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Laparoscopic detection of sentinel lymph nodes followed by lymph node dissection in patients with early stage cervical cancer.

OBJECTIVE: The purpose of this study was to investigate the feasibility of sentinel node detection through laparoscopy in patients with early cervical cancer. Furthermore, the results of laparoscopic pelvic lymph node dissection were studied, validated by subsequent laparotomy. METHODS: Twenty-five patients with early stage cervical cancer who planned to undergo a radical hysterectomy and pelvic lymph node dissection received an intracervical injection of technetium-99m colloidal albumin as well as blue dye. With a laparoscopic gamma probe and with visual detection of blue nodes, the sentinel nodes were identified and separately removed via laparoscopy. If frozen sections of the sentinel nodes were negative, a laparoscopic pelvic lymph node dissection, followed by radical hysterectomy via laparotomy, was performed. If the sentinel nodes showed malignant cells on frozen section, only a laparoscopic lymph node dissection was performed. RESULTS: One or more sentinel nodes could be detected via laparoscopy in 25/25 patients (100%). A sentinel node was found bilaterally in 22/25 patients (88%). Histological positive nodes were detected in 10/25 patients (40%). One patient (11%) had two false negative sentinel nodes in the obturator fossa, whereas a positive lymph node was found in the parametrium removed together with the primary tumor. In seven patients (28%), the planned laparotomy and radical hysterectomy were abandoned because of a positive sentinel node. Bulky lymph nodes were removed through laparotomy in one patient, and in six patients only laparoscopic lymph node dissection and transposition of the ovaries were performed. These patients were treated with chemoradiation. In two patients, a micrometastasis in the sentinel node was demonstrated after surgery. Ninety-two percent of all lymph nodes was retrieved via laparoscopy, confirmed by laparotomy. Detection and removal of the sentinel nodes took 55 +/- 17 min. Together with the complete pelvic lymph node dissection, the procedure lasted 200 +/- 53 min. CONCLUSION: Laparoscopic removal of sentinel nodes in cervical cancer is a feasible technique. If radical hysterectomy is aborted in the case of positive lymph nodes, sentinel node detection via laparoscopy, followed by laparoscopic lymph node dissection, prevents potentially harmful and unnecessary surgery.

Adult↗

Lymphadenopathy in drug addicts. A study of the distribution of T lymphocyte subsets in the lymph nodes.

Lymph node biopsies from 24 male heroin addicts and 9 control patients were studied using immunohistochemical, and in 1/3 of cases, quantitative methods. 5 out of these 24 patients were also homosexual. All presented diffuse lymphadenopathy but none had any signs or symptoms of opportunistic infections nor Kaposi's sarcoma. Histologically the lymph nodes showed a very peculiar follicular hyperplasia with atrophy of the paracortex. The germinal centers appeared irregular, ill defined and contained clusters of small lymphocytes. The mantle zone was atrophic. Immunolabelling of T lymphocytes by monoclonal antibodies showed that germinal centers were invaded by small nests of Leu 2a (and OKT8) positive lymphocytes, i.e. chiefly cytotoxic-suppressor phenotype; the number of these cells increased by about 100 times in the follicles. OKT4 (and Leu 3a) positive cells, i.e. chiefly helper-inducer phenotype, appeared to decrease. These histological and immunohistochemical changes are considered to be suggestive of drug addicts' lymphadenopathy, and also possibly of other conditions increasing the risk of AIDS.

Adolescent↗

Basement-membrane components associated with the extracellular matrix of the lymph node.

Lymph nodes contain an extensive array of extracellular matrix fibers frequently referred to as "reticular fibers" because of their reticular pattern and positive reaction with silver stains. These fibers are known to contain primarily type-III collagen. In the present study, frozen and plastic-embedded sections of mouse and human lymph nodes were subjected to immunostaining with a panel of monospecific antibodies directed against type-IV collagen, type-III collagen, laminin, entactin, and heparan sulfate proteoglycan. Immunofluorescent staining revealed that, in addition to being uniformly stained with antibodies to type-III collagen, these fibers also stained positively with antibodies to type-IV collagen and to other basement-membrane-specific components. Furthermore, the basement-membrane-specific antibodies stained the outer surface of individual fibers. These same type-III collagen-rich fibers were distinct from blood vascular basement membranes since they did not react with antibodies to factor VIII-related antigen, an endothelial-cell-specific marker. The role of these basement-membrane-specific components associated with the reticular fibers of lymphoid tissue is unknown. However, it is possible that the ligands promote attachment of reticular fibroblasts as well as macrophages and lymphocytes to the extracellular matrix fibers.

Animals↗

A mathematical model of axillary lymph node involvement considering lymph node size in patients with breast cancer.

BACKGROUND: Surgical sampling for assessing axillary status has not been considered as a well defined surgical procedure. We have reported that MRI is a good instrument for assessing lymph node size and identifying lymph node position. We also developed a mathematical model that takes into consideration the size of axillary lymph nodes, and retrospectively determined the number and size of the axillary lymph nodes that need to be sampled from level I-II to achieve a greater than 90% probability of metastasis detection after surgical sampling, with the future aim of using MR-axillography to assess lymph node size. METHODS: One thousand nine hundred and thirty four lymph nodes from 102 level I-II dissections performed on T1 and T2 breast cancer patients with nodal metastases were examined histologically and the greatest long-axis dimension on histologic slides was measured. RESULTS: This model permitted determination of the cutoff level necessary for an expected probability of detection of metastasis of over 90%. The cutoff level, regardless of tumor size, is a maximum of 6 nodes removed from level I-II in which the greatest long-axis measurement is greater than or equal to 6 mm. The cutoff level in patients with macrometastatic nodes is a maximum of 3 or 4 nodes in which the long-axis dimensions are greater than or equal to 9 or 7 mm, respectively, removed from level I-II. CONCLUSIONS: This model showed that surgical sampling on the basis of lymph node size might have good potential to detect lymph nodes metastases.

Adult↗

Cyclophosphamide-dependent lymph node modification in lymph node metastasis of MM48 tumor cells in syngeneic mice.

We investigated the role of immunosuppressive activity induced in the regional lymph nodes (RLN, popliteal lymph nodes) in the establishment of lymph node metastasis by cyclophosphamide (CY) administration. The CY treatment led to the elimination of suppressive activity with the appearance of positive immune responses, and the inhibition of lymph node metastasis of MM48 tumor cells. In CY-treated mice, the removal of RLN together with the primary tumor lowered the survival rate compared with the mice in which the RLN remained intact. During 4 days after primary tumor resection, the proliferation of tumor cells in the RLN was significantly decreased in CY-treated mice. These results suggested that the induction of suppressive activity in the lymph node is closely associated with the establishment of lymph node metastasis.

Animals↗

[The magnetic resonance tomographic differential diagnosis between reactively enlarged lymph nodes and cervical lymph node metastases].

A prospective study was carried out involving 27 patients to determine whether MRT can distinguish between lymph node metastases and reactive lymph node enlargement. The results of MRT were compared with the pathological findings. Using T1 and T2 weighted sequences and proton density sequences it was not possible to differentiate between reactively enlarged lymph nodes and lymph node metastases. Following the administration of Gd-DTPA the observation of central hypo-intensity with marginal hyper-intensity is a reliable sign of a lymph node metastasis. Using the criterion of length greater than 10 mm for lymph node metastases results in a specificity of 32% and sensitivity of 75%. The use of the sonographic maximal/cross measurement quotient > 2 in the axial/coronary/sagittal dimension improves specificity and sensitivity to 94%.

Contrast Media↗

[Detection of atypical site of "sentinel lymph nodes" by lymph drainage scintigraphy in patients with breast carcinoma].

OBJECTIVE: Sentinel lymph node (SLN) localization in breast cancer allows biopsy of directly tumor drained lymph nodes. The objective was to study the association of tumor and SLN localization. PATIENTS AND METHODS: SLN was identified in 39 (81%) of 48 patients with histologically proven breast cancer, clinically and sonographically unsuspected axillary lymph nodes after peritumoral application of 40-50 Mbq 99mTc-Nanocolloid. Patients age, tumor size and localization, histology and localization of the SLN as well as removed axillary lymph nodes were analyzed. RESULTS: Axillary lymph node metastases were found in 11 (28%) of 39 patients. Involvement of the SLN was confirmed by intraoperative frozen sections (n = 9) and paraffin embedded histology (n = 1). One (9%) patient with a positive node revealed a false-negative SLN. In 24 patients with a tumor in the lateral hemisphere of the breast the SLN were identified in the ipsilateral axilla. In 6 (40%) of 15 patients with a central or medial localized tumor the SLN was observed infraclavicular (n = 3), parasternal (n = 2) or in the contralateral axilla (n = 1). In the latter one the SLN of the contralateral axilla showed metastases, whereas the simultaneous SLN and all removed lymph nodes of the ipsilateral axilla were not involved. More than one SLN were found in 12 (31%) of the 39 cases. CONCLUSION: A correlation between tumor localization and localization of the SLN is suggested, but the lymph drainage seems more variable in cases of medial tumor size. Using blue dye for map of extraaxillary SLN seems inappropriate. Currently the diagnostic and therapeutic impact of the detection of extraaxillary SLN is still unclear.

Adult↗

The architecture of rat lymph nodes. III. The lymph nodes and lymph-borne cells of the congenitally athymic nude rat (rnu).

The lymph nodes (LN) of the congenitally athymic nude rat(rnu) were compared with the LN of non-nude littermates. The mesenteric and coeliac LN were smaller in the rnu rats, but the axillary and the cervical LN were larger. Germinal centres were found in the LN of nude rats. They were scarce and often very small, but some were of normal structure, especially in the cervical LN. The endothelium of post-capillary venules in the LN or normal rats, was seen. The paracortex was extremely depleted of lymphocytes but remained a distinct area occupied predominantly by pale interdigitating cells. In some LN the medullary sinuses were distended and the cords engorged with plasma cells. The predominant cells in thoracic duct lymph were immunoglobulin-positive B lymphocytes. The hourly output of these cells was the same as that in non-nude littermates. However, small numbers of thoracic duct cells were positive for the markers identified by the monoclonal antibodies W3/13 and W3/25, although in normal rats these are not expressed on small B lymphocytes.

Animals↗

Lymph node mapping and sentinel lymph node biopsy for evaluation of axillary lymph node status in early invasive breast cancer. Our experience.

The Authors show their preliminary experience with the sentinel lymph node biopsy (SLNB) in clinical early invasive breast cancer (T1N0). During a period of 15 months, forty-two patients were submitted to SLNB upon Tc99-colloid albumin injection and SLN identification by lymphoscintigraphy. The middle number of lymph nodes found in the SLNB was 1 (1-3), whereas the middle number of lymph nodes identified in level I/II ALND specimens was 15. The SLN was identified with success in all cases (100%). The axilla was positive for metastasis in 4/42 cases. The SLN was positive in all four cases in which nodal metastasis was identified. The negative predictive value of SLN was 100%. The SLN was the only site of metastasis in 3/4 cases. The SLN pathological status accurately reflected the lymphatic basin status, but further investigation is needed to define the optimal timing of colloid injection and method of examination of the SLN.

Adult↗

[Study on extensive lymph node dissection: metastatic lymph nodes in papillary carcinoma of the thyroid].

Bilateral cervical lymph node dissection was performed in 71 cases of papillary thyroid carcinoma, considered to be relatively early cases because of mobility, irrespective of the size of tumor or presence of node enlargement. Of these, 33 cases received additional node dissection of the anterosuperior mediastinum through longitudinal sternotomy. The number of lymph nodes examined per subject averaged 89.9, the number of metastatic nodes was 13.8, and metastasis was noted in 88.7% of all cases. Lymph node metastasis tended to be more frequent on the affected side, but was simultaneously scattered over the whole cervical area. As to sites, metastasis of paratracheal nodes on the affected side occurred at a frequency of 66.2%, inferior and superior jugular nodes at 62.0% and 59.0% respectively, pretracheal nodes at 50.7%, and tracheoesophageal nodes at 47.9%. The high incidence of para- and pretracheal nodes suggests that the lymph flow in this direction is of great importance in metastasis. In fact, lymph nodes in the mediastinum, which were directly continuous with these nodes, showed as high as 39.4% metastasis in cases of anterosuperior mediastinal extirpation. This extensive node dissection is considered to be very preferable as at least the agony of survival with carcinoma can be lessened.

Adult↗

Occurrence of salmonella in the ileum, ileocolic lymph nodes, tonsils, mandibular lymph nodes and carcasses of pigs slaughtered for consumption.

This study evaluates the occurrence of Salmonella in pork carcasses and in some risk tissues (ileum, ileocolic and mandibular lymph nodes and tonsils), that can be involved in Salmonella contamination during slaughter. Salmonella was identified in 27 (26.7%) pigs and in 13 (12.9%) carcasses. From these positive carcasses, 69.2% presented the same serotype as that identified in the corresponding pig, which emphasize the pigs importance as a source of Salmonella during the slaughter, suggesting that measures should be taken at the level of pig production in order to reduce the slaughtering of Salmonella-positive animals. The highest value of Salmonella occurrence was reached in the ileocolic lymph nodes (18.8%) and in the ileum (13.9%), representing Salmonella potential faecal source during pork processing at the abattoir. In these samples, a high level of Salmonella was observed in the ileocolic lymph nodes in comparison with the ileum. The mandibular lymph nodes (12.9%) also presented a higher occurrence in comparison with the tonsils (9.9%). These results indicate that the lymph nodes analysis could be more sensitive in the detection of Salmonella than the closer drainage tissue. Otherwise, the presence of Salmonella in the lymph nodes indicates lymphatic spread of the organism, which reflects an increased risk of pork contamination. These results also indicate that, in order to achieve a better control of Salmonella contamination during the slaughter process, it is important to consider the improvement of the evisceration practices and the tonsils as well the extraction of mandibular lymph nodes after slaughter.

Abattoirs↗

Sentinel nodes outside lymph node basins in patients with melanoma.

BACKGROUND: Lymphoscintigraphy occasionally reveals hot spots outside lymph node basins in patients with melanoma. The aim of this study was to evaluate such abnormally located hot spots. METHODS: Sentinel node biopsy was studied prospectively in 379 patients with clinically localized cutaneous melanoma. One day after lymphoscintigraphy, sentinel node biopsy was performed guided by vital blue dye and a gamma ray detection probe. RESULTS: Persisting hot spots outside the regional node basins were seen in 25 patients (6.6 per cent). Several specific drainage patterns were discerned. In five patients, aberrant sentinel nodes were not explored. The hot spot represented a lymphangioma in two patients. Radioactive lymph nodes were identified in the remaining 18 patients (4.7 per cent). Four patients had metastasis in one of these aberrant lymph nodes. CONCLUSION: Sentinel nodes were found outside a lymph node basin in 5 per cent of patients. Particular drainage patterns exist. It is recommended to incorporate such sites in the late scintigraphy images and to pursue aberrant sentinel nodes, as they may be the only sites of metastasis.

Biopsy↗

Sentinel lymph node versus axillary lymph node dissection for early-stage breast carcinoma: a comparison using a utility-adjusted number needed to treat analysis.

BACKGROUND: The current study was performed to compare the value of sentinel lymph node dissection (SND) and axillary lymph node dissection (AND) in improving the utility-adjusted survival for early-stage breast carcinoma patients. METHODS: A number needed to treat (NNT) analysis was used to compare SND with AND. In the NNT equation, 1/(S(SND) - S(AND)), S is the 5-year utility-adjusted survival. A literature review was performed to estimate 1) the prevalence of axillary lymph node disease for early-stage breast carcinoma, 2) the sensitivity and specificity of SND and AND, 3) the 5-year overall survival as a function of axillary lymph node involvement, 4) the risk of arm lymphedema as a function of the intervention performed, and 5) the utility correction (Uc; impairment of quality of life) for arm lymphedema. RESULTS: The NNT method of analysis favored SND over nearly the entire range of parameters with a sign change to a negative value occurring only as Uc becomes very close to unity. This suggests the superiority of the SND approach. Only when there is minimal loss of utility does AND become favored and then only minimally. CONCLUSIONS: Compared with AND, SND improves the utility-adjusted survival in patients with early-stage breast carcinoma. This finding is quite robust and was found to remain constant over a range of values for utility and lymph node prevalence.

Breast Neoplasms↗

Identification of occult tumor cells in node negative lymph nodes of colorectal cancer patients by cytokeratin 20 gene and protein expression.

BACKGROUND AND AIMS: Evaluation of cytokeratin 20 (CK20) specific quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) and immunohistochemistry (IHC) for detection of occult tumor cells in lymph nodes of 72 patients with colorectal carcinoma (UICC stage I and II). METHODS: Serial sections of formalin-fixed, paraffin-embedded lymph nodes (mean 14.3/case) were used for microdissection, RNA isolation and QRT-PCR and for CK20 IHC using routine protocols. Results of QRT-PCR and IHC were compared and correlated to the CK20 expression pattern of the primary tumors and clinical follow-up. RESULTS: IHC revealed CK20-positive tumor cells in lymph nodes of 14.5% (10/69) and 0% (0/3) cases with a CK20-positive and CK20-negative primary tumor, respectively. CK20 mRNA was detected in the lymph nodes of 36.8% (7/19) cases by QRT-PCR with all 7 cases also expressing CK20 mRNA in the primary tumor. CK20 mRNA (QRT-PCR) and protein (IHC) detection in serial sections did not agree in 25% (5/20) of cases. A trend was seen towards a worse disease course for patients with CK20-positive lymph nodes by IHC (incidence of recurrent disease) and QRT-PCR (disease-free survival, incidence of recurrent disease). CONCLUSION: CK20-specific IHC and QRT-PCR are supportive tools to conventional histology for detection of occult tumor cells in archival tissues, with the restriction that a laborious QRT-PCR procedure is necessary to achieve appropriate specificity. A prognostic value of CK20 IHC or QRT-PCR for stratification of UICC stage I and II patients into those likely to develop recurrent disease was not evident.

Biomarkers, Tumor↗

Isolated tumour cells in pathological node-negative lymph nodes adversely affect prognosis in cancer of the oesophagus or oesophagogastric junction.

AIMS: To determine the prevalence of isolated tumour cells (ITC) in lymph nodes of patients with pathological node-negative (pN0) tumours and to assess their impact on disease-free and overall survival. METHODS: Paraffin embedded lymph nodes from oesophagogastrectomy specimens were examined immunohistochemically using monoclonal anti-cytokeratin antibody (MNF118). Clinical and pathological features were summarised and overall and relapse-free survival were estimated. RESULTS: Isolated tumour cells were detected in 12 of 146 patients (8%), and 24 of 1694 (1%) lymph nodes. With a median follow-up time of 28 months (range 0-160 months), both relapse-free and overall survival were significantly (p<0.05) associated with the presence of ITC in pN0 lymph nodes. There was no significant difference in the prevalence of ITC between patients who underwent multimodal therapy and those treated with surgery alone. CONCLUSIONS: ITC in pN0 lymph nodes may be less frequent than previously considered, but their presence is associated with poorer outcomes compared with true node negative disease.

Adenocarcinoma↗

[Endoscopic-radiological demonstration of the gastrointestinal lymph nodes and lymph vessels].

Using an intragastric contrast medium (Lipiodol) the paragastric lymph nodes of 23 patients were lymphangiographed prior to laparotomy. The patients suffered from gastric or duodenal ulcers (15 cases), postresectional ulcers (3 cases), or gastric carcinoma (5 cases). The surgically resected material was examined by radiological and histological techniques. The following results were obtained: 1. After application of the contrast medium the paragastric lymph nodes could firstly be seen 5 hours later and even after 7 days and more. 2. The radiographs presented typical storage phenomena with granular or clod-like structures as an equivalent of the inflammatory lymph node alterations. Histologically a marked sinus catarrh with lipid laden reticulum cells and multinuclear giant cells of the foreign body types was observed. 3. In gastric carcinoma characteristic storage defects up to complete destruction of the lymph nodes were found as a roentgenological equivalent of lymph nodes metastases. In addition there were occasionally abnormal courses of the lymphatic vessels with variations in diameter and bizarre storage formations. 4. The described method provides a helpful tool in the diagnosis of gastric lesions. No side effects have been observed.

Adolescent↗

[Role of crural inguinal lymphadenectomy and dynamic sentinel lymph node biopsy in lymph node staging in squamous-cell carcinoma of the penis. Our experience].

PURPOSE: We determine the value of dynamic sentinel node biopsy for staging squamous cell carcinoma of the penis. MATERIALS AND METHODS: During a period of 2 years 17 patients with penile cancer was performed after lymphoscintigraphy pre and intraoperatively with gamma ray detection probe at biopsy of the sentinel node with the aid of perilesional administered patent blue dye. After 20 days regional lymph node dissection was performed in all patients. RESULTS: Sentinel node metastasis was found in 5 patients; in one case lymphoscintigraphy not visualized sentinel node. All negative node biopsy was confirmed with the regional lymph node dissection. No major complication did occur after sentinel node biopsy. CONCLUSIONS: Occult lymph node metastases can be detected by dynamic sentinel node biopsy including preoperative lymphoscintigraphy, vital dye and gamma ray detection probe with a sensitivity of 78%, predictive negative value of 100% and with low morbidity.

Aged↗

Comparison of side effects between sentinel lymph node and axillary lymph node dissection for breast cancer.

BACKGROUND: Axillary lymph node dissection (ALND) is often associated with permanent arm side effects. Side effects after sentinel lymph node dissection (SLND) should be less common, because the surgery is less extensive. METHODS: The study compared side effects and interference with daily life between 169 women who underwent an SLND and 78 who underwent an ALND for breast cancer. Patients rated symptom severity and interference with daily life caused by pain, numbness, limitation of arm range of motion (ROM), and arm swelling at 1, 6, and 12 months after surgery by using the Measure of Arm Symptom Survey. Repeated-measures and regression analyses for each time period were used to determine associations between symptoms and dissection type. RESULTS: At 1 month, SLND patients reported less pain, numbness, limitation in ROM, and seromas than ALND patients. At 6 months, SLND patients had less pain, numbness, and arm swelling, and at 12 months, SLND patients had less numbness, arm swelling, and limitation in ROM than ALND patients. At 1 month, pain, numbness, and limitation in ROM interfered significantly more with daily life for ALND patients. At 6 and 12 months, only numbness interfered more with daily life for ALND patients. CONCLUSIONS: SLND was associated with fewer side effects than ALND at all time points.

Adult↗