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Vascular endothelial growth factor-C expression in human prostatic carcinoma and its relationship to lymph node metastasis.

Lymph node dissemination is a major prognostic factor in human cancer. However, the molecular mechanisms underlying lymph node metastasis are poorly understood. Recently, vascular endothelial growth factor-C (VEGF-C) was identified as a ligand for VEGF receptor-3 (VEGFR-3/Flt-4) and the expression of VEGFR-3 was found to be highly restricted to the lymphatic endothelial cells. In this report, we investigated the expression of VEGF-C and VEGFR-3 in human prostatic carcinoma tissue by using in situ hybridization and immunohistochemical staining respectively. Expression of VEGF-C mRNA in prostatic carcinoma was significantly higher in lymph node-positive group than in lymph node-negative group. In addition, the number of VEGFR-3-positive vessels was increased in stroma surrounding VEGF-C-positive prostatic carcinoma cells. These results suggest that the expression of VEGF-C in prostatic carcinoma cells is implicated in the lymph node metastasis.

Adenocarcinoma↗

First drainage lymph node(s) in gastric cancer: analysis of the topographical pattern of lymph node metastasis in patients with pN-1 stage tumors.

BACKGROUND: We attempted to identify the first lymph node(s) involved in metastasis of gastric cancer by studying the topographical pattern of metastasis to regional lymph nodes in patients with pN-1 stage tumors. MATERIALS AND METHODS: A total of 190 patients (108 males and 82 females; age range, 27 to 83 years; mean, 59.7 years), who had undergone curative resection combined with lymphadenectomy for solitary carcinoma of the stomach and were histologically diagnosed as having pN-1 stage tumors, were enrolled in the present study. The topographical patterns of metastasis to regional lymph nodes were reviewed from the pathology records of these patients. RESULTS: A total of 7561 lymph nodes (mean, 39.8/patient; range 15-99/patient) were dissected and metastasis was histologically observed in 523 nodes (6.9%, mean, 2.7/patient). Although perigastric lymph nodes were a common site of metastasis, the distribution of positive nodes depended on tumor location. As the number of positive nodes increased, a more diffuse pattern of regional involvement was noted. Skip metastasis was identified in 10 (5%) out of 190 patients. This unusual pattern of metastasis was found in 9 (14%) out of 63 patients with single positive nodes, while only one (1%) out of 127 patients with 2-6 positive nodes exhibited this pattern of metastasis. The difference between the two groups was statistically significant (p < 0.0001). CONCLUSION: Although perigastric lymph nodes are important first sites of drainage from pN-1 stage gastric tumors, the pattern of lymph node metastasis varies widely within a regional area even in pN-1 stage patients.

Adult↗

Intramammary lymph nodes and breast cancer: a marker for disease severity, or just another lymph node?

BACKGROUND: Axillary lymph node status is still considered the most significant prognostic factor for breast cancer outcome, and treatment decisions are based on the presence or absence of nodal disease. Intramammary lymph nodes (IMLNs) can be a site of regional spread. Is this a marker for more aggressive disease? METHODS: We reviewed the cancer center pathology database from 1991 to 2005 for all cases of breast cancer with IMLNs. RESULTS: IMLNs were identified in 64 breast cancer patients, with metastatic spread in 20 patients, and benign IMLNs described in 44 patients. Positive IMLNs were associated with more aggressive disease, including higher rates of invasive versus noninvasive cancers (5% ductal carcinoma-in-situ [DCIS] with positive IMLNs vs. 23% with negative IMLNs), lymphovascular invasion (55% vs. 11%), and a higher rate of axillary lymph node involvement (72% vs. 18%). Patients with positive IMLNs were also more likely to undergo mastectomy (75% vs. 54%). CONCLUSIONS: IMLN metastases are a marker for disease severity; recognition of this may influence choice of adjuvant therapy. The presence of metastatic disease in an IMLN is associated with a high rate of axillary nodal involvement, and should mandate axillary dissection. Preoperative lymphoscintigraphy may help identify these extra-axillary metastases.

Adult↗

[Tumor size and regional lymph node metastasis in patients with M0 renal cell carcinoma: analysis in those having regional lymph node dissection].

We evaluated the relationship between regional lymph node metastasis and tumor size in patients with M0 renal cell carcinoma who received regional lymph node dissection. The study involved 234 of the 247 patients with localized renal cell carcinoma who underwent radical nephrectomy with lymph node dissection at our institute between 1985 and 1999. Patients were arbitrarily classified into 3 groups by the greatest diameter of the tumor on preoperative computed tomography (CT): 4.0 cm or less (group A), 4.1 to 7.0 cm (group B), and 7.1 cm or more (group C). The incidence of lymph node metastasis was assessed in each group. The current study showed that 11 (4.7%) of the 234 patients with lymph node dissection together with radical nephrectomy were lymph node positive. The incidences of lymph node metastasis were 4.0% in group A, 2.3% in group B, and 8.4% in group C (p = 0.79). Of these 11 patients with lymph node metastasis, 2 (18.2%) have so far survived for over 5 years following surgery. Although the role of regional lymph node dissection with radical nephrectomy might be limited and controversial in renal cell carcinoma, urological surgeons should always be aware of possible metastasis for any tumor size.

Adult↗

Utility fo gallium-67 in determining the radicality of lymph node dissections of the neck for metastatic lymph nodes with extranodal spread in patients affected by carcinoma of the head and neck.

AIMS AND BACKGROUND: Based on the fact that scintigraphy more readily reveals uptake of a radioisotope in a superficial position owing to incomplete surgical radicality, the authors examined by 67Ga scintigraphy a group of patients who had undergone dissection of lymph nodes of the neck from carcinoma with extranodal spread. They then checked the follow-up to ascertain the efficacy of 67Ga scintigraphy in relation to the eventual recurrences in the soft tissues of the neck. METHODS: A group of 136 patients were examined by 67Ga scintigraphy and followed for a minimum of 3 years after complementary radiotherapy. A group of 20 patients with no lymph node metastases was used as control to evaluate eventual false positives or false negatives. RESULTS: Recurrences in the soft tissues of the neck occurred in 35 (42.7%) of the 82 patients positive at 67Ga scintigraphy and in 6 (11.1%) of the 54 patients negative at the examination (P = 0.0001). All the patients in the control group were negative at 67Ga scintigraphy and without recurrences. CONCLUSIONS: 67Ga scintigraphy can give reliable information on the risk of recurrences in the soft tissues of the neck. Since in spite of postoperative radiotherapy the percentage of local recurrences in cases with positive 67Ga scintigraphy was rather high (42.7%), the authors propose a scheme of radiotherapy based on administration of a higher dose per fraction on the scintigraphically positive area.

Adult↗

Detection of lymph node micrometastases and isolated tumor cells in sentinel and nonsentinel lymph nodes of colon cancer patients.

About 20% to 30% of colon cancer patients classified as node negative by routine hematoxylin-eosin (H&E) staining are found to have micrometastases (MM) or isolated tumor cells (ITC) in sentinel lymph nodes (SLNs) if analyzed by step sections and immunohistochemistry (IHC). Whether SLNs are in this respect representative for all lymph nodes was addressed in this study. SLNs were identified using the intraoperative blue dye detection technique. If all lymph nodes (SLNs and non-SLNs) of a patient were negative by routine H&E staining, they were step-sectioned and analyzed by IHC using pancytokeratin antibodies. We identified at least one SLN in 47 of the 55 patients (85%) and examined a median of 26 lymph nodes per patient (range 10-59). By routine H&E staining, 14 of the 47 patients showed lymph node metastases (30%); the remaining 33 were classified as node-negative. In this group (33 patients), 1011 lymph nodes were analyzed by step sections and IHC: 14 of 70 SLNs. (20%) but only 37 of 941 non-SLNs (4%) had MM/ITC (p < 0.001). Furthermore, 13 of the 33 H&E-negative patients were found to have MM/ITC (39%). In 11 of the 13 patients, MM/ITC were identified in both SLNs and non-SLNs in 1 patient in the SLN only, and in 1 patient in a non-SLN only (sensitivity for the identification of MM/ITC: 92%; negative predictive value: 95%). The SLN biopsy is a valid tool to detect, as well as exclude, the presence of MM/ITC in colon cancer patients. Our results may be of prognostic relevance and influence patient stratification for adjuvant therapy trials.

Aged↗

Solitary lymph node metastasis of gastric cancer as a basis for sentinel lymph node biopsy.

BACKGROUND/AIMS: In order to examine the biology of sentinel lymph node of stomach cancer, we investigated solitary lymph node metastases that were hypothesized to represent sentinel lymph node. METHODOLOGY: In the 4,620 primary gastric cancers between 1964 and 1997, 1271 cases with a localized tumor were selected and the localization of the solitary metastases in relation to the primary tumors were studied. RESULTS: Of the 130 tumors with a single basin metastasis, only 71% of the tumors in the upper third, 75% of the middle and 80% of the lower involved the node basins in the close vicinity. In the anterior wall and the greater curvature the rates of adjacent metastasis were more than 90%, while in the posterior wall and the lesser curvature they were 76% and 43%, respectively. Metastases of the remaining cases were found at more distant basins. CONCLUSIONS: In stomach cancer sensitivity of sentinel lymph node biopsy would be very low by the exploration of the adjacent basin especially for the lesions in the lesser curvature and posterior wall.

Adenocarcinoma↗

Changes in human lymphocyte subpopulations in tonsils and regional lymph nodes of human head and neck squamous carcinoma compared to control lymph nodes.

BACKGROUND: Lymphoid tissues constitute basic structures where specific immune responses take place. This leads to the development of germinal centres (GCs), migration of cells and the generation of memory cells. Here, we have compared human tumour reactive lymph nodes and tonsils with control lymph nodes. RESULTS: The study by flow cytometry shows that in control lymph nodes the majority of cells were naive T-lymphocytes (CD45RA+/CD7+). In reactive nodes, although the percentage of CD45RO+ T cells remains constant, there is an increase in the number of B-lymphocytes, and a reduction in naive T cells. The percentage of cells expressing CD69 was similar in reactive nodes and in controls. In both cases, we have found two populations of B cells of either CD69- or CD69dull. Two populations of T cells, which are either negative for CD69 or express it in bright levels (CD69bright), were also found. The analysis of tissue sections by confocal microscopy revealed differences between control, tonsils and tumor reactive lymph nodes. In control lymph nodes, CD19 B cells are surrounded by a unique layer of CD69bright/CD45RO+ T cells. GCs from tonsils and from tumour reactive nodes are mainly constituted by CD19 B cells and have four distinct layers. The central zone is composed of CD69- B cells surrounded by CD69bright/CD45RO+ T cells. The mantle region has basically CD69dull B-lymphocytes and, finally, there is an outer zone with CD69-/CD45RO+ T cells. CONCLUSIONS: Human secondary lymphoid organs react with an increase in the proportion of B lymphocytes and a decrease in the number of CD45RA+ T cells (naive). In tonsils, this is due to chronic pathogen stimulation, whereas in lymph nodes draining head and neck carcinomas the reaction is prompted by surrounded tumors. During this process, secondary lymphoid organs develop secondary follicles with a special organization of T and B cells in consecutive layers, that are described here by confocal microscopy. This pattern of cellular distribution may suggest a model of cell migration into the secondary lymphoid follicles.

Adult↗

Lymph node recovery from colorectal resection specimens removed for adenocarcinoma. Trends over time and a recommendation for a minimum number of lymph nodes to be recovered.

Recovery of pericolorectal lymph nodes from colectomy specimens has long been part of colorectal cancer staging. Recently, adjuvant therapy has been added for high stage carcinomas, providing further impetus for performing careful lymph node dissections. Pericolorectal lymph nodes were examined to determine if there has been a change over time in the number of lymph nodes recovered and proportion of specimens with pericolonic lymph node metastases from colorectal carcinoma resection specimens. Also, the authors attempted to establish a recommendation for a minimum number of lymph nodes that should be recovered before a colon can be considered free of metastases. Slides and reports of the first 20 consecutive pT3 colorectal carcinoma resections in each year from 1955 to 1995 at William Beaumont Hospital that did not have known metastases at the time of surgery were reviewed (750 specimens total). The mean number of lymph nodes recovered per specimen and incidence of detected lymph node metastases increased over the 41-year period, with the greatest increase occurring during 1992-1995. The greatest proportion of patients with lymph node metastases detected occurred in the 17 to 20 lymph nodes recovered per specimen group. Specimens with more than 20 lymph nodes did not have a higher proportion of lymph node metastases detected compared to specimens with 17 to 20 lymph nodes. Approximately 20% of the specimens with metastases had more than 17 lymph nodes recovered. These results suggest that pathologists should retrieve all the lymph nodes that can be recovered, but at least 17 lymph nodes should be recovered to insure accurate documentation of nodal metastases when present.

Adenocarcinoma↗

[Lymph node biopsy].

Lymph node biopsy is often easy to perform but final histologic diagnosis and accuracy depends on its technical quality: adequate biopsy and proper fixation and processing. This technical note defines advice on the selection of the lymph node biopsy site, shows the interest of a previous lymph node needle aspiration and gives the principles of histopathological techniques: cytology on imprints from the excised fresh unfixed node, fixation, staining methods ad immunohistochemistry. A place is given to the indications of frozen section diagnosis, frozen tissue, electron microscopy, microbiological, cytogenetic and molecular studies for gene rearrangement.

Biopsy↗

[Glomus cell clusters of the lymph node].

Nine lymph nodes with so-called benign nevus cell nevi were studied by light microscopy. In three cases the lymph nodes were also examined by electron microscopy. The solitary or multiple cell clusters were 35-645 mu in diameter and were usually found in the lymph node capsule or cortex. They were more frequent in the older patients. There was no predisposition for either sex. Specific morphologic features allowing clear cytologic identification of the cells were not evidient. In particular, there was no indication that they represented nevus cells. However, they showed a great morphologic similarity to glomus cells. In addition, they were usually found near blood vessels. We assume that the cell clusters were hamartias related to glomangiomas. We call them glomus cell clusters.

Adult↗

Lymph-node staining with activated carbon CH40: a new method for axillary lymph-node dissection in breast cancer.

OBJECTIVE: To demonstrate the usefulness of activated carbon particles (CH40) as a vital staining dye for visualizing lymphatic vessels and lymph nodes in breast cancer. DESIGN: A retrospective evaluation. SETTING: Department of Surgery in Sendai National Hospital, Japan, a 716-bed teaching hospital. METHODS: To identify as many lymph nodes as possible in the axillary fat, by which we might decrease the possibility of the presence of undetected metastatic nodes, an emulsion of activated carbon particles (CH40) was injected into the centre of the mammary gland, close to the tumour site, 3 days before radical surgery. MAIN OUTCOME MEASURE: The number of lymph nodes found by the traditional method and by the CH40-injection method were recorded. RESULTS: After injection, the CH40 was readily adsorbed into regional lymphatics and streamed along with the lymph flow to blacken regional lymph nodes. The CH40-guided method increased the mean number of nodes per case found in the axilla from 8.4, by the traditional method, to 14.0 nodes per case. CONCLUSIONS: The use of the CH40 technique has two technical advantages; one is that it allows surgeons to locate the blackened lymph nodes at the time of surgery and the other is that it allows pathologists to look for the nodes in fatty tissue. Lymph-node dissection with the aid of activated carbon particles is inexpensive, easy to perform and enables the smallest lymph nodes to be easily recognized. CH40 is the technique of choice for the detection of axillary lymph nodes in cases where the number of lymph nodes detected by the traditional method is too small for accurate surgery. In conclusion, the present study demonstrates that CH40 could be an appropriate tool for more accurate staging of breast cancer axillary specimens.

Adult↗

[Angio-immunoblastic lymphadenopathy with fibrosis of bone marrow, lymph node, liver and spleen, and proliferation of epithelioid cells in lymph nodes].

We report a 47-year-old man diagnosed as angio-immunoblastic lymphadenopathy with dysproteinemia (AILD) with fibrosis of the bone marrow, lymph node, liver and spleen, and proliferation of epithelioid cells in lymph node. He was admitted to a hospital in May, 1980 because of general fatigue, cough, fever and systemic lymphadenopathy. The diagnosis of AILD was based on a biopsy of right cervical lymph node. His symptoms were improved but recurred with the addition of icterus and progressive pancytopenia with decrement of prednisolone. He was referred to our hospital in July, 1980 and his physical examination revealed generalized lymphadenopathy, icterus and hepatosplenomegaly. Hemogram showed pancytopenia, and needle biopsy of the bone marrow disclosed fibrosis. Sections from the lymph node showed AILD with proliferation of epithelioid cells. Administration of 60 mg/day of prednisolone improved the fever, lymphadenopathy and hepatosplenomegaly. However he died suddenly of acute respiratory failure on July 30. Autopsy showed fibrosis of bone marrow, lymph node, liver and spleen with infiltration of abnormal lymphocytes, and pulmonary aspergillosis.

Cell Division↗

Detection of pelvic lymph node metastases in patients with clinically localized prostate cancer: comparison of [18F]fluorocholine positron emission tomography-computerized tomography and laparoscopic radioisotope guided sentinel lymph node dissection.

PURPOSE: Accurate detection of lymph node metastases in prostate cancer has important implications for prognosis and approach to treatment. We investigated whether preoperative [18F]fluorocholine combined in-line positron emission tomography-computerized tomography and intraoperative laparoscopic radioisotope guided sentinel pelvic lymph node dissection can detect pelvic lymph node metastases in patients with clinically localized prostate cancer as reliably as extended pelvic lymph node dissection. MATERIALS AND METHODS: A total of 20 patients (mean age 63.9 +/- 6.7 years, range 52 to 75) with clinically localized prostate cancer, prostate specific antigen greater than 10 ng/ml, and/or a Gleason score sum of 7 or greater and negative bone scan were enrolled in the study. [18F]fluorocholine combined in-line positron emission tomography-computerized tomography was performed before surgery. Sentinel pelvic lymph node dissection preceded extended pelvic lymph node dissection including the area of the obturator fossa, external iliac artery/vein and internal iliac artery/vein up to the bifurcation of the common iliac artery. Laparoscopic radical prostatectomy was performed afterward. RESULTS: In 10 of the 20 patients (50%) lymph node metastases were detected, and were exclusively found outside the obturator fossa in 62%. These metastases would not have been identified with standard lymph node dissection of the obturator fossa only. [18F]fluorocholine combined in-line positron emission tomography-computerized tomography was true positive in 1, false-positive in 2, false-negative in 9 and true negative in 8 patients. The largest lymph node metastasis not seen with [18F]fluorocholine combined in-line positron emission tomography-computerized tomography was 8 mm. Laparoscopic sentinel guided lymph node dissection revealed lymph node metastases in 8 of 10 patients. In the other 2 patients sentinel lymph node dissection was not conclusive. In 1 patient normal nodal tissue was completely replaced by cancer and, therefore, there was no tracer uptake in the involved pelvic sidewall/node, and the other patient had no tracer activity at all in the involved pelvic sidewall. Extended pelvic lymph node dissection missed 1 lymph node metastasis (2 mm diameter near pudendal artery) which was detected by sentinel pelvic lymph node dissection only. CONCLUSIONS: Extended pelvic lymph node dissection reveals a higher number of lymph node metastases as described for obturator fossa dissection only. [18F]fluorocholine combined in-line positron emission tomography-computerized tomography is not useful in searching for occult lymph node metastases in clinically localized prostate cancer. Sentinel guided pelvic lymph node dissection allows the detection of even small lymph node metastases. The accuracy of sentinel pelvic lymph node dissection is comparable to that of extended pelvic lymph node dissection when the limitations of the method are taken into consideration.

Aged↗

The architecture of rat lymph nodes. I. Combined light and electron microscopy of lymph node cell types.

Non-lymphoid cells in rat lymph nodes are described as seen by combined light and electron microscopy of normal adult, congenitally athymic, germ-free, irradiated, or newborn rats. The cells are divided into stromal and non-stromal. The latter category consists of a variety of morphologically distinct cell types with characteristic distribution patterns. The presence of paracortical interdigitating cells in lymph nodes of germ-free rats, athymic rats, and newborn euthymic and athymic rats, refutes the ideas that interdigitating cells differentiate from macrophages under immune stimulation or T cell influences. Follicular dendritic cells are more clearly visualized and appear to be polynucleated after emptying the follicles of lymphoid cells by irradiation. Follicular dendritic cells and tingible body macrophages are found in conventionally raised euthymic and athymic rats, but not in germ-free rats. The interrelationships of these and other types of non-lymphoid cells are discussed.

Animals↗

[The valves of the marginal sinus of the lymph nodes].

Popliteal lymph nodes of male Wistar rats were studied in scanning regime of electron microscope. On the base of the data obtained it is concluded that on the lymph node surface and in the thickness of a capsule afferent lymphatic vessels branch into thin rami supplied with valves from the inside of the capsule in the site of falling into marginal sinus. Valvular apparatus found obviously gives possibility to regulate lymph flow in the lymph node.

Animals↗