Clinical Significance of Lymph Node Sampling in Endometrial Carcinoma

OBJECTIVE To study the clinical significance of pelvic and para-aortic lymph node sampling in endometrial carcinoma.METHODS Data were analyzed from 311 patients who received surgical treatment in our hospital during the period from January 1995 to December 2002.Among the patients,197 underwent lymph node sampling or lymph-adenectomy.The patients were divided into 2 groups based on the nature of their lymph node dissection,i.e.a)The sampling group included 114 patients with an extrafascial hysterectomy or modified radical hysterectomy plus pelvic or paraaortic lymph node sampling of the abdominal aorta;b)The dis-section group,included 83 patients with a radical or modified radical hyster-ectomy plus systemic pelvic lymph node clearance or paraaortic lymph node dissection of the abdominal aorta.RESULTS The median of the sampling sites for lymph node removal was 5 in the sampling group,and the median of the lymph nodes removed was 15 per case.Lymph node metastasis was found in 8 cases.In the dissection group,the median of the cases for lymph node removal was 8,and the me-dian of the lymph nodes removed was 27 per case.Lymph node metastasis was found in 6 cases.The 5-year survival rates were 90.2% and 90.9% in the 2 groups,respectively.CONCLUSION Lymph node sampling of endometrial cancer is a good way of precisely finding lymphatic metastases,and is suitable for surgical staging without causing immoderate surgical treatment and without affecting the survival rate.     

Prognostic Significance of Axillary Lymph Node Micrometastases and Microvessel Count in Breast Cancer

Objective  To investigate the influence of axillary lymph node micrometastases and the microvessel count on the prognosis of patients with breast cancer. Methods  Forty-eight patients with breast cancer, who had no tumor cells in their regional lymph nodes based on conventional histopathologic examination, were re -examined with immunohistochemical LSAB techniques. H&E, anti-EMA, CK 19 and FVIII factor staining was used to identify tumor cells in both lymph nodes and tumor tissues and to count the mtcrovessels. A total of 882 lymph nodes were examined. Results  Immunostaining-positive tumor cells were found in 9.0 %( 79/882) of the dissected lymph nodes. The positive rates were not significantly different between a surviving group and a deceased group (P>0.05). The microvessel count was significantly higher in group that had died (P<0.001). Conclusion  The lymph node micrometastases did not show any correlation with patients’ survival, but the microvessel density had a negative correlation with the survival period in breast cancer patients who had negative axillary lymph nodes.     

Prospective Feasibility Trial of Sentinel Lymph Node Biopsy in the Setting of Inflammatory Breast Cancer

Background

Most inflammatory breast cancer (IBC) patients have axillary disease at presentation. Current standard is axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NACT). Advances in NACT have improved pathologic complete response (pCR) rates increasing interest in performing sentinel lymph node (SLN) biopsy (SLNB). Previous studies on SLNB for IBC patients did not assess nodal response with imaging or use dual tracer mapping. We sought to prospectively determine false negative rates of SLNB in IBC patients using dual tracer mapping, and to correlate pathology with preoperative axillary imaging.

Involvement of Abdominal and Pelvic Lymph Nodes in Non-Hodgkin Lymphoma： the Nodal Distribution in Chinese Patients

Objective To study the distribution of abdominal and pelvic lymphadenopathy in non-Hodgkin lymphoma (NHL) in Chinese patients. Methods CT images of 241 NHL patients with abdominal and/or pelvic lymphadenopathy were reviewed. Among them, clinical and image data from 96 patients fulfilled the requirements for the analysis: 1. Abdominal and/ or pelvic lymphadenopathy detected by CT in untreated patients (n=74). 2. Recurrent patients: new lesions in abdominal or pelvic lymph nodes who never had any nodular lesion by previous abdominal and/or pelvic CT (n = 14). 3. Treated patients who did not have abdominal and/or pelvic CT previously, showed regression of initial disease for at least 6 months after chemotherapy and subsequently showed abdominal and/or pelvic lymphadenopathy (n=8). According to the Clinical Schema for Lymphoid Tissue, these patients were divided into 3 histologic subtypes: indolent (IL; n=31), aggressive (AL; n=61) and very aggressive (VAL; n=2) lymphoma. The remaining 2 cases were unclassified lymphoma (UCL). Both abdominal and pelvic CT scans were undertaken in 46 patients, abdominal CT only in 47 patients and pelvic CT only in 3 patients. Enhanced CT was obtained in 80 patients. The anatomic sites involved were designated as retroperitoneal (ie. paraaortic), mesenteric, abdominal (i.e. celiac, paracardiac, gastrohepatic and hepatic hilum, etc.), retrocrural, subdiaphragmatic, common iliac, internal iliac, external iliac and inguinal nodes respectively. Results The lesions located in the retroperitoneum were most common for IL and AL, the incidences being 83.3% (18/25) and 83.1% (49/59) respectively, results being similar. Among those, lymphadenopathy distributed mainly in the retroperitoneum, superior and inferior renal hila, with an incidence of 72.0% (18/25) in IL and 67.3% (33/49) in AL. Pelvic lymphadenopathy came next, with the overall incidence of 41.9% (126/301), 57.5% (50/87) in IL and 35.5% (76/214) in AL respectively. Mesenteric lymph nodes stood third with the overall incidence of 37.1 % (33/89), 43.3% (13/30) in IL and 33.9% (20/59) in AL. Statistical analysis showed that external iliac lymph node involvement to be more common in IL than in AL (P<0.05), while comparisons of other groups showed no statistical significance. Conclusion For Chinese NHL patients, retroperitoneal lymph nodes were mostly involved, followed by iliac and mesenteric lymphadenopathy, which was different from that of the Western countries. The involved retroperitoneal lymph nodes in NHL of Chinese patients were predominantly located in the superior and inferior renal hilum.     

Molecular Upstaging of Sentinel Lymph Nodes in Melanoma: Where Are We Now?

The presence of lymph node metastasis is the best predictor of disease progression and overall survival in patients who have melanoma. Lymphatic mapping and selective lymphadenectomy allows directed pathologic analysis of the node or nodes most likely to have metastatic disease. To diagnose metastatic disease in SLNs reliably requires a coordinated effort by nuclear medicine physicians, surgeons, and pathologists. Errors may occur if quality assurance is not emphasized at any point during the process. This, along with the presence of occult metastatic disease, may lead to disease recurrence and progression, even when SLN histologically are free of disease. Molecular up-staging of occult malignant disease has the potential to provide important information to facilitate the diagnosis, surveillance, and treatment of cancer. The detection of occult tumor cells in SLNs and blood provides a powerful tool for assessing early regional and systemic disease spread in patients who have AJCC stage II and III-not only melanoma but also other solid tumors. The use of varying panels of markers from different laboratories has hampered the interpretation of data and made it difficult to unravel the merits of molecular up staging. Molecular approaches have made a major impact on the field of infectious disease and should one day be of equal usefulness in the diagnosis of cancer.     

Magnetic Resonance Evaluation of Transplanted Endometrial Carcinoma and Its Lymph Node Metastasis in Rabbits

Objective： To establish a rabbit model of transplanted endometrial carcinoma with lymph node metastasis and observe its magnetic resonance imaging （MRI） features. Methods： VX2 tumor grafts were orthotopically embedded in the endometrium of rabbits, and 3 weeks after the transplantation, thetumor and its metastasis to the retroperitoneal lymph nodes were examined by MRI, and the signal intensities and size of the lymph nodes were compared with those of normal rabbits. Results： The orthotopic transplantation of the tumor grafts resulted in tumor growth in all the 12 recipient rabbits. The tumors infiltrated the serosa of the uterus and metastasized to the retroperitoneal lymph nodes 3 w after transplantation. MRI demonstrated that the lymph nodes of the tumor-bearing rabbits were larger in size than those of normal control rabbits, but the signal intensity of the lymph nodes was not significantly different between them. Conclusion： This transplanted endometrial carcinoma model is characterized by high success rate and similar tumor metastasis behaviors with human endometrial carcinoma, therefore may serve as a good model for testing the efficacy of contrast agents for MR lymphography.     

The Significance of CXCR4 Expression for the Prediction of Lymph Node Metastasis in Breast Cancer Patients

OBJECTIVE The chemokine receptor(CXCR4)CXC chemokine receptor 4)plays an important role in cancer metastasis.We therefore studied differential expression of the CXCR4,as well as that of the biomarker HER2,so as to evaluate whether these biomarkers can be used to predict axillary lymph node metastasis in breast cancer patients. METHODS Immunohistochemistry was used to evaluate the CXCR4 and HER2 expressions and to examine the paraffin sections of the breast cancers at various stages.Positive lymph node expression was found in 80 of the cases,and in 7 there was negative expression. RESULTS Compared to the cases with negative lymph nodes, there was a high expression of CXCR4(26.3% vs.14.3%,P=0.013), and an over-expression of HER2(28.8% vs.14.3%,P=0.011). Moreover,there was a direct correlation between the CXCR4 and HER2 expressions and the tumor staging(P=0.000)and lymph node metastasis(P=0.032).When the two biomarkers,i.e.CXCR4 and HER2,were concurrently labeled,a high expression of one of the biomarkers could be seen in the cases with positive lymph nodes(51.3% vs.28.6%,P<0.003). CONCLUSION The chemokine receptor,CXCR4,is a new-type biomarker in predicting axillary lymph-node metastasis in breast cancers.Compared with the other markers,such as HER2 etc., assessment of CXCR4 can improve the prediction of the presence and extent of lymph node involvement.     

Does the Result of Completion Axillary Lymph Node Dissection Influence the Recommendation for Adjuvant Treatment in Sentinel Lymph Node–Positive Patients?

ObjectiveThe Hungarian National Institute of Oncology has just closed a single-center randomized clinical study. The Optimal Treatment of the Axilla–Surgery or Radiotherapy (OTOASOR) trial compares completion axillary lymph node dissection (cALND) with regional nodal irradiation (RNI) in patients with sentinel lymph node-positive (SLN+) primary invasive breast cancer. In the investigational treatment arm, patients received 50 Gy RNI instead of cALND. In these patients we had information only about the sentinel lymph node (SLN) status, but the further axillary nodal involvement remained unknown. The aim of this study was to investigate whether the result of cALND influenced the recommendation for adjuvant treatment in patients with SLN+ breast cancer.Patients and MethodsPatients with SLN+ primary breast cancer were randomized for cALND (arm A, standard treatment) or RNI (arm B, investigational treatment). Adjuvant systemic treatments were given according to the standard institutional protocol, and patients were followed according to the actual institutional guidelines.ResultsBetween August 2002 and June 2009, 474 SLN+ patients were randomized to cALND (arm A, standard treatment = 244 patients) or RNI (arm B, investigational treatment = 230 patients). The 2 arms were well balanced according to the majority of main prognostic factors. However, more patients were premenopausal (34% vs. 27%; P = .095) and had pT2-3 tumors (57% vs. 40%; P = .003) in the completion axillary lymph node dissection (ALND) arm. On the other hand, there were more patients with known human epidermal growth factor receptor type 2 positive tumor (12% vs. 17%, P = .066) in the RNI arm. In the ALND and RNI arms, 78% (190/244) and 69% (159/230), respectively, received chemotherapy (P = .020). Endocrine therapy was administered in 87% (213/244) of the patients in the ALND arm and 89% (204/230) of the patients in the RNI arm (P = .372). Six patients (2.5%) on arm A and 13 patients (5.7%) on arm B received adjuvant trastuzumab treatment (P = not significant). Subgroup analyses explored that more frequent administration of adjuvant chemotherapy in arm A was associated with the higher percentage of premenopausal patients and patients with larger (pT2-3) tumors.ConclusionsThe result of cALND after positive SLN biopsy seems to have no major impact on the administration of adjuvant systemic therapy.     

Significance of Sentinel Lymph Node Biopsy and Immunohistochemistry in Diagnosis and Staging of Stage-cNO Oral Squamous Cell Carcinoma

OBJECTIVE To assess the significance of sentinel lymph node biopsy （SLNB）, serial section and cytokeratin immunohistochemical staining in the diagnosis and staging of Stage-cNO oral squamous cell carcinoma （OSCC）, METHODS A blue stain, 99mTc-dextran SPECT lymphoscintigrapgy and intraoperative y-ray probes were used to examine the sentinel nodes in 31 cases with Stage-oNO oral cancer, The H＆E staining and a cytokeratin AE1/ AE3 immunohistochemistry （IHC） assessment, with serial sections, were conducted to provide results obtained from a routine pathological examination of lymph nodes, The value of the routine pathological examination of the sentinel lymph node （SLN）, serial sections and IHC determination for cervical lymph node metastasis of Stage-cN0 OSCC was appraised, RESULTS A total of 45, 55 and 51 SLNs were examined in 25 （80%）, 31 （100%） and 30 （96,5%） of the cases, by using the blue stain, y-ray probes, and SPECT lymphoscintigraphy, respectively, The average SLNs found in each case of the groups was 1,4 （1 to 3） and there were 1,302 non-NSLNs, Six positive SLN metastases were detected by routine pathological examination, among which 1 case was found to be an accompanied positive metastasis of non-SLN, One positive SLN metastasis was found after examination of serial sections plus routine H＆E staining and 2 were detected using serial sections plus AE3 immunohistochemical staining methods, No positive NSLNs were found in the study, CONCLUSION In order to make more progress in accurate SLNB diagnosis, serial sections and IHC （AE1/AE3） methods can be used for examination of the micrometastases which are difficult to identify by routine pathological sections and H＆E staining.     

Location of Sentinel Lymph Node in Gastric Cancer： A Modified, Painless And Noninvasive Approach

Objective:The presence of lymph node metastases is an important factor in the prognosis of gastric cancer patient. Therefore, the precise identification of sentinel lymph nodes (SLN) in these patients is critical. In this work, we investigated the feasibility and preciseness by injection of99mTc-sulfur colloid (SC) 2 hours before operation after general anesthesia, instead of one day before surgery.Methods:Thirty-one patients of gastric cancer diagnosed as T1-T3 were enrolled in this study. During operation, a SLN was defined as those containing 10 times more radioactivity than surrounding tissue with a hand-held gamma probe and removed. All the patients underwent radical gastrectomy with extended lymphadenectomy. All resected nodes were examined postoperatively by routine H&E stain and those negative SLNs were examined with further cytokeratin immunohistochemistical staining.Results:The incidence of metastasis was significantly higher in SLNs than in non-SLNs (x2=67.48, P<0.001). The overall sensitivity, specificity and accuracy of the SLN status in the diagnosis of the lymph node status of the patient were 86.36%, 100% and 96.77%, respectively. The positive predictive value and negative predictive value of SLN biopsy were 100%, and 75.0%, respectively. SLNs were used to diagnose the lymph node status with 100% accuracy in the T1 group. In the T2 and T3 groups, the sensitivity, specificity, and diagnostic accuracy were 92.3%, 100%, and 94.44%, 60.0%, 100%, and 66.66%, respectively. Most of the SLNs were located in the #1, #2, #3, #4, #5, and #6, except in 3 patients (9.68%).With cytokeratin immunohistochemical staining, lymphatic pathologic staging in 1 patient was upstaged.Conclusion:SLN biopsy with the above approach is a feasible and accurate diagnostic procedure for detecting lymph node metastasis in patients with gastric cancer, which is painless, noninvasive, easily accepted by patients and suitable for extensive clinical applications.     

Anticonvulsant-induced Suppression of IFN-γ Production by Lymphocytes Obtained from Cervical Lymph Nodes in Glioma-bearing Mice

It is well known that phenytoin can cause impairment of cellular immunity. The authors investigated the potential role of other anticonvulsant drugs in the development of antitumor immunity in murine malignant glioma models.The survival rate was determined in murine glioma models using syngeneic 203 glioma cells following treatment with four anticonvuisants, which are most commonly administered to glioma patients, i.e., phenytoin, phenobarbital, valproate and zonisamide. In a second set of experiments, we further examined the effect of these drugs on interferon- (IFN-) secretion by lymphocytes prepared from cervical lymph nodes (CLN) in the same models. The IFN- production of CLN lymphocytes as measured by ELISA method was markedly impaired in the early stage of tumor-bearing mice treated with phenytoin or zonisamide, and the median survival time (MST) of controls and of mice treated with either phenytoin or zonisamide was 13, 10 and 11 days, respectively, which was not a statistically significant difference. Phenobarbital and valproate did not affect either IFN- production or their survival rate. In addition, immunohistochemistry showed a reduction in tumor-infiltrating lymphocytes containing CD4 and CD8 antigens in the mice treated with phenytoin and zonisamide.Two anticonvulsants, phenytoin and zonisamide, showed a significant inhibitory effect on IFN- production by CLN lymphocytes in murine glioma models, although there was no statistically significant difference in MST between controls and the anticonvulsant-treated mice. These drugs might have some detrimental influence on the prognosis of brain tumor patients when combined with the latent immune dysfunction accompanying the tumor-bearing state.     

Signif icance of Sentinel Lymph Node Biopsy and Immunohistochemistry in Diagnosis and Staging of Stage-cN0 Oral Squamous Cell Carcinoma

OBJECTIVE To assess the signifi cance of sentinel lymph node biopsy (SLNB), serial section and cytokeratin immunohistochemical staining in the diagnosis and staging of Stage-cN0 oral squamous cell carcinoma (OSCC). METHODS A blue stain, 99mTc-dextran SPECT lymphoscintigrapgy and intraoperative γ-ray probes were used to examine the sentinel nodes in 31 cases with Stage-cN0 oral cancer. The H&E staining and a cytokeratin AE1/ AE3 immunohistochemistry (IHC) assessment, with serial sections, were conducted to provide results obtained from a routine pathological examination of lymph nodes. The value of the routine pathological examination of the sentinel lymph node (SLN), serial sections and IHC determination for cervical lymph node metastasis of Stage-cN0 OSCC was appraised. RESULTS A total of 45, 55 and 51 SLNs were examined in 25 (80%), 31 (100%) and 30 (96.5%) of the cases, by using the blue stain, γ-ray probes, and SPECT lymphoscintigraphy, respectively. The average SLNs found in each case of the groups was 1.4 (1 to 3) and there were 1,302 non-NSLNs. Six positive SLN metastases were detected by routine pathological examination, among which 1 case was found to be an accompanied positive metas-tasis of non-SLN. One positive SLN metastasis was found after examination of serial sections plus routine H&E staining and 2 were detected using serial sections plus AE3 immunohistochemical staining methods. No positive NSLNs were found in the study. CONCLUSION In order to make more progress in accurate SLNB diagnosis, serial sections and IHC (AE1/AE3) methods can be used for examination of the micrometastases which are diffi cult to identify by routine pathological sections and H&E staining.     

Patients’ Choice on Axillary Lymph Node Dissection Following Sentinel Lymph Node Micrometastasis — First Report on Prospective Use of a Nomogram in Very Low Risk Patients

The optimal locoregional treatment of patients diagnosed with sentinel node (SN) micrometastasis is controversial. A previously reported and validated nomogram was used to calculate the risk of non-SN metastasis in patients with SN micrometastasis over a period of 2 years. Patients were given detailed information about the risk, consequences and treatment options of non-SN involvement, the risk and potential complications of unnecessary completion axillary lymph node dissection (ALND), the imperfectness of the nomogram, and other factors that may influence their selection of further treatment. They also received a questionnaire to monitor factors influencing their decisions. Of the 25 patients participating in the study, 10 have opted for ALND. The only factor that seemed to influence their choice was fear from disease recurrence. Giving detailed information to SN micrometastatic patients is a patient-centered alternative to current recommendations on performing ALND in all such patients or omitting ALND in all of them.     

The Prognostic Significance of a Combined Determination of Cathepsin D and Estrogen Receptors in Breast Carcinomas with Positive Axillary Lymph Nodes

It has been reported that cathepsin-D (Cath-D), which is a pro- teinase, may enhance the growth of the tumor cells by degrading the basement membranes and extracellalar matrix. This action allows the cancer cells to easily invade the regional tissues and …     

How Much is Enough? Pathologic Evaluation of Sentinel Lymph Nodes

It is well accepted that detailed analysis of sentinel lymph nodes (SLNs) may upstage breast cancer, but generally involves the identification of low-volume metastases (including isolated tumor cells and clusters). Although several guidelines recommend therapeutic interventions for micrometastases, there is also evidence supporting therapeutic interventions only for macrometastases. There is also evidence in support of means of regional disease control other than axillary lymph node dissection (ALND). The pathologic evaluation of SLNs should consider the clinical setting. Intraoperative assessment is indicated only if ALND is an immediate interventional option for SLN positivity. Generally, hematoxylin and eosin-stained sections taken at 2-mm step intervals are sufficient to disclose macrometastases, but if micrometastases are also considered in further treatment planning, smaller intervals and immunohistochemistry as well as quantitative molecular methods may also be considered.     

The Sentinel Lymph Node Concept

The sentinel lymph node concept is meeting with steadily growing interest and is being extended to the different sites of the primaries. In addition, the concept is being applied in an increasingly sophisticated manner. In this book the practical