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PubMed2006

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↗
PubMed1977

The influence of the lymph node on the protein concentration of efferent lymph leaving the node.

1. Experiments have been performed in sheep to determine the contribution of lymph formed within a lymph node to the total protein output in lymph leaving the node. 2. The lymphatic duct leaving the popliteal lymph node was cannulated and the protein and lymphocyte output in efferent lymph determined. The afferent lymph flow to the popliteal node was then diverted and lymph formed only within the lymph node collected from the efferent cannula. It appeared from the results that the popliteal lymph node forms lymph at the rate of approximately 1 ml. per hour and may contribute 30-50% of the protein output observed in efferent lymph. 3. The importance of lymph formation within the lymph node varied between nodes found in different regions of the body. This was due in part to the different protein concentrations in the afferent lymph to the different nodes. 4. A positive correlation was found between the protein and lymphocyte concentrations in efferent lymph from the popliteal lymph node in seven out of eleven sheep and in lymph formed within the popliteal lymph node in two out of three sheep. It is suggested that this relationship may be due to an increased transfer of plasma proteins through the post-capillary venules in the lymph node accompanying the continual traffic of lymphocytes across the wall of these vessels. The results indicated that the protein transfer across the post-capillary venules was not an indiscriminate transfer of plasma per se but a selective transport from the blood plasma compartment based on molecular size.

Animals↗
PubMed2005

The prognostic significance of the percentage of positive/dissected axillary lymph nodes in breast cancer recurrence and survival in patients with one to three positive axillary lymph nodes.

BACKGROUND: Adjuvant therapy for women with T1-T2 breast carcinoma and 1-3 positive lymph nodes is controversial due to discrepancies in reported baseline locoregional recurrence (LRR) risks. This inconsistency has been attributed to variations in lymph node staging techniques, which have yielded different numbers of dissected lymph nodes. The current study evaluated the prognostic impact of the percentage of positive/dissected lymph nodes on recurrence and survival in women with one to three positive lymph nodes. METHODS: The study cohort was comprised of 542 women with pathologic T1-T2 breast carcinoma who had 1-3 positive lymph nodes and who had undergone mastectomy and received adjuvant systemic therapy without radiotherapy. Ten-year Kaplan-Meier (KM) LRR, distant recurrence (DR), and overall survival (OS) rates stratified by the number of positive lymph nodes, the number of dissected lymph nodes, and the percentage of positive lymph nodes were examined using different cut-off levels. Multivariate analysis was performed to evaluate the prognostic significance of the percentage of positive lymph nodes in disease recurrence and survival. RESULTS: The median follow-up was 7.5 years. LRR, DR, and OS rates correlated significantly with the number of positive lymph nodes and the percentage of positive lymph nodes, but not with the number of dissected lymph nodes. The cut-off level at which the most significant difference in LRR was observed was 25% positive lymph nodes (the 10-year KM LRR rates were 13.9% and 36.7% in women with < or = 25% and > 25% positive lymph nodes, respectively; P < 0.0001). Higher DR rates and lower OS rates were observed among patients who had > 25% positive lymph nodes compared with patients who had < or = 25% positive lymph nodes (DR: 53.0% vs. 30.3%, respectively; P < 0.0001; OS: 43.4% vs. 62.6%, respectively; P < 0.0001). In the multivariate analysis, the percentage of positive lymph nodes and the histologic grade were significant, independent factors associated with LRR, DR, and OS. CONCLUSIONS: The presence of > 25% positive lymph nodes was an adverse prognostic factor in patients with 1-3 positive nodes and may be used to identify patients at high risks of postmastectomy locoregional and distant recurrence who may benefit with adjuvant radiotherapy and more aggressive systemic therapy regimens.

Adult↗
PubMed2001

Lymph draining from foot joints in rheumatoid arthritis provides insight into local cytokine and chemokine production and transport to lymph nodes.

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by inflammatory reactions in joints and adjacent tissues unaccompanied by clinically evident changes in lymphatics and lymph nodes draining the inflamed areas. The explanation for this phenomenon, which contrasts with infectious processes in joints and soft tissues that evoke major changes in the lymphatic system, is unclear. To determine which inflammatory factors produced in the joints of RA patients are transported in lymph to lymph nodes, we measured levels of immunoglobulins, cytokines, and chemokines in prenodal lymph from the foot joints of RA patients and quantified their rate of transport to regional lymph nodes. METHODS: Lymph was collected from the cannulated lymphatics draining the foot joints, tendons, fascia, and skin of 20 RA patients. Lymph flow rate and concentrations of proteins and immunoglobulins were measured. Cytokine and chemokine levels were quantified by enzyme-linked immunosorbent assays. Results were compared with those obtained in 20 control subjects. RESULTS: In the cannulated vessel, the mean +/- SEM lymph flow rate in RA patients was almost 2-fold that in control subjects (22.6 +/- 3.2 ml/24 hours versus 13.2 +/- 1.1 ml/24 hours; P < 0.01). Lymph concentrations of total protein, IgG, and IgM were 1.80 +/- 0.14 gm/dl, 384 +/- 45 mg/dl, and 32.0 +/- 1.5 mg/dl, respectively, in RA patients and 1.66 +/- 0.14 gm/dl, 238 +/- 32 mg/dl, and 15.0 +/- 1.3 mg/dl, respectively, in control subjects. The corresponding lymph:serum (L:S) ratios were 0.21 +/- 0.02, 0.22 +/- 0.02, and 0.15 +/- 0.02, respectively, in RA patients and 0.22 +/- 0.02, 0.19 +/- 0.02, and 0.11 +/- 0.02, respectively, in control subjects. The L:S ratios of <1 and the absence of significant differences between groups suggested a lack of local production of immunoglobulins. In RA patients, lymph concentrations (in pg/ml) were as follows: interleukin-1beta (IL-1beta) 14.8 +/- 3.9, IL-6 511 +/- 143, tumor necrosis factor alpha (TNFalpha) 9.9 +/- 1.1, IL-1 receptor antagonist (IL-1Ra) 4,274 +/- 737, IL-10 13.3 +/- 4.4, IL-8 846 +/- 174, IL-15 6.2 +/- 0.9, granulocyte-macrophage colony-stimulating factor (GM-CSF) 2.30 +/- 0.15, vascular endothelial growth factor (VEGF) 80.4 +/- 8.6, and macrophage inflammatory protein 1alpha (MIP-1alpha) 171 +/- 34. In control subjects, these values were as follows: IL-1beta 1.50 +/- 0.25, IL-6 79.0 +/- 14.6, TNFalpha 4.4 +/- 1.1, IL-1Ra 208 +/- 52, IL-10 0.0, IL-8 216 +/- 83, IL-15 5.00 +/- 0.45, GM-CSF 0.40 +/- 0.05, VEGF 42.0 +/- 2.4, and MIP-1alpha 3.4 +/- 1.7 (P < 0.05 versus RA patients for all except IL-15). The L:S ratio was >1 in all RA patient samples for IL-1beta, IL-6, IL-1Ra, IL-8, GM-CSF, IL-10, IL-15, TNFalpha, and MIP-1alpha, indicating local production of cytokines. Great variability in lymph cytokine concentrations, presumably reflecting differences in the intensity of local inflammation, was not reflected in serum cytokine concentrations. Intravenously infused methylprednisolone decreased lymph cytokine levels to normal within 12 hours. In contrast, their concentrations in serum showed little or no change. CONCLUSION: High lymph concentrations of cyto kines and chemokines, exceeding those in serum, were found in RA patients. The L:S concentration ratios of > 1 indicate the local production of these cytokines and chemokines in the inflamed tissues. High flow rates of lymph containing high cytokine concentrations through the regional lymph nodes are likely to affect node lymphocytes and dendritic cells. Analysis of cytokines in lymph should provide insight into events in inflamed tissues in RA and in regional lymph nodes.

Adult↗
PubMed2004

Sentinel lymph node biopsy is not accurate in predicting lymph node status for patients with cervical carcinoma.

BACKGROUND: The authors evaluated the accuracy of sentinel lymph node biopsy in predicting lymph node status for patients with early cervical carcinoma. In particular, the authors set out to determine the false-negative rate associated with sentinel lymph node biopsy in this setting. METHODS: Twenty-nine consecutive patients with early cervical carcinoma who were treated with pelvic laparoscopic lymphadenectomy and radical surgery underwent sentinel lymph node biopsy following lymphatic mapping with patent blue dye. All sentinel and nonsentinel lymph nodes were evaluated for micrometastases via multilevel sectioning followed by immunohistochemical staining. RESULTS: At least one sentinel lymph node was identified for each patient. On routine pathologic evaluation, 3 patients (10%) were found to have positive lymph nodes. Among the remaining 26 patients, multilevel sectioning in conjunction with immunohistochemical analysis identified 5 patients (19%) who had micrometastases in the pelvic lymph nodes. Two of these five patients had micrometastases in a sentinel lymph node; however, the more notable finding was that the other three patients had micrometastases in nonsentinel pelvic lymph nodes despite having negative findings on sentinel lymph node biopsy. Thus, the negative predictive value of sentinel lymph node biopsy in the current study was 87.5%. CONCLUSIONS: Multilevel sectioning followed by cytokeratin immunohistochemistry may identify additional patients who have lymph node micrometastases; in the current study, this technique identified cases in which micrometastases were present in nonsentinel lymph nodes even when sentinel lymph nodes were found to be negative for disease on biopsy. This high false-negative rate associated with sentinel lymph node biopsy, raises questions regarding the validity of the sentinel lymph node concept in cervical carcinoma.

Adenocarcinoma↗
PubMed2002

Lymph node recoveries from 2427 pT3 colorectal resection specimens spanning 45 years: recommendations for a minimum number of recovered lymph nodes based on predictive probabilities.

This study investigates the relationship between the number of recovered lymph nodes and lymph node metastases in colorectal resection specimens. All of the slides from 2427 pT3 colorectal resection specimens from patients operated on at William Beaumont Hospital during the 45 years from 1955 through 2000 were reviewed. Lymph node metastases were present in 333 of 1499 (22.2%) specimens with fewer than 15 recovered lymph nodes, compared with 789 of 928 (85.0%) specimens with 15 or greater recovered lymph nodes (p <0.01). The proportion of lymph node metastases increased as a function of the number of recovered lymph nodes (p <0.01). Similarly, in patients without lymph node metastases, survival increased as a function of the number of recovered lymph nodes. Among these patients, the 5-year overall survival rate was 62.2% among patients with seven or fewer recovered lymph nodes and 75.8% among patients with 18 or more recovered lymph nodes (p = 0.018). Statistical analysis found the predictive probability of identifying the single lymph node metastasis in a theoretical specimen with a single lymph node metastasis is 0.25 if 12 lymph nodes are recovered and 0.46 if 18 lymph nodes are recovered. The predictive probability increased as the number of recovered lymph nodes increased, suggesting there is no minimum number that reliably or accurately stages all patients. Thus, all palpable lymph nodes should be recovered, including those that are 1 or 2 mm.

Adenocarcinoma↗
PubMed1996

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↗
PubMed2006

Surgical management of the groin lymph nodes in melanoma in the era of sentinel lymph node dissection.

HYPOTHESIS: Intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL) has become an increasingly popular surgical technique for staging the regional lymph nodes in early-stage melanoma. The technique of LM/SL has potentially great advantage for the groin, where the morbidity of superficial groin dissection or iliac dissection can be high. The surgical management of these basins is unknown for patients with tumor-positive sentinel lymph nodes (SNs). DESIGN: Cohort of successive patients undergoing LM/SL over 18 years. Those patients found to have tumor-positive SNs underwent sentinel complete lymph node dissection. Postoperatively, patients were followed up on a routine basis with serial examinations and chest radiography. The median follow-up was 50 months. SETTING: Tertiary cancer center. PATIENTS: The technique of LM/SL was performed for 431 consecutive patients. Sentinal lymph nodes were identified in each case. Patients with tumor-positive SNs underwent sentinel complete lymph node dissection. INTERVENTION: Cutaneous lymphoscintigraphy and blue dye with or without use of the gamma probe-directed LM/SL. Sentinel lymph nodes were examined by hematoxylin-eosin staining and immunohistochemistry staining with HMB-45 and S100 protein. Only patients with tumor-positive SNs had sentinel complete lymph node dissection. Main Outcome Measure Computer-assisted database with statistical analyses using log-rank tests and Cox regression models. RESULTS: Of the 431 patients, 264 (61%) were women and the median age was 50 years (age range, 15-89 years). A majority (86%) of the primary tumors were on the lower extremities, 54% were of Clark level IV or V, and there was a mean +/- SD thickness of 1.89 +/- 1.59 mm (range, 0.30-14.00 mm). Ninety-three patients (21%) were found to have tumor-positive SNs. After LM/SL and sentinel complete lymph node dissection, 62 patients (67%) were found to have a single tumor-positive lymph node, 25 (27%) had 2 tumor-positive lymph nodes, and 6 (6%) had 3 or more tumor-positive lymph nodes. Only 12 patients (4%) with tumor-negative SNs have had recurrence in the dissected basin. The 5-year overall survival was significantly better for patients with tumor-negative lymph nodes (mean +/- SD 5-year overall survival, 94% +/- 5%) than for patients with tumor-positive lymph nodes (mean +/- SD 5-year overall survival, 75% +/- 4%) (P < .01). The tumor status of the Cloquet lymph node was predictive of the tumor status of the iliac lymph nodes. Multivariate analyses with a Cox regression model identified tumor-positive SN (P = .001), primary tumor thickness (P = .03), and ulceration (P = .001) as being predictive of survival. Sex, age, Clark level, and primary site were not significant (P > .05). CONCLUSIONS: Our results demonstrate the prognostic significance of LM/SL for early-stage melanoma draining to the groin basin. The accuracy of LM/SL measured by the rare recurrences suggests that this surgical procedure should become standard for patients with early-stage melanoma of the lower extremities and trunk. Sampling of the Cloquet node should be used to determine the need for iliac dissection when a tumor-positive SN is identified in the groin.

Adolescent↗
PubMed1996

Assessment of metastases to aortic and pelvic lymph nodes in epithelial ovarian carcinoma. A proposal for essential sites for lymph node biopsy.

BACKGROUND: In staging epithelial ovarian carcinoma, it is necessary to assess the presence of lymph node metastases. However, the essential sites of selective lymph node biopsy have yet to be determined. METHODS: The distribution of metastatic aortic and pelvic lymph nodes was studied in 48 patients with positive lymph nodes of 110 patients with ovarian carcinoma who underwent systematic lymphadenectomy of the aortic and pelvic regions extending to the level of the renal vessels. For purpose of analysis, the lymph nodes were classified into five subgroups: the aortic lymph nodes above the inferior mesenteric artery (A1), the aortic lymph nodes below the inferior mesenteric artery (A2), the common iliac and sacral lymph nodes (P1), the internal and external iliac and obturator lymph nodes (P2), and the suprainguinal (the lowest external iliac) lymph nodes (P3). RESULTS: The incidence of metastases to A1, A2, P1, P2, and P3 was 79%, 71%, 46%, 77%, and 40%, respectively. Provided that 2 of the 5 lymph node subgroups were selected for biopsy, the combination of A1 and P2 gave the best results in sensitivity (94% [45 of 48 patients]) and negative (95% [62 of 65 patients]) predictive value for detection of lymph node metastases. CONCLUSIONS: These data indicate that aortic lymph nodes above the inferior mesenteric artery and the internal and external iliac and obturator lymph nodes are essential sites for selective lymph node biopsy in staging epithelial ovarian carcinoma.

Adult↗
PubMed2004

The size of metastatic foci and lymph nodes yielding false-negative and false-positive lymph node staging with positron emission tomography in patients with lung cancer.

BACKGROUND: We examined the sizes of lymph nodes and metastatic foci within the lymph nodes that affect false-positive and false-negative lymph node staging by positron emission tomography in lung cancer. METHODS: Preoperative positron emission tomography and computed tomography scans were performed for 564 lymph node stations in 80 patients with peripheral-type lung cancer. The sizes of both the lymph nodes and the metastatic foci within the lymph nodes were measured, and these measurements were compared with those obtained with positron emission tomography scanning. To establish general sizes of metastatic foci within the lymph nodes, 277 metastatic lymph nodes in operative specimens previously resected from another 111 patients with lung cancer were examined as a control. RESULTS: The sensitivity was significantly higher for positron emission tomography than for computed tomographic scanning (P =.026). The sizes of metastatic foci within lymph nodes that showed false-negative (n = 8) and true-positive (n = 28) with positron emission tomography ranged from 0.5 to 9 mm (3 +/- 1 mm) and from 4 to 18 mm (10 +/- 3 mm), respectively (P <.001). None of the metastatic foci smaller than 4 mm could be detected with positron emission tomography scanning. The review of the 277 previously resected metastatic lymph nodes showed that 89 (32%) had metastatic foci smaller than 4 mm. The sizes of true-positive (n = 28) and false-positive (n = 10) lymph nodes ranged from 6 to 15 mm (10 +/- 2 mm) and from 9 to 16 mm (12 +/- 2 mm), respectively (P <.01). None of the false-positive lymph nodes was smaller than 9 mm. CONCLUSIONS: Although positron emission tomography was superior to computed tomography scanning in lymph node staging in lung cancer, positron emission tomography was unable to distinguish metastatic foci smaller than 4 mm, which were not unusual sizes for lymph node metastases in lung cancer. Positive lymph nodes with positron emission tomography smaller than 9 mm are likely to be true-positive rather than false-positive.

Adenocarcinoma↗
PubMed1999

Lymph node revealing solution: is it effective on detecting minute lymph nodes?

AIMS: The aim of this prospective study is to detect the efficiency of a previously described lymph node revealing solution (LNRS) in comparing with conventional lymph node dissection and re-dissection in colon, breast and urinary bladder carcinomas. METHODS: Total 30 cases in which less than 10 lymph nodes were found by conventional method, were immersed for 6-8 hours in LNRS, dissected and processed. Control group, 12 cases, was first dissected then a second conventional dissection was performed. At the end, specimens were again immersed in LNRS for 6-8 hours and last dissections were done. MAIN RESULTS: In the first group, a total of 150 lymph nodes, 46 of them with metastasis were detected. After using LNRS, 26 additional lymph nodes among which 10 were positive were detected. When compared with the results of conventional dissection, the increase in number of total and metastatic lymph nodes with LNRS was significant (p<0.01). The mean size of the lymph nodes detected by the conventional and LNRS methods was 6.8 and 4.2 mm, respectively. The pathologic lymph node stage was changed in three bladder carcinoma cases, and one breast carcinoma. In the control group, 75 lymph nodes (11 with metastases), 19 lymph nodes (3 with metastases), 14 lymph nodes (one with metastases) were detected after first and second conventional dissection and LNRS methods, respectively. CONCLUSION: LNRS enhanced the number of total and metastatic lymph nodes and is effective in detecting small lymph nodes. This method is useful for accurate staging where the number of detected lymph nodes is too small by the conventional method.

Adenocarcinoma↗
PubMed1992

[Experimental study of lymph node metastasis in thoracic esophageal carcinoma--regarding lymph node metastasis and changes in lymphatic flow by ultrafine charcoal in rabbit esophageal carcinoma model].

Esophageal carcinoma models were created by transplanting VX2 cells to rabbit esophagus endoscopically. By injecting finely divided activated charcoal into normal rabbit esophagus and tumor sites of esophageal carcinoma model, lymph flow was observed directly. Existence of lymph node metastasis was studied in detailed pathology. In 30 rabbits with upper esophageal carcinoma, lymph node metastasis was seen in 77%. Metastasis to bilateral intrathoracic paratracheal lymph node was seen in 50%, and also concentration of lymphatic flows from tumor site was seen. However, there were no metastasis and no lymph flow to abdominal lymph nodes. While, metastasis to cervical lymph nodes showed around 13%. Esophageal lymphatic flows were also seen reaching the cervical area along the esophagus. In 40 models with mid lower esophageal carcinoma, lymph node metastasis were seen in 88%. Metastasis to right and left thoracic paratracheal lymph nodes was 75% and 53%, respectively, and 25% of metastasis went to cardia lymph nodes. The lymph flows were going up and down around these lymph nodes, and reaching to lymph nodes at upper highest mediastinum or left gastric artery. The metastatic rate to the cervical lymph nodes was about 5%. There were no significant differences in lymphatic metastasis between right and left mediastinum. These findings suggest the necessity of radical dissection for both sides of the mediastinum.

Animals↗
PubMed1980

A comparison of lymphocyte migration through intestinal lymph nodes, subcutaneous lymph nodes, and chronic inflammatory sites of sheep.

The migration of 51Cr- and 111In-labeled lymphocytes from blood to various lymph compartments was studied in sheep. When lymphocytes were isolated from lymph, radiolabeled, and returned intravenously to the same animal, nonrandom patterns of lymphocyte migration were observed, which depended on the source of the labeled cells. Lymphocytes isolated from intestinal (jejunum, ileum, or ileocecal junction) efferent lymph always produced greater specific activity in the efferent intestinal lymph than in the efferent lymph of subcutaneous (popliteal or prefemoral) lymph nodes. Conversely, lymphocytes isolated from the efferent lymph of subcutaneous lymph nodes produced greater specific activity in the efferent lymph of subcutaneous lymph nodes than in the intestinal efferent lymph. Unit gravity sedimentation of the free-floating lymphocytes in intestinal efferent lymph demonstrated that small, recirculating lymphocytes, but not lymphoblasts, were responsible for the radioactivity recovered in lymph. The most dramatic examples of nonrandom lymphocyte migration were seen when the migration of lymphocytes was compared between the intestinal efferent lymph and through sites of chronic inflammation.

Animals↗
PubMed2001

Appropriate lymph node dissection for early gastric cancer based on lymph node metastases.

BACKGROUND: Lymph node dissection in patients with early gastric cancer is controversial because lymph node metastases are much less common than in advanced cancer. Therefore, routine extensive lymph node dissection with wide resection of the stomach may be excessive, and an appropriate lymph node dissection procedure in patients with early gastric cancer should be established. METHODS: Retrospectively, 588 consecutive patients with early gastric cancer were analyzed by univariate and multivariate analysis to predict lymph node metastases with clinicopathologic variables. The sites and rates of lymph node metastases for each tumor location were mapped. RESULTS: In early gastric cancer, depth of invasion was an independent predictive factor of lymph node metastases. In cancer confined to the mucosa, however, tumor diameter was the only predictive factor. In contrast, tumor diameter, macroscopic appearance, and histologic type were not predictive factors in early gastric cancers invading the submucosa. In mucosal cancer, metastasis to lymph nodes was confined to the paragastric lymph nodes on the same side of the stomach as the tumor. In submucosal cancer, the incidence of lymph node metastasis was 2% to 17% in group 1 and 1% to 3% in group 2 lymph nodes. CONCLUSIONS: In mucosal cancer, lymph node dissection is unnecessary for tumors measuring less than 30 mm, and limited lymph node dissection with local gastrectomy is appropriate when tumor diameters are 30 mm or greater. In submucosal cancer, gastrectomy with dissection of group 1 and some group 2 lymph nodes should be sufficient to remove all nodal metastases.

Algorithms↗
PubMed1994

Dynamics of glucose production and uptake are more closely related to insulin in hindlimb lymph than in thoracic duct lymph.

We previously reported a striking similarity between the dynamics of both glucose turnover and thoracic duct lymph insulin during euglycemic clamps (J Clin Invest 84:1620, 1989), which suggested that transendothelial insulin transport (TET) is rate-limiting for insulin action in vivo. Thoracic duct lymph, however, is primarily derived from insulin-insensitive tissues, which raises questions as to the physiological significance of this relationship. The relationship between glucose turnover and TET was thus examined in insulin-sensitive tissues by the simultaneous measurement of insulin in plasma, thoracic duct lymph, and hindlimb lymph during euglycemic clamps in normal anesthetized dogs (n = 8). Clamps consisted of two 3-h phases: a 0.6 mU.min-1.kg-1 insulin infusion (activation phase) followed by termination of the insulin infusion (deactivation phase). Lymph insulin was less than plasma insulin during both phases (P < 0.01) with steady-state hindlimb (120 +/- 12 pM) and thoracic duct lymph insulin (138 +/- 12 pM) 38 and 45%, respectively, lower than steady-state plasma insulin (222 +/- 24 pM) at the end of the activation phase (P < 0.05). Also, the rate of increase of lymph insulin was slower than plasma insulin during hormone infusion; half-time to steady-state was 8.8 +/- 2.0 min for plasma insulin, but longer for thoracic (25.8 +/- 3.5) and hindlimb lymph insulin (40.7 +/- 5.7 min). A very close relationship was observed during activation between the rate of increase of glucose uptake (Rd) and the increase in hindlimb lymph insulin (r2 = 0.92); this relationship was weaker for thoracic lymph (r2 = 0.74) and much weaker between glucose uptake and plasma insulin (r2 = 0.35). These data support the concept that interstitial insulin (represented by hindlimb lymph) is the signal that determines glucose uptake by insulin-sensitive tissues and that the rate of increase of glucose uptake is determined by transendothelial insulin transport into insulin-sensitive tissue. Also, during activation, hindlimb lymph insulin was a very strong predictor of the rate of suppression of hepatic glucose output (HGO) (r2 = 0.96), and the correlation with HGO was stronger than that for thoracic lymph (r2 = 0.85). The evidence that the rate of increase of Rd and the rate of suppression of HGO during insulin infusion are very strongly predicted by the time course of insulin in hindlimb lymph is consistent with the single-gateway hypothesis: the insulin transport rate across endothelium in insulin-sensitive tissue (skeletal muscle) determines the rate of glucose utilization and the suppression of hepatic glucose output.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗
PubMed2005

Does the number of lymph nodes examined in patients with lymph node-negative breast carcinoma have prognostic significance?

BACKGROUND: There are conflicting data on the prognostic significance of the number of lymph nodes examined in patients with lymph node-negative breast carcinoma. Therefore, the authors analyzed the impact of the number of tumor-free axillary lymph nodes on disease-free survival (DFS) in two distinct patient populations. METHODS: Eight hundred thirty-three consecutive patients with breast carcinoma who underwent mastectomy between 1927 and 1987 and 1094 consecutive patients with breast carcinoma who underwent with breast-conservation therapy between 1984 and 2001 were diagnosed pathologically with negative axillary lymph node status. Patients were stratified into 4 groups according to the number of lymph nodes examined: Group 1 had 1-3 lymph nodes examined, Group 2 had 4-9 lymph nodes examined, Group 3 had 10-20 lymph nodes examined, and Group 4 had >20 lymph nodes examined. RESULTS: In the mastectomy cohort, with a median follow-up of 153 months, the 10-year DFS rate was 70%, 65%, 79%, and 81% for Groups 1-4, respectively. On multivariate analysis, pathologic tumor size (P<0.001) and the number of lymph nodes examined (P=0.010) were significant predictors for long-term DFS. In the breast-conservation cohort, with a median follow-up of 53 months, the 5-year DFS rate was 90%, 91%, 92%, and 95% for Groups 1-4, respectively. On multivariate analysis, the only predictors of DFS were method of detection (clinically vs. mammographically) (P=0.003) and tumor size (P=0.035). CONCLUSIONS: The recovery of <10 lymph nodes in lymph node-negative patients who underwent mastectomy resulted in a 10-15% decreased long-term DFS rate compared with patients who had a more extensive axillary assessment. However, the number of lymph nodes examined did not have an impact on the DFS rate in a contemporary cohort of patients who underwent breast-conservation therapy, which included radiation.

Adult↗
PubMed2002

Lymph node recovery from colorectal tumor specimens: recommendation for a minimum number of lymph nodes to be examined.

Lymph node involvement is the most important prognostic factor for patients who have undergone radical surgery for colorectal carcinoma. An accurate examination of the surgical specimens is mandatory for the correct assessment of the lymph node status of the tumor. The risk of understaging is particularly high for patients with tumors classified as Dukes B (TNM stage II). The aim of this study was to determine if a specified minimum number of lymph nodes examined per surgical specimen could have any effect on the prognosis of patients who had undergone radical surgery for Dukes B colorectal cancer. Between 1988 and 1995 a total of 140 patients underwent radical resection of Dukes B colorectal cancer by the same surgeon (C.C.). The relation between clinicopathologic variables and survival was estimated using the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify the variables that can independently influence survival. A median of 12 lymph nodes (range 3-38) was examined per tumor specimen. The 5-year survival rate of Dukes B patients who had had eight or fewer lymph nodes examined after surgery was 54.9%, whereas the survival rate for those who had had nine or more lymph nodes examined was 79.9% (p < 0.001). Cox regression analysis identified the number of lymph nodes as the only independent prognostic factor (p = 0.01). Seventy patients with one to four metastatic lymph nodes (Dukes C patients) who had been operated on during the same period were included in the survival analysis for comparison. The 5-year survival rate of the Dukes B patients with eight or fewer lymph nodes examined was similar to that of the 70 Dukes C patients (54.9% and 51.8%, respectively). Examination of eight or fewer lymph nodes in Dukes B colorectal patients may be considered a high risk factor for missing positive lymph nodes in the surgical specimens. Our results suggest that harvesting and examining a minimum of nine lymph nodes per surgical specimen may be sufficient for reliable staging of lymph node-negative tumors.

Age Factors↗
PubMedDate not supplied

Paratracheal lymph node metastasis is associated with cervical lymph node metastasis in patients with thoracic esophageal squamous cell carcinoma.

BACKGROUND: We determined which lymph node metastases were associated with cervical lymph node metastases of thoracic esophageal squamous cell carcinoma. METHODS: A total of 6464 lymph nodes derived from 155 consecutive patients with thoracic esophageal squamous cell carcinoma were stained by immunohistochemistry (antibody: AE1/AE3). Lymph node metastases were mapped according to the mapping scheme of the American Thoracic Society, as modified by Casson et al. (Ann Thorac Surg 1994;58:1569-70). Patients were divided into two groups: those with and without cervical lymph node metastasis (CLNM). Mapping data were examined by uni- and multivariate analysis. RESULTS: Hematoxylin and eosin-positive and AE1/AE3-positive lymph node metastases were found in 59% and 77% of patients, respectively. Twenty-one (55%) of 38 patients in the CLNM(+) group and 30 (26%) of 117 patients in the CLNM(-) group had AE1/AE3-positive lymph node metastasis in the thoracic paratracheal lymph node. Paratracheal lymph node metastasis is only one independent factor for (CLNM), whereas upper thoracic paraesophageal lymph node and pulmonal hilar lymph node status were also significant in univariate analysis. Three (43%) of seven patients with cervical jumping metastasis from the thoracic esophagus had micrometastasis in the paratracheal lymph node. CONCLUSIONS: The paratracheal lymph node is most associated with (CLNM) of thoracic esophageal squamous cell carcinoma.

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