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[Lymphocyte migration in syngeneic lymph node implants].

Lymph nodes implanted subcutaneously to syngeneic recipients were shown to regenerate after mass cell destruction. Regenerated lymphoid tissue has a resemblance to the cortical zone of intact lymph nodes. Microenvironment of regenerated lymphoid tissue provides homing of lymphocytes. However, migration of 51Cr-labelled lymphocytes to implants declined drastically, as compared to lymphocyte migration to intact lymph nodes. Attenuation of proliferative activity and the data of morphological analysis indicate a more prolonged retention of lymphocytes in implanted lymph nodes. The results obtained could be attributable to only partial recovery of sinus and vessel systems regulating the inflow and outflow of lymphocytes in lymph nodes.

Animals↗

[A case treated successfully with low-dose CDDP and 5-FU for the treatment of liver and para-aortic lymph node metastases and second metastasis to anterior mediastinum lymph nodes from gastric cancer after gastrectomy].

A 64-year-old-male had recurrent paraaortic lymph node and liver metastases eight months after total gastrectomy and with distal pancreatectomy and splenectomy for advanced gastric cancer. Combined chemotherapy with 5-FU and a low-dose of CDDP was effective and the both lesions disappeared. Thirteen months later, a second recurrence of anterior mediastinum lymph node metastases occurred. After the same protocol, the lesions showed a partial response and lymph node dissection was performed. Histopathological examination showed that the resected lymph nodes had 99% necrosis and fibrotic change. Immunohistochemical examination of p53 of the primary gastric cancer showed negative staining. The patient has been followed for three years after the operation, and has no recurrent lesions.

Antineoplastic Combined Chemotherapy Protocols↗

Sentinel lymph node concept in gastric cancer with solitary lymph node metastasis.

AIM: To study the localization of the solitary metastases in relation to the primary gastric cancers and the feasibility of sentinel lymph node (SLN) concept in gastric cancer. METHODS: Eighty-six patients with gastric cancer, who had only one lymph node involved, were regarded retrospectively as patients with a possible sentinel node metastasis, and the distribution of these nodes were assessed. Thirteen cases with jumping metastases were further studied and followed up. RESULTS: The single nodal metastasis was found in the nearest perigastric nodal area in 65.1% (56/86) of the cases and in 19.8% (17/86) of the cases in a fairly remote perigastric area. Out of 19 middle-third gastric cancers, 3 tumors at the lesser or greater curvatures had transverse metastases. There were also 15.1% (13/86) of patients with a jumping metastasis to N2-N3 nodes without N1 involved. Among them, the depth of invasion was mucosal (M) in 1 patient, submucosal (SM) in 2, proper-muscular (MP) in 4, subserosal (SS) in 5, and serosa-exposed (SE) in 1. Five of these patients died of gastric cancer recurrence at the time of this report within 3 years after surgery. CONCLUSION: These results suggest that nodal metastases occur in a random and multidirectional process in gastric cancer and that not every first metastatic node is located in the perigastric region near the primary tumor. The rate of "jumping metastasis" in gastric cancer is much higher than expected, which suggests that the blind examination of the nodal area close to the primary tumor can not be a reliable method to detect the SLN and that a extended lymph node dissection (ELND) should be performed if the preoperative examination indicates submucosal invasion.

Gastrectomy↗

Malignant melanoma: a search for occult lymph node metastases.

Lymph nodes regarded as "negative" following routine pathologic examination were reexamined in seven patients with malignant melanoma who later developed systemic metastases. A total of 185 lymph nodes were serially sectioned; five to seven levels of each lymph node were examined for the presence of occult metastases. In this manner previously undetected tumor was found within a solitary lymph node of one patient. It is concluded that attempts to detect occult melanoma metastases by routine serial sectioning of lymph nodes is not of practical applicability.

Adolescent↗

Lymph node revealing solution and traditional 10% buffered formaldehyde for detecting lymph nodes in colorectal carcinoma.

BACKGROUND: Cancer stage has been the most important factor in evaluating the prognosis and treatment of colorectal carcinoma, and the presence of lymph node metastasis in the resected specimen plays a key role in serial staging. We evaluated a newly proposed "lymph node revealing solution" (LNRS) that proponents claim is inexpensive, easy, rapid, and innocuous, and that could help to establish the stage of disease more accurately than buffered formaldehyde (formalin). Our study compared traditional 10% formalin and LNRS as second search solutions to determine whether LNRS is a more useful and practical solution than formalin. METHODS: Thirty randomly selected colorectal carcinomas from low anterior resection (LAR) were studied. The specimens were handled routinely on the first day. Then, the entire fat of odd-numbered cases was immersed in three times its volume of LNRS, and the entire fat of even-numbered cases was immersed in 10 times its volume of formalin overnight. The chi-squared test was used to evaluate the results. RESULTS: Of 145 cassettes in the second search by LNRS, seven had no lymph nodes. Of 107 cassettes in the second search by formalin, 18 had no lymph nodes. Totally, 792 lymph nodes were found with an average number of 26.4 per case and 1.53/cm (per centimeter of specimen) in all 30 cases. By the LNRS method, 138 lymph nodes were found in the 15 odd-numbered cases, and by the formalin method, 89 lymph nodes were found in the 15 even-numbered cases. We were able to adjust the stage upward in two cases by LNRS-fixation method. There were no changes in staging in the formalin-fixation method cases. CONCLUSIONS: LNRS showed no statistically significant difference from formalin in the numbers of total lymph nodes, positive lymph nodes, or minute (less than 1 mm) lymph nodes found. Nonetheless, we do believe that LNRS is a potential replacement solution for formalin due to its fast fixation, ease of searching, high identification rate and time-saving procedure.

Colorectal Neoplasms↗

An analysis of cervical lymph nodes metastasis in oral squamous cell carcinoma. Relationship between grade of histopathological malignancy and lymph nodes metastasis.

Cervical lymph nodes metastasis is well known to be an indicator of poor prognosis in patients with oral cancer. This study was considered 38 patients of oral squamous cell carcinoma who were treated at our department from 1993 to 1997. Histological malignancy of initial biopsy in the pretreatment period was evaluated by Anneroth's classification. The relationship of degree of histological malignancy with cervical lymph nodes metastasis were analysed in this study. Metastasis in the cervical lymph nodes was histologically confirmed in 17 out of 38 cases (44.7%). The metastasis located predominantly in the submandibular nodes and superior internal jugular nodes. According to T classification, the rate of metastasis in the cervical lymph nodes in T1 and T2 cases was around 30%, while the rate in T3 and T4 cases tended to be as high as around 60%. However, there was no significant difference. A significant relation was evident between the degree of histological malignancy and metastasis in the cervical lymph nodes (P< 0.01), indicating that the histological malignancy could be served as a predictor for metastasis in the cervical lymph nodes. Among the six parameters, a significant difference was observed only in the degree of keratinization and the mode of invasion (P< 0.05). When the sum of the degree of histological malignancy exceeds 15, metastasis in the cervical lymph nodes should be considered.

Carcinoma, Squamous Cell↗

Surface markers on lymphocytes leaving pig lymph nodes.

Mesenteric lymph nodes of normal young pigs were perfused in vitro at physiological temperature. Cell-free perfusion medium was pumped into the artery for more than 2.5 hr, and lymphocytes were continuously released into the venous effluent. Recirculating lymphocytes emigrate from pig lymph nodes by entering the blood vasculature directly and not via efferent lymphatics. The presence of lymphocytes in paracortical venular walls after 2 hr of perfusion with new medium suggests that these are the sites of emigration. The rate of emigration of lymphocytes from mesenteric lymph nodes was estimated to be 6 X 10(7)/hr. Study of the lymphocyte populations emerging from the perfused lymph nodes showed that B lymphocytes and E-rosette forming T lymphocytes, but almost no Null lymphocytes, are involved. While the proportion of B lymphocytes remained constant during the perfusion period, E-rosette forming lymphocytes increased significantly. Lymphocyte subpopulations differ profoundly in their capacity to migrate through lymph nodes.

Animals↗

Negative sentinel lymph node accurately predicts negative status of pelvic lymph nodes in uterine cervix carcinoma.

OBJECTIVE: The significance of negative sentinel lymph nodes (SLN) is important in the staging and treatment of melanoma and a few other cancers, but is controversial in uterine cervix carcinoma. Our study was aimed at correlating the SLN status in cervical carcinoma with non-sentinel lymph nodes (non-SLN), in a uniform and well controlled population. METHODS: This study includes 36 patients with stage I and IIA cervical carcinoma and bilaterally negative SLN on final pathology. SLN were identified using blue dye and radioisotopic techniques. Frozen section examination was performed for all SLN; the rest of the tissue was formalin fixed and paraffin embedded. The protocol used for SLN was also applied for non-SLN. For each block, six 4-micro m thick sections were cut at 40 micro m intervals and stained with H and E; an additional section taken between the 3rd and 4th levels was imunostained using AE1/AE3 cytokeratin. RESULTS: The mean age for the study population was 39 years (range 25-76); the number of SLN ranged from 2 to 6 (mean 2.7) and the non-SLN from 8 to 49 (mean 23) per case. No metastasis was found in any SLN and non-SLN by step sections and IHC. CONCLUSION: Our study demonstrates that bilaterally negative SLN on final pathology accurately predict the absence of metastases in non-SLN in cervical carcinoma. If confirmed by larger trials, these results may influence the clinical management of early cervical cancer.

Adult↗

Number of lymph node metastases is better predictor of prognosis than level of lymph node metastasis in patients with node-positive colon cancer.

BACKGROUND: Lymph node metastasis is the most important prognostic factor for colon cancer patients. Survival is also related to the number and level of positive lymph nodes (PLNs). Definitions of degree of PLNs for colon cancer differ greatly between the number and level of PLNs. STUDY DESIGN: The aim of this study is to compare number and level of PLNs to see which is a better predictor of prognosis for node-positive colon cancer. One hundred eighteen patients underwent histologically curative resection for node-positive colon cancer. We calculated the cumulative 5-year survival rates and examined prognostic factors for multivariate analysis based on the number and level of PLNs and additional factors. The number of PLNs was classified as either one to three PLNs or more than four PLNs, and level of PLNs was classified as either Level I (pericolic lymph node metastasis) or Level II (lymph node metastasis along the major named vessel supplying the tumor, and that around the origin of a main artery). RESULTS: Cumulative 5-year survival rates were statistically different between the 1 to 3 PLNs group and the more than 4 PLNs group, but not significantly different between Level I group and Level II group. Multivariate analysis showed that number, not level, of PLNs was an independent prognostic factor. CONCLUSIONS: In node-positive colon cancer, number of PLNs predicted prognosis better than level of PLNs.

Adult↗

Predictors of positive axillary lymph nodes in breast cancer patients with metastatic sentinel lymph node.

INTRODUCTION: Breast cancer with metastatic sentinel lymph nodes (SLN) may have clinico-pathologic factors associated with the presence of positive non-sentinel axillary nodes (NSLN). The aim of the present study was to determine factors that predict involvement of NSLN in breast cancer patients with positive SLN. MATERIAL AND METHODS: A prospective database search identified 80 patients who underwent SLN biopsy for invasive breast cancer between January 1999 and August 2002. Clinico-pathologic data was analyzed to determine factors that predicted additional positive axillary nodes. RESULTS: A total of 23 patients had positive SLN and underwent conventional axillary lymph node dissection. Statistical analysis revealed that lympho-vascular invasion (p~0.00000), SLN metastasis >2 mm (p=0.002), and the presence of extra-nodal involvement (p=0.002), were positive predictors of the metastatic involvement of NSLN. CONCLUSIONS: The likelihood of positive NSLN correlates with pathologic parameters such as the presence of lympho-vascular invasion, size of the SLN metastasis, and extra-nodal involvement. These data may be helpful with the regard to the decision to undertake axillary dissection in breast cancer patients with metastatic sentinel lymph nodes.

Adult↗

Lymph node infarction associated with infectious mononucleosis: report of a case resembling lymph node infarction associated with malignant lymphoma.

A completely infarcted lymph node should alert the pathologist to the high possibility of malignant lymphoma. The lymph node lesion of infectious mononucleosis (IM) shows marked histologic diversity and occasionally may be confused with malignant lymphoma. We report a rare case of IM showing extensive lymph node infarction whose lymph node lesion was similar to lymph node infarction associated with malignant lymphoma. This case describes a 32-year-old Japanese man who had signs and symptoms consistent with IM, which he was later proven serologically to have, but whose cervical lymph node showed extensive lymph node infarction with a thin area of granulation tissue beneath the capsule. The infarcted tissue contained numerous eosinophilic ghosts of large lymphoid cells. The thin granulation tissue was composed of numerous small lymphocytes, plasma cells, and histiocytes, in addition to large lymphoid cells including immunoblasts and granulocytes. CD20, CD3, and CD45RO immunostains revealed the mixed B- and T-cell nature of the ghosts of large lymphoid cells in the infarcted tissue as well as viable large cells in the granulation tissue. The patient was free from disease after 50 months' follow-up.

Adult↗

Detection of early lymph node metastases in prostate cancer by laparoscopic radioisotope guided sentinel lymph node dissection.

PURPOSE: Radioisotope guided sentinel lymph node (SLN) dissection (SLND) for prostate cancer has been shown to increase the sensitivity of detecting early metastases in open pelvic lymph node dissection. We developed a technique that allows SLND to be performed by laparoscopy in conjunction with laparoscopic radical prostatectomy. MATERIALS AND METHODS: In 71 consecutive patients SLND was performed by 1 surgeon preceding laparoscopic radical prostatectomy. Mean preoperative prostate specific antigen was 8.88 ng/ml (range 2.1 to 25.4). At 24 hours prior to surgery 3 ml (200 MBq) Tc labeled human albumin colloid were injected into the prostate gland under transrectal ultrasound guidance. An especially designed laparoscopic gamma probe was used to measure radioactivity during surgery. SLNs were identified and removed. If frozen section analysis showed metastases, extended pelvic lymph node dissection was performed. RESULTS: Radioactivity was detected on 2, 1 and no sides in 50 (70.4%), 19 (26.7%) and 2 patients (2.8%), respectively. In 81 of the 142 pelvic side walls (54.7%) SLNs were exclusively outside of the obturator fossa. Histopathological examination showed metastases to SLNs in 9 patients (12.9%). Eight of the 11 detected metastases (72.7%) were outside of the obturator fossa. Lymph node metastases were exclusively found in Tc marked lymph nodes. Mean tumor size was 1.7 mm (range 0.2 to 3.9). CONCLUSIONS: SLND is feasible by laparoscopy. It detects micrometastases outside of the obturator fossa in a significant number of patients. We noted that the transperitoneal approach allowing wide exposure and a gamma probe with a 90-degree lateral energy window is the most important factor to enable successful laparoscopic SLND.

Aged↗

Overexpression of Bcl-xL in human breast cancer cells enhances organ-selective lymph node metastasis.

Lymph node metastasis are the first prognostic factor in breast cancer diagnosis and an early event in metastatic spread. To assess the role of anti-apoptotic proteins in lymph node metastatic progression of human breast cancer cells we analyzed the metastatic activity of MDA-MB-435 cells transfected with the Bcl-xL gene, after orthotopic inoculation in Nude Balb/c and in SCID mice. The luciferase gene was introduced by permanent transfection in the 435/Bcl-xL and 435/Neo cells and used as a tumor marker to measure the number of tumor cells lodged in lymph nodes. We found that 435/Bcl-xL tumor cells had enhanced organ-specific metastatic activity, preferentially lodging in peripheral lymph nodes, where at 45 days post-implantation we found 7 x 10(6) +/- 6 x 10(6) 435/Bcl-xL.luc and 2 +/- 1.1 435/Neo.luc luciferase tagged tumor cell equivalents (TCEs). Metastases were abrogated in mice in which orthotopic tumors were induced with 435/Bcl-xL-antisense cells. Additionally, in vitro experiments show that in 435 cells Bcl-xL-antisense can override the emergence of resistance to apoptosis induced by TNF- alpha and TGF- beta in cells overexpressing Bcl-xL, increasing also adhesion to extracellular matrix proteins. These results point to the relevance of Bcl-xL overexpression inducing lymph node metastasis of breast cancer cells, and to the value of this gene as a target for therapy in order to prevent metastasis.

Animals↗

Nodular spindle-cell vascular transformation of lymph nodes. A benign process occurring predominantly in retroperitoneal lymph nodes draining carcinomas that can simulate Kaposi's sarcoma or metastatic tumor.

We describe a vasoproliferative nodular spindle-cell lesion representing a variant of vascular transformation of lymph-node sinuses and designated a nodular spindle-cell vascular transformation of lymph nodes. The lesion is most frequently identified in retroperitoneal lymph nodes excised in association with radical nephrectomies for renal cell carcinoma, but it can also be present in association with other malignant tumors. Occasionally it is seen in superficial lymph nodes in patients with no history of malignant neoplasms. This lesion can be confused with Kaposi's sarcoma or with a metastatic sarcomatoid carcinoma because of its spindle-cell composition, cellularity, occasional high mitotic activity, and frequent occurrence in the regional lymphatic drainage of a known malignancy.

Adult↗

Lymph node revealing solution: a new method for detection of minute axillary lymph nodes in breast cancer specimens.

The staging and prognosis of patients with breast cancer is related to the presence or absence of axillary lymph node involvement. However, in some cases no lymph nodes or too small a number of lymph nodes are revealed by the traditional method of palpating and sectioning the axillary fat. In the present study we demonstrate the usefulness of the lymph node revealing solution (LNRS) in breast cancer. Specimens from 13 patients, in whom <10 lymph nodes were identified in the axilla by the traditional method, were included in the study. After excising the lymph nodes by the traditional method, axillary tissue was immersed in LNRS for 6-12 hours. Additional lymph nodes, which stood out as white chalky nodules, were excised and processed as usual. The LNRS increased the mean number of nodes per case from 6.0+/-2.5 found by the traditional method to 12.54+/-4.61 nodes per case (p < 0.01). The size of the nodes identified by the LNRS was significantly smaller (p < 0.01) than those detected by the traditional method. The LNRS changed the lymph node stage of the disease in four of the studied cases (30%). LNRS seems to be the technique of choice for detection of axillary lymph nodes in cases where the number of detected lymph nodes by the traditional method is too small for accurate staging.

Axilla↗

Laparoscopy-assisted distal gastrectomy with systemic lymph node dissection: a critical reappraisal from the viewpoint of lymph node retrieval.

BACKGROUND: Laparoscopy-assisted surgery has proved useful in the treatment of early gastric cancer, but its use in advanced cancer may be hindered by limitations in lymphadenectomy. STUDY DESIGN: Data on lymph node retrieval after distal gastrectomy with D1 or D2 lymphadenectomy (n = 89) performed by the laparoscopy-assisted approach were collected between 1998 and 2002 and compared with data obtained from conventional open surgery performed for T1 cancer at a high-volume hospital (n = 342) during the same period. Comparisons of total number of lymph nodes, retrieval at each lymph node station, and the rate of noncompliance (no nodal tissue documented at a node station that should have been resected) were conducted using Student's t-test and the chi-square test. RESULTS: D2 resection by the laparoscopy-assisted approach harvested a sufficient number of nodes for adequate TNM classification (>15 nodes) in 86% of patients. Nevertheless, a significantly greater number of lymph nodes were harvested by open surgery. The difference was significant for the perigastric lymph nodes along the major curvature (Nos. 4 and 6) and second tier nodes along the celiac and splenic arteries (Nos. 9 and 11). CONCLUSIONS: The extent of lymphadenectomy achieved by current laparoscopic procedure approaches the global standard for accurate staging, although performing extended resection as recommended in Japan remains a challenge.

Feasibility Studies↗

Ontogeny of human fetal lymph nodes.

Developing lymph nodes from 30 human embryos and fetuses with crown-rump lengths (CRL) of 18 mm (5.6 wk) to 245 mm (26 wk) were examined by light microscopy. The nodes were embedded in araldite, and the sections examined were approximately 1 mu in thickness. The development of nodes was divided into three stages: 1. the lymphatic plexus and connective tissue invagination (30 mm to 67 mm CRL); 2. the early fetal lymph node (43 mm to ,5 mm CRL); and 3. the late fetal lymph node (CRL greater than 75 mm). The lymphatic plexus was formed by connective tissue invaginations and bridges which divided a lymph sac into a meshwork of channels and spaces. Connective tissue invaginations were endothelially-lined and were surrounded by lymphatic space. Reticular cells, macrophages, and blood vessels were found in these invaginations. Early fetal lymph nodes were formed from invaginations when the cellular density and lymphocyte content increased. The lymphatic space surrounding the early node was the developing subcapsular sinus. With further development the early node became packed with lymphocytes, increasing the cellular density and size of the node. The connective tissue surrounding the subcapsular sinus condensed to form the capsule. Afferent lymphatic vessels pierced the capsule. Capillaries, veins, postcapillary venules, and occasional arteries were found in early and late nodes.

Blood Vessels↗