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Number of lymph nodes examined and its impact on colorectal cancer staging.

The status of lymph nodes is the most important prognosticator in colorectal cancer patients. Patients with lymph node involvement have a lower survival rate and are candidates for adjuvant therapy. The purpose of our study was to determine the number of lymph nodes that needs to be examined to accurately detect nodal metastasis. We conducted a retrospective study of 151 patients who underwent colorectal cancer operation at Harbor-UCLA Medical Center. Data from the operative report and pathology report were collected and analyzed. Fourteen (33.3%) patients with five to nine nodes examined had positive nodes. Twenty-six (57.8%) patients with 10 to 14 nodes examined had positive nodes. Patients who had 10 to 14 nodes examined were significantly more likely to have positive lymph nodes (P = 0.03). Patients with advanced T stage had a significantly higher number of positive lymph nodes (78.1% in T4 vs 11.1% in T1, P < 0.0001). Patients with poorly differentiated cancer showed a trend toward a higher positive node rate. Tumor differentiation and T stage seem to correlate with higher nodal metastasis rate. A higher number of lymph nodes examined was associated with a higher nodal metastasis rate. Examination of at least 10 lymph nodes would increase the yield of positive lymph nodes and avoid under-staging of patients with colorectal cancer.

Cohort Studies↗

Detection of disseminated tumor cells in mediastinoscopic lymph node biopsies and lymphadenectomy specimens of patients with NSCLC by quantitative RT-PCR.

OBJECTIVE: Detection of disseminated tumor cells in mediastinoscopic biopsies could improve staging and might be helpful concerning indications for neoadjuvant therapy regimens. This prospective study was performed to evaluate a simple and observer-independent polymerase chain reaction (PCR)-based method for the detection of disseminated tumor cells in regional lymph nodes. METHODS: Lymph nodes of 32 consecutive patients without neoadjuvant therapy were removed by systematic lymphadenectomy during resection of primary NSCLC. One hundred of these lymph nodes were cut into two equal halves which were examined using either routine histopathology or quantitative reverse transcriptase PCR (qRT-PCR). qRT-PCR amplification of cytokeratin 19 (CK19) transcripts was applied for the detection of tumor cell-specific RNA. We differentiated between illegitimate marker gene transcription and cancer-specific expression by using a cut-off value that was obtained from the analysis of 18 lymph nodes of patients with benign lung diseases. Subsequent to the evaluation of qRT-PCR, a pilot project with five additional patients was conducted to examine 19 mediastinoscopic biopsies, which were cut into two equal halves and proceeded as described above. RESULTS: Ninety-four (94%) lymph nodes were tumor-free by histopathology. qRT-PCR detected disseminated tumor cells in 26 (28%) of these lymph nodes. All of the remaining six lymph nodes that were judged by the pathologist to contain tumor cells exhibited CK19 transcripts. Twenty-three patients had a pN0 status. qRT-PCR detected disseminated tumor cells in 13 (56%) of these pN0 patients. The mediastinoscopic biopsies showed disseminated tumor cells in four (21%) out of 19 histopathologically tumor-free samples. CONCLUSIONS: CK19 qRT-PCR is a sensitive and specific tools for the detection of disseminated tumor cells in regional lymph nodes of patients with operable NSCLC. Further studies are required to asses if this molecular method might improve mediastinoscopic staging.

Aged↗

Radiographic demonstration of intercostal lymphatics and lymph nodes.

The anatomy of the posterior intercostal lymphatics and lymph nodes is reviewed. These lymph nodes are occasionally visualized by bipedal conventional lymphography. Opacified and/or enlarged posterior intercostal lymph nodes may also be identified with computed tomography of the chest. Familiarity with the lymphatic drainage patterns of the intercostal spaces and recognition of abnormal intercostal lymph nodes may provide additional information regarding disease status in patients with inflammatory or malignant disease of the thorax.

Female↗

[The lymph node dissection in thyroid carcinoma].

Rule and indications of lymph node dissection (LD) in thyroid carcinoma is still under debate because of the biological variety of different histological types and the difficulty to have an accurate preoperative diagnosis of metastatic lymph nodes; moreover prognostic factors of metastatic lymph nodes are still unclear. The AA. have separately analyzed different thyroid carcinomas and different clinical situations requiring thyroid LD. Metastatic lymph nodes from differentiated carcinomas, including papillary and follicular type, range from 12 to 90% and apparently do not worsen the prognosis. Level II-VI LD is indicated in presence of metastatic lymph nodes or macroscopic nodal recurrence after a previous LD. No prognostic advantages have been demonstrated when LD is performed without clinical or instrumental evidence of metastatic disease, including suspected recurrence characterised only by plasma Thyreoglobulin increased values. Lymph node metastases from medullary carcinoma range from 25 to 63%. Level II-VI LD is indicated if node metastases are present, whereas prophylactic LD, confined to level VI, is always recommended. Controversies still remain about: 1) LD extension whether it is prophylactic (level VI vs. II- VI) or in case of nodal involvement (levels II- VI monolateral or bilateral), 2) LD indications in case of an increased plasma Calcitonin levels during the follow-up after total thyroidectomy, without clinical or instrumental evidence of nodes involvement. Anaplastic carcinoma represents 5% of all thyroid carcinomas; it is the most aggressive type with an early tendency to invade surrounding organs and to give metastases; prognosis is very poor. LD is indicated only for a palliation in cases with compression syndromes.

Carcinoma↗

Preservation of in vitro biological functions in regional lymph node lymphocytes in squamous head and neck cancer.

Regional lymph node lymphocytes from patients with squamous cancer of the head and neck were tested in vitro for their ability to proliferate in response to phytohemagglutinin, concanavalin A, and allogeneic stimuli in one-way mixed lymphocyte culture. Their ability to act as cytotoxic effectors in phytohemagglutinin-dependent cellular cytotoxicity was also evaluated, and all results were compared to normal lymph node or blood lymphocytes. The regional lymph node lymphocytes retained proliferative capabilities equal to those in control lymph nodes or blood, whereas they were unable to mediate phytohemagglutinin-dependent cellular cytotoxicity. However, this was not a tumor-related effect because normal lymph node lymphocytes were also ineffective in this assay. The failure of the regional immune response to control early tumor growth could not be accounted for by generalized nonspecific immunosuppression in regional lymph node lymphocytes, inasmuch as these cells demonstrated normal in vitro activity.

Adult↗

[Cervical lymph node metastases].

The investigative procedure of clinically diagnosed cervical lymph node metastases is discussed. Cervical lymph node metastases can be the first manifestation of a carcinoma. The corresponding primary tumor is diagnosed in the ENT area (mouth, pharynx, larynx) in 80% of the cases and in bronchi or esophagus in 10%; therefore, a detailed ENT examination and an upper panendoscopy must be undertaken. Wedge excisions of lymph node metastases are contraindicated, since they produce an artificial rupture of capsule and open the door to extranodal tumor growth. Excision of cervical lymph nodes, which are clinically related to a cervical lymph node metastasis, should only be carried out within the framework of a diagnostic and therapeutic concept.

Bronchial Neoplasms↗

Suppression of VEGFR-3 signaling inhibits lymph node metastasis in gastric cancer.

In gastric cancer, lymph node metastasis is one of the major prognostic factors and forms the basis for surgical removal of local lymph nodes. Recently, several studies have demonstrated that overexpression of lymphangiogenic growth factor VEGF-C or VEGF-D induces tumor lymphangiogenesis and promotes lymphatic metastasis in mouse tumor models. We examined whether these processes could be inhibited in naturally metastatic tumors by blocking of their cognate receptor VEGFR-3 signaling pathway. Using a mouse orthotopic gastric cancer model which has a high frequency of lymph node metastasis, we estimated lymphatic vessels in gastric cancers by immunostaining for VEGFR-3 and other specific lymphatic markers, LYVE-1 and prox-1. Then we systemically administered anti-VEGFR-3 blocking antibodies. This treatment resulted in the inhibition of regional lymph node metastasis and reduction of lymphatic vessel density in the primary tumors. In addition, increased density of LYVE-1-positive lymphatic vessels of primary tumors was closely correlated with lymph node metastasis in human samples of gastric cancer. Antilymphangiogenesis by inhibiting VEGFR-3 signaling could provide a potential strategy for the prevention of lymph node metastasis in gastric cancer.

Adult↗

[Ex vitro sentinel lymph node mapping in colorectal carcinoma].

OBJECTIVE: To investigate the feasibility of ex vitro sentinel lymph node (SLN) mapping with methylene blue staining and its clinical value of predicting regional lymph node metastasis in colorectal cancer. METHODS: Methylene blue (1 ml) was injected submucosally around the tumor immediately after resection. After 2-5 minutes, the first blue-dyed lymph nodes, sentinel lymph nodes (SLNs), were harvested for pathological examination, and compared with the pathological results of other lymph nodes. RESULTS: Of the total 32 patients, 57 SLNs were successfully identified in 30 patients with an average of 1.9 nodes per person. The successful labeling rate was 93.8% (30/32). Among the 13 patients with positive SLNs, there were 5 patients with positive non-SLNs and 8 patients with negative Non-SLNs. Among the 17 patients with negative SLNs, there were 15 patients with negative non-SLNs and 2 patients with positive Non-SLNs. The accuracy of SLNs for regional lymph node metastasis was 93.3% (28/30), the false negative rate was 11.8% (2/17), and the specificity was 100% (13/13). CONCLUSIONS: Ex vitro sentinel lymph node mapping with methylene blue staining in colorectal carcinoma is technically feasible and can effectively reflect the metastatic situation of regional lymph nodes.

Adult↗

The value of prophylactic R2 lymph node dissection for gastric cancer.

Three hundred and eleven patients with an R2 lymph node dissection for gastric cancer were reviewed in order to examine the efficacy of prophylactic R2 lymph node dissection. In 246 patients, who were all macroscopically determined to have either N0 or N1 lymph node metastasis at the time of operation, 30 showed histologic lymph node metastasis in the N2 group. When the 5-year survival rates in the 61 patients with histologic N2 lymph node metastasis were compared according to the macroscopic evaluation of lymph node metastasis at the time of operation, 30 patients who were determined to have either N0 or N1 lymph node metastasis showed a better prognosis than the 31 patients who were determined to have N2 lymph node metastasis (p < 0.01). Therefore, prophylactic R2 lymph node dissection contributes to an improved prognosis for gastric cancer patients who are found to macroscopically have either N0 or N1 lymph node metastasis on the basis of an intra-operative evaluation.

Female↗

Phenotypic analysis by flow cytometry of surface immunoglobulin light chains and B and T cell antigens in lymph nodes involved with non-Hodgkin's lymphoma.

The objective of this study was to demonstrate the diagnostic usefulness of flow cytometric analysis of surface membrane immunoglobulin light chain and monoclonal antibody reactivities in B cell non-Hodgkin's lymphoma. For this purpose, lymph node cell suspensions from 80 patients (20 normal lymph nodes, 11 lymph nodes with benign lymphoid hyperplasia, and 47 lymph nodes with B cell non-Hodgkin's lymphoma) were studied to detect the expression of surface B and T cell differentiation antigens recognized by a panel of monoclonal antibodies (anti-Leu-1, anti-Leu-5, anti-HLA-DR, J-5, anti-BL-1, anti-BL-2, and anti-BL-7). The clonal excess calculation, percent kappa-positive minus percent lambda-positive/percent kappa-positive plus percent lambda-positive cells per discrete level of fluorescence intensity, was used to study the clonality of surface membrane immunoglobulin light chain expression. Among the BL surface antigens, BL-7 proved to be most consistently expressed in B cell non-Hodgkin's lymphoma (79 percent). It was also present in 57 percent of lymph nodes with benign hyperplasia. No significant relationships were detected between the patterns of reactivity with the anti-BL monoclonal antibodies and histologic subtypes, although the small number of cases tested in each category precludes any definitive conclusions. Immunophenotypic heterogeneity within subgroups was also observed with expression of the other antigens examined. Monoclonal expression of surface membrane immunoglobulin light chain was seen in 43 of 47 (91 percent) of lymph nodes with non-Hodgkin's lymphoma, three of 11 (27 percent) hyperplastic lymph nodes, and one of 22 (4 percent) normal lymph nodes. When the presence of BL-7 and clonal excess was examined as a panel, 83 percent of B cell non-Hodgkin's lymphomas were positively identified, whereas one normal lymph node and no hyperplastic lymph nodes gave positive results. The simultaneous presence of clonal excess and BL-7 can be a useful diagnostic aid in the differentiation of lymphomatous from hyperplastic lymph nodes. Cytofluorimetry provides a rapid, objective, and reproducible technology to confirm the diagnosis of lymph node involvement in B cell non-Hodgkin's lymphoma.

Antibodies, Monoclonal↗

Lymphadenectomy for cure in patients with early gastric cancer and lymph node metastasis.

The anatomic distribution, size, and histologic mode of involvement of 98 metastatic lymph nodes in 49 of 370 patients were examined to determine to what extent lymphadenectomy should be performed in addition to gastrectomy in patients with early gastric cancer. Nodal involvement in the marginal sinus (30 nodes) and partial medullary sinus (37 nodes) were commonly seen, and the lymph nodes of those types were enlarged compared with 1,086 patients with no metastatic lymph nodes (control group). Lymph nodes of the wide medullary sinus (11 nodes), small nodule (3 nodes), and massive involvement types (17 nodes) did not enlarge compared with those of the other types and those of the control group. Most of the metastatic sites (76.6 percent) were in the perigastric lymph nodes along the lesser and greater curvatures, about a fifth were in the extraperigastric nodes along the left gastric, common hepatic, celiac, and splenic arteries, and the least were in the extraperigastric nodes (3.1 percent) along the hepatoduodenal ligament. Since the rate of macroscopic diagnosis during operation was so poor, regardless of the histologic modes of nodal involvement, and also in cases of metastatic lymph nodes less than 15 mm in widest diameter, for curative operation of patients with early gastric cancer, perigastric and extraperigastric lymph nodes along the main arteries near the stomach should be completely dissected, in addition to resection of the stomach.

Adenocarcinoma↗

Drug concentrations in axillary lymph nodes after lymphatic chemotherapy on patients with breast cancer.

BACKGROUND: Lymph node status is one of the decisive prognostic factors in breast cancer. Chemotherapy targeting regional lymphatic tissues has emerged as a promising therapy for the treatment of malignancies with a high tendency to disseminate lymphatically. The present study determined the drug concentrations in axillary lymph nodes after lymphatic chemotherapy (LC) in patients with breast cancer and compared the results with those receiving intravenous chemotherapy (VC) to investigate whether LC could improve the accumulation of anticancer drug in regional lymph nodes. METHODS: Sixty patients with breast carcinoma confirmed by preoperative puncture-biopsy were divided into two groups at random. The LC group (n = 30) received a subcutaneous injection of 4 ml of carboplatin-activated carbon suspension, containing 20 mg of carboplatin, adjacent to the primary tumour. The VC group (n = 30) received an intravenous administration of an equal dose of aqueous carboplatin. At 1, 12, 24, 36 and 48 hours after administration, modified radical mammectomies were performed on 12 patients at each time point, with 6 from each group. Axillary lymph nodes were removed for pathological examination. The platinum concentrations in nodes were determined by Zeeman atomic absorption spectrometry. RESULTS: A total of 275 axillary lymph nodes were resected, with 154 in the LC group and 121 in the VC group. Of the 275 lymph nodes, 136 (49.5%) from 23 patients (38.3%) had histopathologically detected metastases. At 1, 12, 24, 36 and 48 hours after injection, the carboplatin concentrations in the LC group were 11.82 +/- 3.50, 23.58 +/- 7.34, 18.22 +/- 4.93, 16.70 +/- 5.15 and 14.62 +/- 4.29 microg/g (means +/- SD), respectively, whereas those in the VC group were 0.06 +/- 0.02, 0.11 +/- 0.05, 0.10 +/- 0.02, 0.05 +/- 0.02 and 0 microg/g, respectively. Significant differences were found in each corresponding comparison (P < 0.001). Lymph node metastasis was uncorrelated with drug concentration (P > 0.05). CONCLUSION: LC can effectively and continuously improve the drug concentrations in axillary lymph nodes in patients with breast cancer, in comparison with VC.

Adult↗

Immunohistochemical assessment of localization and frequency of micrometastases in lymph nodes of colorectal cancer.

PURPOSE: Micrometastases are often found in regional lymph nodes of colorectal cancer (CRC). The aim of this study is to examine the extent and distribution of such lymph nodes. EXPERIMENTAL DESIGN: We immunohistochemically assessed localization and frequency of micrometastases in 878 lymph nodes from 98 patients with CRC. The anatomical position of lymph nodes was defined as level 1 to level 3 according to distance from the main tumor. RESULTS: The frequency of micrometastasis increased through observation of the 4-microm-thick lymph node sections, from one to two to five slices. With five slices, micrometastasis was frequently and extensively present in 49.1, 35.7, and 53.3% patients of histologically node-negative patients, node-positive patients at level 1, and node-positive patients at level 2, respectively. We then assessed the value of the presence of micrometastasis in node-negative patients with regard to prognosis, but no significant impact was obtained. To examine the reproducibility of the results obtained with immunohistochemistry, serial sectioning (four consecutive slices at seven different levels) of lymph nodes was additionally performed in lymph nodes initially diagnosed as micrometastasis positive. Immunohistochemical detection revealed that the sectioning level highly affected the results. CONCLUSIONS: Our results indicated frequent presence of micrometastasis in lymph nodes of CRC and that micrometastasis in node-negative CRC patients did not help in predicting the outcome, in part because of the limited reproducibility with immunohistochemistry.

Adult↗

Technology insight: radioguided sentinel lymph node dissection in the staging of prostate cancer.

Pelvic lymph node dissection is the only reliable method of staging for clinically localized prostate cancer. Despite the obvious prognostic advantages conferred by accurate staging, pelvic lymph node dissection is associated with significant morbidity and prolonged operative time. A substantial decrease in the sensitivity to lymph node metastasis occurs by simple reduction of the dissection area to the obturator fossa. Radioguided sentinel lymph node dissection provides accurate staging despite use of a minimal-area dissection template. Results from studies in prostate cancer indicate that this method has a high sensitivity for very early detection of lymphatic spread. A substantial number of the detected metastases are of a small size, solitary and widely distributed throughout the pelvic lymph nodes. These features make metastases undetectable by preoperative imaging modalities, and by the current, standard method of lymph node dissection limited to the obturator fossa.

Humans↗

Can sentinel node navigation surgery reduce the extent of lymph node dissection in gastric cancer?

Our group has conducted several studies of sentinel node navigation surgery (SNNS) for the management of early gastric cancer. To determine the distribution of nodal metastases and micrometastases, we used immunohistochemical staining with anticytokeratin antibody to examine 2605 lymph nodes obtained from 108 consecutive patients with submucosal gastric cancer. When nodes were negative by routine hematoxylin and eosin (H&E) examination, micrometastases were confined to one regional lymphatic pathway near the primary tumor; however, when nodes were H&E-positive, micrometastases were distributed more widely. The wide and complicated lymphatic stream from a gastric tumor contributed to the relatively high (23%) incidence of micrometastases and the frequent occurrence of skip metastasis. In another study, we used a combination of blue dye and radiopharmaceutical to perform SNNS in 18 patients with early gastric cancer. The rate of sentinel node detection was 94%, and the average number of sentinel nodes per patient was three. Technical issues included size of particles, method of injection, accuracy of frozen section examination, and standard criteria for defining a sentinel node. SNNS for gastric cancer is a promising technique; further study of various anatomic and pathologic factors will indicate whether it can be used to determine the extent of lymphadenectomy necessary in patients with early gastric cancer.

Coloring Agents↗

Lymph node involvement in Waldenström's macroglobulinemia.

The pattern of lymph node involvement in Waldenström's macröglobulinemia (MG) is described according to clinical and histological materials from 2 biopsy and 4 autopsy cases. The histological features of biopsy were well-differentiated, diffuse, lymphocytic lymphoma in one case (case 1) and sinus histiocytosis (SH) with nodular aggregates of lymphoid cells as observed by the first biopsy in the other case (case 2). An immunofluorescent study of lymph nodes revealed monoclonal proliferation of B lymphocytes (IgM, gamma) in both cases. In case 2, a majority of circulating lymphoid cells bore membrane-bound monoclonal IgM. The histological features of lymph nodes obtained by the second biopsy in case 2 was comparable with the well-differentiated, lymphocytic lymphoma in some nodes, and diffuse and nodular proliferation with preservation of sinuses in the other nodes. The pattern of lymph node involvement of 4 autopsy cases were also analysed. According to these investigations. It is suggested that lymph node showing SH is a pattern of lymph node involvement of MG.

Aged↗

Lymph node control in cervical cancer.

PURPOSE: The aim was to evaluate pretreatment lymph node size, irradiation dose, and failure patterns. METHODS: Pretreatment PET and CT were performed in 208 patients. Lymph nodes were scored as either positive or negative by PET and lymph node size was measured by CT. Lymph node irradiation dose and sites of failure were recorded. RESULTS: The mean pelvic lymph node doses were: PET negative nodes, < or =1 cm, 66.8 Gy, and 0/76 failures; PET positive nodes, < or =1 cm, 66.8 Gy, and 3/89 failures; 1.1-< or =2 cm, 66.9 Gy, and 0/21 failures; 2.1-< or =3 cm, 69.4 Gy, and 2/15 failures; and 3.1 to < or =4 cm, 74.1 Gy, and 0/5 failures. The mean paraaortic lymph node dose was 43.3 Gy and there were no paraaortic failures for 24 patients with PET positive < or =1 cm nodes, 0/5 failures for 1.1 to < or =2 cm, and 0/4 failures for 2.1 to < or =3 cm. The most common site of failure was distant metastases. CONCLUSIONS: The irradiation doses given in this study were adequate to control most lymph node metastases. Positive lymph nodes of any size at diagnosis were the most significant predictor for developing distant metastases.

Adult↗

MR imaging in squamous cell carcinoma of the head and neck with no palpable lymph nodes.

PURPOSE: To assess the efficacy of MR imaging in the detection of lymph node metastasis in patients with no palpable lymph nodes ("N0 neck") who have squamous cell carcinoma of the head and neck region. MATERIAL AND METHODS: MR neck imagings in 18 patients who underwent neck dissection (bilaterally in 2) for squamous cell carcinoma of the head and neck region were examined preoperatively for the purpose of detecting lymph node metastases. The imaging features taken into consideration were: size (cutoff point 10 mm), grouping, presence of central necrosis, and appearance of extracapsular spread. The MR examinations comprised spin-echo T1- and T2-weighted sequences. The MR findings were compared with those of surgery and histopathological examination. RESULTS: MR suggested metastatic lymph node involvement in 5 necks. In 2 of these, central necrosis was seen in the enlarged lymph nodes. In a third, a grouping of the lymph nodes was noted. Extracapsular spread was not present. Histopathological examination revealed metastatic lymph nodes in 7 of the 20 necks, the rate of clinically occult disease being 35%, and 4 of them had been accurately graded by MR. There was one false-positive MR examination. The MR sensitivity was 57.1% and specificity 92.3%. CONCLUSION: MR may reveal metastatic lymph nodes in patients with no clinical evidence of metastasis. However, conventional MR techniques are not always sufficient for decision-making on surgery in cases of "N0 neck".

Adult↗