Strategy of lymph nodes dissection for the lower thoracic esophageal cancer without metastasis to the upper-mediastinal lymph nodes

The incidence of metastasis to the lymph nodes in preoperative untreated patients with Ei, T2 or T3 esophageal cancer is 70.7% (41 of 58 cases) in our institute. Especially, a high incidence of metastasis to the abdominal lymph nodes has been noted. In contrast, metastasis to the cervical lymph nodes is not common. The majority of recurrence appear as a distant metastasis to the liver, lung or bone through the hematogenic route. However, recurrence in the peritoneum through the lymphatogenic route is not uncommon. Therefore, current strategy of lymph nodes dissection for esophageal carcinoma would be inadequate for the complete inhibition of recurrence, so that chemotherapy remains to be needed. Since the diagnostic procedure with ultrasonographic endoscopy and computerized tomography is highly accurate for the assessment of metastasis to the uppermediastinal lymph nodes, operative procedure suitable for each case should be determined on the basis of preoperative examination.     

Malignant neoplastic disease of the parotid lymph nodes

OBJECTIVES: To review the management and outcome of patients with malignant neoplastic disease of the parotid lymph nodes excluding those with primary salivary gland tumors. STUDY DESIGN: Retrospective review of 14 patients who had malignant parotid lymph nodes from metastatic cutaneous malignancies, direct extension from primary cutaneous malignancies, or lymphoproliferative disorders. METHODS: Charts were reviewed from three institutions and tabulated for age, gender, histopathology, treatment, and outcome. RESULTS: Fourteen patients met the criteria for study. Ten patients had neoplastic nodes from cutaneous malignancies. Seven involved squamous cell carcinoma, two were metastatic from melanoma, and one was metastatic from basal cell carcinoma. Four patients had involvement from lymphoproliferative disorders. CONCLUSIONS: Metastatic disease to the parotid nodes or direct extension to nodes from primary cutaneous malignancy demonstrates a poor prognosis in this series. Prognosis of lymphoproliferative disorder is more favorable.     

Skip metastasis to the mediastinal lymph nodes in non-small cell lung cancer

BACKGROUND: Whether any difference exists in clinical characteristics between resected non-small cell lung cancer with either skip or ordinary mediastinal lymph node metastases (N2 disease) needs to be clarified. METHODS: There were 110 patients with stage IIIA N2 disease. Thirty-three patients demonstrating no metastasis at the hilar nodes [skip (+) group] were compared with the other 77 patients [skip (-) group]. To investigate the extent of nodal involvement, we classified the mediastinal lymph nodes into three regions (superior, inferior, or aortic). RESULTS: There were no significant differences regarding histologic type, T status, or the site of the primary tumors between the skip (+) and the skip (-) N2 groups. In the skip (+) group, mediastinal node metastasis was found in only one region (level 1) in 30 patients (90.9%) and in two regions (level 2) in 3 (9.1%), whereas 28 patients (36.4%) from the skip (-) group revealed mediastinal metastasis at two or three regions (level 2 or 3). The overall survival rate at 5 years after operation was 35% in the skip (+) group and 12.7% in the skip (-) group (p = 0.054). This favorable clinical outcome in the skip (+) group could be explained partially by the higher proportion of patients with level 1 metastases. Furthermore, regarding patients with level 1 disease, the skip (+) group tended to have a better prognosis than the skip (-) group (p = 0.096). CONCLUSIONS: These results suggest that patients with skip mediastinal lymph node metastases represent a unique subgroup of N2 disease.     

直肠癌患者周围淋巴结转移的临床及病理特征分析

目的:总结保留盆腔植物神经的直肠癌扩大根治术中直肠周围各组淋巴结的转移规律,探讨现阶段侧方淋巴结清扫的意义.方法:接受保留盆腔植物神经的直肠癌扩大根治术患者114例,清除淋巴结并行常规病理学方法(HE染色)观察,分析直肠周围淋巴结转移情况.结果:114例患者中有46例发生淋巴结转移,总的淋巴结转移率为40.4%(46/114),其中直肠系膜淋巴结转移率为39.5%(45/114),肠系膜下动脉根部淋巴结转移率为3.9%(2/51),侧方淋巴结转移率为9.6%(11/114);共取出淋巴结2 463枚,转移淋巴结数209枚,总转移度为8.5%(209/2 463),其中直肠系膜淋巴结转移度为14.8%(187/1 264),肠系膜下动脉根部淋巴结转移度为1.7%(3/175),侧方淋巴结转移度为1.9%(19/1 024).直肠系膜淋巴结的转移率及转移度明显高于肠系膜下动脉根部淋巴结及侧方淋巴结(P<0.05);直肠系膜淋巴结的转移率及转移度与Duke's分期、肿瘤浸润深度有明显关联性(P<0.05),侧方淋巴结转移率及转移度Duke's分期和分化程度具有明显关联性(P<0.05).结论:选择性的直肠癌扩大根治术在现阶段是可行的.     

Giant cell tumor of bone with selective metastases to mediastinal lymph nodes

We examined the efficiency of disease-specific "standard" chemotherapies epirubicin, cyclophosphamide (EC); cyclophosphamide, vincristine, doxorubicin, etoposide, prednisolone (CHOEP); epirubicin, ifosfamide (EPI/IFOS) for peripheral blood progenitor cell (PBPC) mobilization in comparison to well-characterized mobilization protocols, i.e. etoposide, ifosfamide, cisplatin, epirubicin (VIPE) and dexamethasone, carmustine, etoposide, cytarabine, melphalan (DexaBEAM). Twenty-seven patients with various malignancies underwent 75 apheresis procedures for PBPC collection. Median cell yields from all 75 aphereses were 1.18 x 10(5) mononuclear cells/kg [range (0.28-3.7) x 10)8)], 1.4 x 10(5) granulocyte/macrophage-colony-forming units (CFU-GM)/kg [range (0.2-11) x 10(5)] and 3.3 x 10(6) CD34+cells/kg [range (0.35-17.7) x 10(6). CD34+/ CD90+ cells could be mobilized by all mobilization regimens used. The difference observed in the mobilization of CD34+ cells was only of low significance when the mobilization regimens were compared, whereas the mobilizations of MNC and CFU-GM were significantly different between the groups. Breast cancer patients treated with the VIPE regimen (including pretreated women) had a significantly higher CFU-GM rate than patients treated with EC (P=0.0005). Mobilized CD34+ PBPC were correlated with CFU-GM in all apheresis products. The linear correlation coefficients differed for the various mobilization groups: DexaBEAM (r=0.9, P < 0.0001), VIPE (r=0.68, P=0.0024), CHOEP (r=0.52, P=0.022), EPI/ IFOS (r=0.34, P=0.11) and EC (r=0.23, P=0.2). We conclude that clonogenic assays can provide additional information about the autotransplant quality, particularly when alternative or new mobilization regimens are being investigated.     

Molecular mechanisms of lymphocyte homing to peripheral lymph nodes

To characterize the adhesion cascade that directs lymphocyte homing to peripheral lymph nodes (PLNs), we investigated the molecular mechanisms of lymphocyte interactions with the microvasculature of subiliac lymph nodes. We found that endogenous white blood cells and adoptively transferred lymph node lymphocytes (LNCs) tethered and rolled in postcapillary high endothelial venules (HEVs) and to a lesser extent in collecting venules. Similarly, firm arrest occurred nearly exclusively in the paracortical HEVs. Endogenous polymorphonuclear (PMNs) and mononuclear leukocytes (MNLs) attached and rolled in HEVs at similar frequencies, but only MNLs arrested suggesting that the events downstream of primary rolling interactions critically determine the specificity of lymphocyte recruitment. Antibody inhibition studies revealed that L-selectin was responsible for attachment and rolling of LNCs, and that LFA-1 was essential for sticking. LFA-1-dependent arrest was also abolished by pertussis toxin, implicating a requirement for G alpha i--protein-linked signaling. alpha 4 integrins, which play a critical role in lymphocyte homing to Peyer's Patches, made no significant contribution to attachment, rolling, or sticking in resting PLNs. Velocity analysis of interacting LNCs revealed no detectable contribution by LFA-1 to rolling. Taken together, our results suggest that lymphocyte- HEV interactions within PLNs are almost exclusively initiated by L-selectin followed by a G protein-coupled lymphocyte-specific activation event and activation-induced engagement of LFA-1. These events constitute a unique adhesion cascade that dictates the specificity of lymphocyte homing to PLNs.     

In situ analysis of lymphocyte migration to lymph nodes

Blood-borne lymphocytes migrate continuously to peripheral lymph nodes (PLN) and other organized lymphoid tissues where they are most likely to encounter their cognate antigen. Lymphocyte homing to PLN is a highly regulated process that occurs exclusively in specialized high endothelial venules (HEV) in the nodal paracortex. Recently, it has become possible to explore this vital aspect of peripheral immune surveillance by intravital microscopy of the subiliac lymph node microcirculation in anesthetized mice. This paper reviews technical and experimental aspects of the new model and summarizes recent advances in our understanding of the molecular mechanisms of lymphocyte homing to PLN which were derived from its use. Both lymphocytes and granulocytes initiate rolling interactions via L-selectin binding to the peripheral node addressin (PNAd) in PLN HEV. Subsequently, a G protein-coupled chemoattractant stimulus activates LFA-1 on rolling lymphocytes, but not on granulocytes. Thus, granulocytes continue to roll through the PLN, whereas LFA-1 activation allows lymphocytes to arrest and emigrate into the extravascular compartment. We have also identified a second homing pathway that allows L-selectin low/(activated/memory) lymphocytes to home to PLN. P-selectin on circulating activated platelets can mediate simultaneous platelet adhesion to PNAd in HEV and to P-selectin glycoprotein ligand (PSGL)-1 on lymphocytes. Through this mechanism, platelets can form a cellular bridge which can effectively substitute for the loss of L-selectin on memory cell subsets.     

Differentiation between benign and metastatic cervical lymph nodes with ultrasound

OBJECTIVE: The differentiation between benign and metastatic lymph nodes with ultrasound (US) is based primarily on the evaluation of size, shape, margin and internal echo structure. The aim of this study is to determine whether these parameters are reliable indicators and to correlate internal echo structure and histopathological findings. MATERIALS AND METHODS: Seventy-one nodes in 21 patients with pathologically proven oral squamous cell carcinoma were examined. The shortest diameter, the short/long diameter ratio (S/L ratio), margins and internal echo structure of the lymph node were evaluated by US. The internal echo structure was divided into six patterns: homogeneous hypoechoic, homogeneous hyperechoic, heterogeneous, eccentric hyperechoic, centric hyperechoic and anechoic pattern. In addition, internal echo structure was correlated with histopathological findings. RESULTS: In 71.4% of the metastatic nodes, the shortest diameter was more than 10 mm and the S/L ratio was higher than that of benign nodes (average 0.71). Eleven (84.6%) of the 13 lymph nodes with irregular margins were metastatic. Heterogeneous and anechoic patterns were observed in metastatic nodes, whereas homogeneous hypoechoic and eccentric hyperechoic patterns were present in benign nodes. On ultrasonography with the corresponding histopathological findings, echogenic areas in the homogeneous hyperechoic, heterogeneous and centric hyperechoic patterns of metastatic nodes proved to be necrosis or fibrosis. Eccentric hyperechoic areas in benign nodes corresponded to the hilus and surrounding fatty tissue. CONCLUSIONS: The shortest diameter, S/L ratio, margin and internal echo structure were considered to be critical indicators to differentiate between benign and metastatic nodes. Secondary changes caused by tumour infiltration, necrosis, or fibrosis should be assessed when metastatic lymph nodes are differentiated from benign ones by internal echo structure.     

Allelic imbalance at NME1 in microdissected primary and metastatic human colorectal carcinomas is frequent but not associated with metastasis to lymph nodes or liver

Allelic imbalance at the NME locus on chromosome 17q21 was analyzed in colorectal cancer patients using a highly polymorphic microsatellite repeat sequence within NME1 itself. Duplicate samples of carcinoma and adjacent normal tissue was obtained by microdissection from 6 to 7-microns paraffin sections of 94 primary carcinomas (treatment years 1979-1993) and available lymph node and liver secondaries. In 55 patients informative (heterozygous) at this locus, allelic imbalance was examined in primary and secondary carcinomas. Microsatellite instability prevented assessment of allelic balance in two cases, and there was no evidence of homozygous loss at NME1 in any case analyzed. Allelic imbalance at the NME locus in carcinomas was frequent (27/53; 51%), and concordant results were obtained between primary carcinoma and secondary deposits in 30 of 33 (91%) cases. Three discordant cases showed allelic imbalance in secondary deposits but not the primary lesion. Although frequent, allelic imbalance at NME1 had no relationship to Dukes' stage at presentation or with subsequent hepatic metastasis, nor with the primary carcinoma site (proximal versus distal), tumor size, or mitotic or apoptotic index. Moreover, neither disease-free nor overall survival differed between patients with carcinomas showing NME1 allelic imbalance and patients with carcinomas that did not. Our results show that although allelic imbalance is frequent at the NME locus in primary and secondary colorectal carcinomas, there is no evidence to link this with clinical or pathological features or with metastatic potential. Microsatellite PCR and microdissection of enriched populations of carcinoma cells allowed uniformly successful analysis of samples from archival formalin-fixed paraffin-embedded tissue up to 15 years old and clear assessment of allelic imbalance in tumor specimens. Target sequences (e.g., microsatellites and minisatellites) up to approximately 200-250 bp may be reliably analyzed for allelic balance, suggesting that this method is of general utility in the genetic analysis of primary and metastatic neoplasia.     

Clear cell odontogenic carcinoma with lymph node metastasis

Clear cell odontogenic tumors are rare. Review of the literature showed 9 cases with a prominent clear cell component. These lesions have exhibited an aggressive behavior characterized by an infiltrative local growth pattern, recurrence, or metastases. We report a case of an odontogenic tumor that exhibited a biphasic pattern and was characterized by lymph node involvement identical histologically to the primary tumor. We conclude that the presence of a clear cell component in an ameloblastomatous tumor should be viewed as a sign of de-differentiation, and that a malignancy with or without metastases should be considered and ruled out in such cases.     

Gastric cancer with p53 overexpression has high potential for metastasising to lymph nodes

Overexpression of the tumour suppressor gene p53 was investigated immunohistochemically in 96 primary gastric carcinomas and 26 corresponding metastatic perigastric lymph nodes. Abnormalities in p53 expression were found in 52 (54%) of the 96 primary carcinomas. Tumours stained positively for p53 frequently metastasised to lymph nodes (the metastatic rate: 85%) compared to findings in those with negative p53 staining (64%, P < 0.05). Ninety-two percent (24/26) of the malignant cells in the lymph nodes stained positively for p53. When the DNA ploidy pattern of the tumour was determined by flow cytometry, the aneuploid tumours in p53 positive and negative groups accounted for 69% and 45%, respectively (P < 0.05). Proliferative activity of the tumour, as measured by Ki-67 labelling, was significantly higher (30.6 +/- 12.0%) in the p53 positive group than that (25.1 +/- 10.7%) in the p53 negative group (P < 0.05). Thus, gastric cancer with a mutant p53 has high proliferative activity and metastasis to lymph nodes will probably occur.     

Breast carcinoma associated with necrotic granulomas in axillary lymph nodes

Administration of leptin during undernutrition improves reproductive function, but whether this occurs at the level of the brain, pituitary, or gonads is not yet clear. The present study tested the hypothesis that one important mechanism is the control of pulsatile gonadotropin-releasing hormone (GnRH) secretion. Our approach was to determine if leptin could prevent the marked suppression of pulsatile luteinizing hormone (LH) secretion which occurs during fasting. Leptin (3 micrograms/g i.p.; three times/48 h) or vehicle was administered during a 48-hour fast in adult ovariectomized and estrogen-treated ovariectomized rats (n = 5-7/group). LH was measured in blood samples collected every 6 min for 2 h before and after fasting. In vehicle-treated animals, plasma insulin and leptin levels decreased after fasting. As expected, the LH pulse frequency also decreased markedly. When circulating leptin remained artificially elevated during fasting, the suppression of LH pulse frequency did not occur. Leptin treatment maintained a high LH pulse frequency in the presence or absence of estrogen. The finding that leptin modulates LH pulse frequency indicates that this fat-derived hormone conveys information about nutrition to mechanisms which regulate pulsatile gonadotropin-releasing hormone secretion. Because this occurs in the absence of estrogen, the mechanism does not necessarily involve modulation of negative feedback.     

Pathology of the lymph nodes in patients with malignant melanoma

The poor survival rate for patients with regional lymph node metastases of malignant melanoma reflects the strong association between lymph node and subsequent visceral metastases. The authors discuss clinical considerations, pathologic risk factors, selective lymphadenectomy, examination of lymph node dissections, difficulties of diagnosis, and prognosis.     

Differentiation of benign and malignant cervical lymph nodes with color Doppler sonography

OBJECTIVE: This study proposed to evaluate the efficacy of color Doppler sonography in detecting possible differences in blood flow patterns between malignant and benign cervical lymph nodes. SUBJECTS AND METHODS: During a period of 12 months, the palpable cervical lymph nodes of 48 untreated patients were prospectively evaluated with color Doppler sonography and Doppler flow wave analysis. Histopathologic diagnoses were obtained by sonographically guided fine-needle aspiration biopsy and/or excisional biopsy. RESULTS: We found 16 benign lymph nodes (four were tuberculous lymphadenitis, four were reactive hyperplasia, and eight were unspecified) and 32 malignant lymph nodes (13 were squamous cell carcinomas, nine were adenocarcinomas, four were small-cell carcinomas, three were lymphomas, and three were miscellaneous). Color Doppler flow patterns were seen in six (38%) of the 16 benign lymph nodes and in 29 (91%) of the 32 malignant lymph nodes. Twenty-six (81%) of the 32 malignant lymph nodes had abnormal flow patterns, with resistance indexes less than 0.6. However, three (19%) of the 16 benign lymph nodes also had abnormal flow patterns, and only seven (54%) of 13 squamous cell carcinomas had abnormal flow patterns. CONCLUSION: Color Doppler sonography has limited clinical value in differentiating malignant from benign cervical lymph nodes and in obviating biopsy.     

Juvenile thyroid carcinoma with metastasis to the bilateral cervical lymph nodes--a case report

A case of juvenile thyroid carcinoma with metastasis to the bilateral cervical lymph nodes in a 9-year-old male is reported. The clinical picture of juvenile thyroid carcinoma is characterized by early metastasis to the lungs and cervical lymph nodes. In Europe, there have been many reports of thyroid carcinoma after radiation. However, our patient had received no radiation. Surgery consisted of subtotal thyroidectomy and right modified neck dissection. The tumor was a papillary adenocarcinoma and metastasis was seen in 24 out of 38 lymph nodes removed. The serum thyroglobulin level, determined by radioimmunoassay, was 184 ng/ml preoperatively, but by 8 months postoperatively the level fell to 48 ng/ml. No signs of recurrence have been found to date (30 months after the operation).     

Inhibition of tumor cell adhesion to lymph nodes by laminin-related peptide and neuraminidase

BACKGROUND: Adhesion to lymph nodes, rather than growth stimulation, accounted for preferential colonization of lymph nodes by a metastatic B16 melanoma. We investigated these adhesive interactions. METHODS: Four classes of molecules were tested for inhibition of melanoma adhesion to cryostat sections of lymph node. RESULTS: Calcium chelators ethylenediaminetetraacetic acid and ethyleneglycol-bis-(beta-aminoethylether)-N,N,N',N'-tetra ace tic acid completely inhibited adhesion (50% adhesion, half-maximal inhibition, at 1 to 3 mmol/L). Cytochalasin B, which impairs contractile microfilaments, inhibited adhesion (60% adhesion at .001 mmol/L, 28% at .01 mmol/L). Colchicine, which disaggregates microtubules, had a similar effect (20% at .01 mmol/L, lowest dose tested). Trypsin slightly increased adhesion (125% adhesion at 10 micrograms/ml). Neuraminidase, which removed sialic acid residues, inhibited it (50% adhesion at 5 micrograms/ml). Gly-arg-gly-asp-ser, a peptide with a cell binding sequence of fibronectin, did not consistently inhibit adhesion (69% adhesion at 0.1 mg/ml, 83% adhesion at 1 mg/ml) or substantially differ from gly-arg-gly-glu-ser-pro (59% adhesion at 0.1 mg/ml, 90% adhesion at 1 mg/ml). In contrast, a peptide with a cell binding region of laminin (tyr-ile-gly-ser-arg) inhibited adhesion (50% adhesion at .05 mg/ml). CONCLUSIONS: Tumor cell-lymph node adhesion is a calcium-dependent process, requiring a functional cytoskeleton, that is mediated by both sialic acid moieties and trypsin-resistant, laminin-related, adhesion molecules.     

L-selectin and beta7 integrin synergistically mediate lymphocyte migration to mesenteric lymph nodes

Mesenteric lymph nodes (MLN) drain the gut where nutritive antigens and pathogens are encountered by lymphocytes of the gut-associated lymphoid tissue. We sought to determine how lymphocytes enter the MLN by studying mice double deficient for beta7 integrins and L-selectin. beta7/L-selectin double-deficient lymphocytes did not migrate into MLN. Most importantly, MLN formation was drastically impaired in beta7/L-selectin double-deficient mice. Lymphocyte numbers in MLN from beta7/L-selectin double-deficient mice were tenfold reduced compared to control mice. A high percentage of the few lymphocytes still detected in MLN from beta7/L-selectin double-deficient mice were CD44hi CD18hi, suggesting alternate migration pathways independent of L-selectin and beta7 integrin for these cells. We conclude that the combination of both molecules, L-selectin and beta7 integrin, is indispensable for MLN formation and that these molecules may mediate lymphocyte migration to MLN in a sequential and synergistical manner.