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Use of in situ spermatic cord patch for inguinal lymph node dissection.

Inguinal lymph node dissection for diagnosis of metastatic squamous cell carcinoma of the penis can cause significant morbidity and mortality for patients due to local wound breakdown, lymphedema, and vascular erosion. Various methods have been described to cover exposed femoral vessels to preserve their integrity, the most common being transposition of the sartorius muscle. We describe the successful use of in situ spermatic cord for coverage of the femoral artery and vein after inguinal lymph node dissection for squamous cell carcinoma of the penis in two patients. To our knowledge, this has not been previously described and is a simple and successful alternative way to cover the femoral vessels after inguinal lymphadenectomy.

Aged↗

The role of sentinel lymph node biopsy for melanoma.

Regional lymph nodes are a common site of melanoma metastases, and the presence or absence of melanoma in regional lymph nodes is the single most important prognostic factor for predicting survival. Furthermore, identification of metastatic melanoma in lymph nodes and excision of these nodes may enhance survival in a subgroup of patients whose melanoma has metastasized only to their regional lymph nodes and not to distant sites. Sentinel lymph node (SLN) biopsy was developed as a low morbidity technique to stage the lymphatic basin without the potential morbidity of lymphedema and nerve injury. The presence or absence of metastatic melanoma in the SLN accurately predicts the presence or absence of metastatic melanoma in that lymph node basin. When performed by experienced centers, the false-negative rate of SLN biopsy is very low. As such, the nodal basin that contains a negative SLN will usually be free of microscopic disease. Since occult micrometastatic disease affects only 12% to 15% of patients with melanoma, selective SLN dissection allows up to 85% of patients with melanoma to be spared a formal lymph node dissection, thus avoiding the complications usually associated with that procedure. While standard pathologic evaluation of lymph nodes may miss metastatic melanoma cells, more sensitive techniques are developing which may identify micrometastases more accurately. The clinical significance of these micrometastases remains unknown and is the subject of active investigations.

Coloring Agents↗

Electrophoretic fractionation of guniea pig lymphocytes: evidence for different subsets of T and B cells in spleen and lymph node.

Guinea pig lymph node and blood lymphocytes have been physically fractionated in preparative cell electrophoresis into two functionally viable populations, the high mobility cell population (HMC) and the low mobility cell population (LMC). By using cell surface markers and functional tests known to be specific for T and B lymphocytes, respectively, it is shown that the T lymphocytes localize in the HMC population and the B lymphocytes in the LMC population. The spleen lymphocytes do not separate into the two populations. They move into one single broad peak containing both T and B cells. This finding indicates the presence of electrokinetically different subsets of T and B lymphocytes in the spleen on one hand and in the lymph node and blood on the other hand.

Animals↗

Predictors for nonsentinel node involvement in breast cancer patients with micrometastases in the sentinel lymph node.

Sentinel lymph node (SLN) biopsy in breast cancer allows for a more thorough pathologic assessment with serial sectioning and cytokeratin staining. This has resulted in increased detection of micrometastatic disease (tumor size < 2 mm) in the SLN. Unfortunately, the value of completion axillary dissection after finding micrometastatic disease in the SLN remains poorly defined. Over a 2-year period, a prospective database of 305 patients who underwent SLN biopsy for breast cancer at Baylor University Medical Center was reviewed. Eighty-four (27.5%) of the patients had evidence of metastatic disease in the SLN. Twenty-four of the 41 patients identified as having micrometastatic disease in the SLN underwent completion axillary lymph node dissection. In these patients, all nonsentinel nodes were further studied by serial sectioning and immunohistochemistry. The median age of these 24 patients was 52 years (range, 34-83). Their primary tumor stages were T1a and T1b (n = 5), T1c (n = 15), and T2 (n = 4). A total of 328 nonsentinel lymph nodes were examined, including 225 from patients with infiltrating ductal carcinoma (n = 17) and 103 from patients with infiltrating lobular carcinoma (n = 7). In the patients with infiltrating ductal carcinoma, no additional nodal metastases were identified, while in those with infiltrating lobular carcinoma, additional nodal disease was found in 5 lymph nodes (2 of 12 patients, 17%). Primary tumor characteristics were not predictive of additional nodal disease. These data suggest that patients with micro-metastasis in the SLN from infiltrating lobular carcinoma have a significant risk of harboring additional nodal disease and should undergo completion axillary dissection. However, those with micrometastatic disease from infiltrating ductal carcinoma have a very low incidence of additional metastasis and may not need completion axillary dissection.

Journal Article↗

Accuracy of pathologic techniques for the diagnosis of metastatic melanoma in sentinel lymph nodes.

BACKGROUND: Sentinel lymph node (SLN) biopsy can accurately predict the presence of metastatic melanoma (MM) and has been used to identify patients with occult metastases. We present an analysis of the sensitivity and specificity of standard pathological techniques including intraoperative frozen section, permanent section, and immunohistochemistry in diagnosing MM within the SLN. METHODS: Sixty-nine consecutive patients with primary malignant melanoma thickness of >1.0 mm or thinner lesions invading the reticular dermis (Clark level IV) who underwent SLN biopsy were reviewed. Lymph nodes were examined intraoperatively by frozen section (FS), permanent section (H&E), and by immunohistochemistry (IH) for S-100 protein and HMB45. RESULTS: MM was found in 14 of 69 cases (20%). Permanent section H&E was performed in all cases, FS in 64 cases, and IH in 65 cases. FS analysis diagnosed MM in 4 of 14 cases (29%), was suspicious in 2 of 14 (14%), and falsely negative (FN) in 8 of 14 (57%) ultimately found to be positive with further workup. Within the FN group, MM was identified on review of the original FS slides in 3 of 8 cases (38%). Furthermore, within the FN group, the remaining 5 cases were identified as positive for MM by either permanent and/or deeper H&E sections and IH. IH alone with permanent H&E sections would have diagnosed MM in only 8 of 10 cases (80%) that were FS negative or suspicious. In no cases was MM identified by IH alone with the permanent and deeper H&E sections being negative. It is noteworthy that no false-positive cases were identified. CONCLUSIONS: Intraoperative FS has low sensitivity in identifying MM within the SLN. IH alone does not increase the diagnostic yield. A combination of permanent H&E sections with deeper levels and S-100 and HMB45 IH dramatically increases the overall diagnostic sensitivity of SLN biopsy. Definitive diagnosis should await permanent H&E sections and IH staining.

Adult↗

Development of 125I-methylene blue for sentinel lymph node biopsy.

BACKGROUND: Sentinel lymph node biopsy is an established alternative to complete lymph node dissection in some patients. We have developed a novel, radiolabeled methylene blue dye that may be a useful alternative to the traditional two-step procedure involving 99mTc-labeled colloid and unlabeled blue dye. We hypothesize that 125I-labeled methylene blue will be rapidly absorbed into the lymphatics and transported to the drainage basin containing the sentinel nodes. MATERIALS AND METHODS: Rabbits footpads were injected with 1 mCi of 125I-labeled methylene blue admixed with unlabeled dye. A hand-held gamma detection device allowed tracking of radiolabeled dye to nodes in the popliteal and inguinal regions. At pre-established time points animals were sacrificed, and the nodal basin dissected. Nodal radioactivity as well as uptake of blue dye was recorded. RESULTS: The spread of the radiolabeled methylene blue compound from the footpad to the popliteal lymph nodes occurred in 5-10 min. CONCLUSION: The radiolabeled dye rapidly progresses through lymphatics to the draining nodes. Use of radiolabeled methylene blue may be an attractive alternative to current two-step sentinel node techniques, as it may be less painful, and may reduce the cost associated with the time-delay between the injection of the radioactive compound and surgery.

Animals↗

The unique ultrastructure of high-endothelial venules in inguinal lymph nodes of the pig.

Lymph nodes in pigs are unique in their inverted structure, with the medulla in the periphery and the cortex in central areas. Furthermore, in this species most migrating lymphocytes do not use the classical route via efferent lymphatics to leave the lymph node. High-endothelial venules (HEV) are the entry sites for lymphocytes and in pigs probably also the exit site for recirculating lymphocytes. Therefore, the blood vessels and especially the HEV of the pig superficial inguinal lymph node were investigated as to whether morphological peculiarities could be found in the vascular system, using vascular casting, transmission- and scanning electron microscopy. A thin layer of capillary network surrounded the periphery of the lymph node and HEV branched acutely. The endothelial cells of HEV possessed well developed cytoplasmic organelles, interdigitated with each other, and demonstrated local cell-cell contacts. There were unusual cells bridging the adluminal wall of HEV. These cells were called intravascular bridging cells. They were characterized by an often invaginated nucleus, few pinocytotic vesicles, many microvilli on the surface, wide, flat, cytoplasmic processes like a pseudopod, Weibel-Palade bodies and local cell-cell contacts with endothelial cells. The pseudopod-like processes ramified over the endothelial junctions and covered lymphocytes. Lymphocytes were seen in different phases of migration between endothelial cells and in the intercellular junctions. The previous functional studies on the peculiar route of lymphocyte recirculation in pig lymph nodes are extended by these morphological data, showing a unique structure of HEV in pigs.

Animals↗

Overexpression of vascular endothelial growth factor-C correlates with lymph node micrometastasis in submucosal esophageal cancer.

Lymph node metastasis, including lymph node micrometastasis (LMM), is one of the most important prognostic factors in esophageal squamous cell carcinoma (ESCC). Vascular endothelial growth factor C (VEGF-C) plays a key role in the process of lymphangiogenesis. We examined VEGF-C expression and tumor microvessel density of the primary tumors in ESCC and analyzed relationships between VEGF-C expression and clinicopathologic findings including LMM in submucosal ESCC. The subjects were 87 patients with submucosal ESCC. Immunohistochemical staining of VEGF-C and CD34 was performed with primary tumors, and staining of cytokeratin was performed with dissected lymph nodes. Microvessel density was calculated from CD34 expression, and LMM was detected by cytokeratin staining. VEGF-C overexpression significantly correlated with depth of tumor invasion, lymphatic invasion, and lymph node metastasis (P < 0.05, P < 0.0001, and P < 0.0001, respectively). High microvessel density also correlated with lymphatic invasion and lymph node metastasis (P < 0.005 and P < 0.05, respectively). LMM was detected in 8 cases and 14 lymph nodes by cytokeratin staining. VEGF-C overexpression and high microvessel density were found in tumors with lymph node metastasis and/or LMM, compared with tumors without nodal metastasis or LMM (P < 0.0001 and P < 0.01, respectively). The present findings indicate that in ESCC with submucosal invasion, VEGF-C overexpression of the primary tumor is a strong high risk factor for lymph node metastasis, including LMM.

Adult↗

[An anatomical and pathological study of autopsy material on the metastasis of pancreatic cancer to para-aortic lymph nodes].

The purpose of the present study was to clarify the anatomy of the lymphatic system of the para-aortic region with special reference to lymphatic pathways from the pancreas, and the incidence and extent of lymphatic metastases of pancreatic cancer to para-aortic lymph nodes. Lymph nodes were found mostly on the bilateral and anterior sides of the aorta, and rarely on its posterior side. Lymphatic vessels from the pancreas (peripancreatic nodes) were closely related to the para-aortic lymph nodes on the bilateral and anterior surfaces of the aorta ranging from the root of the celiac artery and that of the inferior mesenteric artery. Out of 10 autopsy cases of relatively small pancreatic cancer, 4 cases were found to have microscopic metastases in a few para-aortic lymph nodes. The localization of involved para-aortic nodes was compatible with that of anatomically related para-aortic lymph nodes. Lymph node dissection of the para-aortic region, if carried out in a patient with a possibility of radical resection of the primary pancreatic cancer, should be an en bloc resection of lymph nodes and surrounding soft tissues in the area ranging between the root of the celiac artery and that of the inferior mesenteric artery.

Aged↗

Intraoperative evaluation of sentinel lymph nodes for breast carcinoma: current methodologies.

Sentinel lymph node biopsy is an important new addition to the surgical management of patients with breast carcinoma. Sentinel nodes have a higher chance of containing metastases than do nonsentinel nodes. Sentinel lymph node biopsy provides an opportunity to stage breast carcinoma patients more accurately and to modify subsequent treatment. One of the most exciting current roles of sentinel lymph node biopsy is the ability to stage patients intraoperatively, allowing a one-step axillary lymph node dissection if the sentinel lymph node contains metastatic carcinoma. Currently, intraoperative evaluation of sentinel lymph nodes is performed using imprint cytology with or without rapid cytokeratin staining, frozen sectioning with or without rapid cytokeratin staining, scrape preparations, or some combination of these techniques. We review the relative strengths and weaknesses of these different methodologies. A great deal of controversy exists regarding the management of patients with metastatic breast carcinoma, particularly those patients with occult and micrometastatic disease. These issues are beyond the scope of this article.

Breast Neoplasms↗

The sequence of changes in blood flow and lymphocyte influx to stimulated rat lymph nodes.

The rat popliteal lymph node was studied from 1 hr to 8 days after the footpad injection of either sheep erythrocytes or syngeneic rat erythrocytes. The following were measured relative to the contralateral (unstimulated) lymph node: (i) blood flow; (ii) lymph node weight; (iii) influx of lymphocytes from the blood; (iv) [3H]-thymidine incorporation; (v) [35S]-sulphate incorporation into macromolecular form (chiefly by high endothelial venules). After the arrival of sheep erythrocytes all five quantities showed substantial increases which began in a definite sequence. The blood flow started to rise first and may have been the main factor contributing to the later increase in lymphocyte influx. Increased sulphate incorporation began later than the rise in lymphocyte influx. After the injection of rat erythrocytes a small increase in lymphocyte influx was found without a corresponding increase in blood flow. In rats irradiated before the footpad injections lymphocyte influx increased three-fold after sheep erythrocytes, rat erythrocytes or PBS, again without a corresponding increase in blood flow. Thus while variation in blood flow to high endothelial venules is one important factor in determining the supply of lymphocytes to the lymph node other factors are operative in certain situations.

Animals↗

Evaluation of sentinel node concept in gastric cancer based on lymph node micrometastasis determined by reverse transcription-polymerase chain reaction.

OBJECTIVE: To determine the adequacy of sentinel node (SN) concept based on micrometastasis using immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) in gastric cancer. SUMMARY BACKGROUND DATA: The SN concept has recently been introduced in gastrointestinal tract cancers. The precise detection of lymph node metastasis including micrometastasis is important for SN navigation surgery. METHODS: Sixty-one patients with gastric cancer who were preoperatively diagnosed with T1-T2 (cT1-T2) and N0 (cN0) were enrolled. They underwent standard radical gastrectomy with lymph node dissection. One day before surgery, 4 mCi of (99m)Technetium-tin colloid was endoscopically injected into the submucosa around the tumor. During surgery, radioisotope uptake in the lymph node was measured using Navigator GPS. All dissected lymph nodes were examined by RT-PCR in addition to hematoxylin and eosin staining and IHC. RESULTS: Sentinel nodes were identified in all patients (100%). The incidences of metastasis determined by hematoxylin and eosin and IHC were 8.2% (5 of 61) and 13.1% (8 of 61), respectively. Micrometastases undetectable by IHC were identified in 14 patients (23.0%) by RT-PCR. Only 1 patient had micrometastasis detectable by RT-PCR in lymph nodes other than SN, but this patient had a cT2 tumor. In patients with cT1 and cN0 tumors, the false negative and accuracy rates were 0% and 100%, respectively. CONCLUSIONS: Although the incidence of micrometastasis detected by RT-PCR was quite high, SN navigation identified such metastasis in all patients except one. Thus, the SN concept was applicable to patients with cT1 and cN0 gastric cancer, even when micrometastasis was detectable by RT-PCR.

Adenocarcinoma↗

Should internal mammary nodes be sampled in the sentinel lymph node era?

BACKGROUND: Controversy exists regarding internal mammary lymph nodes (IMNs) in the staging and treatment of breast cancer. Sentinel lymph node identification with radiocolloid can map drainage to IMNs and directed biopsy can be performed with minimal morbidity. Furthermore, recent studies suggest that IMN drainage of breast tumors may be underestimated. To gain further insight into the prognostic value of IMNs, we reviewed the outcome of patients in whom the IMN status was routinely assessed. METHODS: A retrospective review of 286 patients with breast cancer who underwent IMN dissection between 1956 and 1987 was conducted. RESULTS: Median follow-up is 186 months, age was 52 years (range, 21-85 years), tumor size was 2.5 cm, and number of IMNs removed was 5 (range, 1-22); 44% received chemotherapy, 16% endocrine therapy, and 5% radiotherapy. Presence of IMN metastases correlated with primary tumor size (P < .0001) and number of positive axillary nodes (P < .0001) but did not correlate with primary tumor location or age. Overall, the 20-year disease-free survival is significantly worse for the 25% of patients with IMN metastases (P < .0001). In patients with positive axillary nodes and tumors smaller than 2 cm, there was a significantly worse survival (P < .0001) in the patients with IMN metastases. This difference in survival was not seen in women with tumors larger than 2 cm. CONCLUSIONS: Patients with IMN metastases, regardless of axillary node status, have a highly significant decrease in 20-year disease-free survival. Treatment strategies based on knowledge of sentinel IMN status may lead to improvement in survival, especially for patients with small tumors. At present, sentinel IMN biopsies should be performed in a clinical trial setting.

Adult↗

[A clinical study of immunological status in gastric cancer patients--with special reference to T-cell subsets in the lymphocytes of regional lymph nodes].

Non-metastatic regional lymph node lymphocytes of 41 patients with gastric cancer were studied by using different monoclonal antibodies and flow cytometry. Used monoclonal antibodies were OKT3 (total T; CD3), OKT4 (helper/inducer T; CD4), OKT8 (suppressor/cytotoxic T; CD8) and Leu11 (NK/K cell; CD16). The results were as follows: 1. The percentage of CD3 cells and CD4 cells were about ten point fewer in lymph nodes than in peripheral blood. 2. CD8 cells were found to be one half or one third lesser in lymph nodes than in peripheral blood. 3. CD16 cells were found to be rare in lymph nodes. 4. The percentage of CD3, CD4 and CD8 cells were higher in distal lymph nodes than proximal ones. 5. The percentage of CD3, CD4 and CD8 cells were not different with progression of the cancer, whereas CD3 cells and CD8 cells were decreased in lymph nodes of stage IV. 6. The percentage of CD8 cells was higher in distal nodes of stage III. Regional lymph nodes are necessary to protect against cancer metastasis, and killer T cells and cytotoxic T cells were fewer in lymph nodes. These results suggested that killer activity and cytotoxicity of the lymph node lymphocytes are inactive and anergy.

Adult↗

Diagnostic excision of the Rosenmüller's node. Screening for occult metastases before elective regional lymph node dissection in patients with lower limb melanoma?

Elective radical groin dissection was performed on 297 consecutive patients with high-risk melanoma of the leg, Anderson Stages I, IIA, IIIA. By separate histologic examination of the so-called "Rosenmüller's node," the other inguinal, and the external iliac lymph nodes, the diagnostic excision of the Rosenmüller's node was tested as a suitable mode of screening for metastases before a planned elective regional lymph node dissection. Eighty patients (27%) presented with what was histologically determined to be occult groin metastases. Rosenmüller's node was involved in 30 of these cases; in the remaining 50, however, it was not affected; that is, 63% of the cases were false-negative. Thus, the involvement of Rosenmüller's node is not representative of metastases in the other ilioinguinal lymph nodes, but is rather a matter of chance. In women with superficial spreading melanoma the rate of occult lymph node metastases was significantly lower than that in men with melanomas of the other type. Iliac lymph node involvement was observed in 18 patients (22%) depending on clinical stage and depth of invasion of the primary tumor.

Female↗

Prognostic factors for patients with node-negative gastric cancer: Can extended lymph node dissection have a survival benefit?

BACKGROUND AND OBJECTIVES: For the patients with node-negative gastric cancer, there is no agreement on which clinicopathological factors influence the final results except T stage. The aim of this study was to investigate the prognostic factors, and to reveal whether the extent of lymph node dissection is associated with survival benefit for these patients. METHODS: Clinicopathological data of 506 patients with node-negative gastric cancer were studied. We divided the patients into D1 and D2 groups and carried out univariate and multivariate survival analyses. RESULTS: On the univariate analysis, the factors influencing survival were age, tumor size, Borrmann type, resection type, and the T stage. However, multivariate analysis with the Cox proportional hazard model disclosed age and the T stage to be significant variables. The extent of lymphadenectomy was revealed to be the independent prognostic factors for survival only for the patients with T3 stage. CONCLUSIONS: For the patients with clinically node-negative gastric cancer, an extended D2 lymph node dissection for the patients with T1 and T2 stage has no survival benefits. Although it might have some benefit for T3 stage by multivariate analysis, we should ascertain its value through a large randomized prospective study.

Aged↗

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↗