3%) of these patients had either endometrial or cervical cancer. RESULTS: Paraaortic lymph node biopsies led to a survival rate of 9.1% for cervical carcinoma and 46.6% for endometrial carcinoma and were associated with acceptable morbidity. CONCLUSIONS: We believe that paraaortic lymph node biopsies should be part of the routine evaluation of patients with gynecologic cancers. The knowledge gained by this procedure along with appropriately administered radiation therapy can save lives.

Adult↗

[Paraaortic lymph node micrometastasis in advanced gastric cancer and its significance in prognosis].

OBJECTIVE: Paraaortic lymph nodes dissection in advanced gastric carcinoma is controversial. Investigation of micrometastasis in these critical lymph nodes is important in the evaluation of prophylactic lymphadenectomy. METHODS: A total of 2 339 lymph nodes, including 390 paraaortic nodes, obtained from 47 patients with advanced gastric carcinoma were examined immunohistochemically using cytokeratin antibody. RESULTS: Paraaortic lymph node metastasis was found in 95 of 390 nodes of 14 patients by routine histological examination. Micrometastasis in the paraaortic lymph nodes was immunohistochemically detected in 45 of 295 negative nodes from 15 of 33 patients. The 5-year-survival rate in patients with paraaortic lymph node metastasis was 56.0% in the node negative group, 25.2% in the cytokeratin positive group and 9.0% in the hematoxilin and eosin positive group. CONCLUSIONS: We have demonstrated a high rate of micrometastasis in the paraaortic lymph nodes of patients with advanced gastric carcinoma and have confirmed that prophylactic lymphadenectomy of these nodes is effective for such patients.

Adult↗

Risk stratification in penile carcinoma: 25-year experience with surgical inguinal lymph node staging.

OBJECTIVES: In penile carcinoma, the most reliable staging method for lymph node involvement remains radical dissection with its associated high morbidity. However, the patient's prognosis is closely associated with lymph node status, and radical dissection is potentially curative. We report our experience with surgical lymph node staging and evaluate which group of patients could be assigned to a wait-and-see strategy or dynamic sentinel node biopsy and which group should undergo groin dissection. METHODS: From 1979 to 2004, 56 consecutive patients with penile cancer underwent surgical inguinal lymph node staging. On the basis of the histopathologic results, we defined risk stratification into low, high, and intermediate-risk groups according to the clinical examination findings, stage, and grade. RESULTS: Tumor stage (P = 0.019) and tumor grade (P <0.001) correlated significantly with lymph node status. Stratification into low (pT1G1, pT1G2), high (all G3 tumors), and intermediate-risk (all others) groups found 7.7% of low-risk patients with metastases. In the intermediate and high-risk groups, 28.6% and 75.0% had nodal metastases, respectively. Correlation with nodal involvement according to risk group was R2 = 0.608 (P <0.001). CONCLUSIONS: Risk stratification might enable a modified staging strategy for lymph node status according to stage, grade, and clinical examination findings. Highly motivated low-risk patients could be included in a surveillance program; however, high-risk patients should undergo bilateral inguinal dissection. Dynamic sentinel lymph node biopsy might be encouraged for intermediate-risk patients in the future.

Adult↗

[Lymph node metastasis in bladder cancer].

Forty patients who had transitional cell carcinoma of the bladder with positive pelvic lymph node metastasis, treated at Chiba University Hospital between April 1975 and March 1991 were investigated to evaluate the significance of pelvic lymph node dissection. The frequency of the patients with positive lymph node was 9.1% in all patients with transitional cell carcinoma of the urinary bladder, 4.0% in the clinical T1, 3.4% in T2, 35.7% in T3a, 32.1% in T3b, 46.2% in T4, and none in Tis and Ta. Of the 40 patients, 16 underwent cystectomy pelvic lymph node dissection, 19 had biopsy of suspicious lymph nodes which turned out to be positive for metastasis, and 5 were defined by computed tomography. Pelvic lymph node dissection was performed at the common iliac, presacral, external iliac, internal iliac, and obturator nodes. In the 16 patients who underwent cystectomy with pelvic lymph node dissection, the frequency of metastasis in each nodal group was 38% in common iliac, 31% in external iliac and obturator, and 25% in presacral and internal iliac. Out of the 16 patients, eight had regional lymphatic metastasis, three had only extra regional lymph node metastasis, and five had both regional and extra regional metastasis. Three of nine patients who had single positive node had common iliac or presacral positive node without regional lymph node metastasis.

Adult↗

Lymph node metastasis in squamous cell carcinoma of the intrathoracic esophagus.

BACKGROUND: In esophageal carcinoma lymph node metastasis is one of the most important factors of prognosis. This prospective study evaluated the incidence and extent of lymph node metastasis, and assessed the relationship between the depth of tumor invasion and lymph node metastasis in esophageal carcinoma. METHODS: Between 1985 and 1996, tissue samples from 112 patients undergoing radical esophagectomy and gastric substitution for squamous cell carcinoma of the intrathoracic esophagus were collected. Patients with distant organ metastasis were excluded. All specimens were evaluated and sent for histopathologic examination. RESULTS: In 108 men and four women with a mean age of 63.1 years, the average number of dissected lymph nodes in one surgical procedure, was 30 per person. The most commonly involved nodes were the periesophageal (42.9%) and the perigastric (42.9%) nodes, followed by the recurrent laryngeal nerve (23.8%) and thoracic paratracheal (22.2%) nodes. For tumors in the upper third of the esophagus, the most frequently involved nodal groups were the periesophageal (28.6%) and the paratracheal (28.6%) nodes, followed by the recurrent laryngeal nerve (21.4%) the deep cervical (21.4%), and the perigastric (21.4%) nodes. For tumors in the middle third of the esophagus, the periesophageal nodes (27.3%) were most commonly involved, followed by the perigastric (18.2%) and the subcarina (10.6%) nodes. For tumors in the lower third of the esophagus, the perigastric lymph nodes (37.5%) were the most common nodal metastatic site, followed by the celiac (18.8%) and the recurrent laryngeal nerve (18.2%) nodes. Depth of tumor invasion was also found to correlate significantly with lymph node metastasis (p = 0.0015). CONCLUSIONS: Wide lymph node metastasis between the neck and the upper abdomen occurs frequently in squamous cell carcinoma of the esophagus. For potentially curable esophageal carcinomas, en-bloc esophagectomy with complete locoregional lymph node dissection may provide favorable local control of the lesion and more accurate tumor staging.

Adult↗

The prognostic significance of pelvic lymph node morphology in carcinoma of the uterine cervix.

Pelvic lymph nodes from 80 patients with primary invasive cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy were evaluated morphologically. Six to 25 (mean 14) lymph nodes from each patient were examined histologically and classified as follows: lymphocyte preominant, germinal center predominant, unstimulated, or lymphocyte depleted. Tumors were classified according to their primary cell type: large cell non-keratinizing, keratinizing squamous cell, small cell, and adenocarcinoma. There was no direct relationship between lymph node morphology and patient age, lesion size, or tumor cell type. A lymphocyte predominant nodal pattern was associated with a statistically significant decrease in lymph node metastases, and tumor recurrence, and an increase in patient survival. In contrast, patients with a lymphocyte depleted nodal pattern had a high incidence of metastatic disease and tumor recurrence, and a decreased survival. Patients with lymph nodes showing an unstimulated or germinal center predominant pattern had an intermediate incidence of nodal metastases and tumor recurrence. These findings suggest that regional lymph nodal morphology may be of prognostic significance in patients with invasive carcinoma of the uterine cervix.

Adenocarcinoma↗