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Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer.

UNLABELLED: A retrospective study was performed on 101 consecutive medullary thyroid cancer (MTC) patients who underwent at Institut Gustave-Roussy (IGR) total thyroidectomy with central and bilateral lymph node dissection. At histology, lymph node metastases were found in 55% of patients. In sporadic MTC, lymph node metastases were observed in the central compartment in 50% of patients, in the ipsilateral jugulocarotid chain in 57%, and in the contralateral jugulocarotid chain in 28%. In hereditary MTC, lymph node metastases were identified in the central compartment in 45% of patients, in the ipsilateral jugulocarotid chain in 36%, and in the contralateral jugulocarotid chain in 19%. Contralateral lymph nodes were found in 37% of metastatic patients with an unilateral tumoral involvement of the thyroid gland. A strong association was observed between tumor size and lymph node involvement for both hereditary and sporadic MTC (P < 0.02). Permanent hypoparathyroidism occurred in 4% of patients and laryngeal nerve palsy in 5%. An undetectable calcitonin level was obtained after surgery in 61% of patients, in 95% of patients without lymph node metastases, and in 32% of patients with lymph node metastases. Among patients with lymph node involvement, undetectable calcitonin level was obtained in 57% of patients with less than or with 10 lymph node metastases and in 4% of patients with more than 10 (P < 0.01). IN CONCLUSION: 1) lymph node metastases occur early in the course of MTC; 2) the pattern of lymph node metastatic distribution in neck areas varied between patients and was not related to the thyroid tumor size; 3) contralateral lymph node metastases were observed even in patients with small thyroid tumor; 4) total thyroidectomy with central and complete bilateral neck dissection should be performed routinely in all patients with sporadic and hereditary MTC, even in those with small thyroid tumors-a contralateral neck dissection may be avoided only in sporadic MTC patients with unilateral involvement of the thyroid gland in the absence of central and ipsilateral neck involvement; and 5) the number of lymph node metastases was predictive of biological cure after surgery.

Adult↗

Sentinel lymph node mapping for staging breast cancer: preliminary results of a prospective study.

Axillary lymph node dissection is the gold standard for staging breast cancer, but it is associated with significant morbidity and complications. Sentinel lymph node mapping technique has demonstrated a successful detection of the node or nodes more likely to have metastasis. Two techniques are being used to detect sentinel lymph node-intraoperative use of gamma detecting probe after injection of radio tracer preoperatively and the injection of blue dye and lymphatic mapping intraoperatively. We used both techniques. Twenty-four patients underwent sentinel lymph node mapping. Blue dye and gamma detecting probe identified sentinel lymph nodes in 78% and 77% of patients, respectively. Overall, 23 of 24 patients had a sentinel lymph node identified (96%). Ten patients had metastatic disease in the axilla. Out of these ten patients the only positive node/nodes were the sentinel lymph node in six patients. The other four patients had positive non-sentinel lymph node along with positive sentinel lymph node. All of the patients who had metastatic disease in the axilla were detected by the sentinel lymph node mapping technique. Therefore, no patient had positive non-sentinel lymph node if the sentinel lymph node was negative. This technique was 100% predictive of the axillary status. Sentinel lymph node mapping technique will change the management of breast cancer and will allow two-thirds of the patients with breast cancer to be managed without axillary lymph node dissection with a resulting reduction in morbidity and cost.

Axilla↗

Radioguided sentinel lymph node biopsy in malignant cutaneous melanoma.

The procedure of sentinel lymph node biopsy in patients with malignant cutaneous melanoma has evolved from the notion that the tumor drains in a logical way through the lymphatic system, from the first to subsequent levels. As a consequence, the first lymph node encountered (the sentinel node) will most likely be the first affected by metastasis; therefore, a negative sentinel node makes it highly unlikely that other nodes in the same lymphatic basin are affected. Although the long-term therapeutic benefit of the sentinel lymph node biopsy per se has not yet been ascertained, this procedure distinguishes patients without nodal metastases, who can avoid nodal basin dissection with its associated risk of lymphedema, from those with metastatic involvement, who may benefit from additional therapy. Sentinel lymph node biopsy would represent a significant advantage as a minimally invasive procedure, considering that an average of only 20% of melanoma patients with a Breslow thickness between 1.5 and 4 mm harbor metastasis in their sentinel node and are therefore candidates for elective lymph node dissection. Furthermore, histologic sampling errors (amounting to approximately 12% of lymph nodes in the conventional routine) can be reduced if one assesses a single (sentinel) node extensively rather than assessing the standard few histologic sections in a high number of lymph nodes per patient. The cells from which cutaneous melanomas originate are located between the dermis and the epidermis, a zone that drains to the inner lymphatic network in the reticular dermis and, in turn, to larger collecting lymphatics in the subcutis. Therefore, the optimal route for interstitial administration of radiocolloids for lymphoscintigraphy and subsequent radioguided sentinel lymph node biopsy is intradermal or subdermal injection. (99m)Tc-Labeled colloids in various size ranges are equally adequate for radioguided sentinel lymph node biopsy in patients with cutaneous melanoma, depending on local experience and availability. For melanomas along the midline of the head, neck, and trunk, particular consideration should be given to ambiguous lymphatic drainage, which frequently requires interstitial administration virtually all around the tumor or surgical scar from prior excision of the melanoma. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy because images are used to direct the surgeon to the sites of the nodes. The sentinel lymph node should have a significantly higher count than that of the background (at least 10:1 intraoperatively). After removal of the sentinel node, the surgical bed must be reexamined to ensure that all radioactive sites are identified and removed for analysis. Virtually the entire sentinel lymph node should be processed for histopathology, including both conventional hematoxylin-eosin staining and immune staining with antibodies to the S-100 and HMB-45 antigens. The success rate of radioguidance in localizing the sentinel lymph node in melanoma patients is approximately 98% in institutions that perform a high number of procedures and approaches 99% when combined with the vital blue-dye technique. Growing evidence of the high correlation between a sentinel lymph node biopsy negative for cancer and a negative status for the lymphatic basin-evidence, therefore, of the high prognostic value of sentinel node biopsy-has led to the procedure's being included in the most recent version of the TNM staging system and starting to become the standard of care for patients with cutaneous melanoma.

Colloids↗

[Clinical study of the sentinel lymph node of patients with laryngeal and hypopharyngeal carcinomas].

OBJECTIVE: To investigate the methods of detecting the sentinel lymph node of laryngeal and hypopharyngeal carcinomas and its predictive value in the cervical metastasis of the carcinoma. METHODS: In 29 patients who suffered from laryngeal or hypopharyngeal carcinoma with NO neck, the patent blue was injected into the surrounding tissue of the tumor during the operation to identify the sentinel lymph nodes. The sentinel lymph nodes were dyed blue. The frozen histopathology was done during the operation, the lymph nodes at the ipsilateral side of the neck were dissected completely, and the routine histopathology was done as the gold standard to study the predictive value of the sentinel lymph node in the metastasis of the cervical node. RESULTS: Of 29 patients, 28 patients' sentinel lymph nodes were detected successfully during operation. There was an average of 2.5 lymph nodes per side per patient. Most of the sentinel lymph nodes were in the level II and level III regions of the ipsilateral side of the neck, and there were bilateral sentinel nodes in patients suffered from superglottic carcinoma. Three patients' sentinel lymph nodes were found to be positive in the frozen inspection, and the routine histopathology confirmed the result. The micrometastasis rate was 10.7% (3/28). There were no metastatic lymph nodes found in patients who were negative for the sentinel lymph nodes during the operative frozen histopathology. The predicted value of the sentinel lymph nodes to the cervical lymph node metastasis was 100 per cent. CONCLUSION: There is a very important predicted value of sentinel lymph nodes in the cervical metastasis of patients suffered from laryngeal and hypopharyngeal carcinomas. It could reduce the neck dissection in patients with laryngeal and hypopharyngeal carcinomas.

Adult↗

The distribution of prostaglandins in afferent and efferent lymph from inflammatory sites.

Arachidonic acid labeled with (14)C was injected directly into lymph nodes that had been stimulated at various times with Escherichia coli. The efferent lymph was collected, and labeled catabolites were extracted and analyzed chromatographically. The pimary conversion product recovered was Prostaglandin E(2) (PGE(2)), with the lesser products thromboxane, prostacyclin and prostaglandin F(2alpha) (PGF(2alpha)) also detected. When the efferent lymph was analyzed by radioimmunoassay after subcutaneous injectino of E coli into the hock, PGE and PGF levels rapidly increased, reached the highest levels in the first 10 hours, and then returned to normal by 24 hours. When the afferent lymph plasma draining inflammatory sites was compared directly with efferent lymph, PGF levels were similar, but the PGE level was always several times higher in the afferent lymph. To examine the catabolism of PG, either (3,)H-PGF(2alpha) of (3)H-PGE(2) was injected into the node, and the efferent lymph plasma was analyzed. No conversion of PGF(2alpha) to other products was found. In contrast, catabolic products of PGE(2) were detected. With the use of equilibrium dialysis techniques, the binding of PGE(2) and PGF(2alpha) to proteins in lymph and to bovine serum albumin (BSA), human serum albumin (HSA), and BSA stripped of its fatty acids was established. The binding to lymph proteins correlated with the albumin concentrations in the lymph. This albumin binging probably facilitated the retention and transport of PG in the lymph. PG appears in the lymph at a time corresponding to the uptake and processing of antigen by the node and near the time when lymphokines are detected in lymph and could modulate several steps in the immune response. The PGE detectable in the lymph draining an inflammatory site may play a role in the modulation of blood flow.

Animals↗

Histological evaluation of lymph node metastasis on serial sectioning in gastric cancer with radical lymphadenectomy.

BACKGROUND/AIMS: Lymph node metastasis is one of the most important prognostic factors in gastric cancer patients. To evaluate the real extent of lymph node metastasis from gastric cancer, histological examination by serial sectioning was performed. METHODOLOGY: Histological examination of serial sections of lymph nodes was performed in 111 gastric cancer patients who underwent radical gastrectomy, to evaluate methods of examining lymph node metastasis. A total of 58430 cross-sections of 3449 lymph nodes were examined. The extent of lymph node metastasis was evaluated by the routine one-section method, the 3-section method and the serial sectioning method for lymph node examination. RESULTS: The frequency of lymph node metastasis was 81.1% (90/111) and metastatic foci were detected in 23.0% of all lymph nodes by serial sectioning. Serial sectioning of distant lymph nodes showed metastasis in 23.8% by the 1 section method, and 8.4% by the 3-section method. Micrometastasis was detected in 10.5% of metastatic lymph nodes, and distant lymph nodes had a higher rate of micrometastasis. CONCLUSION: Serial sectioning resulted in more accurate evaluation of the extent of lymph node metastasis, and it was also shown that distant lymph nodes had a higher rate of micrometastasis.

Gastrectomy↗

Cervical sentinel lymph node biopsy for melanomas of the head and neck and upper thorax.

OBJECTIVE: To describe a clinical experience with sentinel lymph node biopsy (SLNB) of head and neck nodal basins for clinical stage I melanomas draining to these areas. DESIGN: Consecutive clinical case series with a mean follow-up of 10.7 months. SETTING: University tertiary care referral medical center. PATIENTS: Seventy patients with clinical stage I cutaneous melanoma who underwent SLNB of cervical and/or parotid lymph node basins. INTERVENTIONS: Patients underwent same-day preoperative technetium Tc 99m lymphoscintigraphy followed by SLNB using gamma probe and blue dye (66 patients) and blue dye alone (4 patients). Patients with histological evidence of tumor (here in after "positive") according to SLNB results underwent modified cervical completion lymph node dissection, including parotidectomy, as appropriate. Patients without histological evidence of tumor (hereinafter "negative") according to SLNB results were followed up clinically without undergoing completion lymph node dissection. MAIN OUTCOME MEASURES: The rates of SLNB success, SLNB positivity, completion lymph node dissection positivity, complications, and SLNB false-negative results were determined by clinical follow-up. RESULTS: Locations of melanomas in the 70 patients were the face (n = 20), neck (n = 14), ear (n = 9), scalp (n = 9), and upper thorax (n = 18). Locations of basins that underwent biopsy (n = 104) were in the cervical (n = 68), parotid (n = 19), and axillary (n = 17) regions. The mean Breslow thickness was 2.1 mm (range, 0.4-12.0 mm). Sentinel lymph node biopsy was successful in 103 basins (99%). The mean number of sentinel lymph nodes per basin was 2.5 (range, 1.0-8.0). Positive sentinel lymph nodes were found in 12 patients (17%) and 15 basins (14%). Sentinel lymph node biopsy results correlated with the American Joint Committee on Cancer tumor stage (P = .05) and a Breslow thickness of 1.23 mm or greater (P = .03). Additional tumor-containing nodes were noted in 5 (42%) of the 12 patients who underwent completion lymph node dissection, and these results correlated with the presence of multiple positive sentinel lymph nodes (P = .01). There were complications in 3 patients (4%) (seromas in 2 patients and temporary spinal accessory nerve paresis in 1 patient). One nodal recurrence in a basin that was negative according to SLNB results (SLNB with blue dye only) was noted (false-negative rate, 2%). The results of SLNB were accurate in 69 patients (99%). CONCLUSIONS: Sentinel lymph node biopsy using lymphoscintigraphy and blue dye to manage cutaneous melanomas draining to the head and neck nodal areas is reliable and safe. Sentinel lymph node biopsy results correlated with a Breslow thickness of 1.23 mm or greater and the American Joint Committee on Cancer tumor stage. Completion lymph node dissection is recommended after determining positive SLNB results.

Adolescent↗

Correlation between computed tomographic density of lymph node metastases and response to cisplatin-based chemotherapy in patients with head and neck squamous cell carcinoma in an area in which betel quid chewing is prevalent.

BACKGROUND: Identifying the factors predicting response to chemotherapy is important for patients with head and neck squamous cell carcinoma (HNSCC). It allows more rational selection of subsets of patients who may benefit from multidisciplinary treatment. Correlation of lymph node density in contrast-enhanced computed tomographic (CT) scans of HNSCC with response to chemotherapy was observed in the recent literature. This prospective study was designed to validate this clinical issue. METHODS: From January 1992 to March 1995, 71 patients with untreated HNSCC were included in this study in which the following criteria were met: 1) a lymph node > 3 cm by physical examination or > or = 2 cm by scanographic examination; 2) clinically evaluable disease treated by cisplatin-based neoadjuvant chemotherapy; and 3) availability of a pretherapeutic contrast-enhanced CT scan showing the cross-sections of relevant lymph node metastases. The density of the largest lymph node was compared with that of the nuchal muscles by a radiologist blinded to the patient's therapeutic outcome. A lymph node was classified as hypodense if more than 33% of the lymph node surface area was comprised of a hypodense zone, and isodense if less than a third of the lymph node surface area was comprised of a hypodense zone. RESULTS: Fifty-one patients (72%) had the largest lymph node classified as hypodense, and 63 patients (89%) were found to have extranodal spread (ENS) in the relevant lymph nodes. Fifty-nine patients were betel quid chewers. Lymph node density was not related to T classification, primary site, or histologic differentiation of the primary tumor. There was also no correlation between lymph node density and lymph node N classification. The lymph node chemotherapy response rate was 35% (7 of 20) of the isodense group and 47.1% (24 of 51) of the hypodense group (P = 0.36). ENS was found to have no impact on the chemotherapy response. CONCLUSIONS: Computed tomographic density of lymph node metastases did predict chemotherapy response in the HNSCC patients in the current study from an area in which betel quid chewing is prevalent.

Adult↗

Preoperative diagnosis of lymph node metastases in gastric cancer by magnetic resonance imaging with ferumoxtran-10.

BACKGROUND: Knowledge regarding the presence and location of lymph node metastasis in gastric cancer is essential in deciding on the operative approach. Lymph node metastases have been diagnosed with imaging tests such as computed tomography (CT) and ultrasonography (US); however, the accuracy of such diagnoses, based on size and shape criteria, has not been adequate. Ferumoxtran-10 (Combidex; Advanced Magnetics) is a lymphotropic contrast agent for magnetic resonance imaging (MRI) whose efficacy for the detection of metastatic lymph nodes in various cancers has been reported by several investigators; however, its efficacy for this purpose has not been reported for gastric cancer. We investigated the efficacy of ferumoxtran-10-enhanced MRI for the diagnosis of metastases to lymph nodes in gastric cancer. METHODS: Seventeen consecutive patients who were diagnosed with a nonearly stage of gastric cancer were enrolled in the study. All the patients were examined by MRI (Signa Horizon 1.5 T; GE Medical; T2*-weighted images) before and 24 h after the intravenous administration of ultrasmall particles of superparamagnetic iron oxide--ferumoxtran-10 (2.6 mg Fe/kg of body weight)--and the presence or absence of metastasis was determined from the enhancement patterns. The imaging results were compared with the corresponding histopathological findings following surgery. RESULTS: Of 781 lymph nodes dissected during surgery, the imaging results of 194 nodes could be correlated with their histopathological findings. Fifty-nine lymph nodes from 11 patients had histopathological metastases. In nonaffected normal lymph nodes, we observed dark signal intensity on MRI caused by the diffuse uptake of the contrast medium by macrophages resident in the lymph nodes, which phagocytose the iron oxide particles of ferumoxtran-10. The number of phagocytic macrophages was decreased in metastatic lymph nodes, and they showed various patterns of decreased uptake of ferumoxtran-10. Three enhancement patterns were observed in lymph nodes: (A) lymph nodes with overall dark signal intensity due to the diffuse uptake of ferumoxtran-10; (B) lymph nodes with partial high signal intensity due to partial uptake; and (C) no blackening of lymph nodes due to no uptake of ferumoxtran-10. Patterns (B) and (C) were defined as metastatic. The sensitivity, specificity, positive predictive value, negative predictive value, and overall predictive accuracy of postcontrast MRI were 100% (59/59), 92.6% (125/135), 85.5% (59/69), 100% (125/125), and 94.8% (184/194), respectively. These parameters for predictive accuracy were much superior to these parameters previously evaluated by CT or US. Nodes in the retroperitoneal and paraaortic regions were more readily identified and diagnosed on the MR images than those in the perigastric region. CONCLUSION: The present study confirmed that ferumoxtran-10-enhanced MRI is useful in the diagnosis of metastatic lymph nodes and that the use of this modality will be helpful in treatment decision-making for gastric cancer patients.

Adult↗

Bony landmarks are not an adequate substitute for lymphangiography in defining pelvic lymph node location for the treatment of cervical cancer with radiotherapy.

PURPOSE: Curative radiotherapy (RT) for carcinoma of the cervix requires adequate irradiation of regional lymph node groups. The best nonsurgical method of defining lymph node anatomy in the pelvis remains the lymphangiogram (LAG). This study was designed to determine if bony landmarks could accurately substitute for LAG as a means of determining lymph node position for the purpose of pelvic RT treatment planning. METHODS AND MATERIALS: The post-LAG simulation films of 22 patients treated at the Fox Chase Cancer Center for cervical cancer were examined. On anterior/posterior (A/P) simulation films, the distance of lymph nodes was determined from the top, middle, and bottom of the sacroiliac joint, and at the pelvic rim, 1 and 2 cm above the acetabulum. On lateral (LAT) simulation films, lymph node position was measured at points 0, 4, and 8 cm along a line from the bottom of L5 to the anterior aspect of the pubic symphysis. Positive values represent lateral and anterior distances relative to the reference point on A/P and LAT films, respectively. Negative values represent distances in the opposite direction. The adequacy of standard pelvic fields as defined by the Gynecologic Oncology Group (GOG) (A/P: 1.5 cm margin on the pelvic rim; LAT field edge is a vertical line anterior to the pubic symphysis) was also examined. Data are expressed as the mean +/- two standard deviations, (i.e. 95% confidence level). RESULTS: On A/P simulation films, the distance of visualized lymph nodes had mean values of -1.6 +/- 1.7 cm (range -4.1 to -0.4 cm), -1.3 +/- 1.5 cm (range -3.4 to 0.0 cm), and 1.2 +/- 1.8 cm (range -1.0 to 2.6 cm) from the sacro-iliac (SI) joint at the superior, middle, and inferior points, respectively. The mean distance of the nodes from the pelvic rim at points 1 and 2 cm above the acetabulum was 0.3 +/- 1.2 cm (range -0.6 to 1.8 cm) and 0.2 +/- 1.8 cm (range -1.6 to 2.1 cm), respectively. On LAT simulation films, the distance of lymph nodes from points 0, 4, and 8 cm from the previously described reference line had mean values of 2.0 +/- 1.0 cm (range 1.3 to 3.0 cm), 0.9 +/- 3.9 cm (range -1.9 to 5.1 cm), and 1.8 +/- 2.1 cm (range -0.8 to 3.5 cm), respectively. Ten of 22 (45%) patients would have had inadequate nodal irradiation if their fields had been designed according to standard GOG parameters. In all cases, these incompletely irradiated lymph nodes were from the lowest of the lateral external iliac group. CONCLUSION: Great variability in pelvic lymph node location is demonstrated when LAG is used to directly visualize their location. Bony structures are inaccurate landmarks for pelvic lymph node position. The GOG standard pelvic fields are not consistently adequate to cover all lateral external iliac lymph nodes, although the clinical significance of this subgroup of lymph nodes is not known. At this time, LAG remains the ideal radiographic modality to define anatomic location of regional lymph nodes for pelvic RT treatment planning. The clinical importance of the most lateral group of external iliac lymph nodes in various stages of cervical cancer represents a potential area of future research.

Acetabulum↗

Contralateral cervical and mediastinal lymph node metastasis in medullary thyroid cancer: systemic disease?

BACKGROUND: The current American Joint Committee on Cancer/International Union Against Cancer classification designates cervical and mediastinal lymph nodes as regional lymph nodes. In a unilateral thyroid neoplasm, however, involvement of the contralateral cervical lymph node compartment or the mediastinal lymph node compartment, both of which have been designated "distant" lymph nodes, may serve as a surrogate parameter of distant metastases. METHODS: This institutional series consisted of 105 consecutive patients with medullary thyroid cancer who underwent systematic dissections of both distant lymph node compartments. RESULTS: Thirty-eight patients had no distant lymph node metastasis, 36 patients had involvement of only 1, and 31 patients of both distant lymph node compartments. Significant associations (P < .001) were seen on univariate analysis between the number of involved "distant" lymph node compartments (none, one, or both) and extrathyroidal extension (3%, 33%, and 58%), the number of positive lymph nodes (means of 3, 13, and 33), and distant metastasis (8%, 36%, and 61%). In a multivariate logistic regression model, only involvement of one or both "distant" lymph node compartments (versus no distant lymph node metastasis) remained significantly related to distant metastasis in a dose-dependent fashion. CONCLUSIONS: "Distant" lymph nodes in medullary thyroid cancer should be regarded as nonregional lymph nodes because their involvement is indicative of distant metastasis.

Female↗

Lymph node size does not correlate with the presence of prostate cancer metastasis.

OBJECTIVES: To determine whether lymph node size is a surrogate marker for lymph node metastasis. METHODS: We reviewed 980 patients who underwent radical retropubic prostatectomy with bilateral pelvic lymph node dissection for clinically localized prostate cancer, of whom 63 had lymph node metastases. A comparable group of patients with prostate cancer undergoing radical prostatectomy who did not have lymph node involvement was identified using the following parameters: serum prostate-specific antigen level, clinical and pathologic stage, and pre- and postoperative Gleason score. The axial and longitudinal dimensions of the nodes from patients with and without metastases were analyzed to assess the significance of lymph node size in predicting the presence of metastases. All patients had negative preoperative computed tomography (CT) and bone scans. Of the 63 patients with lymph node metastases, 48 had tissue available for measuring the dimensions of the lymph nodes. RESULTS: A total of 76 metastatic and 92 negative lymph nodes were identified from the patients with and without metastatic nodes, respectively. The mean nodal longitudinal size was 1.65 cm (range 0.2 to 6.5) and 3.50 cm (range 0.5 to 9) for positive and negative nodes, respectively (P = 0.0001). The mean axial nodal size was 0.8 cm (range 0.2 to 3.2) and 1.0 cm (range 0.2 to 2.2) for positive and negative lymph nodes, respectively. In 56 metastatic nodes (74%), the axial size was less than 1 cm and in 20 (26%) less than 5 mm. CONCLUSIONS: Lymph node size should not be used as a surrogate for the presence of lymph node metastases. Although no patient had enlarged lymph nodes by CT scan criteria (greater than 1.5 cm), 6 (8%) of 48 and 19 (12%) of 48 patients with and without lymph node metastases, respectively, had nodes with an axial dimension greater than 1.5 cm.

Aged↗

Utility of mapping lymph nodes cleared from rectal adenocarcinoma specimens.

The lymph node clearing technique improves the detection of lymph nodes in colorectal cancer specimens. The purpose of this study was to determine the utility of mapping the lymph nodes cleared from rectal adenocarcinoma specimens by evaluating the possible relationship between the pattern of lymph node metastases to the site of the recurrent disease. A retrospective medical record review was performed in 40 patients with primary rectal adenocarcinoma. The specimens were analysed by lymph node clearing technique and mapped after surgery. The lymph nodes were mapped according to their location in the cleared specimens. Statistical analysis was performed using the chi 2-test. A total of 1290 lymph nodes were cleared in 40 specimens. Of these, 1126 (87%) lymph nodes were < or = 5 mm. One-hundred and ten (9%) lymph nodes were metastatic. Sixty-seven (61%) of these 110 lymph nodes were 5 mm or less in size. The majority of lymph nodes with or without metastases were in the pelvis, as opposed to an extrapelvic location (P = 0.0001). Eleven patients recurred. In nine of these patients the recurrence showed a direct relationship between the level of metastatic lymph node location (pelvic vs. extrapelvic) and the site of the recurrent disease (loco-regional or systemic, P = 0.05). The majority of lymph nodes, both normal and metastatic, cleared from specimens from rectal adenocarcinoma were < or = 5 mm in diameter. The lymph node mapping technique may help in predicting the site of recurrence.

Adenocarcinoma↗

Three-field lymphadenectomy and pattern of lymph node spread in T3 adenocarcinoma of the distal esophagus and the gastro-esophageal junction.

OBJECTIVE: Lymph node metastasis in carcinoma of the esophagus and the gastro-esophageal junction is often underestimated by clinical staging. It is the aim of this study to provide support to the fact that three-field lymphadenectomy leads to a better pathological staging also in adenocarcinoma. METHODS: The pattern of lymph node metastasis in adenocarcinoma of the gastro-esophageal junction (GEJ) and the distal esophagus was charted in a prospective way by using a database. An analysis was performed with regard to lymphatic spread in T3, N+ adenocarcinomas of the distal esophagus and the GEJ junction, which were treated with a radical resection including a three-field lymphadenectomy. Out of 324 patients with adenocarcinoma of the esophagus and GEJ, we selected a group of 37 patients with an adenocarcinoma T3, N+ of the distal (n = 17) or GEJ junction (n = 20), treated with a radical resection and three-field lymphadenectomy ( > 25 lymph nodes resected). RESULTS: In total, 2240 lymph nodes were removed, with a mean of 59.5 per patient. In the GEJ group the ratio of positive nodes was 15.9, in the distal 1/3 group this ratio was 12.7%. Abdominal lymph nodes were positive in all GEJ tumors and in 70% of the distal third carcinomas. Thoracic lymph nodes were positive in 40% of GEJ tumors, and 70.6% of the distal group. Cervical lymph nodes were positive in 20% of the GEJ tumors and in 35.3% of the distal tumors. In six patients only right-sided cervical nodes were affected. Three patients in the GEJ group had positive lymph nodes in the neck without any involvement of thoracic lymph nodes. CONCLUSIONS: (1) Three-field lymphadenectomy improves accuracy of staging. (2) Cervical nodes are frequently involved. (3) Especially in tumors of the GEJ there is an important skipping phenomenon, i.e. positive lymph nodes in the neck in the absence of involvement of thoracic nodes. (4) Clinical staging remains deficient in regard to lymph node metastasis, especially cervical nodes. (5) The frequent unforeseen involvement of cervical lymph nodes in adenocarcinoma of the distal esophagus and GEJ tumors makes the interpretation of results of induction chemoradiotherapy questionable. (6) For the same reason, cervical lymph nodes should be included in the radiation field in case of induction chemoradiotherapy. (7) The similar pattern of lymph node involvement suggests similar oncological behavior of adenocarcinoma of the distal esophagus and the GEJ, questioning the actual TNM classification of these tumors as gastric carcinomas.

Adenocarcinoma↗

Photodynamic detection of diseased axillary sentinel lymph node after oral application of aminolevulinic acid in patients with breast cancer.

Benign as well as malignant tumour tissues of the breast demonstrate higher fluorescence intensity (FI) than normal breast tissue after application of a photosensitiser. As a follow-up study, we evaluated the FI of metastatic sentinel lymph nodes and metastatic axillary lymph nodes compared to nonmetastatic sentinel and axillary lymph nodes in patients with breast cancer. In all, 11 patients received 30 mg 5-aminolevulinic acid (ALA) kg(-1) bodyweight orally 3 h prior to surgery. The sentinel lymph node was marked with Nanocoll preoperatively and with a blue dye intraoperatively. Tumour excision, excision of the sentinel lymph node and an axillary lymph node dissection were performed during the same surgical session. The operation site was illuminated with blue light (400 nm) to obtain macroscopic tissue characterisation of fluorescence. Tissue samples were stored protected from light, and analysed using a fluorescence microscope. Results were correlated with histopathology. In all, 14 sentinel lymph nodes, seven axillary lymph nodes and seven primary tumours were analysed. Metastatic sentinel lymph nodes demonstrated a statistically significant higher FI than nonmetastatic sentinel lymph nodes (2630 vs 526, P<0.0001). The FI of metastatic sentinel lymph nodes, of metastatic axillary lymph nodes and of the primary tumour were comparably high, and were statistically significantly higher compared to the normal mammary tissue. Intraoperatively, only in a few cases, it was possible to recognise the metastatic sentinel lymph node macroscopically with blue light. Our study indicates that photodynamic diagnosis with ALA has a potential in the diagnosis and detection of the sentinel lymph node in patients with breast cancer, and is worth to be further investigated and developed for intraoperative photodynamic diagnosis and possibly therapy.

Administration, Oral↗

3D ultrasound examination of the superficial lymph nodes--does it provide additional information?

PURPOSE: To compare the appearance of superficial lymph nodes on standard two-dimensional (2D) ultrasound examination and on three-dimensional (3D) ultrasound examination. MATERIALS AND METHODS: Fifty two lymph nodes (35 cervical, 16 axillary, 1 inguinal) in 52 patients were examined with ultrasound in 3D mode. In standard 2D grey-scale examination and on a C-plane of 3D mode (parallel to the surface of the probe), the shape of a lymph node and its hilum were assessed. Final histopathological diagnoses included 36 lymphomas, 11 reactive or inflammatory lymph nodes, 3 metastases and 2 plasmocytoma infiltrations. RESULTS: The appearance of hilums and lymph nodes as a whole changed on a C-plane of 3D mode (as compared with 2D presentation) in 28 % and 37 %, respectively. The differences in lymph node shape on 2D and 3D ultrasound were apparent in a comparable percentage of reactive lymph nodes (45 %) and lymphomatous lymph nodes (39 %). The differences in lymph node hilum shape on 2D and 3D ultrasound applied to 56 % of reactive lymph nodes and 20 % of lymphomatous lymph nodes. CONCLUSION: Three-dimensional imaging on a C-plane (parallel to the surface of the probe) may supply the examiner with different information concerning the shape of the lymph node and its hilum in comparison to standard 2D ultrasound. Changes in the shapes of hilum and lymph node occurred in reactive or inflamed lymph nodes as well as in lymphomas. Clinical significance of this fact demands further investigation.

Humans↗

Incidence, location, and significance of periprostatic and periseminal vesicle lymph nodes in prostate cancer.

Pelvic lymph node metastases in prostate cancer (PCa) carry an ominous prognosis. Periprostatic/periseminal vesicle (PP/PSV) lymph nodes are present in some individuals, but their incidence and involvement by metastases are unknown. A total of 832 of 1233 (67.5%) patients who underwent radical retropubic prostatectomy for clinically localized PCa at the Methodist Hospital from 1983 to 1998 by one surgeon (P.T.S.) had whole-mount slides available for review. Of these, 92 (11.1%) had received preoperative therapy (radiation in 48 [5.8%], hormonal in 44 [5.3%]). Slides were examined with the naked eye by placing them on a white illuminated background, and any area suggestive of a lymph node in PP/PSV fat was confirmed microscopically and assessed for the presence of metastases. Thirty-seven of 832 patients (4.4%) had 39 PP/PSV lymph nodes-one bilateral, one with two ipsilateral lymph nodes, and the rest solitary. Sizes ranged from 0.7 to 4.5 mm (mean 1.8 mm). Distribution was 2 of 39 (5.1%) apical, 3 of 39 (7.7%) mid, 17 of 39 (43.6%) base, and 17 of 39 (43.6%) seminal vesicle. Five patients (0.6%) had metastatic PCa to the PP/PSV lymph nodes. All five patients were of advanced pathologic T stage [one pT3a (extraprostatic extension) and four pT3b (seminal vesicle invasion)]. Only two of those five (40%) had metastases (all ipsilateral) to pelvic lymph nodes. In three of five (60%) the metastases were isolated to the PP/PSV lymph nodes. Metastases were to the lymph nodes in the periseminal vesicle fat in four of five (80%) of the cases and in the fat surrounding the base of the prostate in one of five (20%). Four of five (80%) patients recurred. Histologic grade (Gleason score), tumor volume, and failure (recurrence) rates were significantly different between the five patients with metastases and the 32 patients without metastases to the PP/PSV lymph nodes (p <0.0001, p <0.0001, and p = 0.005, respectively). However, there was no evidence that an individual patient's probability of having a PP/PSV lymph node increased with resection of the neurovascular bundle (p = 0.7698). PP/PSV lymph nodes are uncommon, but based upon these limited data, it appears that patients with metastases limited to PP/PSV lymph nodes have a poor prognosis (similar to pelvic lymph node metastases) and should be included in the American Joint Committee on Cancer (AJCC) Staging Manual to indicate "N1" if positive for metastases.

Adenocarcinoma↗

Post-hemorrhagic shock mesenteric lymph is cytotoxic to endothelial cells and activates neutrophils.

The goal of these experiments was to test the hypothesis that after a nonlethal episode of hemorrhagic shock, factors carried in the mesenteric lymph would promote endothelial cell injury and activate neutrophils to a greater extent than portal vein plasma. Catheters were placed in the efferent lymphatic duct draining the mesenteric lymph node complex, after which male rats were subjected to sham or actual shock (30 mmHg for 90 min), and lymph was collected. Portal vein plasma was collected from the sham-shock and shocked rats at 6 h post-shock or sham-shock. When the effect of lymph or portal blood plasma was tested on endothelial cell (HUVEC) monolayer permeability, it was found that post-shock lymph, but not post-shock portal vein plasma, increased HUVEC permeability to both 10 kDa and 40 kDa permeability probes. Subsequent experiments documented that only post-shock lymph was cytotoxic to endothelial cells as manifest both by decreased trypan blue dye exclusion and the increased release of Chromium-51 from chromium-loaded endothelial cells. Furthermore post-shock lymph induced a greater increase in neutrophil superoxide formation than pre-shock lymph, pre-shock, or post-shock portal vein plasma. Lastly, neutrophil-mediated endothelial cell injury was potentiated by the presence of post-shock lymph, and the magnitude of HUVEC injury was greater in endothelial cells incubated with post-shock lymph plus neutrophils than in monolayers incubated with post-shock lymph or neutrophils alone. These results suggest that post-shock lymph is cytotoxic to endothelial cells and activates neutrophils. Since the lung is the first organ that is exposed to mesenteric lymph, lung injury after hemorrhagic shock may be mediated by factors contained in mesenteric lymph.

Animals↗