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Detection of contact sensitivity of metal salts using the murine local lymph node assay.

The local lymph node assay (LLNA) is a predictive test for the detection of contact allergens. Nickel and chromium sensitization are common cases in man. However, in a previous study topical application of nickel sulfate and potassium dichromate in aqueous solution failed to induce activation in the draining lymph node. This study describes the application of LLNA to evaluate the contact sensitivity of metal salts. The metal salts were applied in dimethylsulfoxide or aqueous ethanol solution. In some experiments, the skin of the ears was gently abraded using a needle prior to application of metal salts. The ability of seven metal salts to induce lymph node cell (LNC) proliferation was compared. Nickel, cobalt, chromium and copper salts increased LNC proliferation, whereas zinc, manganese and iron salts failed to induce LNC proliferation in this assay.

Animals↗

99mTc-Tetrofosmin pinhole-SPECT (P-SPECT) and radioguided sentinel node (SN) biopsy and in breast cancer axillary lymph node staging.

We compared 99mTc-Tetrofosmin P-SPECT with radioguided SN biopsy in 101 T1/T2 BC pts to predict axillary lymph node status. The day before surgery all pts underwent lymphoscintigraphy (LS) to mark the SN, following subdermal injection of 99mTc-colloidal sulphur surrounding the breast lesion. LS was combined with pre and intraoperative gamma probe. Previously, all pts had also undergone P-SPECT. ALND was performed in all cases. The SN(s) was detected in 97/101 cases (96%) by LS and gamma probe; in the 4 missed cases P-SPECT predicted lymph node status. In the 97 comparable cases, radioguided SN biopsy showed a slightly higher accuracy than P-SPECT (94.8% vs 93.8%), but a higher false-negative rate (14.3% vs 8.6%); P-SPECT had a higher NPV (95.2% vs 92.5%). The two procedures when combined achieved 100% accuracy. Radioguided SN biopsy alone had 100% accuracy only in pts with BC < 15 mm. P-SPECT had 3 false negative cases, 2 of which were micrometastatic SNs, and 3 false positives. P-SPECT identified 81.2% of cases with a single node, determined the exact number of nodes in 82.6% of cases with 1 to 3 node and correctly classified 93.7% of pts as having < or = 3 or > 3 metastatic nodes. Radioguided SN biopsy seems indicated in selected, early stage, small BC pts, while P-SPECT shows a high sensitivity independent of primary tumor size, giving additional important preoperative prognostic information. The two procedures combined provided a better axillary lymph node status prediction in T1/T2 carcinomas, and could thus improve ALND pt selection.

Adult↗

Regulation of lymph node vascular growth by dendritic cells.

Lymph nodes grow rapidly and robustly at the initiation of an immune response, and this growth is accompanied by growth of the blood vessels. Although the vessels are critical for supplying nutrients and for controlling cell trafficking, the regulation of lymph node vascular growth is not well understood. We show that lymph node endothelial cells begin to proliferate within 2 d of immunization and undergo a corresponding expansion in cell numbers. Endothelial cell proliferation is dependent on CD11c+ dendritic cells (DCs), and the subcutaneous injection of DCs is sufficient to trigger endothelial cell proliferation and growth. Lymph node endothelial cell proliferation is dependent on vascular endothelial growth factor (VEGF), and DCs are associated with increased lymph node VEGF levels. DC-induced endothelial cell proliferation and increased VEGF levels are mediated by DC-induced recruitment of blood-borne cells. Vascular growth in the draining lymph node includes the growth of high endothelial venule endothelial cells and is functionally associated with increased cell entry into the lymph node. Collectively, our results suggest a scenario whereby endothelial cell expansion in the draining lymph node is induced by DCs as part of a program that optimizes the microenvironment for the ensuing immune response.

Animals↗

[A controlled survey comparing 2 short-term therapeutic regimes in lymph node tuberculosis].

To study the efficacy of short term chemotherapy in the treatment of peripheral glandular tuberculosis a controlled trial was carried out in Algiers in March 1982 comparing two therapeutic regimes. All the patients admitted to the study presented with glandular tuberculosis which was proved either histologically or bacteriologically. They were recruited in three clinics serving the Algerian population and were required to live in Algiers. The two anti-tuberculous regimes used consisted of an initial phase of four drugs: Rifampicin (R), Isoniazid (H), Streptomycin (S) and Pyrazinamide (Z) every day for two months. This initial phase was followed by R.H. every day for four months in regime A, making six months treatment in all and for seven months in regime B making nine months treatment in all. 141 patients were thus admitted to the study, of whom 117 could be used for analysis at the end of treatment. Of these 68 were female making up 58% of the total. 12 patients or 10% were under 15 years of age. After two years of review following the end of treatment there were nine therapeutic failures (7.7%) of whom five were in regime A and four were in regime B (no significant difference). Amongst the failures large volume nodes persisted in three patients and two patients presented with new nodes. The lymph nodes increased in volume at the end of treatment in two cases; and finally two patients presented again with fistulae at the end of treatment. There were eight unfavourable outcomes in nine patients under observation during treatment or at the end of chemotherapy. There was only one failure noted some time after the finish of treatment at the end of two years of follow up.

Adolescent↗

Laparoscopic approach to retroperitoneal lymph node dissection.

Laparoscopic retroperitoneal lymph node dissection is a new surgical procedure used to enhance staging in men with clinical stage I nonseminomatous germ cell tumors of the testis. The procedure has been performed in a limited number of patients at several centers with extensive laparoscopic experience. Laparoscopic retroperitoneal lymphadenectomy is a technically demanding procedure which can be successfully completed in the majority of patients. However, the risk of complications is greater than in patients who undergo standard open retroperitoneal lymph node dissection. The primary advantage of a laparoscopic approach is shortened hospitalization and rapid return to normal activity. The role of laparoscopy in the management of patients with testis malignancy has not been defined. The use of this staging procedure may help minimize the need for surveillance studies following surgery and may be best utilized in men with a lower likelihood of nodal metastases. Ultimately, prospective study in large groups of patients will be necessary to determine the role of laparoscopic retroperitoneal lymph node dissection in patients with testis cancer.

Activities of Daily Living↗

The fertility of patients with clinical stage I testis cancer managed by nerve sparing retroperitoneal lymph node dissection.

Nerve sparing retroperitoneal lymph node dissection reliably preserves emission and ejaculation in patients with clinical stage I nonseminoma. The fertility of 51 patients who underwent nerve sparing retroperitoneal lymph node dissection was assessed by 3 different methods: standard semen analysis, analysis of chromatin content by deoxyribonucleic acid histogram and assessment of ultimate fertility status by a questionnaire. Approximately 75% of these patients have semen analyses generally considered to be in the normal range. Virtually all patients who underwent deoxyribonucleic acid histogram analysis had histograms similar to controls. A retrospective analysis of fertility was performed in 201 patients who had previously undergone nerve sparing retroperitoneal lymph node dissection. Of these patients who attempted pregnancy after nerve sparing retroperitoneal lymph node dissection 76% have been successful. Approximately 75% of patients who present with clinical stage I nonseminoma are potentially fertile. Nerve sparing retroperitoneal lymph node dissection is capable of preserving this potential in allowing these patients to father children.

Female↗

Benign mesothelial cells in mediastinal lymph nodes.

Inclusions of benign tissues in lymph nodes are most often aberrant glandular tissue, including endosalpingiosis, the thyroid, parotid, breast, and pancreas. Nonglandular inclusions are rare and include nevus cells and decidua. Mesothelial cells in lymph nodes are exceedingly rare; only eight cases have been reported in mediastinal lymph nodes and three cases in abdominal lymph nodes. The incidence of benign mesothelial cells in mediastinal lymph nodes in patients with a history of pericarditis or pleuritis is reported in this study. A retrospective search showed eight cases with removal of mediastinal lymph nodes in the absence of neoplasm. Hematoxylin and eosin-stained sections were examined in all cases. Immunohistochemical stains for CAM 5.2 were performed in all cases, and stains for AE1/AE3, Ber-EP4, carcinoembryonic antigen, Leu-M1, B72.3, and S-100 were performed in one case. CAM 5.2-positive cells with features of mesothelial cells were present in five of eight cases. In all cases, the cells were present in nodal sinuses and appeared as single cells or small clusters. The cells were missed on routine hematoxylin and eosin sections in all cases but one, in which they were numerous and mimicked metastatic carcinoma. Malignancy was not found in any of the cases preoperatively, at the time of surgery, or during the follow-up period. Benign mesothelial cells may embolize to regional lymph nodes in pleuritis or pericarditis. In most cases, these cells are few and undetectable on routine sections. Rarely, hyperplastic mesothelial cells may be present and must be distinguished from metastatic carcinoma, mesothelioma, and melanoma.

Adult↗

Frequency distribution of plasma cells in the medullary cords of tumour-draining axillary and paracolic lymph nodes.

Five hundred and ninety-seven axillary lymph nodes draining 104 invasive ductal breast cancers, and 94 paracolic lymph nodes draining 30 invasive adenocarcinomas of the large bowel were investigated immunohistologically to determine the frequency distribution of plasma cells (PC) in the medullary cords (MC). The degree of plasmacytic infiltration was calculated semiquantitatively using the 3-grade scale (0/+, + +, + + +) of Cottier et al. (1973). Statistical analysis yielded the following results: While a marked reactive plasmacytosis (+ + +) was seen in 28.7% of the paracolic lymph nodes, only 1.5% of the axillary lymph nodes exhibited a comparable degree of plasmacytic infiltration (p less than 0.0001). Conversely, low PC counts (0/+) were encountered in 51.1% of the paracolic lymph nodes, but in 83.9% of the axillary lymph nodes. A comparison of axillary lymph nodes with and without nodal metastasation revealed no significant differences (nodal-negative cases: 0/+: 83.6%, + +: 14.3%, + + +: 2.1%; nodal-positive cases: 0/+: 84.3%, + +: 14.9%, + + +: 0.8%). However, significantly more (p less tha 0.001) paracolic lymph nodes of the nodal-negative group revealed a marked plasmacytosis, whereas in the nodal-positive group lymph nodes with low PC counts were more frequent (nodal-negative cases: 0/+: 27.7%, + +: 29.7%, + + +: 42.6%; nodal-positive cases: 0/+ 74.5%, + +: 10.6%, + + +: 14.9%). The degree of plasmacytic reactions in the tumour-regional lymph nodes was not related to the stage of the primary tumour. Moreover, no correlation exists between the PC content of the MC and the amount of PC in metastatic deposits of the same lymph nodes. Altogether, these results do not support the concept that the plasmacytic reactions in the MC of tumour-draining lymph nodes are chiefly determined by effects (stimulating or suppressing) of the primary carcinomas. The topography of the lymph nodes, however, seems to be the main determinant influencing the PC content of MC.

Adenocarcinoma↗

Prognostic role of sentinel lymph node biopsy in breast cancer.

Sentinel lymph node biopsy was shown to be an accurate procedure in the study of axillary lymph nodes; it allowed a marked decrease in surgery-related morbidity of breast cancer and axillary dissection could be avoided. Other parameters as molecular markers, nuclear grading, patient age, tumor size, are not able to predict the axillary lymph node status and consequent local therapeutic approach similar to those provided by sentinel lymph node biopsy. The extent of sentinel lymph node metastatic involvement, the extracapsular spread, the size of primary tumor and peritumoral lymphatic/vascular infiltration are the four characteristics shown to be significant, if considered in association and not separately as predictors of the extent of axillary involvement in presence of a positive sentinel lymph node. However, so far, specific studies did not confirm concordant and reproducible results. Therefore, apart from controlled studies, axillary dissection is always required in presence of a metastatic sentinel lymph node.

Axilla↗

Clinicopathologic features associated with having four or more metastatic axillary nodes in breast cancer patients with a positive sentinel lymph node.

BACKGROUND: The survival benefit of a completion axillary lymph node dissection (ALND) in patients after removal of a metastatic sentinel lymph node (SLN) is uncertain and is under study in ongoing clinical trials. The completion ALND remains necessary, however, for the identification of cases with at least four metastatic lymph nodes, in which extended-field locoregional and/or postmastectomy radiation will be recommended. Our goal was evaluate clinicopathologic features that might serve as surrogates for determining which patients with a positive SLN are likely or unlikely to belong to this high-risk subset. METHODS: Records were reviewed for 285 patients from 2 comprehensive cancer centers who underwent completion ALND after resection of a metastatic SLN from 1995 to 2002. Clinicopathologic features were analyzed by univariate and multivariate logistic regression. Forty-one cases (14%) were found to have at least four positive nodes after ALND. RESULTS: Fisher's exact test revealed the following features to be significantly (P < .05) associated with having four or more nodal metastases: tumor size >2 cm, lymphovascular invasion, an increasing ratio of positive SLNs to the total number of resected SLNs, extranodal extension, and the size of the SLN metastasis. Patients whose largest SLN metastasis was <2 mm had only a 1.4% risk of having four or more metastatic nodes (P < .0001). CONCLUSIONS: We conclude that patients with SLN micrometastases face an extremely low likelihood of having extensive nodal disease on completion ALND. Patients with larger primary tumors, lymphovascular invasion, and extranodal extension are more likely to have ALND findings that will affect their cancer management.

Adult↗

Lymphatic obstruction and lymph node changes--a study of the rabbit popliteal node.

Dense cortical lymph node fibrosis is associated with primary lymphedema and proximal obstructive hypoplasia. The fibrosis is not related to the duration of disease nor to episodes of clinical cellulitis. This suggests that the disease may start in the nodes but the effects of obstruction in the adjacent lymph vessel must be elucidated before the assumption is made. The popliteal nodes of 49 rabbits were studied following the ligation of either afferent or efferent lymphatics, and compared with nodes following a sham operation. The efficacy and late effects of ligation were assessed in half the rabbits by cinelymphangiography. In the rest Patent Blue Violet and not Lipoodol was used to minimize any spurious effect on node histology. The rabbits were sacrificed between 6-84 days. Node area was measured on serial x-rays and node volume after removal of the node. Afferent ligation resulted in a significant and permanent decrease in size (p less than 0.005) and lymphocytic congestion; efferent ligation resulted in an increase in size (p less than 0.02) and large lymph spaces. The dense node fibrosis of primary lymphedema was not seen.

Animals↗

Prognostic significance and surgical management of lymph node metastasis in gastric cancer.

Regional lymph node metastasis is a critical prognostic factor in gastric cancer, and extended lymph node dissection and routine microscopic examination of all resected nodes could potentially provide accurate information regarding lymph node status. On the other hand, the therapeutic value of extended lymph node dissection is controversial. While retrospective and prospective nonrandomized comparative studies have shown that extended lymph node dissection significantly improves the survival rate, two prospective randomized trials have failed to demonstrate the efficacy of extended dissection, although the number of patients in these studies was limited. There is a further, ongoing, trial involving a larger series of patients; the final results of this study should help to determine whether extended lymph node dissection is of therapeutic or merely prognostic value in gastric cancer.

Humans↗

Reliability of intraoperative frozen section and imprint cytological investigation of sentinel lymph nodes in breast cancer.

AIMS: The sentinel lymph node procedure enables selective targeting of the first draining lymph node, where the initial metastases will form. A negative sentinel node (SN) predicts the absence of tumour metastases in the other regional lymph nodes with high accuracy. This means that in the case of a negative SN, regional lymph node dissection is no longer necessary. Besides saving costs, this will prevent many side-effects of lymph node dissection. The aim of this study was to evaluate the reliability of intraoperative cytological and frozen section investigation of the SN to detect metastases. This would allow the axillary lymph node dissection to be performed in the same session as the SN procedure and the excision of the primary tumour in case of a positive SN. METHODS AND RESULTS: Seventy-four SNs were detected by gamma probe detection of nanocolloid and visual localization of Patent Blue accumulations in 54 women with stage T1-2N0M0 invasive breast cancer. The identified SN were immediately investigated by frozen section and imprint cytological investigation. Diagnoses were confirmed on the paraffin material, and in case of negative frozen section and paraffin haematoxylin and eosin sections, skip sections and immunohistochemistry were performed. Thirty-one SNs (42%) contained metastases, of which 27 were detected by the frozen section procedure (sensitivity 87%). There were no false positives (specificity 100%). The sensitivity of the imprints was 62% with a specificity of 100%. When evaluating the data per patient, for the frozen section procedure the sensitivity was 91% and the specificity 100%, and for the imprints, the sensitivity was 63% and the specificity 100%. There were no SNs in which the imprints showed metastases and the frozen section did not. CONCLUSIONS: Intraoperative frozen section analysis is a reliable procedure by which a high percentage of sentinel lymph node metastases can be detected in breast cancer patients without false positive results. This allows the surgeon to perform an immediate axillary lymph node dissection in case of positive SNs. In up to 10% of cases, the final paraffin sections will reveal micrometastases that were not detected by the frozen section, and in these patients axillary lymph node dissection will have to be performed in a second session. The imprint method is significantly less sensitive than the frozen section but may be used as an alternative when frozen section is not possible.

Adult↗

Penile cancer--the sentinel lymph node controversy.

The management of lymph nodes in penile cancer has always been a problem. Sentinel lymph node biopsy was supposed to solve this problem but has not been universally accepted due to conflicting results. We herein present a case of penile cancer with bilateral pathologically positive inguinal lymph nodes associated with concurrent negative sentinel lymph node biopsies. We discuss the possible reasons for this situation and suggest guidelines to study this issue.

Biopsy↗

The effects of bacterial lipopolysaccharide (LPS) on high endothelial venules and interdigitating cells in mouse lymph nodes.

Migration of lymphocytes into lymph nodes is directly controlled by interaction of lymphocytes with the high endothelial venules (HEV), located in T cell-dependent areas of lymph nodes. Little is known about the mechanisms that regulate the activity of the HEV and the specificity of interaction with lymphocytes in various lymphoid organs. It has been suggested that the non-lymphoid interdigitating cells (IDC) play a role in maintaining the integrity of T cell areas. We therefore wished to determine whether the function of the HEV could be influenced by disturbing the integrity of the T cell area. This was assayed in mice by injecting bacterial lipopolysaccharide (LPS) in the hind footpad. The T cell-dependent areas of mouse popliteal lymph node were studied using immunohistochemistry, and attention was paid to the HEV specificity using short-term in vivo localization assays and in vitro lymphocyte binding assays. After LPS administration, apparent changes in the number of interdigitating cells and T cells in the draining lymph node were found. In addition, interdigitating cells lost their typical dendritic appearance. However, after LPS treatment, neither size, localization nor receptor specificity for lymphocyte subsets of HEV differed from control HEV. Although administered subcutaneously in the footpad, the effect of LPS on T cells and IDC was much more dramatic in the spleen than in the draining lymph nodes. This points to a difference in the processing of the endotoxin in the two organs.

Animals↗