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[Preoperative treatment of lymph node metastases of gastric cancer by local injection of 5-FU adsorbed on activated carbon--clinical study of 5-FU concentration in resected lymph nodes].

The concentration of 5-fluorouracil (5-FU) in blood and lymph node of 55 patients with gastric cancer who were endoscopically injected 250 mg of 5-FU alone or adsorbed on activated carbon into the gastric wall or 300 mg of 5-FU dry syrup orally before operation, were measured chronologically. The concentration of 5-FU in blood were similar in all cases but higher in lymph node in the group given adsorbed preparation than other cases. In the cases given adsorbed preparation, the lymph node concentration was remained high 7 days after injection, and in 37% cases more than the minimum inhibitory concentration of 5-FU remained. Therefore, for the purpose to elicit anticancer effect on micrometastasis in lymph nodes in the patients with gastric cancer, endoscopically preoperative injection of 5-FU adsorbed on activated carbon seemed to be useful.

Adsorption↗

Pathways between lymph vessels and sinuses in lymph nodes: a study in horses.

The pathways through which lymph flows from terminal afferent lymphatics to the lymph sinuses, and from the sinuses to initial efferent lymphatics, were studied in horse lymph nodes by using Microfil casts and electron microscopy. Terminal afferent lymphatics are continuous with the subcapsular sinus through oval holes, about 3 microns wide, along their length, and through larger openings near their end. Other terminal afferents penetrate into the node within trabeculae and are supported by processes across the lumen. They connect with trabecular and medullary sinuses through oval or round holes, generally 20-30 microns across. Some of these have processes, similar to the luminal strands of the adjacent sinuses, extending across them, apparently providing reinforcement. Initial efferent lymphatics receive lymph from medullary sinuses through holes which are similar to those in afferent lymphatics, though more common, especially near the origin of the vessel. Initial efferents within the medulla appear to be supported by the luminal strands of the surrounding medullary sinuses. It seems likely that these strands, like the trabeculae which surround the penetrating afferent lymphatics, may help to keep the lymphatic vessels open as the node swells while draining an area of infection.

Animals↗

The local lymph node assay: an interlaboratory evaluation of interleukin 6 (IL-6) production by draining lymph node cells.

The murine local lymph node assay is a predictive method for the identification of skin-sensitizing chemicals in which activity is measured as a function of proliferative activity induced in lymph nodes draining the site of exposure. In the present study, the induction by topically applied chemicals of draining lymph node cell (LNC) production of the cytokine interleukin 6 (IL-6) has been evaluated as an alternative endpoint for the local lymph node assay. In addition, results derived from studies of IL-6 production by LNC performed independently in two separate collaborating laboratories have been compared. Of the nine skin sensitizing chemicals examined, six provoked detectable levels (> 150 pg ml-1) of IL-6 production by draining LNCs (as measured by enzyme-linked immunosorbent assay) following exposure of mice to at least one test concentration of the material in both of the laboratories. Three other sensitizing chemicals failed to induce measurable IL-6 production at any test concentration in either one or both of the participating laboratories. Both of the non-sensitizing chemicals evaluated (sodium lauryl sulphate and methyl salicylate) also failed to result in detectable IL-6 synthesis. There was a high level of agreement between the two laboratories. The rank order of chemicals with respect to IL-6 production by LNCs was identical in both cases, as was the dose-response relationship observed with each test material. These data reveal that, although inducible IL-6 production by draining LNCs provides a robust approach to the measurement of strong sensitizing activity, as performed here the method is of insufficient sensitivity for the routine identification of skin allergens.

Allergens↗

Cytokeratin deposits in lymph nodes show distinct clinical significance from lymph node micrometastasis in human esophageal cancers.

BACKGROUND: Cytokeratin immunostaining is the most common method used to identify micrometastatic cancer cells from the lymph nodes. However, contamination with hyalinized cytokeratin particles, frequently observed in the lymph nodes of esophageal cancer patients, can lead to misinterpretation of cytokeratin immunostaining. MATERIALS AND METHODS: Cytokeratin immunostaining (AE1/AE3) of surgically removed lymph nodes was performed for 41 cases of node-negative, but locally advanced (T3, T4), esophageal cancer patients. Cytokeratin immunoreactivity (CK) was classified as micrometastasis (MM) or cytokeratin deposit (CD) by the presence or absence of tumor nuclei in serial sections given hematoxylin-eosin staining. RESULTS: CK (+) was observed in 18 patients (44%), including 11 with MM (+) (27%) and 10 with CD (+) (24%). There was no correlation between MM and CD, and neither was associated with clinicopathological factors, except for a high incidence of preoperative chemotherapy in CD (+) patients. The presence of CK did not affect postoperative survival of esophageal cancer patients at this limited stage, showing a 5-year survival rate of 57% for CK (+) and 64% for CK (-) (P = 0.6064). Interestingly, patients with MM (+) showed poorer prognosis than MM (-) (5-year survival: 28% vs 79%, P = 0.0188), while CD (+) patients tended to display better prognosis than CD (-) ones (5-year survival: 78% vs 56%, P = 0.1860). CONCLUSIONS: Evaluation by cytokeratin immunostaining of lymph nodes requires careful discrimination of CD from MM, in order to allow MM to be used as a prognostic factor for esophageal cancer patients.

Esophageal Neoplasms↗

Effects of a protective hydrolyzed casein diet upon the metabolic and secretory responses of pancreatic islets to IL-1beta, cytokine production by mesenteric lymph node cells, mitogenic and biosynthetic activities in Peyer's patch cells, and mitogenic activity in pancreatic lymph node cells from control and diabetes-prone BB rats.

The effects of substituting a plant-based control diabetogenic diet (NIH diet) by a protective hydrolyzed casein diet (HC diet) upon selected metabolic and functional variables were recently investigated in Peyer's patch cells, splenocytes, mesenteric lymph node cells, and pancreatic islets from either control (BBc) or diabetes-prone (BBdp) BB rats. In the present work, the plasma d-glucose and insulin concentrations, the protein and insulin content of pancreatic islets, the metabolism of d-glucose, and its insulinotropic action in islets first cultured for 24 h in the absence or presence of IL-1beta, the production of IFN-gamma and IL-10 by mesenteric lymph node cells cultured for 48 h in the absence or presence of concanavalin A, the mitogenic activity of Peyer's patch cells and pancreatic lymph node cells in the absence or presence of the same lectin, and the biosynthetic activity of Peyer's patch cells were measured in the BBc and BBdp rats fed either the NIH or the HC diet. Two major novel findings emerged from this study. First, in immune cells, diet HC increased to a greater extent the responsiveness to concanavalin A of certain metabolic and functional variables in BBdp rats than in BBc rats. Second, pancreatic islet cells of BBdp rats were less sensitive to IL-1beta than those of BBc rats and this difference was further accentuated when the animals were fed the HC rather than the NIH diet. These findings afford further support to the view that, in BB rats, changes in the biological behavior of Peyer's patch cells, mesenteric and pancreatic lymph node cells, and pancreatic islet cells participate in the pathogenesis of insulin-dependent diabetes mellitus and its prevention by a suitable dietary manipulation.

Animals↗

Radical resection with autonomic nerve preservation and lymph node dissection techniques in lower rectal cancer surgery and its results: the impact of lateral lymph node dissection.

Lateral lymph node metastases occur in 9% of rectal cancer patients. For cancers localized in the lower rectum below peritoneal reflection, the frequency increases to 13% of all cases and to 25.5% in those of Dukes' stage C. The most important technique in colorectal surgery for decreasing local failure in the pelvis is lateral lymph node dissection. Today, however, it is also regarded as crucial that with perfect lymph node dissection of the lateral area outside of the pelvic plexus, the postoperative functions of urination and sexual ability are preserved. Since 1988 we have performed autonomic nerve-preserving curative resection (ANP) with lateral dissection in most patients with advanced lower rectal cancer. The mean 5-year survival rate of patients with lateral lymph node metastasis from the lower rectum was 37.5%, improving from 32.1% to 43.4% during this period. In cases of ANP with lateral dissection the local recurrence rate was 4.8% overall and 7.4% in the Dukes' C group. Postoperative urinary function has been good or fair in all ANP patients. Sexual function remained problematic, especially regarding male ejaculation. We describe our method for preserving the autonomic nervous system in the pelvis and for achieving complete dissection in the lateral area.

Autonomic Nervous System↗

Prediction of gastric cancer lymph node status by sentinel lymph node biopsy and the Maruyama computer model.

AIMS: The extent of lymph node dissection in gastric cancer remains controversial. The Maruyama computer model and the sentinel lymph node biopsy (SLNB) are compared for their value to predict the nodal status and lead to stage-adapted surgery. METHODS: Thirty four patients with stage I-IV gastric cancer underwent both staging procedures. For SLNB, 15 patients underwent endoscopic, peri-tumoural injection of (99m)Tc-colloid, and 19 patients were injected of Patent blue V. All 'hot' or blue sentinel lymph nodes (SLNs) were separately excised and histopathologically assessed. If the SLN was negative after routine staining by H&E, it was processed completely and reanalysed after immunohistochemistry. RESULTS: At least, one SLN was detected by means of SLNB in 33/34 of the patients. The sensitivity to identify a positive nodal status was 22/33 and the specificity/positive predictive value was 10/10 and 22/22. Additional micrometastases or isolated tumour cells in the SLN led to 'upstaging' of 5/15, initially classified as nodal negative by H&E-staining. Using the Maruyama computer model, a sensitivity of 22/23 for the correct prediction of the lymph node involvement was associated with a specificity of 2/10 and a positive predictive value of 22/30. CONCLUSIONS: The clinical impact of the Maruyama computer model is limited due to low specificity and a low positive predictive value, rendering the method less useful as an indicator for individualised surgery.

Diagnosis, Computer-Assisted↗

Th2-biased immune response in cervical lymph nodes: animal models of Graves' disease might administer autoantigen to body regions where lymphatics drain to cervical lymph nodes.

It is believed that cervical lymph nodes have an important impact on Th2-biased immune response to central nervous system (CNS)-derived antigens. Obstruction of these nodes prior to a CNS-infusion of antigen markedly lowers the level of serum antibody response to the antigen. Graves' disease is a Th2-biased autoimmunity in which autoantibodies against thyrotropin receptor stimulate thyroid hormone production. The reasons for the distinct Th2-biased immune response in this hyperthyroidism are not fully understood, whereas most of the other human organ-specific autoimmune diseases are believed to be Th1 mediated. It is suggested that the drainage of the thyroid lymphatics to cervical lymph nodes may play a role in the Th2-polarized immune response of Graves' disease. Thus, the generation of Graves' disease models by immunization may become more feasible if animals are administered the autoantigen to body regions whose lymph is drained to cervical lymph nodes.

Animals↗

Removal of more lymph nodes may provide better outcome, as well as more accurate pathologic findings, in patients with bladder cancer--analysis of role of pelvic lymph node dissection.

OBJECTIVES: To examine the role of pelvic lymph node dissection (PLND) in patients who underwent radical cystectomy for bladder cancer. The diagnostic and therapeutic role of PLND is still controversial in bladder cancer. The extent of PLND and the necessary number of lymph nodes to remove have not been defined. METHODS: This retrospective review included 146 patients with refractory superficial and muscle-invasive disease treated with radical cystectomy, regional PLND (internal iliac, external iliac, and obturator nodes) and urinary diversion from January 1990 to December 2002. RESULTS: Lymph node metastases were detected in 25 patients (17.1%). The average number of nodes removed in the node-positive and node-negative patients was 13.9 and 14.2, respectively. Although no difference was found in disease-specific survival in the node-negative patients when stratified by the number of nodes removed (13 or more versus less than 13), a significant survival advantage was found in the node-positive patients with 13 or more nodes removed versus less than 13 nodes removed. The patients with four or more positive nodes had a worse outcome than those with less than four positive nodes. However, even if the patients had less than four positive nodes, the survival of patients with less than 13 nodes removed was as poor as that of the patients with four or more positive nodes. CONCLUSIONS: In this series, the removal of 13 or more pelvic lymph nodes was essential for more accurate pathologic examination to predict patient outcome and contributed to an increased chance of survival.

Adult↗

[Lymph node mapping and axillary sentinel lymph node biopsy in 243 invasive breast cancers with no palpable nodes. The south Lyon hospital center experience].

STUDY AIM: To evaluate the effect of intraoperative lymph node mapping and sentinel lymph node dissection (SLND) on the axillary staging of patients with N0 breast carcinoma. Two techniques were used: blue dye alone (Evans Blue and Patent Blue) and combined technique (blue dye and isotope). METHODS: The incidence of axillary node metastasis in axillary lymph node dissection (ALND) and SLND was compared prospectively. Multiple sections of each SLN were examined by HPS staining and immunohistochemical techniques. Two sections of each non sentinel node in ALND specimens were examined by routine HPS staining. RESULTS: 243 patients underwent ALND after SLN biopsy. The SLN detection rate was 225/243 cases (92.59%): 89.94% with blue dye alone and 100% with the combined technique. The false-negative rate was less than 2%. CONCLUSION: SN biopsy is an accurate staging technique for N0 breast cancer. SLN biopsy with multiple sections and immunohistochemical staining of the SLN can identify significantly more patients with lymph node metastases than ALND with routine HPS staining.

Biopsy↗

Primary and secondary responses of the ovine lymph node to Toxoplasma gondii: cell output in efferent lymph and parasite detection.

Efferent lymphatic cannulation was used to study the dissemination of strain S48 of Toxoplasma gondii and the cell output from the prefemoral lymph node, after infection of both "naive" and vaccinated sheep. In the former the mean cell output decreased for 3 days before reaching a peak at 11 and 12 days, but in vaccinated ewes a similar drop in cell output and subsequent peak occurred significantly earlier, at 24 h and 5 days, respectively. The cellular response in both types of sheep was largely due to a marked increase in blast cells. The detection of live toxoplasms and parasite DNA by mouse inoculation and the polymerase chain reaction, respectively, gave similar results; the parasite was demonstrated in lymph from days 3 to 12 during a primary infection but with a sharp cut-off after day 9 coinciding with the peak blast cell response. Very little evidence of T. gondii was found in lymph of vaccinated sheep after challenge. Immunity, which is thought to be largely T-cell mediated and is sustained without continuous antigenic stimulation, suppresses dissemination of the parasite in the lymph and therefore to other sites, which might include the gravid uterus.

Animals↗

Fibrinogen in rat gastrointestinal lymph before, during and after intraduodenal administration of emulsified triglyceride: fibrinogen bound to chylomicrons in gastrointestinal lymph is functional.

Samples of gastrointestinal lymph were collected from fasted, male, Sprague-Dawley rats before, during and after intraduodenal administration of either a phospholipid-stabilized, triglyceride-rich emulsion or the dextrose-saline diluent of the emulsion. In lipid-treated rats, the triglyceride, total protein, and functional fibrinogen contents of lymph increased significantly during the 4 h of continuous lipid infusion, with all analytes returning to near baseline values by 20 h later. Levels of the same analytes changed little, if at all, in control animals. As assessed using immunoblotting, chylomicrons in gastrointestinal lymph are coated with fibrinogen. Fibrinogen-coated chylomicrons readily incorporate into solution phase clots and, in the presence of thrombin, adhere in heparin-preventable fashion to each other and to other fibrinogen-coated surfaces. Taken together, these data indicate that lipid feeding creates in gastrointestinal lymph a condition that is conducive temporally to the physical association of fibrinogen with newly ingested lipids before they reach the circulatory system.

Adhesiveness↗

Induction of lymph follicle formation with endotoxin lipopolysaccharide in the draining lymph node of athymic nude mice.

Formation of lymph follicles in draining popliteal lymph nodes in athymic nude mice and their phenotypically normal littermates (PN mice) was investigated after footpad injection with either endotoxin lipopolysaccharide (LPS) or phytohemagglutinin in soluble and precipitated forms (PHA). The dose of LPS injected ranged from 10 to 100 micrograms, and that of PHA was 50 micrograms. After any dose of LPS, draining nodes of nude mice produced new lymph follicles in the peripheral cortex outside pre-existing follicles, though the number of follicles induced was somewhat less than in the case of PN mice treated with LPS. After injection of PHA in soluble or precipitated form, PN mice developed a significant number of new follicles in the draining nodes, but nude mice failed to do so. The present results are consistent with the view that nude mice have the ability to develop lymph follicles by way of a thymus-independent mechanism in response to exogenous stimuli.

Animals↗

The human peripheral lymph node vascular addressin is a ligand for LECAM-1, the peripheral lymph node homing receptor.

The trafficking of lymphocytes from the blood and into lymphoid organs is controlled by tissue-selective lymphocyte interactions with specialized endothelial cells lining post capillary venules, in particular the high endothelial venules (HEV) found in lymphoid tissues and sites of chronic inflammation. Lymphocyte interactions with HEV are mediated in part by lymphocyte homing receptors and tissue-specific HEV determinants, the vascular addressins. A peripheral lymph node addressin (PNAd) has been detected immunohistologically in mouse and man by monoclonal antibody MECA-79, which inhibits lymphocyte homing to lymph nodes and lymphocyte binding to lymph node and tonsillar HEV. The human MECA-79 antigen, PNAd, is molecularly distinct from the 65-kD mucosal vascular addressin. The most abundant iodinated species by SDS-PAGE is 105 kD. When affinity isolated and immobilized on glass slides, MECA-79 immunoisolated material binds human and mouse lymphocytes avidly in a calcium dependent manner. Binding is blocked by mAb MECA-79, by antibodies against mouse or human LECAM-1 (the peripheral lymph node homing receptor, the MEL-14 antigen, LAM-1), and by treatment of PNAd with neuraminidase. Expression of LECAM-1 cDNA confers PNAd binding ability on a transfected B cell line. We conclude that LECAM-1 mediates lymphocyte binding to PNAd, an interaction that involves the lectin activity of LECAM-1 and carbohydrate determinants on the addressin.

Antigens, Surface↗

Ratio between positive lymph nodes and total dissected axillaries lymph nodes as an independent prognostic factor for disease-free survival in patients with breast cancer.

The number of positive axillary lymph nodes involved by tumor is one of the main prognostic factors for women with locoregional breast cancer (BC) for whom adjuvant chemotherapy is being considered. The prognostic importance of the ratio (P/D) between positive lymph nodes (P) and total dissected lymph nodes (D), previously demonstrated in the high-dose chemotherapy (HDC) setting has not yet been tested, however, in the conventional adjuvant chemotherapy setting. The data of 168 patients who were from 2 institutions and who were treated with adjuvant chemotherapy for BC were retrospectively analyzed, and univariate and multivariate analysis were performed, including the other traditional prognostic factors and P/D ratio as possible predictors of disease free survival (DFS). Disease-free survival for quartile 4 of P/D ratio (ratio >0.30) was statistically different from that for the other quartiles (log-rank test p < 0.001). Mean DFS for this series was not reached as well as for quartiles 1, 2, and 3, while mean DFS for quartile 4 was 44.5 months. In univariate analysis, number of positive lymph nodes (r2 = 0.055; p = 0.023), P/D ratio (r2 = 0.213; p < 0.001), and stage (r2 = 0.105; p = 0.002) were predictive of relapse, while in multivariate analysis, only P/D ratio remained an independent predictor of relapse (r2 = 0.213; p < 0.001). It is concluded that P/D ratio could become a simple, inexpensive, and easily available prognostic factor for patients undergoing conventional chemotherapy for BC.

Adult↗

Intravenous saline infusion in rat increases hyaluronan efflux in intestinal lymph by increasing lymph flow.

The output of hyaluronan in mesenteric lymph was studied in anaesthetized rats to allow estimation of the turnover rate. The duodenum/jejunum contained 45 micrograms of this glycosaminoglycan per g wet tissue weight. In fasted rats the concentration of hyaluronan in postnodal lymph averaged 15 micrograms ml-1 and the mean efflux was 2.1 micrograms h-1, corresponding to a daily removal of 10% of the intestinal hyaluronan content. An intravenously injected bolus of 0.9% saline 4 ml 100 g-1 followed by an infusion of the same amount per hour increased the hyaluronan concentration in lymph transiently to 22 micrograms ml-1. During the 8-h i.v. infusion the hyaluronan output remained five times above control due to the high lymph flow. Water and hyaluronan content of the small intestine remained unaltered despite the saline load, the maintained tissue level of hyaluronan suggests an increased rate of synthesis.

Animals↗

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↗

[Adenocarcinoma of the esophagus: prognostic comparison between transthoracic esophageal resection with expanded 2-field lymph node dissection and trans-hiatal esophageal dissection with abdominal lymph node excision].

A retrospective analysis should compare the two operative approaches, transhiatal or transthoracic resection in patients suffering from adenocarcinoma of the esophagus. Between 1985 and 2002 123 cases were presented with adenocarcinoma of the esophagus, treated in 65% by transhiatal resection including abdominal lymph node dissection and in 35% by the transthoracic approach with standardized extended mediastinal and abdominal lymph node dissection. Hospital mortality was 14% (6/43) after transthoracic resection and 3.8% (3/80) after transhiatal resection (ns). Die number of removed and examined abdominal lymph nodes following transhiatal resection was 14.1 (mean) versus 12.3 (mean) after transthoracic resection (ns). Die number of removed and examined mediastinal lymph nodes by transhiatal resection was 6.3 (mean) versus 19.7(mean) after transthoracic resection (p < 0.001). The median survival after transthoracic approach was 19 months versus 20 months after transhiatal approach (ns). Median survival of curatively resected patients (R0) were in both operative procedures similar (21 months). A more differentiated analysis referred to the UICC stages also demonstrated no differences in the survival between transthoracic and transhiatal resection. With respect to less mortality and less morbidity after transhiatal resection and because of the not detectable prognostic advantage of the transthoracic resection we suggest the transhiatal approach as the treatment of choice in patients with adenocarcinoma of the esophagus.

Abdomen↗