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The action of pharmacologically active substances on the flow and composition of cat hind limb lymph.

1. Lymph flow, blood flow and lymph protein concentrations have been measured in cat hind limb.2. When naturally occurring pharmacologically active compounds were infused close arterially to the hind limb it was found that histamine, bradykinin and acetylcholine were the most potent in increasing lymph flow.3. Dilatation of blood vessels per se is not sufficient to cause an increase in lymph flow since potent vasodilator agents such as isoprenaline and prostaglandins were not very active in increasing lymph flow.4. The effect on blood flow was rapid in onset and in return to basal flow, whereas the effect on lymph flow was delayed and prolonged. The duration of the effect on lymph flow was considerably greater with histamine and bradykinin than with acetylcholine.5. An increase in the protein concentration in the interstitial fluid is not a pre-requisite of an increase in lymph flow because (a) in some experiments an increase in lymph flow was not accompanied by an increase in lymph protein concentration after infusion of vasoactive substance and (b) the glucofuranoside, Glyvenol, was found to inhibit the increase in protein concentration but not the increase in lymph flow caused by infusion of histamine or bradykinin.6. In contrast the specific antihistamine, mepyramine, abolished the effect of histamine on lymph flow and lymph protein concentration and considerably reduced the effect on blood flow.7. An increase in venous pressure alone caused a small increase of lymph flow in about 50% of experiments, but when the venous pressure was increased at a time when vascular permeability was high, there was an increase in lymph flow in all experiments.8. When the venous pressure was low only histamine caused a significant increase in the lymph protein concentration, whereas bradykinin sometimes caused a small increase and acetylcholine mostly caused a decrease in the concentration of lymph protein.9. When the venous pressure was high, bradykinin and histamine and occasionally acetylcholine caused an increase in protein concentration in the lymph.10. Infusions of histamine, bradykinin or prostaglandin E(1) did not increase the leakage of intracellular enzymes into the lymph.

Acetylcholine↗

Temporary shielding of hot spots in the drainage areas of cutaneous melanoma improves accuracy of lymphoscintigraphic sentinel lymph node diagnostics.

Detection of the "true" sentinel lymph nodes, permitting correct staging of regional lymph nodes, is essential for management and prognostic assessment in malignant melanoma. In this study, it was prospectively evaluated whether simple temporary shielding of hot spots in lymphatic drainage areas could improve the accuracy of sentinel lymph node diagnostics. In 100 consecutive malignant melanoma patients (45 women, 55 men; age 11-91 years), dynamic and static lymphoscintigraphy in various views was performed after strict intracutaneous application of technetium-99m nanocolloid (40-150 MBq; 0.05 ml/deposit) around the tumour (31 patients) or the biopsy scar (69 patients, safety distance 1 cm). The images were acquired with and without temporary lead shielding of the most prominent hot spots in the drainage area. In 33/100 patients, one or two additional sentinel lymph nodes that showed less tracer accumulation or were smaller (<1.5 cm) were detected after shielding. Four of these patients had metastases in the sentinel lymph nodes; the non-sentinel lymph nodes were tumour negative. In 3/100 patients, hot spots in the drainage area proved to be lymph vessels, lymph vessel intersections or lymph vessel ectasias after temporary shielding; hence, a node interpreted as a non-sentinel lymph node at first glance proved to be the real sentinel lymph node. In two of these patients, lymph node metastasis was histologically confirmed; the non-sentinel lymph nodes were tumour free. In 7/100 patients the exact course of lymph vessels could be mapped after shielding. In one of these patients, two additional sentinel lymph nodes (with metastasis) were detected. Overall, in 43/100 patients the temporary shielding yielded additional information, with sentinel lymph node metastases in 7%. In conclusion, when used in combination with dynamic acquisition in various views, temporary shielding of prominent hot spots in the drainage area of a malignant melanoma of the skin leads to an improvement in the accuracy of identification and localisation of sentinel lymph nodes by lymphoscintigraphy.

Adolescent↗

A strategy for determining which thoracic esophageal cancer patients should undergo cervical lymph node dissection.

BACKGROUND: There is controversy about performing cervical lymph node dissections in all middle and lower thoracic esophageal squamous cell carcinoma patients. The purpose of this study was to evaluate whether intraoperative examination of thoracic paratracheal lymph node by real-time reverse transcription-polymerase chain reaction was worthwhile for selecting patients for cervical lymph node dissection. METHODS: Under informed consent, 30 middle and lower thoracic esophageal squamous cell carcinoma patients were examined for thoracic paratracheal lymph node metastasis intraoperatively by hematoxylin-eosin staining and real-time reverse transcription-polymerase chain reaction for messenger RNA encoding squamous cell carcinoma antigen. When thoracic paratracheal lymph node metastasis was found, cervical lymph node dissection was performed. If the patients had no thoracic paratracheal lymph node metastasis, a randomized study for selection of cervical lymph node dissection was performed. RESULTS: Eleven of 30 patients with middle or lower third thoracic esophageal squamous cell carcinoma had thoracic paratracheal lymph node metastasis. Five of these 11 patients had cervical lymph node metastasis. Nineteen patients who had no metastasis in the thoracic paratracheal lymph nodes were enrolled in a randomized study. Eight of the 19 patients received cervical lymph node dissection and they were found not to have cervical lymph node metastasis. The other 11 patients did not receive cervical lymph node dissection, and there was no cervical lymph node recurrence. CONCLUSIONS: The intraoperative diagnosis of metastasis in the thoracic paratracheal lymph node may be used as an indicator for cervical lymph node dissection in middle and lower thoracic esophageal cancer patients.

Carcinoma, Squamous Cell↗

Intraoperative identification of esophageal sentinel lymph nodes with near-infrared fluorescence imaging.

OBJECTIVE: In esophageal cancer, selective removal of involved lymph nodes could improve survival and limit complications from extended lymphadenectomy. Mapping with vital blue dyes or technetium Tc-99m often fails to identify intrathoracic sentinel lymph nodes. Our purpose was to develop an intraoperative method for identifying sentinel lymph nodes of the esophagus with high-sensitivity near-infrared fluorescence imaging. METHODS: Six Yorkshire pigs underwent thoracotomy and received submucosal, esophageal injection of quantum dots, a novel near-infrared fluorescent lymph tracer designed for retention in sentinel lymph nodes. Six additional pigs underwent thoracotomy and received submucosal esophageal injection of CW800 conjugated to human serum albumin, another novel lymph tracer designed for uptake into distant lymph nodes. Finally, 6 pigs received submucosal injection of the fluorophore-conjugated albumin with an endoscopic needle through an esophagascope. These lymph tracers fluoresce in the near-infrared, permitting visualization of migration to sentinel lymph nodes with a custom intraoperative imaging system. RESULTS: Injection of the near-infrared fluorescent lymph tracers into the esophagus revealed communicating lymph nodes within 5 minutes of injection. In all 6 pigs that received quantum dot injection, only a single sentinel lymph node was identified. Among pigs that received fluorophore-conjugated albumin injection, in 5 of 12 a single sentinel lymph node was revealed, but in 7 of 12 two sentinel lymph nodes were identified. There was no dominant pattern in the appearance of the sentinel lymph nodes either cranial or caudal to the injection site. CONCLUSION: Near-infrared fluorescence imaging of sentinel lymph nodes is a novel and reliable intraoperative technique with the power to assist with identification and resection of esophageal sentinel lymph nodes.

Animals↗

Patterns of initial recurrence and prognosis after sentinel lymph node biopsy and selective lymphadenectomy for melanoma.

The histologic status of the sentinel lymph node is a highly significant prognostic factor for patients with clinically localized cutaneous melanoma. The patterns of initial treatment failure of patients with positive sentinel lymph node biopsy versus those with negative results have not been well described. The purpose of this study was to determine the relative prognostic importance of sentinel lymph node status and to compare patterns of initial treatment failure and prognosis of node-positive versus node-negative cutaneous melanoma patients staged by sentinel lymph node biopsy and selective lymphadenectomy. The authors reviewed the pertinent demographic and surgical data in a consecutive series of patients with cutaneous melanoma who underwent sentinel lymph node staging of nonpalpable regional nodes. Sentinel lymph node biopsy was performed using a combination of blue dye and radiolocalization. Patients with positive biopsy results underwent selective lymphadenectomy, whereas those with negative results were observed. Site(s) and date(s) of initial recurrence and death were determined, and disease-free and overall survival probabilities were compared between positive and negative groups using the log-rank test and multivariable Cox regression analysis. Between February of 1994 and August of 2000, 408 patients with melanoma underwent sentinel lymph node biopsy to stage 518 regional lymph node basins. Mean Breslow tumor thickness was 2.27 mm (range, 0.2 to 14.0 mm). Eighty-five patients (20.8 percent) had at least one histologically positive sentinel lymph node, and selective lymphadenectomy yielded additional positive lymph nodes in 18 of 84 patients (21.4 percent). Recurrences were noted in 70 patients (17 percent) at a median follow-up period of 31.4 months. Recurrences were more frequent in patients with positive biopsy results (36.5 percent) than in those with negative results (12.1 percent, p < 0.0001). Distant sites of initial recurrence were more likely in the positive group than in the negative group (71 percent versus 49 percent of recurrences, respectively; p = 0.06). The false-negative rate for sentinel lymph node staging was 4.5 percent and overall accuracy was 99 percent compared with clinical follow-up. Disease-free and overall survival correlated significantly with tumor thickness, ulceration, sentinel lymph node status, and the number of tumor-positive lymph nodes (two-sided p < 0.0001 for all comparisons). Multivariable analysis revealed that sentinel lymph node status (p = 0.003), tumor thickness (p = 0.016), ulceration (p = 0.006), and age (p = 0.003) were significant independent predictors of survival for the entire group. Tumor thickness and ulceration were significant predictors of recurrence and survival in sentinel node-negative patients but not in sentinel node-positive patients. Sentinel lymph node histology is possibly the most important negative predictor of early recurrence and survival in patients with American Joint Committee on Cancer stage I and II melanoma. The number of positive lymph nodes provides additional prognostic information. Although sentinel node-negative patients are a prognostically favorable group, various combinations of local and regional recurrences comprise the most common pattern of initial relapse after a negative sentinel lymph node biopsy result.

Adolescent↗

Pattern of lymph node metastases in patients with squamous cell carcinoma of the thoracic esophagus who underwent three-field lymphadenectomy.

BACKGROUND/AIMS: Lymph nodes in patients with squamous cell carcinoma of the thoracic esophagus might be involved with metastases at cervical, mediastinal, and abdominal sites. The range of lymph node dissection is still controversial. The pattern of lymph node metastasis and factors that are correlated with lymph node metastasis affect the surgical procedure of lymph node dissection. The purpose of the present study was to explore the pattern of lymph node metastasis and factors that are correlated with lymph node metastasis in patients with esophageal cancer who underwent three-field lymphadenectomy. METHODS: Lymph node metastases in 230 patients who underwent radical esophagectomy with three-field lymphadenectomy were analyzed. The metastatic sites of lymph nodes were correlated with tumor location by chi-square test. Logistic regression was used to analyze clinicopathological factors related to lymph node metastasis. RESULTS: Lymph node metastases were found in 133 of the 230 patients (57.8%). The average number of resected lymph nodes was 25.3 +/- 11.4 (range 11-71). The proportions of lymph node metastases were 41.6, 19.44, and 8.3% in neck, thoracic mediastinum, and abdominal cavity, respectively, for patients with upper thoracic esophageal carcinomas, 33.3, 34.7, and 14%, respectively, in those with middle thoracic esophageal carcinomas, and 36.4, 34.1, and 43.2%, respectively, for patients with lower thoracic esophageal carcinomas. We did not observe any significant difference in lymph node metastatic rates among upper, middle, and lower thoracic carcinomas for cervical or thoracic nodes. The difference in lymph node metastatic rates for nodes in the abdominal cavity was significant among upper, middle, and lower thoracic carcinomas. The lower thoracic esophageal cancers were more likely to metastasize to the abdominal cavity than tumors at other thoracic sites. A logistic regression model showed that depth of tumor invasion and lymphatic vessel invasion were factors influencing lymph node metastases. CONCLUSIONS: Based on our data, cervical and mediastinal node dissection should be performed independent of the tumor location. Abdominal node dissection should be conducted more vigorously for lower thoracic esophageal cancers than for cancers at other locations. Patients with deeper tumor invasion or lymphatic vessel invasion were more likely to develop lymph node metastases.

Carcinoma, Squamous Cell↗

Intraoperative pathological investigation of recurrent nerve nodal metastasis can guide the decision whether to perform cervical lymph node dissection in thoracic esophageal cancer.

Three-field lymph node dissection has been widely used to treat thoracic esophageal cancer, but is very invasive and can cause serious complications. Whether cervical lymph node dissection should be performed in all patients with thoracic esophageal cancer remains controversial. We pathologically examined the recurrent nerve lymph nodes during surgery in patients with thoracic esophageal cancer to determine the presence or absence of lymph node involvement. In patients without recurrent nerve nodal involvement, cervical lymph node dissection was not performed. Treatment outcomes were analyzed to evaluate whether intraoperative pathological investigation was a useful procedure. Among 71 patients with thoracic esophageal cancer who underwent 3-field lymph node dissection, the rate of cervical lymph node metastasis was 40.9% in patients with recurrent nerve nodal metastasis on intraoperative pathological investigation, as compared with 10.2% in patients without recurrent nerve nodal metastasis (p=0.007). Multiple logistic-regression analysis showed that recurrent nerve nodal metastasis was a strong predictor of cervical lymph node metastasis (odds ratio, 2.98; 95% confidence interval, 1.139-7.775; p=0.03). Among 41 patients who underwent intraoperative pathological investigation, 10 had recurrent nerve nodal metastasis and underwent cervical lymph node dissection. Two of these patients had histological evidence of cervical lymph node metastasis. The remaining 31 patients had no recurrent nerve nodal metastasis on intraoperative pathological examination and therefore did not receive cervical lymph node dissection. None of these patients had cervical lymph node recurrence on follow-up. We compared patients who underwent intraoperative pathological investigation with those who underwent conventional 3-field lymph node dissection (without performing intraoperative pathological investigation). The rates of cervical lymph node recurrence were similar among the groups (2.6% vs. 6.7%), but the 3-year survival rate was significantly higher in the patients who underwent intraoperative pathological dissection (83.3%) than in those who underwent 3-field dissection (57.2%; p<0.05). Although this was a retrospective study, our results suggest that outcomes of patients undergoing cervical lymph node dissection according to the results of intraoperative pathological investigation are at least as good as those in patients undergoing 3-field lymph node dissection. We conclude that intraoperative pathological investigation of recurrent nerve nodal metastasis is useful for determining whether cervical lymph node dissection should be performed in patients with thoracic esophageal cancer.

Aged↗

Sentinel lymph nodes with technetium-99m colloidal rhenium sulfide in patients with esophageal carcinoma.

BACKGROUND: The authors assessed the detection of sentinel lymph nodes in patients with esophageal squamous cell carcinoma (SCC) using technetium-99m colloidal rhenium sulfide. They studied whether an analysis of sentinel lymph nodes using cytokeratin (CK) immunohistochemistry increased the accuracy of staging. METHODS: The authors observed 25 patients with thoracic esophageal carcinomas who underwent radical esophagectomy. The day before surgery, technetium-99m colloidal rhenium sulfide was injected into the submucosa at four sites around the primary tumor. Lymphoscintigraphy was performed. Esophagectomy and regional lymph node dissection were performed 17 hours after the technetium-99m injection. After surgery, the resected lymph nodes were evaluated by CK staining. RESULTS: Lymphoscintigraphy detected sentinel lymph nodes in 92% of the patients (23 of 25 patients). The accuracy of sentinel lymph node was 91.3% (21 of 23 patients), the sensitivity was 86.7% (13 of 15 patients), and the false-negative rate was 8.7% (2 of 23 patients). A comparison of the number of sentinel lymph nodes and clinicopathologic factors showed that there was a significant association between the number of sentinel lymph nodes and lymph node status (P < 0.01), pathologic stage (P < 0.05), and the number of metastatic lymph nodes (P < 0.05). Occult metastasis was detected by CK staining in 14 (56%) of the 25 patients and in 23 (1.7%) of 1406 lymph nodes. Because the 2 false-negative (sentinel lymph node-negative and nonsentinel lymph node-positive) patients who had occult metastases in the sentinel lymph nodes, the accuracy of sentinel lymph node evaluation using CK staining was 100% (23 of 23). CONCLUSIONS: Lymphatic mapping with technetium-99m colloidal rhenium sulfide was used to identify the lymphatic basin and was feasible in patients with esophageal SCC. An analysis of sentinel lymph nodes using CK immunohistochemistry increased the accuracy of sentinel lymph node.

Aged↗

Variability of the depth of supraclavicular and axillary lymph nodes in patients with breast cancer: is a posterior axillary boost field necessary?

PURPOSE: To determine the variability of the depth of supraclavicular (SC) and axillary (AX) lymph nodes in patients undergoing radiation therapy for breast cancer and to relate this variability with the patient's anterior/posterior (A/P) diameter. The dosimetric consequences of the variability in depth are explored and related to the need for a posterior axillary boost field. METHOD AND MATERIALS: In 49 patients undergoing treatment-planning computed tomography (CT) scanning in the treatment position, the maximum depth of the SC and AX lymph nodes was measured on CT images. The A/P diameter was measured at the location of the SC and AX, respectively. The relationship between the SC/AX lymph node depth and patient diameter was determined using linear regression. For an anterior SC and AX field, the relative dose to the SC and AX lymph nodes were calculated for a 6 MV photon beam. RESULTS: The maximum depth of the SC lymph nodes ranged from 2.4 to 9.5 cm (median, 4.3 cm). The depth was less than 3 cm in 4 patients, 3-6 cm in 39 (80%), and greater than 6 cm in 6 patients. There was a linear relationship between the SC lymph node depth and the A/P diameter. The depth of the SC lymph nodes in cm equals approximately one-half of the A/P diameter minus 3.5 (r(2) = 0.69). In 94% (46 of 49) of patients, the SC lymph node depth was between one-fifth and one-half of the A/P diameter. The depth of the axillary lymph nodes ranged from 1.4 to 8 cm (median, 4.3 cm). The depth was less than 3 cm in 8 patients, 3-6 cm in 32 (65%), and greater than 6 cm in 9 patients. The AX lymph node depth in cm equals approximately one-half of the A/P diameter minus 3 (r(2) = 0.81). In all patients, the AX lymph nodes were shallower than mid-depth. The depth of the SC and AX lymph nodes was within +/- 1 cm in 53% (26 of 49) of patients. The AX lymph nodes were located at >/= 1 cm shallower or greater depth than the SC in 24.5% (12 of 49) and 22.5% (11 of 49) of patients, respectively. If an anterior 6-MV beam only is used to treat the SC and AX lymph nodes in these 49 patients, the dose to the AX is within +/- 5% of the SC dose in 53% (26 of 49) patients and is 90% or more of the dose delivered in the SC in 90% (44 of 49) of patients. CONCLUSION: The maximum depth of the SC and AX lymph nodes varies widely and is related to the patient's size represented by the A/P diameter. In most patients, the AX lymph nodes lie at approximately the same depth or shallower than the SC. Therefore, the rationale for a posterior axillary boost field needs to be further assessed. When the AX and SC lymph nodes are deep, opposed supraclavicular and axillary fields and/or the use of a higher energy beam might be reasonable.

Adult↗

Differentiation of metastatic versus non-metastatic mediastinal lymph nodes in patients with non-small cell lung cancer using respiratory-triggered short inversion time inversion recovery (STIR) turbo spin-echo MR imaging.

OBJECTIVES: To differentiate between metastatic and non-metastatic lymph nodes in patients with non-small cell lung cancer using respiratory-triggered short inversion time inversion recovery (STIR) turbo spin-echo (SE) MR imaging. METHODS AND PATIENTS: One hundred and forty mediastinal lymph nodes were detected in 25 patients with non-small cell lung cancer who underwent respiratory-triggered STIR turbo SE imaging. Ratios of signal intensity of lymph nodes to 0.9% saline phantoms (lymph node-saline ratio) were compared by Student's t-test using the pathological diagnosis as the gold standard. The threshold value of the lymph node-saline ratio was determined for a positive test, and tested for its capability to provide a differential diagnosis. RESULTS: One hundred and forty lymph nodes were diagnosed and classified into two groups: metastatic lymph node (n=21) and non-metastatic lymph node (n=119). The mean lymph node-saline ratio in the non-metastatic lymph node group (0.42+/-0.01; mean+/-standard error) was significantly lower than that of the metastatic lymph node group (0.77+/-0.02, P<0.0001). When 0.6 was adapted as the threshold for a positive test, sensitivity, specificity, and accuracy for differentiating metastatic lymph node from non-metastatic lymph node per lymph nodes were 100, 96, and 96%, and sensitivity, specificity, and accuracy for differentiating metastatic lymph node from non-metastatic lymph node per patients were 100, 75, and 88%, respectively. CONCLUSIONS: Both metastatic and non-metastatic lymph nodes in patients with non-small cell lung cancer were well differentiated using respiratory-triggered STIR turbo SE imaging.

Adult↗

Superiority of ratio based lymph node staging for bladder cancer.

PURPOSE: The current study evaluated lymph node staging and the outcome in patients with lymph node positive bladder cancer after radical cystectomy. MATERIALS AND METHODS: A total of 162 patients with lymph node positive bladder cancer were followed a median of 7.5 years after radical cystectomy and pelvic lymph node dissection for survival and local recurrence. Lymph node disease was stratified by pN stage, the number of positive lymph nodes and the number of positive lymph nodes in relation to the number removed (ratio based pN stage). RESULTS: A median of 13 lymph nodes (range 2 to 32) was examined, showing an average of 3.3 positive lymph nodes per specimen. An increased number of lymph nodes correlated with the identification of lymph node positive cases. The ratio of the number of positive-to-total number of lymph nodes removed better defined surgical outcome than conventional lymph node staging. CONCLUSIONS: Ratio based lymph node staging, which reflects the number of lymph nodes examined and the quality of lymph node dissection, was a significant prognostic variable for survival and local control in patients with lymph node positive bladder cancer after radical cystectomy.

Adult↗

Flow and composition of lymph from the ovary and uterus of cows during pregnancy.

Ovarian or uterine lymph was collected continuously for periods of up to 25 days from 16 cows cannulated at stages of pregnancy ranging from 96 to 278 days post coitum. Blood samples were taken acutely from the ovarian and uterine veins during surgery and periodically from the jugular vein during the course of lymph collection. The flow rate and cell content of lymph was measured and blood and lymph plasma samples were analysed for progesterone, pregnenolone, pregnenolone sulphate, androstenedione, testosterone, oestrone, oestrone sulphate, oestradiol-17 beta, prostaglandin (PG) F-2 alpha, total protein and albumin. There was a high flow rate of protein-rich lymph from luteal ovaries with rates up to 101.7 ml/h occurring in individual lymphatics over short periods. Peripheral ovarian and uterine lymph contained a low concentration of cells (mean less than 10(5) cells/ml) comprising about 82-87% lymphocytes, 11-14% macrophages and monocytes and 2-4% other cells. At all stages of pregnancy, the concentration of progestagens and androgens was higher in ovarian lymph than in uterine lymph or blood plasma. The differences were greatest for progesterone and androstenedione which occurred at 200-fold and 60-fold greater concentration respectively in ovarian lymph than in jugular plasma. When serial 10 min samples were collected over a 12-h period, the concentration and output of progesterone in ovarian lymph varied in a phasic manner, ranging from 3.5 to 7.6 microM and from 31.7 to 293.1 nmol/h respectively. There was a positive correlation between the output of progesterone in lymph and the progesterone concentration in jugular blood samples taken every 20 min. During most of pregnancy there was little difference between the concentration of oestrogens in ovarian lymph, ovarian venous plasma and jugular plasma but, during the 3-5 days before calving, these hormones occurred at slightly higher concentration in ovarian lymph. Apart from pregnenolone and androstenedione, all steroids occurred at lower concentrations in uterine lymph than in jugular plasma. Shortly before parturition there was an abrupt increase in the concentration of PGF-2 alpha in uterine lymph. Lymph reflects more accurately the milieu of tissue cells than efferent blood and further analysis of differences in the concentration of substances in lymph relative to the output in the ovarian and uterine arterial and venous blood may lead to the identification of factors important in local regulatory mechanisms in the reproductive tract.

Androgens↗

[Lymph node evaluation in colorectal cancer].

BACKGROUND: In Brazil, colorectal carcinoma is the third cause of death by malignant tumors among women, and the fifth among men. Lymph node involvement is one of the most relevant prognostic maker in these tumors. AIM: To study lymph node involvement in colorectal carcinoma in relationship to biological behavior and tumor location. PATIENTS AND METHODS: One hundred and eight five colorectal carcinoma cases were studied. Lymph node involvement was analyzed according to tumor location, diameter, vessel invasion, and TNM staging. RESULTS: Three thousand nine hundred and six lymph nodes were harvested in 185 patients (21.1 lymph nodes/patient). Metastasis were detected in 399/2,573 peritumoral lymph nodes (15.5%) and in 72/1,333 non-peritumoral lymph nodes (5.4%). Eighty-six patients presented metastasis; in these patients 471/1942 lymph nodes were compromised. In 26 patients peritumoral and non-peritumoral lymph nodes were involved; in 57 cases metastasis were detected only in peritumoral lymph nodes and in 3, only non-peritumoral lymph nodes were involved. The number of lymph node was higher among cecal tumors and smaller in the rectum and sigmoid. There was a positive correlation between the number of metastatic lymph node and pT, tumor diameter and lymphatic and venous invasion; there was a negative correlation between lymph node involvement and lymphocytic response; pN was significantly associated with pT. CONCLUSIONS: Colorectal carcinoma involves preferentially peritumoral lymph node, but in 29 patients (15,7%) non-peritumoral lymph nodes were affected, which is important for tumor staging and prognosis. pN and the number of metastatic lymph nodes were associated with other behaviour markers.

Colorectal Neoplasms↗

The extent of lymph node dissection for colon carcinoma: the potential impact on laparoscopic surgery.

BACKGROUND: The surgeon is no longer able to palpate the mesocolon for lymph node metastases during laparoscopic colectomy. The extent of lymph node dissection should be determined beforehand for cancer control. METHODS: The distribution of lymph node metastases was obtained by the clearing method on colon carcinomas for 164 patients. RESULTS: For pericolic spread: for pT1 tumors, the distance from the primary tumor to a metastatic lymph node was 2.5 cm; for pT2, the distance was within 5 cm; for 97.0 % of pT3 tumors with lymph node metastases, the distance was within 7 cm; for 93.3 % of pT4 tumors with lymph node metastases, the distance was within 7 cm. For central spread: for pT1 tumors, the rate of metastasis to central lymph nodes was 0 %; for pT2, the rate of metastasis was 20.0 % to intermediate lymph nodes; for pT3, the rate of metastasis was 30.6 % to intermediate lymph nodes and 15.3 % to main lymph nodes; for pT4, the rate of metastasis was 44.4 % to intermediate lymph nodes and 22.2 % to main lymph nodes. CONCLUSIONS: Central lymph node dissection is not required for patients with T1 carcinomas, but proximal and distal 3-cm margins of resection are required. For T2, central lymph node dissection that includes the intermediate lymph node should be performed, as well as 5-cm proximal and distal margins of resection. For T3 and T4, central lymph node dissection including the main lymph node should be performed, as well as 7-cm proximal and distal margins of resection. [See editorial on pages 177-8, this issue.]

Colectomy↗

[Distribution of sentinel lymph nodes in gastric cancer and factors correlated with its metastasis].

OBJECTIVE: To investigate the distribution of sentinel lymph nodes in gastric cancer, and evaluate clinicopathologic characteristics leading its metastasis. METHODS: The location of metastatic lymph nodes was analyzed retrospectively in 27 patients of gastric carcinoma with solitary lymph node metastases, and in 80 cases metastasis was limited to only 1 station in Japanese nodal classification. The clinicopathologic characteristics of the patients with solitary lymph node metastases and 111 cases without lymph node metastases were compared. RESULTS: Twenty-five in 27 cases with solitary lymph node metastases were limited in level I. Skip metastasis occurred in 2 cases. Sentinel lymph nodes of 16 cases in 21 patients with the tumors in the lower and middle third stomach were located in less curvature (No. 3) and in greater curvature (No. 4). Sentinel lymph nodes of 3 cases in 6 patients in the upper third stomach were located in right cardia (No. 1). Multivariate analysis showed that the frequency of sentinel lymph node metastasis of pT(3) lesion was significantly higher than that of pT(1) lesion with an odds ratio of 4.926 (P < 0.01). The frequency of sentinel lymph node metastasis in the tumor located in the upper third stomach was significantly higher than that in lower third stomach, with an odds ratio of 4.381 (P < 0.05). Early gastric cancer had lower risk for sentinel lymph node metastasis than that in Borrmann type I cancer, with an odds ratio of 0.082 (P < 0.05). CONCLUSIONS: Majority of sentinel lymph nodes are located in the regional perigastric lymph node groups close to the tumor. Skip metastasis is rare. Depth of invasion and location of tumor are correlated with sentinel lymph node metastasis. Sentinel lymph node assessment can instruct to determine extent of lymph node dissection for gastric cancer.

Adult↗

Risk of prostate carcinoma death in patients with lymph node metastasis.

BACKGROUND: The presence of lymph node metastasis is a poor prognostic sign for patients with prostate carcinoma. Results of published reports on survival among patients with lymph node metastasis are difficult to assess because of treatment selections. The extent to which lymph node status will have an impact on a patient's survival is uncertain. METHODS: The authors analyzed 3463 consecutive Mayo Clinic patients who underwent radical prostatectomy and bilateral pelvic lymphadenectomy for prostate carcinoma between 1987 and 1993. Of these patients, 322 had lymph node metastasis at the time of surgery, and 297 lymph node positive patients also received adjuvant hormonal therapy within 90 days of surgery. The progression free rate and the cancer specific survival rate were used as outcome endpoints in univariate and multivariate Cox proportional hazards models. The median follow-up was 6.3 years. Progression was defined by elevation of serum prostate specific antigen (PSA) > or = 0.4 ng/mL after surgery, development of local recurrence, or distant metastasis documented by biopsy or radiographic examination. RESULTS: The 5-year and 10-year progression free survival rates (+/- standard error [SE]) for patients with lymph node metastasis were 74% +/- 2% and 64% +/- 3%, respectively, compared with 77% +/- 1% and 59% +/- 2%, respectively, for patients without lymph node metastasis. The 5-year and 10-year cancer specific survival rates were 94% +/- 1% and 83% +/- 4%, respectively, compared with 99% +/- 0.1% and 97% +/- 0.5%, respectively, for patients without lymph node metastasis. Among patients with a single lymph node metastasis, the 5-year and 10-year cancer specific survival rates were 99% +/- 1% and 94% +/- 3%, respectively. After adjustment for extraprostatic extension, seminal vesicle invasion, Gleason grade, surgical margins, DNA ploidy, preoperative serum PSA concentration, and adjuvant therapy, the hazard ratio for death from prostate carcinoma among patients with a single lymph node metastasis compared with patients who were without lymph node metastasis was 1.5 (95% confidence interval, 0.5-5.0; P = 0.478), whereas the hazard ratio for death from prostate carcinoma was 6.1 (95% confidence interval, 1.9-19.6; P = 0.002) for those with two positive lymph nodes and 4.3 (95% confidence interval, 1.4-13.0; P = 0.009) for those with three or more positive lymph nodes. There was no significant difference in the progression free survival rate among patients with or without lymph node metastasis in multivariate analysis after controlling for all relevant variables, including treatments (hazard ratio,1.0; 95% CI, 0.7-1.3; P = 0.90). CONCLUSIONS: Patients with prostate carcinoma who have multiple regional lymph node metastases had increased risk of death from disease, whereas patients with single lymph node involvement appeared to have a more favorable prognosis after radical prostatectomy and immediate adjuvant hormonal therapy. Excellent local disease control was achieved by using combined surgery and adjuvant hormonal therapy in patients with positive lymph nodes.

Adult↗

Effects of UV irradiation with one minimal erythema dose on human afferent skin lymph in vivo.

Ultraviolet (UV) irradiation of the skin induces complex local and systemic immunomodulatory reactions. The biological effects of UV irradiation on human skin derived afferent lymph however are unknown. The aim of this study was to examine the effects of a single combined UV-A and UV-B irradiation with 1 minimal erythema dose (MED) on human skin derived lymph in vivo. After cannulation of a superficial lymph vessel on the lower leg, lymph flow and cell output per hour were determined before and for 6 days after UV irradiation of the lymph draining skin area in 5 volunteers. Furthermore, expression of CD1a, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells and cytokine levels (IL-1alpha, IL-1beta, IL-2, IL-6, IL-8, IL-10, IL-13, TNF-alpha and IFN-gamma) in the afferent lymph were analyzed by cytofluorometry and ELISA. After UV irradiation a small initial enhancement in the daily lymph flow per hour was noticed in correlation with the slight erythematous skin reaction. Following resolution of the skin reaction, a delayed increase in cell output in correlation with an additional peak in the lymph flow was found between the 4th and 6th day after UV irradiation. However, no changes in the expression of CD1a, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells were detectable. Interestingly, in parallel to the increased lymph flow and cell output, only elevated IL-8 protein levels were reproducibly detected in the afferent lymph after UV irradiation. Furthermore, using immunohistochemistry positive staining for IL-8 was found on migrating mononuclear lymph cells. In conclusion, our data demonstrate that a single UV irradiation of the skin with 1 minimal erythema dose leads to a delayed enhancement of lymph flow, number of migrating lymph cells and cytokine levels of IL-8. Moreover, we provide evidence that migrating lymph cells, besides resident epidermal and dermal cells, may contribute to the detected levels of IL-8 in the afferent lymph.

Adolescent↗

A preliminary study of the draining lymph node basin in advanced lower rectal cancer using a radioactive tracer.

PURPOSE: This study was designed to examine the draining lymph node basin at highest risk of metastasis in lower rectal cancer using 99 mTc-tin colloid. METHODS: In 43 patients, the area with highest hot nodes density was defined as the draining lymph node basin using a gamma probe. Metastatic states of all removed lymph nodes were examined histologically. RESULTS: A total of 203 hot nodes were identified in 39 patients (91 percent) with a mean of 5.2 nodes. The number of removed lymph nodes was 808 nodes: 670 nodes in the mesorectum, and 138 nodes in the pelvis. In 21 patients, the metastatic states of 119 nodes were investigated histologically. From the distribution of the identified hot nodes, the draining lymph node basins were classified into two patterns: lateral type (n = 17), and mesorectal type (n = 22). Only 20 (17 percent) of 119 positive nodes were identified as hot node. Tumor cells that occupied the lymph node diffusely or massively probably interfered with the exact diagnosis of metastasis. Lymph node metastasis in the pelvis was observed in 5 patients (13 percent). One false negative was of the mesorectal type with diffuse metastases in the para-aortic lymph nodes. The remaining four patients were of the lateral type and all positive lymph nodes, including positive nonhot nodes, were located within the draining lymph node basin. Consequently, in 20 (95.2 percent) of 21 patients with lymph node metastasis, all positive lymph nodes were located within the draining lymph node basin of the tumor. CONCLUSIONS: Two types of the draining lymph node basin of advanced lower rectal cancer were identified using this method. The concordance between lymph node metastases and the draining lymph node basin is good.

Female↗