A histochemical study of the enzymatic activity of lymph nodes. I. The normal and hyperplastic lymph node.
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Enzymes↗
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Molecular staging of prostatic cancer with RT-PCR assay for prostate-specific antigen in peripheral blood and lymph nodes: comparison with standard histological staging and immunohistochemical assessment of occult regional lymph node metastases.
BACKGROUND: About 30-40% of men with localized prostate cancer undergoing radical prostatectomy will have cancer recurrence. It is estimated that one third recur locally and two thirds develop distant metastases with or without local recurrence. METHODS: In the present study we investigate the detection of prostate-specific antigen (PSA) mRNA in peripheral blood samples (n=200 patients) and pelvic lymph nodes (n=154 patients) by PSA reverse transcriptase polymerase chain reaction (RT-PCR) and compare these results to standard histological and immunohistochemical staging. RESULTS: We have observed a statistically significant correlation of lymph node PSA RT-PCR with standard pathologic risk factors, such as Gleason score (p=0.011), the presence of Gleason patterns 4 or 5 (p=0.005), lymph node metastasis (p<0.001) and a nearly significant correlation with the pT category (p=0.087). 39.5% (57/145) of the pN0 patients had PSA mRNA detectable in their lymph nodes. Blood PSA RT-PCR showed no correlation with the aforementioned factors and was even inversely correlated with preoperative serum PSA and lymph node status. Immunohistochemistry did not detect unsuspected prostate micrometastases in any pN0 patient. CONCLUSIONS: Lymph node PSA RT-PCR correlates with the Gleason score and the presence of Gleason patterns 4 or 5. Further clinical follow-up and correlation of RT-PCR status with overall outcome is required to allow validation of lymph node RT-PCR as a predictor of distant disease recurrence.
Adenocarcinoma↗
Vascular endothelial growth factor-C expression in human gallbladder cancer and its relationship to lymph node metastasis.
Lymph node metastasis is a major prognostic factor in human cancer. Vascular endothelial growth factor C (VEGF-C) is a lymphangiogenic polypeptide that has been implicated in several human solid tumors. However, the clinical significance of VEGF-C has remained unknown in gallbladder carcinoma. Paraffin-embedded tumor specimens of 52 surgically resected gallbladder cancers were immunohistochemically stained for VEGF-C, VEGF, and CD34. The correlations among VEGF-C expression, VEGF expression, microvessel density (MVD), clinicopathologic features, and clinical outcomes were statistically analyzed. Thirty-three (63%) of the 52 gallbladder cancers were highly positive for VEGF-C protein by immunohistochemistry. VEGF-C expression was significantly correlated with lymphatic vessel involvement, lymph node metastasis, and worse outcomes after operation (p<0.001, p<0.001, p<0.001, respectively), but not with MVD. By the Cox regression model, lymphatic vessel involvement emerged as an independent prognostic parameter. These results suggest that VEGF-C may play a role in tumor progression via lymphangiogenesis and lymph node metastasis in human gallbladder cancer.
Aged↗
[Prognostic significance of clinical and morphological features of the lymph nodes in the presence of micrometastases--cytokeratin antigens expression in lymph nodes in laryngeal carcinoma].
In patients treated surgically due to neoplasm, in lymph nodes can be presented micrometastases, focuses 1-2 mm of carcinoma's cells. Lymph node micrometastases in patients with squamous cell carcinoma of the larynx found node-negative by conventional histology may be discovered by immunohistochemistry, particularly by using antibodies which are reactive with epithelial cells eg. cytokeratin antigens. Then tumors classified as pN0 by routine methods could be reclassified more correctly as pN1. Authors investigated the incidence of micrometastases in the neck dissection specimens originally staged as pN0 from 22 patients with laryngeal cancer treated surgically at ENT Department Medical University of Lodz between 1998-1999, according to the survival, using immunostaining with panel of polyclonal antibodies to cytokeratins. The relationship between micrometastases and clinical (pre- and intraoperative) features of lymph nodes were estimated.
Aged↗
Lymph node metastasis along the recurrent nerve chain is an indication for cervical lymph node dissection in thoracic esophageal cancer.
This study examined whether recurrent nerve chain node metastasis serves as an indicative factor for cervical lymph node dissection in thoracic esophageal cancer. The association of recurrent nerve chain lymph node metastasis and cervical node metastasis was analyzed for 91 patients with thoracic esophageal cancer who had undergone three-field lymph node dissection. In patients with upper thoracic esophageal cancer, the incidence of cervical lymph node metastasis was similar regardless of recurrent nerve chain node metastasis. On the other hand, in patients with middle or lower esophageal cancer, the incidence was significantly higher in recurrent nerve-positive (16/31, 51.6%) than in recurrent nerve-negative (5/43, 11.6%) patients. The prognosis of patients with recurrent nerve chain node metastasis was significantly better in the three-field dissection group than in the two-field dissection group, while in patients with no recurrent nerve chain node metastasis, survival was similar between the two groups. In conclusion, cervical lymphadenectomy can be omitted for recurrent nerve chain node-negative patients with middle and lower thoracic esophageal cancer.
Abdomen↗
Impact of the number and extent of positive lymph nodes in 200 patients with thoracic esophageal squamous cell carcinoma after three-field lymph node dissection.
BACKGROUND: Subtotal esophagectomy with three-field lymph node dissection (3FLD) has been reported to improve survival in patients with thoracic esophageal squamous cell carcinoma (SCC). The purpose of this study was to evaluate the prognostic impact of the extent and number of positive lymph nodes for long-term survival of patients who underwent 3FLD. METHODS: From January 1983 to December 2002, a total of 200 patients with thoracic esophageal SCC underwent 3FLD without any neoadjuvant therapy. The prognostic impact of the extent and number of positive lymph nodes was evaluated by both univariate and multivariate analysis. RESULTS: The extent of positive nodes associated with a 5-year survival were as follows: none, 69%; one-field, 50%; two-field, 29%; and three-field, 11%. The number of positive nodes associated with 5-year survival were as follows: single node, 65%; two-nodes, 51%; and more than three-nodes, 20%. Among patients with cervical lymphatic spreading, patients with upper tumors showed significantly better survival than patients with lower tumors (P=0.036). Multivariate analysis indicated that number of positive nodes and the abdominal node status were independent prognostic factors among lymph node status. CONCLUSIONS: Together, number and extent of positive lymph nodes can be considered an independent predictor of a high risk of recurrence. Although cervical lymphatic spreading was risk factor for worse survival, patients with upper tumors may have survival benefit after cervical lymph node dissection.
Abdomen↗
[Rational extent of lymph node dissection for carcinoma of the lower third of the thoracic ESOP-hagus of T2 or T3 stage with abdominal lymph node metastasis].
We discussed the rational extent of the lymph node dissection for carcinoma of the lower third of the esophagus of T2 or T3 stage with abdominal lymph node metastasis. Lymph node metastasis developed in 89.5% of patients. Cervical lymph node metastasis was seen in 35.8%. In the cases with positive abdominal lymph node, 40.9% of the patients had cervical node metastasis. The most frequent site of the positive node in the neck is the area along the right recurrent laryngeal nerve. On the stand point of removal of metastatic lymph node, neck dissection should be required. Three-field dissection yielded better survival rate than two-field dissection but statistical significance was not obtained. When the patients have cervical lymph node metastasis, they have greater possibility of developing blood borne metastasis. However, this observation does not deny the validity of the three-field dissection. Because this dissection may help reducing nodal spread and nodal recurrence. We have to wait for accumulation of the patients to analyze the definite extent of node dissection for T2 or T3 stage of carcinoma of the lower third of the esophagus with positive abdominal lymph node.
Abdomen↗
Lymph node status assessment for gastric carcinoma: is the number of metastatic lymph nodes really practical as a parameter for N categories in the TNM Classification? Tumor Node Metastasis.
BACKGROUND AND OBJECTIVES: The anatomical extent of nodal metastasis has been replaced by the number of metastatic nodes as a key indicator of prognosis (pN categories) in the fifth edition of Tumor Node Metastasis Classification for gastric carcinoma by the International Union Against Cancer. The rate of metastatic nodes among all the nodes harvested is also a good prognostic factor. The object of this study is to evaluate which of the three parameters for the assessment of nodal status is the most appropriate for use in the stage classification. METHODS: Retrospective survival analyses were performed in 656 consecutive patients with advanced gastric carcinoma who underwent D2 lymphadenectomy and for whom histopathologic data of more than 20 lymph nodes were available. RESULTS: Although all three systems served well to classify the patients into distinct groups in terms of survival curves, stratification by the number of metastatic nodes was vulnerable to stage migration because of differences in the number of lymph nodes harvested. Such stage migration was not evident for the other two parameters. CONCLUSIONS: Lymph node metastatic rate can be recommended as an internationally applicable parameter for lymph node involvement of gastric carcinoma.
Adult↗
Micrometastases in axillary lymph nodes and bone marrow of lymph node-negative breast cancer patients--prognostic relevance after 10 years.
The long-term prognostic significance of immunohistochemically detectable occult tumor cells in bone marrow and axillary lymph nodes of breast cancer patients considered to be lymph node-negative in multilevel haematoxylineosin (H&E) lymph node sectioning was analyzed. A total of 212 patients with a median follow-up of 10.3 years were included in the study. Bone marrow was obtained during surgery and stained with anti-cytokeratin and anti-EMA antibodies. Additional consecutive sections of lymph nodes were stained either with H&E or with anti-cytokeratin antibodies. All histological sections were analyzed by the same pathologist. Micrometastases were detected in bone marrow of 67 (32%) patients. Immunohitochemical examination of negative axillary lymph nodes--based on multilevel H&E examination--revealed micrometastases in 14 (7%) cases. There was no difference in overall or disease-free survival between patients with or without epithelial cells in bone marrow. Immunohistological examination of axillary lymph nodes also did not add any prognostic information for overall or disease-free survival. However, patients with occult micrometastases in axillary lymph nodes had a slightly higher rate of local recurrences. Immunohistochemical analysis of bone marrow or axillary lymph nodes does not add prognostic information if multilevel H&E sectioning is performed. Therefore, decision about adjuvant therapy in breast cancer patients considered to be lymph node-negative in multilevel H&E microscopy should not be based on immunohistochemical detection of micrometastases in bone marrow or axillary lymph nodes.
Adult↗
Node retrieval in axillary lymph node dissections: recommendations for minimum numbers to be confident about node negative status.
AIMS: To determine the minimum number of lymph nodes needed in an axillary lymph node dissection (ALND) specimen to be confident that the axilla is free from metastases. METHODS: The Edinburgh Breast Unit selects patients with large and high grade tumours for ALND; 609 consecutive ALNDs performed between October 1999 and December 2002 were reviewed. Full data about the underlying invasive breast cancer were available for 520 patients. Data were collected regarding number of positive nodes and total number of nodes collected, tumour size and grade, and presence of lymphovascular invasion. RESULTS: Axillary node metastases were seen in 64% of patients. The mean number of positive nodes found was 3.56, with a mean of 17.9 nodes collected. The highest proportion of patients with lymph node metastases were in the group with 16-20 nodes recovered/specimen (68%); specimens with >20 nodes recovered did not have a higher rate of nodal involvement. There was a significant difference between the proportion of metastasis positive specimens in those with 1-15 nodes recovered (58.5%) and those with 16 or more recovered (69.1%). A linear association test showed a direct correlation between the number of nodes collected and presence of node metastasis (p = 0.0005). CONCLUSIONS: Although there is no minimum number of nodes that should be recovered in an ALND specimen, 16 nodes should be regarded as a target to ensure a high level of confidence that the nodes are negative. Node positivity in an ALND specimen appears to obey the law of diminishing returns.
Axilla↗
[Strategy of lymph nodes dissection for the lower thoracic esophageal cancer without metastasis to the upper-mediastinal lymph nodes].
The incidence of metastasis to the lymph nodes in preoperative untreated patients with Ei, T2 or T3 esophageal cancer is 70.7% (41 of 58 cases) in our institute. Especially, a high incidence of metastasis to the abdominal lymph nodes has been noted. In contrast, metastasis to the cervical lymph nodes is not common. The majority of recurrence appear as a distant metastasis to the liver, lung or bone through the hematogenic route. However, recurrence in the peritoneum through the lymphatogenic route is not uncommon. Therefore, current strategy of lymph nodes dissection for esophageal carcinoma would be inadequate for the complete inhibition of recurrence, so that chemotherapy remains to be needed. Since the diagnostic procedure with ultrasonographic endoscopy and computerized tomography is highly accurate for the assessment of metastasis to the uppermediastinal lymph nodes, operative procedure suitable for each case should be determined on the basis of preoperative examination.
Endosonography↗
Sentinel lymph node biopsy lowers the rate of lymphedema when compared with standard axillary lymph node dissection.
Arm edema occurs in 20 to 30 per cent of patients who undergo axillary lymph node dissection (ALND) for carcinoma of the breast. Sentinel lymph node biopsy (SLNB) in lieu of ALND for staging of breast cancer significantly lowers this morbidity. We hypothesized that SLNB would have a lower lymphedema rate than conventional axillary dissection. Patients who underwent SLNB were compared with those who underwent level I and II axillary node dissection. A total of 125 patients were evaluated with 77 patients who underwent SLNB and 48 patients who underwent ALND. The arm circumference 10 cm above and 10 cm below the olecranon process was measured on both arms. In this series a difference in arm circumference greater than 3 cm between the operated and nonoperated side was defined as significant for lymphedema. Lymphedema was seen in two of 77 (2.6%) patients in the SLNB group as compared with 13 of 48 (27%) ALND patients. Given the above data patients who underwent sentinel lymph node biopsy show a significantly lower rate of lymphedema than those who had axillary lymph node dissection. This has an important impact on long-term postoperative management of patients with breast cancer.
Breast Neoplasms↗
[Incidence of lymph node involvement in pN2 non-small cell lung carcinoma and reevaluation of the lymph node dissection method].
We reported post operative survival rate of 134 pN2 squamous cell carcinoma and adenocarcinoma patients in our institute, and analyzed the level of the mediastinal lymph node metastasis to evaluate the standard lymph node dissection method (R2b). Post operative survival rate showed no difference between the left and right lung carcinoma but it showed significant difference between the upper lobe and lower lobe of the both side. Compared with the upper lobe lung cancer, the lower lobe cancer showed higher incidence of metastasis to #7, #8 or #9 lymph node. It is suspected that lymph node dissection of ipsilateral #12 (U), contralateral hilar and #4 lymph node should be considered for the lower lobe cancer especially with #7 lymph node metastasis.
Adult↗
-Inguinal irradiation versus no lymph node therapy in small vulvar carcinoma with clinically negative lymph nodes (T1, NO-1)-.
OBJECTIVE: The objective of this retrospective study was to determine if groin radiation was superior to no therapy in patients with small vulvar cancer with not palpable or not suspicious inguinal lymph nodes (T1, N0-N1). METHODS: From 1974 to 1990, 135 patients with invasive T1, NO-1 vulvar cancer underwent radical vulvectomy with hot knife, groin nodes were left in situ. In 65 patients vulvectomy was followed by inguinofemoral irradiation: 70 patients had none. There were more cases with clitoris carcinoma (p < 0.04) in the group with groin irradiation but no other significant difference in prognostic factors was found. RESULTS: The actuarial 5-year survival was 93.7% with groin irradiation versus 92.4% without lymph node therapy. Inguinal relapses occurred in only 4.6% of cases with groin irradiation versus 10% without lymph node treatment (n.s.). CONCLUSIONS: Radiation therapy to the groin seems to reduce groin relapses in early vulvar cancer.
Aged↗
p16 expression in primary malignant melanoma is associated with prognosis and lymph node status.
Lymph node (LN) status is an important prognostic factor in melanoma patients. p16 expression and proliferation rate (MIB-1) of primary melanomas have been suggested as a marker of metastatic potential. In this study, the correlation of p16 expression and the proliferation rate (MIB-1) with LN status and tumor-specific survival was investigated in primary melanomas. MIB-1 and p16 expression were analyzed by immunohistochemistry in 64 patients with primary cutaneous melanoma. Thirty four nevi were used as control. All patients underwent sentinel lymph node staging. Three different p16 staining patterns were observed: a combination of nuclear and cytoplasmic staining, only cytoplasmic staining and absence of p16 expression. All 34 nevi displayed a nuclear and cytoplasmic p16 staining, whereas p16 was negative in 14 of 64 (22%) melanomas. The level of p16 expression gradually decreased from benign nevi to melanoma without metastasis to melanoma with metastasis. There was a significant correlation between cytoplasmic p16 expression and absence of metastasis (p < 0.05). Death of disease correlated with absence of p16 immunostaining (p = 0.01). MIB-1 expression was not associated with survival. These results confirm the relevance of p16 expression as a prognostic marker in melanoma patients. In addition, it was shown that cytoplasmic immunostaining for p16 in primary melanoma might serve as a predictor of the LN status. Therefore, immunohistochemical evaluation for p16 expression is of potential value for treatment planning in melanoma surgery.
Adult↗
[Lymph node excision with laparotomy and chemo-radiation therapy for a hepatocellular carcinoma patient with multiple lymph node metastases].
We reported a case of hepatocellular carcinoma (HCC) with multiple lymph node metastases. The patient was a 67-year-old male with C type liver cirrhosis. He underwent microwave coagulation therapy (MCT) for HCC (5 cm and 1.5 cm) 1.5 years before admission. Abdominal CT scan revealed a well-enhanced tumor (2 cm) in caudate lobe of the liver and excessive lymph node metastases, locating in the inferior phrenic, periportal and para-aortic area. The preoperative serum AFP and AFP-L3 levels were 41.9 ng/ml and 93.1%, respectively. At laparotomy, systematic dissection of the enlarged lymph nodes and MCT of the hepatic tumor was performed. After operation, residual inferior phrenic lymph node was treated with irradiation therapy (total 50.4 Gy). The lymph node showed complete response (CR) for about a year and the AFP-L3 level returned to the normal range. After 9 months, a supra-clavicular lymph node was detected on abdominal CT scan. Irradiation therapy (total 45 Gy) in combination with CDDP (100 mg) and 5-FU (4,000 mg) was applied. The lymph node had been assessed as partial response for 6 months. The patient lived quite well after these therapies, but died of hepatic failure 32 months after the initial operation. In conclusion, we recommend this therapeutic strategy using operative excision and chemo-radiation therapy for HCC with multiple lymph node metastases.
Aged↗
Sentinel lymph node detection by combined dye-isotope technique and its predictive value for cervical lymph node metastasis in patients with lingual carcinoma.
OBJECTIVES: To investigate the clinical value of combined dye-isotope technique in detecting sentinel lymph node (SLN) and to examine whether the characteristics of SLN accurately predict cervical lymph node metastasis in lingual carcinoma. METHODS: Thirty patients with lingual carcinoma without lymph metastasis were injected with a dose of about 18.5 MBq of (99m)Tc-SC (sulfur colloid), around the tumor tissues before surgery, and lymphoscintigraphy was performed 5, 10, 30, 60 minutes, and 6 hours after injection. In the following day, all patients were injected with isosulfan blue dye around the primary tumor during surgery to trace SLN and underwent standard cervical lymph node dissection after SLN dissection. The pathological results of SLN were compared with standard lymph node dissection for their ability to accurately predict the final pathological status of the cervical lymph nodes. RESULTS: SLN was successfully identified in 100% of the patients. Both positive and negative predictive values of SLN were 100%. The accuracy rate was 100%, and there were no false negatives. CONCLUSIONS: The detection of SLN using combined dye-isotope technique could accurately predict cervical lymph node metastasis in lingual carcinoma.
Adult↗
Initial experience in a community hospital with sentinel lymph node mapping and biopsy for evaluation of axillary lymph node status in palpable invasive breast cancer.
BACKGROUND AND OBJECTIVES: To determine the sentinel node detection rate and the accuracy with which the sentinel node histology reflects that of the axilla in a series of patients with palpable invasive breast cancer. METHODS: Forty-four patients with clinically node-negative palpable invasive T1 or T2 breast tumors underwent sentinel node biopsy using isosulfan blue dye, followed immediately by either local excision of the primary lesion with standard axillary lymph node dissection or modified radical mastectomy. All surgeries were performed at Northwest Hospital, Seattle, Washington, between January 1996 and October 1997. RESULTS: The sentinel node was successfully identified in 73% of the patients (32/44). The frequency of sentinel node detection was greater for tumors in the outer quadrants than the inner quadrants (z-test, P < 0.001). Of the 32 patients in whom a sentinel node was identified, 10 (31%) had histologically positive sentinel nodes: 5 (16%) by frozen section, 2 additional patients (6%) after permanent hematoxalin-eosin (H&E) stained sections, and the remaining 3 (9%) after immunohistochemical stains for cytokeratins when the FS and permanent H&E-stained sections were benign. Twenty patients had benign axilla. The sentinel node was falsely negative in 2 patients, yielding an accuracy of 93.8%, sensitivity of 83.3%, and negative predictive value of 91%. CONCLUSIONS: Lymphatic mapping is technically feasible for patients with small (T1 or T2) palpable invasive breast tumors. The sentinel node can be reliably identified in the majority of these patients, and its histology reflects that of the axilla with a high degree of accuracy. Immunohistochemical stains and permanent H&E-stained sections of the sentinel node increased the test's ability to correctly identify axillary metastases. Improving this sensitivity remains a primary goal, however, if benign sentinel node histology is to be used as a criterion to preclude axillary dissection.
Adult↗