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Detection of carbonic anhydrase 9-expressing tumor cells in the lymph nodes of vulvar carcinoma patients by RT-PCR.

Regional lymph node status is an important prognostic factor for vulvar cancer. The goal of our study was to elaborate a reliable test for detecting micrometastases, undetectable by traditional methods, in the lymph nodes of vulvar squamous carcinoma patients. For this purpose, carbonic anhydrase-9 (CA9) was investigated as a cancer-related marker by RT-PCR. Firstly, primary carcinoma specimens were examined for CA9 expression by immunohistochemistry with M75 monoclonal antibody. All 19 tissues exhibited a variable degree of staining, which was mostly confined to the plasma membranes of tumor cells. Correspondingly, all primary tumor specimens and the control A-431 vulvar cancer cell line gave a positive signal in the nested RT-PCR assay designed to detect CA9-expressing cells with a high sensitivity. Analysis of 77 lymph node specimens from 20 patients revealed a full correlation between RT-PCR results and standard hematoxylin-eosin staining in 75% of samples, whereas 25% of specimens were negative by the standard method and positive for CA9 mRNA, accounting for 28% of all histologically negative lymph nodes. There were no false-negatives with RT-PCR. A positive inguinal lymph node with a negative sentinel node was observed in the same groin only once in 38 specimens. Our findings clearly indicate potential value of CA9 as a molecular marker for the assessment of regional lymph node status in vulvar cancer patients and support a possible utility of our RT-PCR assay in the detection of micrometastases.

Antigens, Neoplasm↗

Sentinel lymph node biopsy in children and adolescents with malignant melanoma.

BACKGROUND/PURPOSE: Sentinel lymph node biopsy (SLNB) provides valuable staging information for adult patients presenting with clinically localized cutaneous melanoma. There are little data pertaining to the use of SLNB in the pediatric melanoma population. The objective of this study is to investigate the use of SLNB in the pediatric population, focusing on its diagnostic and therapeutic implications. METHODS: Retrospective identification was made of patients 18 years or younger who underwent sentinel lymph node biopsy for clinically localized melanoma at Indiana University Medical Center between 1994 and 2001. Patient demographics, primary tumor thickness, location of primary tumor, presence of tumor ulceration, number of lymph nodes removed, pathology of examined nodes, and number of lymph nodes involved with tumor were recorded. Disease status and dates of last clinical contact were determined. RESULTS: Twelve patients, 18 years or younger, were identified. Mean age of the study population was 14.1 years (range, 4 to 18). Mean tumor thickness was 1.65 mm (range, 0.36 to 4.7 mm). Three patients (25%) had positive sentinel lymph node biopsies. All 3 patients underwent completion lymph node dissection (CLND). One patient had micrometastatic disease detected on CLND; he had recurrence 6.1 months later and died 7.5 months after his SLND/CLND. At a median follow-up of 11.7 months, the remaining 11 patients had not experienced recurrence. There were no complications related to the SLNB procedure. CONCLUSIONS: The minimally invasive surgical approach and limited complications associated with SLNB make this procedure a useful aid in assisting the physician in making therapeutic decisions in the pediatric melanoma patient.

Adolescent↗

Lymphatic mapping and sentinel lymph node biopsy in patients with melanoma of the lower extremity.

Lymphatic mapping and sentinel lymph node biopsy is a new technique used in the surgical treatment of patients with malignant melanoma. The purpose of this study was to evaluate the results of this approach for patients with melanoma of the lower extremity. Between May of 1994 and June of 1997 at the H. Lee Moffitt Cancer Center and Research Institute, 85 consecutive patients with clinical stage I and II melanoma of the lower extremity underwent lymphatic mapping and sentinel lymph node biopsy. These nodes were identified in all 85 patients by intraoperative lymphatic mapping with both radiolymphoscintigraphy and a vital blue dye injection. Eleven patients (12.9 percent) had histologically positive sentinel lymph nodes, and 10 patients underwent inguinal complete lymph node dissections. All 10 patients had no further histologically positive lymph nodes confirmed by subsequent complete dissection. Among 74 patients with histologically negative sentinel lymph nodes, only 2 patients (2.7 percent) developed inguinal nodal metastases during a mean follow-up period of 21.8 months (range, 13.5 to 58.3 months). The sensitivity of lymphatic mapping and sentinel lymph node biopsy in this series was 100 percent and the specificity was 97.3 percent. Therefore, we conclude that the use of lymphatic mapping and sentinel lymph node biopsy can accurately stage patients with melanoma of the lower extremity and provide a rational surgical approach for these patients.

Adolescent↗

Popliteal lymph node assay: facts and perspectives.

The popliteal lymph node assay (PLNA) derives from the hypothesis that some supposedly immune-mediated adverse effects induced by certain pharmaceuticals involve a mechanism resembling a graft-versus-host reaction. The injection of many but not all of these compounds into the footpad of mice or rats produces an increase in the weight and/or cellularity of the popliteal lymph node in the treated limb (direct PLNA). Some of the compounds known to cause these adverse effects in humans, however, failed to induce a positive PLNA response, leading to refinements of the technique to include pretreatment with enzyme inducers, depletion of CD4(+) T cells or additional endpoints such as histological examination, lymphocyte subset analysis and cytokine fingerprinting. Alternative approaches have been used to improve further the predictability of the assay. In the secondary PLNA, the test compound is injected twice in order to illicit a greater secondary response, thus suggesting a memory-specific T cell response. In the adoptive PLNA, popliteal lymph node cells from treated mice are injected into the footpad of naive mice; a marked response to a subsequent footpad challenge demonstrates the involvement of T cells. Finally, the reporter antigens TNP-Ficoll and TNP-ovalbumin are used to differentiate compounds that induce responses involving neo-antigen help or co-stimulatory signals (modified PLNA). The PLNA is increasingly considered as a tool for detection of the potential to induce both sensitization and autoimmune reactions. A major current limitation is validation. A small inter-laboratory validation study of the direct PLNA found consistent results. No such study has been performed using an alternative protocol. Other issues include selection of the optimal protocol for an improved prediction of sensitization vs autoimmunity, and the elimination of false-positive responses due to primary irritation. Finally, a better understanding of underlying mechanisms is essential to determine the most relevant endpoints. The confusion resulting from use of the PLNA to predict autoimmune-like reactions as well as sensitization should be clarified. Interestingly, most drugs that were positive in the direct PLNA are also known to cause drug hypersensitivity syndrome in treated patients. This observation is expected to open new avenues of research.

Adoptive Transfer↗

[Cervical lymph node metastasis of hypopharyngeal carcinoma].

OBJECTIVE: To investigate the characteristic of cervical lymph node metastasis of hypopharyngeal carcinoma and its influence to the prognosis. METHODS: One hundred and eight hypopharyngeal carcinoma patients who accepted treatments in the 1st Affiliated Hospital of China Medical University from 1985 to 2000 were reviewed retrospectively. All of them accepted surgical treatment without pre-operative chemotherapy or radiotherapy. Stage was made according to the standard of International Union Against Cancer (UICC) in 1992. Specimens of the patients were carefully examined to confirm the primary site of the tumor and the distribution of cervical lymph node metastasis. Pathological differentiations of the tumor were classified into high, middle and low category. Kaplan-Meier method was used to estimate the 3rd, 5th years survival. RESULTS: The rates of lymph node metastasis of was 45.8% for patients with TI and T2 disease, 79.8% for those with T3 and T4, and 75.0% (81/108)for the whole patients(P < 0.05). Patients with pyriform sinus cancer occupied 92.6% (100/108) of all the cases. Cervical lymph node metastasis rate of pyriform sinus cancer and posterior pharyngeal wall cancer were 74. 0% and 87. 5% respectively (P > 0.05). Cervical lymph node metastasis rate of patients with the high, middle and low differentiation tumor were 72. 2% , 67.6% and 85.7% respectively (P > 0.05). The 3rd and 5th years survival rates of all patients were 67.53% and 29.87% respectively. The occurrence of cervical lymph node metastasis was 76.5% in the level II and III, and 8.6% in the level V and VI. CONCLUSIONS Cervical lymph node metastasis rate of hypopharyngeal carcinoma is high. Cervical lymph node metastasis was one of the most significant prognostic factors of hypopharyngeal carcinoma. With the increase of the cervical node metastasis, the 3rd and 5th years survival of the patients declined gradually.

Adult↗

Correlation of regional lymph node in vitro antitumor immunoreactivity histology with colorectal carcinoma.

Lymph nodes from resected specimens of human colorectal carcinoma were investigated for in vitro lymphocyte cytotoxicity against primary cultures of autologous tumor cells. Regional lymph node lymphocytes were cytotoxic in 32 of 142 cases (23%). Altogether 200 nodes were examined and the cytotoxicity correlated directly with sinus histiocytosis, seen in 43 nodes from 35 cases, and with hyperplasia of B- and T-lymphocyte areas combined, seen in 92 nodes from 65 cases. Lymph nodes with combined B- and T-cell hyperplasia were significantly more common in cases of good tumor differentiation. The findings suggest that sinus histiocytosis and hyperplasia of both major lymphocyte populations are morphological expressions of in vitro antitumor immunoreactivity in the regional lymph node.

B-Lymphocytes↗

Impact of isolated tumor cells in sentinel lymph nodes detected by immunohistochemical staining.

AIM: Isolated tumor cells (ITCs) in lymph nodes are defined histologically as node-negative. The clinical impact of ITCs in sentinel lymph nodes (SLNs) remains unclear. We report the prognosis of breast cancer patients with ITC-positive SLNs detected by immunohistochemical staining. PATIENTS AND METHODS: One hundred and sixty-five breast cancer patients with histologically negative SLNs were seen between January 1998 and December 2000. In 69 patients, sentinel node biopsy (SNB) was immediately followed by axillary lymph node dissection, and 96 had undergone SNB alone. Permanent sections of 301 SLNs were re-examined after hematoxylin-eosin staining and cytokeratin 19 immunohistochemical staining. RESULTS: ITCs were found in 18 SLNs of 17 patients and a micrometastasis was found in one SLN of one patient. As of November 2005, only one patient with ITCs in one SLN had supraclavicular lymph node recurrence. In contrast, 18 of the 147 patients with negative SLNs had tumor recurrence. Surgical management of the axilla had no influence on recurrence-free survival in all of the patients. CONCLUSION: This study shows that breast cancer patients with ITC-positive SLNs should be clinically managed as node-negative patients.

Adult↗

[Anatomy and topography of the regional lymph nodes of the liver and gallbladder].

Regional lymph nodes of the liver and gallbladder were examined in the autopsies of 80 adults (aged 17-96) in whom deaths were caused by factors not associated with lymph or gastrointestinal tract lesions. Lymphatic vessels of the liver and gallbladder are discharged into the lymph nodes of ten groups in abdominal cavity and four groups--in thoracic cavity. Also, they are discharged into thoracic duct. All lymphatic vessels of the liver and gallbladder are discharged into hepatic and pancreato-duodenal nodes only. The size of regional lymph nodes of the liver and gallbladder varies within 1-75 mm.

Adolescent↗

[Immunologic significance for regional lymph node histology in uterine cervical cancer].

To evaluate the immunological significance for regional lymph node histology in uterine cervical cancer, 1,144 lymph nodes of 153 cases were studied. Four histological findings in lymph nodes as follows were evaluated: Paracortical Area (PA), Sinus Histiocytosis (SH), Germinal Center (GC) and Degenerative Changes (DC). PA was well developed in early cancer, while hypoplastic in advanced cancer. SH appeared in early stages and disappeared gradually as cancer progressed. GC was most hyperplastic in stage I b and hypoplastic in stage I a and III. DC was remarkable in advanced cancer. The findings of PA of the regional lymph nodes in the cases without metastasis, and those of PA, GC and DC of the metastatic lymph nodes in the cases with metastasis were well correlated with prognosis. These results indicate that investigation of the histology of lymph nodes draining uterine cervical cancer may give valuable information to evaluate the immune response of the patients and to predict their prognosis.

Female↗

Laparoscopic Paraaortic Lymph Node Dissection in Patients with Gynecologic Malignancies

Accurate evaluation of the paraaortic lymph node is important in planning treatment of gynecologic malignancies. Because radiologic methods to detect occult paraaortic lymph node metastases are inaccurate and staging requires a major surgical procedure, we investigated the feasibility of laparoscopic paraaortic lymph node dissection in our preliminary series of five women (3 stage IIb cervical cancer, 1 stage Ib cervical cancer, 1 ovarian cancer). Three patients with stage Ib cervical cancer scheduled for primary radiotherapy underwent selective paraaortic lymph node biopsy only. We performed laparoscopic radical hysterectomy with pelvic lymphadenectomy in the patient with stage Ib disease, in addition to paraaortic lymph node dissection. The average operating time for lymph node dissection was 125 minutes and mean estimated blood loss was 250 ml. The average number of lymph nodes removed was 3.6. We conclude that this laparoscopic procedure is feasible and helps guide the management of these patients.

Journal Article↗

[Clinicopathological examinations of sinus reactions of lymph nodes from tumor-bearing patients].

The sinus reaction of lymph nodes from tumor-bearing patients was classified into 5 categories, normal (N), sinus histiocytosis (SH), mixed sinus reaction (M), sinus catarrh (SC) and not classified (NC), according to the definition of Thoresen (1982). As a result, at the low stage, 93.8% were N and SH, while at the high stage, 97.0% were M, SC and NC. The same results were also obtained, when the transfer of the lymph nodes was taken into consideration. On the other hand, when the lymph nodes were studied from the distant lymph nodes area (DLA) and regional lymph node area (RLA) according to the position of the pathogen, SC was the most with DLA, since all cases were at the high stage. With RLA, SH was the most at 47.6% at the low stage, while at the high stage. SC and NC indicated 66.0%. Therefore, the sinus reaction can be used to estimate the degree of the response to the cancer and the diagnosis of tumor-bearing patients.

Humans↗

Sentinel lymph node biopsy in breast cancer patients after overnight migration of radiolabelled sulphur colloid.

OBJECTIVE: To evaluate the performance and feasibility of sentinel lymph node biopsy in breast cancer patients using technetium-99m (99mTc) sulphur colloid and gamma probe. METHODS: From May 2000 to March 2001, 70 patients with a tumour less than 5 cm with clinically negative axillary lymph nodes underwent sentinel node biopsy followed by standard axillary dissection. 99mTc sulphur colloid was injected around the primary tumour the day before surgery and a gamma probe was used to detect the sentinel lymph node during the surgical procedure. Sentinel lymph node biopsy was compared with standard axillary dissection for its ability to accurately reflect the final pathological status of the axillary nodes. RESULTS: The sentinel lymph node was successfully identified in 67 of 70 patients (95.71%). The number of sentinel lymph nodes ranged from 1-5 (mean 1.5) and non-sentinel nodes ranged from 5-22 (mean 13.3). Of the 67 patients with successfully identified sentinel lymph nodes, 43.28% (29/67) were histologically positive. Sensitivity of the sentinel lymph node to predict axilla was 82.75%; specificity was 100%. Positive and negative predictive values were 100% and 88.3% respectively. The sentinel lymph node was falsely negative in five patients, yielding an accuracy of 92.53%. Sentinel lymph node biopsy was more accurate for T1 tumours than for T2 tumours. CONCLUSIONS: The gamma probe guided method after overnight migration of 99mTc sulphur colloid is technically feasible for detecting sentinel lymph nodes in most breast cancer patients, accurately predicting the axillary lymph node status, and appears more accurate for T1 lesions than for larger lesions. This minimally invasive axillary staging procedure represents a major advance in the surgical treatment of breast cancer.

Adult↗

Lymph node sampling and survival in endometrial cancer.

OBJECTIVE: To determine the impact of pelvic lymph node sampling on survival in women with FIGO stage I and II endometrial adenocarcinoma. METHODS: We reviewed data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program on 9185 women with stage I endometrial cancer and 881 women with stage II endometrial cancer. Life table analysis was used to compare survival rates. RESULTS: Overall, lymph node sampling did not appear to convey survival benefit. The 5-year relative survival for 6363 women with stage I endometrial cancer who did not undergo lymph node sampling was 0.98, compared to 0.96 for 2831 women who did undergo lymph node sampling at the time of hysterectomy, a nonsignificant difference. Lymph node sampling (LNS) was associated with increased survival among those with stage I, grade 3 disease, but not grade 1 or grade 2. Women with stage I, grade 3 disease who underwent LNS had a relative 5-year survival of 0.89, compared to 0.81 for those who did not undergo LNS (P = 0.0110). Nonsignificantly improved survival associated with LNS for women with grade 3 disease was observed in International Federation of Gynecology and Obstetrics stages Ib, Ic, and II. CONCLUSIONS: The observed survival benefit associated with lymph node sampling may be due to identification of women with more advanced endometrial cancer. Accurate determination of grade and extent of tumor is necessary to delineate which patients may benefit from lymph node sampling at hysterectomy. Effective cooperation between surgical pathology and gynecology services may be required to ensure adequate examination of the hysterectomy specimen. A surgeon with expertise in performing lymph node sampling should be available if operative findings render lymph node sampling appropriate.

Adenocarcinoma↗

Lymph-node and thymus pathology in fatal drug addiction.

Lymph-node sections from the porta hepatis, the lung hilus, the para-aortic and axillary regions and from the neck from totally 50 drug addicts submitted for medico-legal autopsy at the Institute of Forensic Medicine in Copenhagen were studied together with tissue sections from 23 normal persons. In addition thymus sections from 30 drug addicts and 20 normal persons were investigated. Enlargement of lymph-nodes was found significantly more often in active drug addicts compared to normals except for the nodes on the neck. Birefringent material was seen in portal lymph-nodes in 42% of addicts, in para-aortic and lung hilus nodes in 18% each and in the axillary nodes in 12%. Signs of antigenstimulation evaluated by the number of germinal centre and plasma cells were found in about 60% or more in active drug addicts compared to about 30-40% in normals. There was not significant relation between the size of the lymph-nodes and the immunoactivity nor to the duration of the abuse. Examination of the thymus showed that the average weight in active drug addicts was 34 g, in normals 25 g. Histologically the tissue was in 48% of the active addicts composed of more than 80% lymphatic tissue compared to 15% of the normals. The results indicate that the enlargement and histological signs of activation in all the lymph-nodes investigated are caused by continuous antigenstimulation due to repeated injections of various antigens. The same may in part be applied to the thymus changes demonstrated.

Adolescent↗

Incidence and prognostic importance of lymph node metastases in dogs with appendicular osteosarcoma: 228 cases (1986-2003).

OBJECTIVE: To determine the incidence of regional lymph node metastasis in dogs with appendicular osteosarcoma and determine whether regional lymph node metastasis was associated with shortened disease-free interval or survival time. DESIGN: Retrospective study. ANIMALS: 228 dogs with appendicular osteosarcoma in which regional lymph nodes were examined histologically at the time of limb amputation. PROCEDURE: Information collected from the medical records included signalment; affected site; initial serum alkaline phosphatase activity; whether treatment involved adjuvant chemotherapy and, if so, chemotherapeutic agents administered and number of treatments; disease-free interval; and survival time. RESULTS: 10 (4.4%) dogs had histologic evidence of regional lymph node metastasis at the time of amputation. Median disease-free interval for dogs without regional lymph node metastasis (238 days; range, 0 to 1,067 days) was significantly longer than median disease-free interval for dogs with regional lymph node metastasis (48 days; range, 2 to 269 days). Median survival time for dogs without lymph node metastasis (318 days; range, 20 to 1,711 days) was significantly longer than median survival time for dogs with lymph node metastasis (59 days; range, 19 to 365 days). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that regional lymph node metastasis is rare in dogs with appendicular osteosarcoma but that dogs with lymph node metastasis have a poorer prognosis than do dogs without.

Amputation, Surgical↗

Mycobacterium paratuberculosis cultured from milk and supramammary lymph nodes of infected asymptomatic cows.

Milk and supramammary lymph node samples were obtained from asymptomatic cows infected with Mycobacterium paratuberculosis at the time of slaughter. Of 81 supramammary lymph node samples, 22 (27%) were culture positive for M. paratuberculosis. Of 77 milk samples, 9 (11.6%) were culture positive. The prevalence of supramammary lymph node or milk infection was highest with heavy fecal shedding of M. paratuberculosis and lowest with light shedding. The serologic status of the cow was not useful for predicting the risk of supramammary lymph node or milk infection. Shedding of M. paratuberculosis occurs in the milk of asymptomatic infected cows but, apparently, less frequently than previously reported for symptomatic cows.

Animals↗

Scalene lymph node metastases with the negative pelvic nodes in invasive cervical carcinoma.

Cervical carcinoma spreads predominantly by lymphatic routes and lymph node metastases may occur even in early stages of disease. Metastases usually first appear in pelvic lymph nodes, then disseminate along the efferent lymphatic chain to the extrapelvic lymph nodes. Cases of positive lymph node metastases with negative pelvic nodes in invasive cervical carcinoma are extremely rare. We report a 50-year-old woman with bulky stage IIA cervical carcinoma who had scalene lymph node metastases in the absence of pelvic lymph node metastases after radical hysterectomy and postoperative pelvic irradiation. This rare "skipping" nodal metastasis was probably via posterior trunk lymphatic drainage of the bulky cervical carcinoma which mainly invaded the posterior vaginal cuff. Neoadjuvant or adjuvant chemotherapy is recommended to prolong survival of patients in such cases.

Carcinoma, Squamous Cell↗

Combined use of magnetic resonance imaging, CA 125 assay, histologic type, and histologic grade in the prediction of lymph node metastasis in endometrial carcinoma.

OBJECTIVE: The aim of this study was to predict retroperitoneal lymph node metastasis during the preoperative examination of patients with endometrial carcinoma and to determine whether lymphadenectomy must be performed. STUDY DESIGN: This study was carried out on 214 patients with endometrial carcinoma. Preoperative evaluators were volume index, depth of myometrial invasion (as assessed by magnetic resonance imaging), serum CA 125 level, histologic type, and histologic grade. With the use of receiver operating characteristic curves, cutoff values of volume index and serum CA 125 levels were determined. The relationships of these evaluators with pelvic lymph node metastasis were investigated by multivariate analysis with a logistic regression model. The relationships of these evaluators with para-aortic lymph node metastasis were investigated in the same way. RESULTS: Histologic type, volume index, histologic grade, and serum CA 125 level were found to be independent risk factors for pelvic lymph node metastasis; serum CA 125 level and volume index were found to be independent risk factors for para-aortic lymph node metastasis. Among 110 cases with no risk factors for pelvic lymph node metastasis, pelvic lymph node metastasis was observed in 4 cases (3.6%). On the other hand, only 1 case of 128 cases (0.7%) with no risk factors for para-aortic lymph node metastasis actually had metastasis. CONCLUSION: Careful consideration of the possibility of the elimination of the requirement of retroperitoneal lymphadenectomy is needed in cases with no risk factors for lymph node metastasis. However, our results suggest that para-aortic lymphadenectomy may not be necessary in cases with no risk factors for para-aortic lymph node metastasis.

Aorta↗