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Detection of melanoma micrometastases in the sentinel lymph node and in nonsentinel nodes by tyrosinase polymerase chain reaction.

The aim of our study was to investigate the metastatic pathways of melanoma cells in sentinel and other regional lymph nodes. The term "sentinel lymph node" means that the first lymph node of the draining site of a primary tumor is never bypassed in malignant melanoma. In this case lymph node dissection would be necessary only when melanoma cells are detected in the sentinel node. Tyrosinase reverse transcriptase-polymerase chain reaction was applied to search for metastatic melanoma in the sentinel lymph node and in further lymph nodes of a complete lymph node basin in patients who underwent lymph node dissection. In 24 patients with malignant melanoma the draining site of the tumor was marked by lymphoscintigraphy and by intraoperative injection of patent blue V in the area around the primary tumor. The lymph nodes of the affected basin were excised and prepared for histopathologic, immunohistochemical, and molecular biologic examinations. Regarding the sentinel lymph node, 10 of 24 patients showed morphologic evidence for metastases, three additional patients showed only tyrosinase transcripts. In 11 of these 13 cases we found one or more nonsentinel lymph nodes with morphologically detectable melanoma cells and/or tyrosinase mRNA. Interestingly, in seven of 24 patients a positive tyrosinase reverse transcriptase-polymerase chain reaction was received in nonsentinel lymph nodes, whereas the sentinel lymph node was negative, not only for all histologic examinations but also by tyrosinase reverse transcriptase-polymerase chain reaction. In five of seven patients of the latter group, gp100 reverse transcriptase-polymerase chain reaction was carried out, showing also gp100 mRNA in nonsentinel lymph nodes only. Our data indicate that the concept of the sentinel lymph node may miss micrometastases. Whether such micrometastases cause a recurrence or a metastasis of malignant melanoma, or can be destroyed by the immune system, remains to be clarified.

Adult↗

Shock mesenteric lymph-induced rat polymorphonuclear neutrophil activation and endothelial cell injury is mediated by aqueous factors.

BACKGROUND: After trauma and hemorrhagic shock (T/HS), mesenteric lymph (ML) activates polymorphonuclear neutrophils (PMNs), injures endothelial cells (ECs), and predisposes to lung injury. The involved mediators, however, are unknown. We studied the ability of aqueous (AQ) and lipid (LIP) extracts of rat T/HS ML to activate PMNs and injure ECs. METHODS: ML was collected from male rats undergoing trauma (laparotomy) plus hemorrhagic shock (30 mm Hg, 90 minutes) or sham shock. AQ and LIP ML fractions were separated using the Bligh-Dyer technique. Human umbilical vein endothelial cells were incubated 18 hours in 5% LIP or AQ lymph fractions and viability was assessed using the MTT assay. Rat PMNs incubated 5 minutes with 3% LIP or AQ fractions were assessed for respiratory burst (RB) and cytosolic calcium ([Ca(2+)](i)) using dihydrorhodamine 123 and fura-2AM. Human PMN responses to AQ and LIP T/HS lymph were studied similarly. RESULTS: EC incubated in AQ showed 19 +/- 4% viability as compared with 65 +/- 11% in LIP (p < 0.001). Whole lymph affected ECs comparably to AQ T/HS lymph. Rat PMN basal [Ca(2+)](i) increased after exposure to AQ but not LIP T/HS lymph extracts. AQ T/HS lymph primed [Ca(2+)](i) responses to macrophage inflammatory protein-2 and platelet-activating factor; neither LIP T/HS nor any trauma and sham shock lymph fraction caused PMN priming. Rat PMN RB was elevated after AQ T/HS lymph incubation when compared with buffer (610 +/- 122 U/s vs. 225 +/- 38 U/s, p = 0.01). Rat PMN incubation in LIP T/HS lymph caused minimal activation (289 +/- 28 U/s, p = NS). Conversely, human PMN showed [Ca(2+)](i) and RB priming by rat T/HS LIP and not AQ extracts. CONCLUSION: T/HS mesenteric lymph contains multiple biologically active mediators. Both AQ and LIP extracts of T/HS lymph are toxic to human umbilical vein endothelial cells, with AQ more active than LIP. Only AQ T/HS lymph activates rat PMNs, although LIP rat lymph extract activates human PMNs. These findings demonstrate the complex nature of gut lymph-derived biologic factors as well as species-specific differences on PMN and EC physiology. Therapies directed at any one specific molecule or mediator are therefore unlikely to be successful.

Animals↗

Peripyloric lymph node metastasis is a rare condition in carcinoma of the pancreatic head.

OBJECTIVES: Pylorus preserving pancreatoduodenectomy (PPPD) was introduced to achieve a better functional result compared with the conventional Kausch-Whipple procedure (PD). In PPPD, peripyloric and perigastric lymphatic tissue is not removed compared with PD. The aim of this prospective study was to identify the frequency of peripyloric and perigastric lymph node metastases in ductal adenocarcinoma of the pancreatic head (PC). METHODS: Fifty specimens following Kausch-Whipple procedure including partial gastric resection for PC were analyzed for peripyloric and perigastric lymph node metastases by a standardized clearing technique. All lymph nodes of the specimens were counted, discriminating between those not removed ("group A") and those removed ("group B") in pylorus preserving resection of the pancreatic head. Additionally, the duodenal wall and paraduodenal tissue at a potential duodenal resection margin 2 cm distal of the pylorus were investigated histologically. RESULTS: Three of the 50 specimens (6%) carried peripyloric lymph node metastases, whereas 32 of the 50 specimens (64%) contained lymph node metastases in total. Four of 362 group A and 90 of 748 group B lymph nodes showed metastatic spread of the carcinoma. The 4 lymph node metastases in group A could be identified exclusively in 88 peripyloric lymph nodes but in none of the 274 perigastric lymph nodes at the lesser or greater curvature. In 2 of the 3 patients with peripyloric lymph node metastases, these lymph nodes were the only lymph nodes with metastatic involvement in the entire specimen. In 1 specimen, a small tumor nest of less than 2 mm in diameter was detected at a distance of less than 1 mm to the pylorus, although pyloric involvement was not suspected intraoperatively. The potential PPPD resection margin of the duodenal wall was not infiltrated by intramural tumor spread in any specimen. CONCLUSION: In a minority of 6%, PC metastasizes in peripyloric lymph nodes. Lymph nodes of the lesser and greater curvature of the stomach are not involved in patients with PC. Thus, we conclude by the data of this prospective study that the limited benefits of the extended lymph node dissection in a conventional Kausch-Whipple resection are far outweighed by the disadvantages construed by this procedure.

Aged↗

Bone marrow failure in male rats following trauma/hemorrhagic shock (T/HS) is mediated by mesenteric lymph and modulated by castration.

Bone marrow (BM) suppression occurs following trauma/hemorrhagic shock (T/HS) in experimental animals as well as following severe injury in humans. Although the pathophysiology of BM suppression remains poorly understood, mesenteric lymph is thought to play an important role in T/HS-induced BM suppression; however, the direct effect of mesenteric lymph on BM in vitro has never been studied. In addition, recent studies in rats have also shown that female and castrated male rats are protected against T/HS-induced BM failure. We therefore hypothesized that mesenteric lymph is a source of factor(s) causing direct BM suppression and that the effects of mesenteric lymph are gender dependent. To test this hypothesis, we subjected noncastrated (NC) and castrated (C) male and proestrus female rats to T/HS or trauma sham shock (T/SS). Mesenteric lymph collected 3 h postshock was plated (4% v/v) with BM cells collected from unmanipulated male or female rats for granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) colony growth. The T/HS lymph collected from NC-male rats but not from female rats caused a 50% inhibition of CFU-GM and BFU-E colony growth compared with cells cultured without lymph (P < 0.05 versus all other groups (ANOVA + Tukey). T/HS lymph collected from C-male rats also caused no significant inhibition of CFU-GM and BFU-E colony growth compared with cells cultured without lymph. Female and male BM progenitor cells had a similar response to mesenteric lymph from all groups tested. These results show that mesenteric lymph from NC-male rats suppresses CFU-GM and BFU-E progenitor growth in vitro, whereas the lymph from C-male and female rats did not. The effects of mesenteric lymph were the same regardless of whether the target BM was from male or female rats. The results therefore indicate that BM failure in male rats is directly mediated by factors present within the mesenteric lymph that appear to be modulated by castration, and protection against BM failure in female rats occurs at a systemic rather than a local level. Further studies are needed to elucidate potential therapeutic effects of lymph manipulation in hematopoiesis after injury.

Animals↗

The lymphatics of the kidney and the formation of renal lymph.

1. The anatomy of the renal lymphatics and the flow and composition of renal lymph have been investigated in sheep. Lymphatic capillaries were demonstrated in the cortex and cortico-medullary areas of the sheep's kidney but not within the medulla. The lymph formed in the sheep's kidney drains from the hilum through several small lymphatics; there is no lymphatic drainage from the renal capsule.2. Lymph flow from the sheep's kidney varied from 0.5 to 3.0 ml./hr. The concentrations of electrolytes and urea in renal lymph were found to be similar to lymph from other regions of the body, but the concentration of endogenous creatinine was lower. The average concentration of protein in renal lymph was 43% of the plasma levels; there was a significantly higher proportion of albumin in renal lymph than in plasma. When labelled albumin was injected intravenously, the specific activities of the plasma and renal lymph albumin equilibrated in about 2 hr.3. When [(14)C]inulin, [(125)I]hippuran or [(14)C]creatinine were infused intravenously radioactivity appeared rapidly in the renal lymph. When steady-state levels were reached in the circulating plasma, the renal lymph/jugular vein plasma ratios for [(14)C]inulin and [(14)C]creatinine were 0.82 while for [(125)I]hippuran the ratio was 0.34. It was considered that the concentration of these substances in renal lymph was similar to the concentration in renal vein plasma.4. The concentration of renin enzyme was on the average about 8 times higher in renal lymph than in jugular vein or renal vein plasma or in lymph from the hind limbs.5. Renal lymph appeared to be formed principally, if not entirely, in the renal cortex and appeared to be a modified filtrate derived from post-glomerular blood capillaries. If any contribution to renal lymph does come from the medulla, it must be small in relation to the volume of lymph formed in the cortex.

Albumins↗

Lymph node staging of oral and maxillofacial neoplasms in 31 dogs and cats.

A retrospective study was performed to report the histologic examination results of regional lymph nodes of dogs and cats with oral or maxillofacial neoplasms. Twenty-eight dogs and 3 cats were evaluated. Histologic examination results of standard and serial tissue sectioning of regional lymph nodes were recorded. When available, other clinical parameters including mandibular lymph node palpation, thoracic radiographs, and pre- and postoperative fine needle aspiration of lymph nodes were compared with the histologic results. Squamous cell carcinoma, fibrosarcoma, and melanoma were the most common neoplasms diagnosed in dogs. Squamous cell carcinoma and fibrosarcoma were diagnosed in cats. Of the palpably enlarged mandibular lymph nodes, 17.0% had metastatic disease histologically. Radiographically evident thoracic metastatic disease was present in 7.4% of cases. Preoperative cytologic evaluation of the mandibular lymph node based on fine needle aspiration concurred with the histologic results in 90.5% of lymph nodes examined. Postoperative cytologic evaluation of fine needle aspirates of regional lymph nodes concurred with the histologic results in 80.6% of lymph nodes examined. Only 54.5% of cases with metastatic disease to regional lymph nodes had metastasis that included the mandibular lymph node. Serial lymph node sectioning provided additional information or metastasis detection. Cytologic evaluation of the mandibular lymph node correlates positively with histology, however results may fail to indicate the presence of regional metastasis. Assessment of all regional lymph nodes in dogs and cats with oral or maxillofacial neoplasms will detect more metastatic disease than assessing the mandibular lymph node only.

Animals↗

Endobronchial ultrasonography for mediastinal and hilar lymph node metastases of lung cancer.

STUDY OBJECTIVES: Conventional radiologic procedures are frequently unreliable in the diagnosis of mediastinal and hilar lymph node metastases of lung cancer. In order to improve diagnostic accuracy, we performed endobronchial ultrasonography (EBUS) during bronchofiberscopic examinations of patients with lung cancer. METHODS AND PATIENTS: To evaluate mediastinal and hilar lymph node metastases, EBUS was performed prospectively using a radial scanning probe of 20 MHz through a bronchofiberscope. RESULTS: We observed hilar lymph nodes (10R, 11R superior, 11R inferior, 12R, 10L, 11L, 12L) in 20 of 37 patients who underwent EBUS, and we could clearly identify whether direct invasion of the pulmonary artery by a lymph node had occurred. Of the 27 patients who showed no hilar lymph nodes on chest CT scan, lymph node swellings < 10 mm or > or = 10 mm in diameter were identified by EBUS in 9 patients and 2 patients, respectively. Interestingly, EBUS also revealed that the pulmonary artery was directly invaded by an interlobar lymph node < 10 mm in diameter in one patient. In most patients, lymph node 7 was easily identified and was clearly differentiated from the surrounding esophagus, vessels, and mediastinal fat tissue by EBUS. However, fused lymph nodes or lymph nodes with low central density when visualized by chest CT scan were occasionally observed as independent lymph nodes by EBUS. When compared with the pathologic diagnosis of lymph node metastasis in 16 patients who underwent surgery, the most specific and sensitive method for identifying lymph node metastases were EBUS alone (92%) and EBUS in combination with CT scan (100%), respectively. The overall accuracy of EBUS was 94% for the diagnosis of direct invasion of the pulmonary arteries by a hilar lymph node. CONCLUSIONS: EBUS in combination with conventional radiologic tools may contribute to improved staging, especially in surgical cases with hilar lymph node metastases.

Adult↗

Relationship between lymph node sinuses with blood and lymphatic metastasis of gastric cancer.

AIM: To elucidate the relationship between lymph node sinuses with blood and lymphatic metastasis of gastric cancer. METHODS: Routine autopsy was carried out in the randomly selected 102 patients (among them 100 patients died of various diseases, and 2 patients died of non-diseased reasons), their superficial lymph nodes locating in bilateral necks (include supraclavicle), axilla, inguina, thorax, and abdomen were sampled. Haematoxylin-Eosin staining was performed on 10 % formalin-fixed and paraffin-embedded lymph node tissue sections (5 um). The histological patterns of the lymph sinuses containing blood were observed under light microscope. The expression of CD31, a marker for endothelial cell, was detected both in blood and non-blood containing lymph node sinuses with the method of immunohistochemistry. RESULTS: Among the 1 322 lymph nodes sampled from the autopsies of 100 diseased cases, lymph node sinuses containing blood were found in 809 lymph nodes sampled from 91 cases, but couldn't be seen in the lymph nodes sampled from the non-diseased cases. According to histology, we divided the blood containing lymph node sinuses into five categories: vascular-opening sinus, blood-deficient sinus, erythrophago-sinus, blood-abundant sinus, vascular-formative sinus. Immunohistochemical findings showed that the expression of CD31 was strongly positive in vascular-formative sinuses and some vascular-opening sinuses while it was faint in blood-deficient sinuses, erythrophago-sinuses and some vascular-opening sinuses. It was almost negative in blood-abundant sinus and non-blood containing sinus. CONCLUSION: In the state of disease, the phenomenon of blood present in the lymph sinus is not uncommon. Blood could possibly enter into the lymph sinuses through the lymphaticovenous communications between the veins and the sinuses in the node. Lymph circulation and the blood circulation could communicate with each other in the lymph node sinuses. The skipping and distal lymphatic metastasis of gastric cancer may have some connection with the blood containing lymph node sinuses.

Adolescent↗

[Cervical lymph node surgery in differentiated thyroid cancer: selective or elective lymphadenectomy?].

The value and prognostic significance of regional lymph node dissection in patients with thyroid cancer remains a matter of controversy. The classification of the cervical lymph nodes and the extent of their resection in patients with different thyroid cancers is also discussed. The aim of the paper was to present the space classification of regional lymph nodes, the incidence of their involvement and the extent of their resection in patients with differentiated thyroid cancer. The results of multicenter studies have indicated that regional lymph node metastases in patients with differentiated thyroid cancer, especially of a papillary type, have been frequent. Ipsilateral central, ipsilateral lateral, contralateral lateral, and mediastinal lymph nodes have been affected in 42-86%, 32-68%, 12-24%, and 3-20% of patients respectively. In 20% of patients only central lymph nodes have been affected, whereas in others metastases have been determined at least in 2 or more lymph node groups. Regional lymph nodes have been classified into Groups I-IV. Moreover, lymph node recurrences have been more frequent in patients who either have not got the regional lymph nodes removed or have only enlarged ones determined as involved excised. Therefore, primary regional lymph nodes dissection is indicated. Elective resection of the lymph nodes of Group I (central lymph nodes) as a part of primary total thyroidectomy in patients with thyroid cancer and more selective excision of the lymph nodes of Groups II-IV are recommended. The author has presented his own experience in lymph node dissection in patients with differentiated thyroid cancer and compared it with other results.

Humans↗

Implications of lymphatic drainage to unusual sentinel lymph node sites in patients with primary cutaneous melanoma.

BACKGROUND: Sentinel lymphadenectomy reliably identifies the first site(s) of regional lymphatic drainage and, therefore, the most likely lymph nodes to contain occult metastasis in patients with primary cutaneous melanoma. Although in most patients lymphatic drainage from the primary melanoma first reaches a standard lymph node basin, a sentinel lymph node (SLN) may be identified in an unusual location. The objective of this study was to determine the frequency and significance of unusual sentinel lymph node drainage patterns in a large cohort of patients with primary melanoma. METHODS: The records of 1145 consecutive primary melanoma patients who underwent SLN biopsy were reviewed. Preoperative lymphoscintigraphy was performed in all patients with truncal melanoma and in many patients with distal extremity lesions. Unusual lymph node sites were defined as epitrochlear, popliteal, or ectopic/interval (in-transit or any other nonstandard lymph node-bearing area). RESULTS: At least one SLN was harvested in 1117 patients (98%). SLN biopsy of an unusual lymph node site was attempted in 59 patients (5%). Successful intraoperative localization and biopsy was performed in 54 (92%) of 59 patients for a total of 56 unusual sites. Of these, 7 (13%) were popliteal, 8 (14%) were epitrochlear, and 41 (73%) were ectopic/interval. Preoperative lymphoscintigraphy was performed in 41 of these 54 patients and correctly identified unusual SLN locations in 12 (29%); the majority of unusual SLNs were identified only with the assistance of the intraoperative gamma probe. In four patients (7%), the unusual lymph node site was the only site from which SLNs were harvested. In the remaining 50 patients (93%), biopsies were performed on SLNs from both unusual sites and from a standard lymph node basin. Among the 54 patients who underwent a SLN biopsy of an unusual nodal site, 7 (13%) had lymph node metastases in that location. In four of the seven patients, the only positive SLN was from the unusual site. CONCLUSIONS: Sentinel lymphatic drainage patterns include lymph node-bearing areas that may be outside established standard lymph node basins and may represent the only site of regional lymph node metastases. Although preoperative lymphoscintigraphy may assist in the identification of unusual SLN drainage patterns, intraoperative use of the gamma probe is recommended to identify accurately and completely all sites of regional lymph node drainage.

Female↗

The diagnostic value of thyroglobulin concentration in fine-needle aspiration of the cervical lymph nodes in patients with differentiated thyroid cancer.

INTRODUCTION: Recurrent differentiated thyroid cancer generally occurs first in the neck. Ultrasound is sensitive in detecting enlarged cervical lymph nodes but is not specific enough. Ultrasound-guided fine-needle biopsy increases the specificity but still may fail to detect a recurrence of the disease in the cystic metastatic lymph nodes. The aim of the study was to estimate the value of Tg concentration in the needle washout after fine-needle aspiration of suspicious lymph nodes. MATERIAL AND METHODS: The 105 patients studied had presented one or more enlarged suspicious cervical lymph nodes. All had undergone total thyroidectomy and (131)I ablative therapy. Serum thyroglobulin (Tg) concentration was within the 0.15-711.5 ng/ml range (mean 22.24 ng/ml) and Tg recovery range 94-100%. The positive Tg washout concentration cut-off value was established as equal to the mean plus two standard deviations of the Tg washout concentration of patients with negative cytology. RESULTS: Lymph node involvement was diagnosed by cytology in 15 patients and in 28 lymph nodes. Positive Tg washout concentration was found in 22 patients and in 48 lymph nodes. All the lymph nodes which turned out to have positive cytology had a positive Tg washout concentration. All lymph nodes with positive cytology were positive in pathology. Seven patients and 20 lymph nodes with negative cytology were positive in the Tg washout concentration test. All but one patients and all but two lymph nodes with a positive Tg washout concentration had positive pathology. CONCLUSIONS: 1. Ultrasound-guided fine-needle biopsy is not sensitive enough to detect all metastatic lymph nodes. 2. The Tg washout concentration test is 100% sensitive in the detection of metastatic lymph nodes. 3. Cytology in ultrasound- guided fine-needle biopsy is 100% specific. 4. The Tg washout concentration test carries a risk of false-positive results. 5. Both methods should be used for early detection of metastatic lymph nodes in patients with differentiated thyroid cancer.

Adolescent↗

Localization of initial lymph node metastasis from carcinoma of the thoracic esophagus.

BACKGROUND: Most surgeons consider esophageal carcinoma with lymph node involvement a systemic disease. However, it is possible that the disease may be localized in the earlier phases of lymphatic metastasis. The distribution of involved lesions in the initial phase of lymph node metastasis has not been thoroughly investigated yet. METHODS: Among 329 patients that underwent curative (R0 International Union Against Cancer [UICC]) esophagectomy with systematic mesoesophageal dissection, 51 cases of patients with only 1 involved lymph node (solitary involvement) were retrospectively investigated and compared with patients with multiple involved lymph nodes. The regional lymph nodes were divided into the thoracocervical junction group (lower deep cervical and recurrent nerve lymph nodes), perigastric group, and intrathoracic group. RESULTS: Lymph node involvement was limited to a solitary lymph node in 46% of lymph node positive patients with esophageal carcinoma confined to the wall (T1 and T2, UICC) and in 17% of lymph node positive patients with cancer that invaded the extramural layer (T3 and T4, UICC). Of patients with solitary involvement, 82% had a positive thoracocervical junction or perigastric lymph node. The 5-year survival rate in solitary involvement cases was 61%, and 65% when solitary involvement was not intrathoracic. Most of the 5-year survivors had involvement of a thoracocervical junction or perigastric lymph node and had not received systemic chemotherapy. CONCLUSIONS: Solitary involvement was not rare and not directly associated with a disseminated disease. Solitary involvement was commonly located in the thoracocervical junction or abdomen that are accessible without thoracotomy. Systematic dissection of the regional lymph nodes including thoracocervical junction and perigastric groups is recommended for resectable esophageal carcinoma at this time. However, less extensive dissection may be performed in selected cases if the sentinel lymph node concept proves valid.

Esophageal Neoplasms↗

Para-aortic lymph node metastasis in carcinoma of the head of the pancreas.

BACKGROUND: Metastasis to para-aortic lymph nodes often occurs in pancreatic head cancer, but factors that predict it are not well known. METHODS: Using histopathologic data of 178 patients who underwent extended lymph node dissection for pancreatic head cancer, we analyzed the distribution of metastases to lymph node groups classified in detail and attempted to identify the lymph node groups that have a strong relation with metastasis to para-aortic lymph nodes. RESULTS: A high incidence of lymph node metastasis was found in para-aortic lymph nodes (No. 16, 19%) as well as in regional lymph nodes, such as those on the posterior aspect of the pancreas head (No. 13, 47%), on the anterior surface of the pancreas head (No. 17, 29%), along the superior mesenteric artery (No. 14, 28%), and along the hepatoduodenal ligament (No. 12, 19%). Statistical analysis showed that metastases to para-aortic lymph nodes had a strong correlation with metastases to Nos. 12, 13, 14, and 17 lymph nodes. Para-aortic lymph node metastases were seldom observed among the patients who had no metastases to Nos.13, 14, and 17 lymph nodes. CONCLUSIONS: Examination of Nos. 13, 14, and 17 lymph nodes may be useful to predict the involvement of para-aortic lymph nodes.

Adult↗

Lymph node metastasis in small peripheral adenocarcinoma of the lung.

OBJECTIVE: Our aim in this study is to clarify the clinical and pathologic features of small peripheral adenocarcinoma of the lung with special emphasis on intraoperative identification of lymph node metastasis. PATIENTS AND METHODS: Between 1980 and 1996, 157 patients underwent lobectomy and complete hilar/mediastinal lymphadenectomy for small (1.1 to 2.0 cm in diameter) peripheral adenocarcinoma of the lung. The intraoperative assessment, the distribution of metastatic lymph nodes, and the association between the tumor's histopathologic characteristics and lymph node metastasis were retrospectively investigated in this study. RESULTS: Postoperative examination revealed lymph node metastasis in 27 (17%) patients. Lymph node metastases were not noticed during the operation in 19 of these 27 patients. Metastases were localized in single lymph nodes in 10 patients; the metastases were distributed over a segmental, a lobar, an interlobar, and a mediastinal lymph node. The prevalence of lymph node metastasis was as follows: Of 92 patients with well-differentiated adenocarcinoma, seven (8%) had lymph node metastases; of the 65 patients with other types of tumors, 20 (31%) had lymph node metastases. Of 120 patients without pleural involvement, 13 (11%) had lymph node metastases; of the 37 with pleural involvement, 14 (38%) had lymph node metastases. Five-year survivals were estimated at 91% +/- 6% (mean +/- 95% confidence interval) for 130 patients with N0 tumor and 30% +/- 22% for 27 patients with N1 or N2 tumor. CONCLUSIONS: Intraoperative assessment is not reliable for identifying lymph node metastasis. Lobectomy and complete hilar/ mediastinal lymphadenectomy are necessary to determine N stage rigidly. Histologic degree of differentiation and pleural involvement are significantly associated with lymph node metastasis.

Adenocarcinoma↗

Biochemical changes in the efferent lymph plasma after oxazolone stimulation.

The lymph node is a specialized microenvironment for the regulation of immune responses. The reticular network of the lymph node provides a structure that facilitates not only intercellular interactions, but the intranodal flow of lymph fluid. To assess biochemical changes in the nodal lymph plasma after antigen stimulation, prescapular lymph nodes in sheep were stimulated with the epicutaneous antigen oxazolone. The efferent lymph from both antigen-stimulated and contralateral control prescapular lymph nodes was continuously monitored for more than 120 h. The oxazolone-stimulated lymph plasma was associated with a selective increase in cholesterol content during the 'recruitment' phase of lymph node enlargement. The peak in cholesterol was followed closely by a significant increase in lymph plasma LDH concentration. In contrast, there was no significant difference between oxazolone-stimulated and control lymph plasma in the concentration of triglycerides, albumin, alkaline phosphatase, and alanine transferase. These selective biochemical changes in the efferent lymph appeared to reflect the dynamics of lymphocyte activation within the lymph node as well as provide a practical measure of the lymph node response to antigen stimulation.

Animals↗

In vitro diagnosis of axillary lymph node metastases in breast cancer by spectrum analysis of radio frequency echo signals.

Axillary lymph node status is of particular importance for staging and managing breast cancer. Currently, axillary lymph node dissection is performed routinely in cases of invasive breast cancer because of the lack of accurate noninvasive methods for diagnosing lymph node metastasis. We investigated the diagnostic ability of ultrasonic tissue characterization based on spectrum analysis of backscattered echo signals to detect axillary lymph node metastasis in breast cancer in vitro compared with in vitro B-mode imaging. Immediately after surgery, individual lymph nodes were isolated from axillary tissue. Each lymph node was scanned in a water bath using a 10-MHz instrument, and radio frequency data and B-mode images were acquired. Spectral parameter values were calculated, and discriminant analysis was performed to classify metastatic and nonmetastatic lymph nodes. Forty histologically characterized axillary lymph nodes were enrolled in this study, including 25 nonmetastatic and 15 metastatic lymph nodes. A significant difference existed in the spectral parameter values (slope and intercept) for metastatic and nonmetastatic lymph nodes. Spectral parameter-based discriminant function classification of metastatic vs. nonmetastatic lymph nodes provided a sensitivity of 93.3%, specificity of 92.0%, and overall accuracy of 92.5%. In comparison, B-mode ultrasound images of in vitro lymph nodes provided a sensitivity of 73.3%, specificity of 84.0%, and overall accuracy of 80.0%. Receiver operating characteristic (ROC) analysis comparing the efficacy of both methods gave an ROC curve area of 0.9888 for spectral methods, which was greater than the area of 0.8980 for B-mode ultrasound. Hence, this in vitro study suggests that the diagnostic ability of spectrum analysis may prove to be markedly superior to that of B-mode ultrasound in detecting axillary lymph node metastasis in breast cancer. Because of these encouraging results, we intend to conduct an investigation of the ability of spectral methods to classify metastatic axillary lymph nodes in vivo.

Adult↗

Lymphatic mapping and sentinel lymph node biopsy in squamous cell carcinoma of the lower lip.

AIMS: The risk of metastases to the submandibular and submental lymph nodes in squamous cell carcinoma (SCC) of the lower lip is closely related to the primary tumour size and the differentiation of the tumour. In order to determine the feasibility of the technique and the possible metastatic lymph nodes in SCC of the lower lip, intraoperative lymphatic mapping and sentinel lymph node biopsy was performed in patients with tumour size greater than 2 cm (T2) and clinically non-palpable regional lymph nodes (N0). METHODS: Intraoperative lymphatic mapping with patent blue dye was performed in 20 patients with SCC of the lower lip. The stained lymph node (sentinel) was identified in each patient and sent for frozen section analysis in order to verify tumour metastasis. All patients had undergone bilateral suprahyoid neck dissection at the same stage. RESULTS: Three of the patients were female and 17 were male. The median age was 66. Sentinel lymph nodes were identified in 18 of the patients (90%). Intraoperative or post-operative histopathologic examination of the sentinel lymph node showed tumour metastasis in three of the patients (16.6%). The histopathologic examination of the remaining 15 patients whose sentinel lymph nodes were free of metastasis, showed no metastasis in the non-sentinel lymph nodes. In two of the three patients with metastatic sentinel lymph nodes, non-sentinel lymph nodes were free of metastases. There were no false negative results and no local or systemic complications of the technique were seen among the patients. CONCLUSIONS: Intraoperative lymphatic mapping and sentinel lymph node biopsy is feasible in patients with SCC of the lower lip who have large tumour size and non-palpable regional lymph nodes. The technique may help to avoid neck dissection when the patient has negative sentinel lymph node and when positive provides useful information for more effective radical treatment.

Adult↗

Sentinel lymph node procedure is highly accurate in squamous cell carcinoma of the vulva.

PURPOSE: To determine the diagnostic accuracy of the sentinel lymph node procedure in patients with squamous cell carcinoma of the vulva and to investigate whether step sectioning and immunohistochemistry of sentinel lymph nodes increase the sensitivity for detection of metastases. PATIENTS AND METHODS: Between July 1996 and July 1999, 59 patients with primary vulvar cancer were entered onto a two-center prospective study. All patients underwent sentinel lymph node procedure with the combined technique (preoperative lymphoscintigraphy with technetium-99m-labeled nanocolloid and intraoperative blue dye). Radical excision of the primary tumor with uni- or bilateral inguinofemoral lymphadenectomy was performed subsequently. Sentinel lymph nodes and lymphadenectomy specimens were sent for histopathologic examination separately. Sentinel lymph nodes, negative at the time of routine pathologic examination, were re-examined with step sectioning and immunohistochemistry. RESULTS: In 59 patients, 107 inguinofemoral lymphadenectomies were performed (11 unilateral and 48 bilateral). All sentinel lymph nodes, as observed on preoperative lymphoscintigram, were identified successfully intraoperatively. Routine histopathologic examination showed lymph node metastases in 27 groins, all of which were detected by the sentinel lymph node procedure. The negative predictive value for a negative sentinel lymph node was 100% (97.5% confidence interval [CI], 95% to 100%). Step sectioning and immunohistochemistry showed four additional metastases in 102 sentinel lymph nodes (4%; 95% CI, 1% to 9%) that were negative at the time of routine histopathologic examination. CONCLUSION: Sentinel lymph node procedure with the combined technique is highly accurate in predicting the inguinofemoral lymph node status in patients with early-stage vulvar cancer. Future trials should focus on the safe clinical implementation of the sentinel lymph node procedure in these patients. Step sectioning and immunohistochemistry slightly increase the sensitivity of detecting metastases in sentinel lymph nodes and should be included in these trials.

Adult↗