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Micrometastases
Kinds of Micrometastases Selected AbstractsSingle-Institution Experience in the Management of Patients with Clinical Stage I and II Cutaneous Melanoma: Results of Sentinel Lymph Node Biopsy in 240 CasesDERMATOLOGIC SURGERY, Issue 11 2005Jordi Rex MD Background. Lymphatic mapping and sentinel lymph node biopsy (SLNB) has been developed as a minimally invasive technique to determine the pathologic status of regional lymph nodes in patients without clinically palpable disease and incorporated in the latest version of the American Joint Committee on Cancer (AJCC) staging system for cutaneous melanoma. Objective. To analyze the results of SLNB and the prognostic value of the micrometastases and the pattern of early recurrences in patients according to sentinel lymph node (SLN) status. Method. Patients with cutaneous melanoma in stages I and II (AJCC 2002) who underwent lymphatic mapping and SLNB from 1997 to 2003 were included in a prospective database for analysis. Results. The rate of identification of the SLN was 100%. Micrometastases to SLN were found in 20.8% of patients. The rate of SLN micrometastases increased according to Breslow thickness and clinical stage. Breslow thickness of 0.99 mm was the optimal cutpoint for predicting the SLNB result. Twenty-four patients (12.3%) developed a locoregional or distant recurrence at a median follow-up of 31 months. Recurrences were more frequent in patients with a positive SLN. Among patients who had a recurrence, those with a positive SLN were more likely to have distant metastases than those with negative SLN. Nodal recurrences were more frequent in patients with a negative SLN compared with those with a positive SLN. Conclusions. The status of the SLN provides accurate staging for identifying patients who may benefit from further therapy and is the most important prognostic factor of relapse-free survival. THIS WORK WAS SUPPORTED BY GRANTS FROM FONDO DE INVESTIGACIONES SANITARIAS (98/0449), BECA DE FORMACIÓ DE PERSONAL INVESTIGADOR (2001/FI0757), AND THE RED ESPÑOLA DE CENTROS DE GENÓMICA DEL CÁNCER (C03/10). [source] CK19 mRNA expression in the bone marrow of patients with esophageal squamous cell carcinoma and its clinical significanceDISEASES OF THE ESOPHAGUS, Issue 5 2010X. Zhang SUMMARY The 5-year survival rate in resectable patients with esophageal cancer is only 20% to 36%. Regional relapse and distant metastasis are responsible for the failure of treatment and the majority of cancer-related deaths. Earlier detection of metastases, especially micrometastases, has the potential for more accurate risk stratification in subsequent therapy decisions. No effective techniques have yet been found to detect metastases in erroneously thought to have early stage disease. This study was designed to investigate the clinical significance of bone marrow micrometastases detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with esophageal cancer. Expression of CK19 mRNA in the bone marrow of 61 patients with esophageal squamous cell carcinoma (ESCC) and 15 benign pulmonary and esophageal disease patients was assessed via RT-PCR. Correlation of CK19 mRNA expression to the clinicopathologic features and prognosis of the 61 patients was analyzed: 21.3% (13/61) were positive for expression of CK19 mRNA in patients with ESCC. No CK19 mRNA was detected of the 15 benign pulmonary and esophageal disease patients. CK19 mRNA expression did not correlate with the clinicopathologic features of the patients with ESCC, but patients with CK19 mRNA-positive bone marrow had earlier recurrence and shorter survival after surgery. In multivariate analysis, CK19 mRNA was found to be an independent predictor of a poor outcome. CK19 mRNA may be used as a molecular maker to detect bone marrow micrometastases in patients with ESCC and may help to select the proper therapy and predict the prognosis. [source] Analysis of micrometastatic disease in histologically negative lymph nodes of patients with adenocarcinoma of the distal esophagus or gastric cardiaDISEASES OF THE ESOPHAGUS, Issue 6 2008C. J. Buskens SUMMARY., Lymphatic dissemination is the most important prognostic factor in patients with esophageal carcinoma. However, the clinical significance of lymph node micrometastases is still debated due to contradictory results. The aim of the present study was to identify the incidence of potentially relevant micrometastatic disease in patients with histologically node-negative esophageal adenocarcinoma and to analyze the sensitivity and specificity of three different immunohistochemical assays. From a consecutive series of 79 patients who underwent a transthoracic resection with extended 2-field lymphadenectomy, all 20 patients with pN0 esophageal adenocarcinoma were included in this study. A total of 578 lymph nodes were examined for the presence of micrometastases by immunohistochemical analysis with the antibodies Ber-EP4, AE1/AE3 and CAM 5.2. Lymph node micrometastases were detected in five of the 20 patients (25%). They were identified in 16 of the 578 lymph nodes examined (2.8%) and most frequently detected with the Ber-EP4 and AE1/AE3 antibody (sensitivity 95% and 79% respectively). In 114 of the 559 negative lymph nodes (20.4%), positive single cells were found that did not demonstrate malignant characteristics. These false-positive cells were more frequently found with the AE1/AE3 staining (specificity of the Ber-Ep4 and AE1/AE3 antibody 94% and 84% respectively). The presence of nodal micrometastases was associated with the development of locoregional recurrences (P=0.01), distant metastases (P=0.01), and a reduced overall survival (log rank test, P=0.009). For the detection of clinically relevant micrometastatic disease in patients operated upon for adenocarcinoma of the distal esophagus or gastric cardia, Ber-EP4 is the antibody of first choice because of its high sensitivity and specificity. Immunohistochemically detected micrometastases in histologically negative lymph nodes have potential prognostic significance and are associated with a high incidence of both locoregional and systemic recurrence. Therefore, this technique has the potential to refine the staging system for esophageal cancer and to help identify patients who will not be cured by surgery alone. [source] Clinical significance of bone marrow micrometastases in esophageal cancerDISEASES OF THE ESOPHAGUS, Issue 4 2004H. Inoue SUMMARY, Using the reverse transcriptase,polymerase chain reaction (RT-PCR), we investigated the clinical significance of bone marrow micrometastases in patients with esophageal cancer. Bone marrow samples from 57 patients with esophageal cancer, who underwent esophagotomy, were investigated by specific RT-PCR for carcinoembryonic antigens (CEA). A total of 40 out of 57 patients (70.1%) were positive for CEA mRNA in the bone marrow. Among curatively resected cases, 34 of 50 patients (68.0%) were positive for CEA. Ten of 13 T1 patients (76.9%) were positive for CEA. Although the CEA-positive rate was high, there was no significant correlation between CEA positivity and any clinical characteristics. Among the 40 CEA-positive patients, 50% have shown recurrence so far. Detection of cancer cells in the bone marrow by RT-PCR may not always correspond to the malignant potential or other characteristics of the tumor. CEA-positive ,micrometastases' might actually represent isolated circulating tumor cells without much biological significance. [source] Detailed examination of lymph nodes improves prognostication in colorectal cancerINTERNATIONAL JOURNAL OF CANCER, Issue 11 2010Fania S. Doekhie Abstract Up to 30% of stage II patients with curatively resected colorectal cancer (CRC) will develop disease recurrence. We evaluated whether examination of lymph nodes by multilevel sectioning and immunohistochemical staining can improve prognostication. Lymph nodes (n = 780) from 36 CRC patients who had developed disease recurrence (cases) and 72 patients who showed no recurrence of disease for at least 5 years (controls) were analyzed. Sections of 4 levels at 200-,m interval were immunohistochemically stained for cytokeratin expression. The first level was analyzed by conventional and automated microscopy, and the 3 following levels were analyzed by automated microscopy for the presence of tumor cells. Overall, cases showed more micrometastases (3 patients) than controls (1 patient). Analysis of a second level led to the additional detection of 1 patient with micrometastases (case) and 1 patient with macrometastasis (case). Examining more levels only led to additional isolated tumor cells, which were equally divided between cases and controls. Likewise, automated microscopy resulted only in detection of additional isolated tumor cells when compared with conventional microscopy. In multivariate analysis, micrometastases [odds ratio (OR) 26.3, 95% confidence interval (CI) 1.9,364.8, p = 0.015], T4 stage (OR 4.8, 95% CI 1.4,16.7, p = 0.013) and number of lymph nodes (OR 0.9, 95% CI 0.8,1.0, p = 0.028) were independent predictors for disease recurrence. Lymph node analysis of 2 levels and immunohistochemical staining add to the detection of macrometastases and micrometastases in CRC. Micrometastases were found to be an independent predictor of disease recurrence. Isolated tumor cells were of no prognostic significance. [source] Real-time RT-PCR detection of CK19, CK7 and MUC1 mRNA for diagnosis of lymph node micrometastases in non small cell lung carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 5 2005Pierre Saintigny Abstract Metastatic lymph nodes (LNs) are the major prognostic factor in resected non small cell lung carcinoma (NSCLC). However, almost 50% of pN0 patients relapse, suggesting metastatic cells undetected by current staging procedures. A combination of markers [cytokeratins 19 and 7 (CK19, CK7) and mucin type 1 (MUC1) mRNAs] was therefore evaluated by real-time RT-PCR in order to detect occult cancer cells. Forty-three NSCLC tumor samples, 4 micrometastatic, 6 metastatic and 84 histologically negative mediastinal LNs from 19 patients with NSCLC were evaluated as well as blood mononuclear cells from 29 healthy volunteers and 17 benign LNs. When tested on cell lines, RT-PCR was particularly efficient for evaluation of CK19, CK7 and MUC1 mRNA expression. All tumor samples were positive for at least 1 marker and 74% of samples were positive for all 3 markers. CK7 and CK19 mRNA were not detected in benign LN and blood cells from healthy donors in contrast with MUC1 mRNA. Only CK7 and CK19 mRNA were therefore used for evaluation of mediastinal LNs: the 6 histologically metastatic and the 4 micrometastatic LNs were positive for at least one marker. Among the 84 histologically negative LNs, 6 (7%) were positive for at least one marker, potentially changing the stage of 2 out of 19 patients. In conclusion, in our feasibility study, parallel molecular detection of CK19 and CK7 mRNA can be considered a specific diagnostic tool for the assessment of microscopic lymphatic spread. Its prognostic impact remains to be evaluated in a prospective study. © 2005 Wiley-Liss, Inc. [source] Technical limits of comparison of step-sectioning,immunohistochemistry and RT-PCR on breast cancer sentinel nodes: a study on methacarn-fixed tissueJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 9b 2009Lorenzo Daniele Abstract The optimal pathological assessment of sentinel nodes (SLNs) in breast cancer is a matter of debate. Currently, multilevel histological evaluation and immunohistochemistry (IHC) are recommended, but alternative RT-PCR procedures have been developed. To assess the reliability of these different procedures, we devised a step-sectioning protocol at 100 micron-intervals of 74 SLNs using methacarn fixation. mRNA was extracted from sections collected from levels 4 to 5. Mammaglobin, CEA and CK19 were used for RT-PCR. mRNA extraction was successful in 69 SLNs. Of these, 7 showed macrometastases (>2mm), 2 showed micrometastases (<2 mm) and 7 showed isolated tumour cells (ITC) by IHC. RT-PCR was positive for the three markers in 6 of 7 macrometastases and in 1 of 2 micrometastases. In the 2 RT-PCR negative cases, metastases were detected only on sections distant from those analysed by RT-PCR. CEA and/or CK19 were positive by RT-PCR in 3 of 7 ITC and in 23 morphologically negative SLNs. In conclusion, the main goal of our study was to show that the use of alternate sections of the same sample for different procedures is the key reason for the discrepancies between molecular and morphological analyses of SLN. We believe that only prospective studies with quantitative mRNA analysis of specific metastatic markers on the whole lymph node can elucidate the utility of molecular assessments of SLN. [source] Mortality association of enhanced CD44v6 expression is not mediated through occult lymphatic spread in stage II colorectal cancerJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2000Gerard Clarke Abstract Background and Aims: In the absence of other metastatic disease, the presence of lymph node metastasis remains the most important determinant of survival in colorectal cancer (CRC). Cluster designation 44 variant 6 (CD44v6) over-expression is associated with worse outcome in all stages of CRC. The CD44v6 is believed to confer metastatic potential through its facilitation of migration, extravasation and proliferation, although the specific means by which it conveys an adverse prognosis in CRC is unknown. The aim of the present study was to determine if CD44v6 over-expression in Stage II CRC subjects was associated with the presence of lymph node micrometastases. Methods: We assessed tumour CD44v6 expression in 43 randomly sampled subjects who had resections for Stage II CRC between 1984 and 1991 by using immunohistochemistry. Micrometastases were sought in corresponding lymph node (LN) sections using keratin immunohistochemistry. Results: There was a statistical trend between tumour CD44v6 over-expression and mortality (P = 0.09) and a significant relationship between LN cytokeratins and mortality (P = 0.01). There was no association between the detection of LN cytokeratins and tumour CD44v6 over-expression. Conclusion: We conclude that the adverse survival effect of CD44v6 over-expression is not mediated though lymphatic spread and postulate that it may therefore facilitate haematogenous metastasis. [source] Intratumoural chemotherapy of lung cancer for diagnosis and treatment of draining lymph node metastasisJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2010Firuz Celikoglu Abstract Objectives Reviewed here is the potential effectiveness of cytotoxic drugs delivered by intratumoural injection into endobronchial tumours through a bronchoscope for the treatment of non-small cell lung cancer and the diagnosis of occult or obvious cancer cell metastasis to mediastinal lymph nodes. Key findings Intratumoural lymphatic treatment may be achieved by injection of cisplatin or other cytotoxic drugs into the malignant tissue located in the lumen of the airways or in the peribronchial structures using a needle catheter through a flexible bronchoscope. This procedure is termed endobronchial intratumoural chemotherapy and its use before systemic chemotherapy and/or radiotherapy or surgery may provide a prophylactic or therapeutic treatment for eradication of micrometastases or occult metastases that migrate to the regional lymph nodes draining the tumour area. Conclusions To better elucidate the mode of action of direct injection of cytotoxic drugs into tumours, we review the physiology of lymphatic drainage and sentinel lymph node function. In this light, the potential efficacy of intratumoural chemotherapy for prophylaxis and locoregional therapy of cancer metastasis via the sentinel and regional lymph nodes is indicated. Randomized multicenter clinical studies are needed to evaluate this new and safe procedure designed to improve the condition of non-small cell lung cancer patients and prolong their survival. [source] Radiofrequency ablation of colorectal liver metastases induces an inflammatory response in distant hepatic metastases but not in local accelerated outgrowthJOURNAL OF SURGICAL ONCOLOGY, Issue 7 2010Maarten W. Nijkamp MD Abstract Background Recently, we have shown in a murine model that radiofrequency ablation (RFA) induces accelerated outgrowth of colorectal micrometastases in the transition zone (TZ) surrounding the ablated lesion. Conversely, RFA also induces an anti-tumor T-cell response that may limit tumor growth at distant sites. Here we have evaluated whether an altered density of inflammatory cells could be observed in the perinecrotic (TZ) metastases compared to hepatic metastases in the distant reference zone (RZ). Methods RFA-treated tumor-bearing mice (n,=,10) were sacrificed. The inflammatory cell density (neutrophils, macrophages, CD4+ T-cells, and CD8+ T-cells) of tumors in the TZ (TZ tumors) was compared to that in tumors in the RZ (RZ tumors). Sham-operated, tumor-bearing mice (n,=,10) were analyzed simultaneously as controls (sham-treated tumors). Results In RFA-treated, tumor-bearing mice RZ tumors contained a significantly higher density of neutrophils and CD4+ T-cells, but not macrophages and CD8+ T-cells compared to sham-treated tumors. Notably, TZ tumors had a significantly lower density of neutrophils, CD4+ T-cells, and CD8+ T-cells, but not macrophages, when compared to RZ tumors. Conclusions The accelerated perinecrotic tumor outgrowth following RFA is associated with a reduced density of neutrophils and T-cells compared to distant hepatic metastases. This may have implications for local tumor recurrence following RFA. J. Surg. Oncol. 2010; 101:551,556. © 2010 Wiley-Liss, Inc. [source] Sentinel lymph node as a new marker for therapeutic planning in breast cancer patientsJOURNAL OF SURGICAL ONCOLOGY, Issue 3 2004Marco Gipponi MD Abstract Background and Objectives Literature review suggests that the sentinel lymph node (sN) represents a reliable predictor of axillary lymph node status in breast cancer patients; however, some important issues, such as the optimisation of the technique for the intraoperative identification of the sN, the role of intraoperative frozen section examination of the sN, and the clinical implications of sN metastasis as regards the surgical management of the axilla, still require further confirmation. The authors aimed (1) to assess the feasibility of sN identification with a combined approach (vital blue dye lymphatic mapping and radioguided surgery, RGS) and the specific contribution of either techniques to the detection of the sN, (2) to determine the accuracy and usefulness of intraoperative frozen section examination of the sN in order to perform a one-stage surgical procedure, and (3) to define how the sN might modulate the therapeutic planning in different stages of disease. Materials and Methods From October 1997 to June 2001, 334 patients with early-stage (T1,2 N0 M0) invasive mammary carcinoma underwent sN biopsy; the average age of patients was 61.5 years (range, 39,75 years). In a subset of 153 patients, both vital blue dye (Patent Blue-V) lymphatic mapping and RGS were used to identify the sN, and the relative contribution of each of the two techniques was assessed. Results In the whole group, the sN was identified in 326 of 334 patients (97.6%), and 105 of 326 patients (37.3%) had positive axillary lymph nodes (pN+). In 9 of 105 pN+ patients, the definitive histologic examination of the sN did not show metastases but these were detected in non-sN, thus giving an 8.6% false-negative rate, a negative predictive value of 94.5% (156/165), and an accuracy of 96.5% (252/261). As regards the specific contribution of the two different techniques used in the identification of the sN, the detection rate was 73.8% (113/153) with Patent Blue-V alone, 94.1% (144/153) with RGS alone, and 98.7% (151/153) with Patent Blue-V combined with RGS (P,<,0.001). Noteworthy, whenever the sN was identified, the prediction of axillary lymph node status was remarkably similar (93,95% sensitivity; 100% specificity; 95,97% negative predictive value, and 97,98% accuracy) whichever of the three procedures was adopted (Patent Blue-V alone, RGS alone, or combined Patent Blue-V and RGS). Intraoperative frozen section examination was performed in 261 patients, who had at least one sN identified, out of 267 patients who underwent complete axillary dissection; 170 patients had histologically negative sN (i.o. sN,) and 91 patients histologically positive sN (i.o. sN+). All 91 i.o. sN+ were confirmed by definitive histology, whereas in 14 of 170 i.o. sN, patients (8.2%) metastases were detected at definitive histology. As regards the correlation between the size of sN metastasis, the primary tumour size, and the status of non-sN in the axilla, micrometastases were detected at final histology in 23 patients and macrometastases in 82 patients. When only micrometastases were detected, the sN was the exclusive site of nodal metastasis in 20 of 23 patients (86.9%) while in 3 patients with tumour size larger than 10 mm micrometastases were detected also in non-sN. Macrometastases were never detected in pT1a breast cancer patients; the sN was the exclusive site of these metastases in 30 patients (36.6%), while in 52 patients (63.4%) there were metastases both in sN and non-sN. Conclusions Sentinel lymphadenectomy can better be accomplished when both procedures (lymphatic mapping with vital blue dye and RGS) are used, because of the significantly higher sN detection rate, although the prediction of axillary lymph node status remains remarkably similar whichever method is used. The intraoperative frozen section examination proved to be rather accurate in predicting the actual pathologic status of the sN, with a negative predictive value of 91.8%; in 35% of patients it allowed sN biopsy and axillary dissection to be performed in a one-stage surgical procedure. Finally, specific clinical and histopathologic features of the primary tumour and sN might be used to tailor the loco-regional and systemic treatment in different clinical settings, such as in ductal carcinoma in-situ (DCIS), early-stage invasive breast cancer, and patients with large breast cancer undergoing neo-adjuvant CT for breast-saving surgery as well as elderly patients with operable breast cancer. J. Surg. Oncol. 2004;85:102,111. © 2004 Wiley-Liss, Inc. [source] Detection of disseminated tumour cells in bone marrow of patients with isolated liver metastases from colorectal cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2003Kristin Bjørnland MD Abstract Background and Objectives In colorectal cancer (CRC) patients, tumour recurrence is common following potentially curative surgery for liver metastases. This may be caused by occult tumour cells present at the time of surgery. Dissemination of micrometastatic cells may occur early in patients with solid cancer, and micrometastases may signify a poor prognosis. The aim of the present study was to evaluate the frequency of micrometastatic cells in the bone marrow of patients with potentially resectable liver metastases. Methods Twenty millilitres of bone marrow was aspirated from both anterior iliac crests from 48 patients. Mononuclear cells were isolated and incubated with superparamagnetic Dynabeads® coated with an anti-epithelial monoclonal antibody (MOC31). Magnetically selected cells were identified by light microscopy as cells with bead rosettes (>5 beads/cell). Results Micrometastatic tumour cells were identified in four of 48 (8%) patients who all had their liver metastases surgically removed. Two of the four died after 17 and 18 months, respectively, whereas two are alive after 10 and 12 months. None of the 19 inoperable patients had micrometastases. Conclusions The frequency of bone marrow micrometastases in patients with clinically isolated liver metastases from CRC was low. This is biologically interesting, but bone marrow status should not affect current treatment protocols. J. Surg. Oncol. 2003;82:224,227. © 2003 Wiley-Liss, Inc. [source] Treatment of Metastatic Breast Cancer with Liver TransplantationTHE BREAST JOURNAL, Issue 2 2003J. M. Wilson MD Abstract: Resection of liver metastases is accepted as an appropriate treatment for colorectal metastases in suitable patients. Liver transplant is not often used for malignant disease as there is a high incidence of undetectable micrometastases elsewhere and recurrence is likely. The effects of immunosuppression may also enhance the growth of malignant cells at other sites. We report a case where a young patient with undiagnosed breast cancer with axillary and liver metastases underwent liver transplantation and is effectively leading a normal life 33 months after transplant., [source] Prognostic Indicators of Occult Metastases in Oral CancerTHE LARYNGOSCOPE, Issue 7 2002Mario Russolo MD Abstract Objective We evaluated the importance of several tumor factors related to predicting the presence of occult metastases in the oral cavity. Study Design Retrospective case study. Methods The study comprises 29 patients treated at the Department of Otorhinolaryngology (University of Trieste, Cattinara Hospital, Trieste, Italy) between January 1990 and December 2000, who had T1-T2 carcinoma of the oral cavity that had or had not extended to the oropharynx and were clinically evaluated as N0 neck. The patients all underwent surgery with removal of tumor and neck dissection. Four tumor-related parameters were examined with the aim of evaluating their predictivity of metastasis: tumor class, degree of keratinization, degree of differentiation according to Brooler's histopathological grading, and invasive cell grading (ICG). With the exception of tumor class, these parameters were evaluated both in the biopsy and in the surgical specimen and the findings were then compared. We evaluated existing correlations between each individual parameter and the histopathological presence of micrometastases (pN+) and extracapsular spread revealed when specimens from the neck were examined. Results There was a highly significant correlation between ICG equal to or greater than 13 (range, 5,20) and the presence of occult metastases (P = .0017). On the basis of our findings, the ICG parameter correctly identified 9 of 10 (pN+) patients and could have reduced overtreatment from 65.5% to 17.2% in histopathologically negative necks (pN0). Conclusion It would appear that with a delay in programming a neck dissection so as to consider ICG in combination with thickness, as in seven recent patients, identification of locoregional occult metastases (pN+) might be more precise. [source] A novel method of generating prostate cancer metastases from orthotopic implantsTHE PROSTATE, Issue 2 2003Eva Corey Abstract BACKGROUND Spontaneous metastasis following implantation at the orthotopic site is a highly desired feature in prostate cancer (CaP) models, since it would enable studies of mechanisms associated with tumor cell dissemination. METHODS LuCaP 23.8 and LuCaP 35, hormone-sensitive CaP xenografts that express PSA and the wild-type androgen receptor, were grown orthotopically in SCID mice. When tumor volumes reached ,250,500 mg, primary tumors were removed to allow micrometastases to grow. RESULTS Using this procedure we generated macroscopic metastases (>20 mg) in 71% (LuCaP 23.8) and 100% (LuCaP 35) of animals, respectively. CONCLUSIONS These models may be used to evaluate new treatment modalities and study mechanisms associated with development of metastases. Prostate 56: 110,114, 2003. © 2003 Wiley-Liss, Inc. [source] Management of the axilla in early breast cancer: is it time to change tack?ANZ JOURNAL OF SURGERY, Issue 4 2000Philip Crowe The standard surgical treatment of the axilla in patients with early breast cancer is about to undergo a radical change. Although axillary dissection is an excellent procedure for both staging and local control, particularly in the clinically positive axilla, it has considerable morbidity and may understage a significant proportion of patients, because it will usually miss micrometastases that can occur in approximately 10% of ,node negative' patients. An increasing number of patients whose tumours are either non-invasive (ductal carcinoma in situ; DCIS), micro-invasive, tubular cancers or low-grade T1a tumours without lymphovascular invasion may be spared axillary surgery because the risk of axillary disease is 0,3%. Many studies, both prospective trials and large retrospective series, show that axillary radiotherapy alone provides similar local control rates to axillary dissection in patients with clinically negative axillas. Primary treatment of the axilla with radiotherapy alone, however, does not allow appropriate staging. Sentinel lymph node biopsy is being increasingly used in patients with breast cancer to provide this information. When a sentinel node is identified it is equal to or better than axillary dissection for staging the axilla and, if the node is positive, it will help select patients who should then proceed to further axillary surgery or axillary radiotherapy. Although sentinel lymph node biopsy is being rapidly adopted in many centres worldwide, the results of randomized controlled trials are needed before it can be recommended as the standard of care. [source] Intraoperative frozen section examination of axillary sentinel lymph nodes in breast cancer,APMIS, Issue 1 2005D. A. GRABAU The study presents the results from intraoperative frozen section assessment of axillary sentinel lymph nodes (SLNs) in breast cancer. Routine histological frozen sections from one level were used, two sections stained with haematoxylin and eosin. Immunohistochemistry for cytokeratins was applied to the permanent SLN paraffin sections only. Axillary dissection was performed on all SLN-positive cases regardless of the size of the metastatic deposits. With a detection rate of 83%, 272 patients entered the study over a period of 46 months. A total of 61 cases were SLN positive by frozen section analysis. The paraffin sections gave an additional 23 SLN-positive cases. The false-negative rate for frozen sections was then 27% (23/84). Micrometastases were found in 28 of 84 cases, and macrometastases in 56. The false-negative rate of frozen sections for micrometastases was 71% (20/28), and for macrometastases 5% (3/56). A total of 73% (61/84) of the patients underwent axillary surgery as a one-step procedure. [source] Characteristics of sentinel lymph nodes' metastatic involvement in early stage of vulvar cancerAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 6 2009Jaroslav KLÁT Background:, Nodal involvement is one of the most significant prognostic factors in early-stage vulvar cancer. Aims:, To determine the diagnostic accuracy of sentinel lymph node (SLN) detection in early-stage vulvar cancer and to describe the characteristics of metastatic lymph node involvement. Methods:, Of 23 women with early-stage squamous cell vulvar cancer included in the study, five had lateral lesions and 18 had midline lesions. SLN detection was performed by using a radioactive tracer and blue dye, followed by radical vulvectomy or radical wide excision with uni/bilateral inguinofemoral lymphadenectomy, depending on tumour size and localization. SLNs were subsequently examined with haematoxylin,eosin and immunohistochemistry. Results:, The SLN detection was successful in all 23 women (100%) and in 38 of 41 groins (92.3%) tested. The total number of SLNs was 67, with an average of 1.76 per groin. In total, 20 positive SLNs were detected in 14 of 23 patients. From a total of 20 positive SLNs, micrometastases were found in five SLNs and isolated tumour cells in one SLN. We experienced one case with a false negativity of SLN. Sensitivity, negative predictive value, accuracy and false negativity of SLN detection were 93.3%, 88.8%, 95.6% and 7.1% respectively. Conclusion:, The SLN biopsy performed by an experienced team is a feasible method, with high accuracy in patients with early-stage vulvar cancer. Prognostic value of micrometastases should be confirmed in further studies. [source] Prospective evaluation of hybrid 18F-fluorodeoxyglucose positron emission tomography/computed tomography in staging clinically node-negative patients with penile carcinomaBJU INTERNATIONAL, Issue 5 2009Joost A.P. Leijte OBJECTIVE To prospectively evaluate the performance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to detect occult metastasis in patients with clinically node-negative (cN0) penile carcinoma, as there is little information on the use of 18F-FDG-PET/CT in penile carcinoma. PATIENTS AND METHODS In 24 patients, scheduled to undergo dynamic sentinel-node biopsy, hybrid PET/CT was used before surgery to assess the nodal status of the cN0-groins. Six of the 24 patients were unilaterally cN0. Thus, 42 cN0-groins were evaluated for occult metastasis using PET/CT. All scans were assessed by two experienced nuclear physicians. The histopathological tumour status of the removed sentinel node was used as the standard of care to evaluate the PET/CT-results. RESULTS Histopathology was tumour-positive in five of the 42 (12%) evaluated cN0-groins, two of which contained only micrometastases (<2 mm). One of the five tumour-positive cN0-groins was correctly predicted on the PET/CT-images. All false-negative PET/CT scans contained metastasis of ,10 mm. Of the remaining 37 tumour-negative groins, 34 were correctly predicted with PET/CT (specificity 92%). CONCLUSION The role of PET/CT in evaluating the groins of patients with cN0 penile cancer appears to be limited, due to its low sensitivity. In this series, only one of the five tumour-positive groins was identified. Surgical staging methods remain necessary at present. [source] Improved sensitivity for detecting micrometastases in pelvic lymph nodes by real-time reverse transcriptase polymerase chain reaction (RT-PCR) compared with conventional RT-PCR in patients with clinically localized prostate cancer undergoing radical prostatectomyBJU INTERNATIONAL, Issue 8 2009Tomoaki Terakawa OBJECTIVE To compare the usefulness between real-time reverse transcriptase polymerase chain reaction (RT-PCR) with that of conventional RT-PCR for detecting micrometastases in pelvic lymph nodes (PLN) dissected during radical prostatectomy (RP) for prostate cancer. PATIENTS AND METHODS In all, 120 patients with clinically localized prostate cancer who underwent RP and pelvic lymphadenectomy were included. Expression of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in 2215 PLNs obtained from these 120 patients were assessed by fully quantitative real-time RT-PCR and as well as conventional RT-PCR. Specimens, in which either PSA or PSMA mRNA was positive, were regarded as showing the ,presence of micrometastasis'. RESULTS Pathological examinations detected tumour cells in 29 PLNs from 11 patients, while real-time RT-PCR and conventional RT-PCR further identified micrometastasis in 143 and 81 PLNs from 32 and 19 patients, respectively, with no pathological evidence of nodal involvement; that is, the sensitivity of real-time RT-PCR for detecting micrometastases was significantly higher than that of conventional RT-PCR. In this series, biochemical recurrence occurred in 32 patients, and in both assays, there were significant differences in biochemical recurrence-free survival between patients with and with no micrometastases. However, despite the significant association of micrometastases detected by both assays with biochemical recurrence on univariate analysis, the presence of micrometastases detected by real-time RT-PCR but not that detected by conventional RT-PCR appeared to be useful as an independent predictor on multivariate analysis. CONCLUSIONS Although micrometastatic tumour foci in PLNs that were missed by routine pathological examination could be diagnosed by both real-time RT-PCR and conventional RT-PCR assays, it would be strongly recommended to use real-time RT-PCR to detect micrometastases considering its high sensitivity and the close association between the outcome of this assay and the probability of biochemical recurrence. [source] Significance of micrometastases in pelvic lymph nodes detected by real-time reverse transcriptase polymerase chain reaction in patients with clinically localized prostate cancer undergoing radical prostatectomy after neoadjuvant hormonal therapyBJU INTERNATIONAL, Issue 2 2007Hideaki Miyake OBJECTIVE To clarify the significance of micrometastases in pelvic lymph nodes in patients treated by radical prostatectomy (RP) for prostate cancer after neoadjuvant hormonal therapy (NHT). PATIENTS AND METHODS The study included 52 patients with clinically localized prostate cancer who received NHT followed by RP. The expression of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in 989 lymph nodes isolated from the 52 patients were assessed by a fully quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR). We regarded specimens in which either PSA or PSMA mRNA were positive as showing the ,presence of micrometastasis'. Lymph node specimens were also stained immunohistochemically with an antibody against PSA. RESULTS Pathological examinations detected tumour cells in 11 lymph nodes from four patients, and real-time RT-PCR further identified micrometastasis in 40 lymph nodes from 19 patients with no pathological evidence of nodal involvement. The presence of micrometastatic cancer cells was confirmed by immunohistochemical staining in 19 lymph nodes from 11 patients with pathologically negative nodes. The presence of micrometastases was significantly associated with other conventional prognostic variables, including the pretreatment serum PSA level, biopsy Gleason score and surgical margin status. The biochemical recurrence-free survival rate in patients with no micrometastasis was significantly higher than that in those with micrometastasis. Furthermore, multivariate analysis identified the presence of micrometastasis as an independent factor predicting biochemical recurrence. CONCLUSIONS Although residual foci of atrophic prostate cancer cells in resected lymph nodes after NHT can be difficult to diagnose by routine pathological examination, the present results show the usefulness of quantitative real-time RT-PCR targeting PSA and PSMA genes for detecting micrometastatic tumour foci in pelvic lymph nodes from patients with localized prostate cancer treated by NHT followed by RP. Furthermore, the present findings suggest that micrometastases in pelvic lymph nodes might be, at least partly, important in the development of biochemical recurrence in some patients undergoing RP after NHT. [source] Clinical evidence of neuroendocrine differentiation in a patient with prostate cancer and bone marrow micrometastasesBJU INTERNATIONAL, Issue 1 2001A. Sciarra No abstract is available for this article. [source] Sentinel lymphonodectomy in nonmelanoma skin malignanciesBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2003C. Michl Summary Background Whereas the value of sentinel lymphonodectomy (SLNE) in malignant melanoma is established, experience with SLNE in nonmelanoma skin cancers is limited. Objectives The feasibility of SLNE in nonmelanoma skin tumours is evaluated. Methods Thirty-seven patients with high-risk nonmelanoma skin tumours underwent SLNE: 11 squamous cell carcinomas (SCCs), seven Merkel cell carcinomas (MCCs), five cutaneous lymphomas, eight adnexal carcinomas and six other skin cancers, all clinical stage N0. Results In nine patients (four MCCs, two SCCs, three lymphomas) the sentinel lymph nodes (SLNs) showed histological evidence of microinvolvement. In five of these nine patients, radical lymph node dissection (RLND) was performed, revealing further micrometastases in three patients (two SCCs, one MCC). No patient with negative SLN showed tumour dissemination during the follow-up over a mean of 2·5 years (range 2 months to 4·5 years, median 2·4 years). Conclusions Our data provide evidence that SLNE is a minimally invasive and highly sensitive staging tool in selected patients with high-risk nonmelanoma skin cancers. [source] Prognostic impact of para-aortic lymph node micrometastasis in patients with regional node-positive biliary cancerBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 5 2009A. Yonemori Background: The presence of para-aortic lymph node metastasis in biliary cancer has a negative impact on prognosis. The relevance of para-aortic lymph node micrometastasis is unknown. Methods: A total of 546 para-aortic lymph nodes from 49 patients with biliary cancer with positive regional nodes and negative para-aortic nodes were immunostained with epithelial marker CAM5·2 (specific for cytokeratins 7 and 8). Immunostained tumour foci were classified as micrometastases or isolated tumour cells (ITCs) according to their size (larger or smaller than 0·2 mm). Results: CAM5·2-positive occult carcinoma cells in para-aortic lymph nodes were detected in nine (18 per cent) of 49 patients and in 18 (3·3 per cent) of 546 para-aortic nodes. There was no difference in postoperative survival between patients with and without CAM5·2-positive para-aortic nodes (P = 0·978), but survival for five patients with micrometastases was significantly worse than that for four patients with only ITCs (P = 0·047). Conclusion: In patients with regional node-positive and para-aortic node-negative biliary cancer, and occult cancer cells in para-aortic lymph nodes, prognosis was significantly worse in those with micrometastases than in patients with only ITCs. An efficient method of intraoperative detection of para-aortic lymph node micrometastases larger than 0·2 mm is needed. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Molecularly targeted therapy and cancer surgeryBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 5 2008I. Judson May reduce micrometastases [source] Feasibility of autonomic nerve-preserving surgery for advanced rectal cancer based on analysis of micrometastasesBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 11 2005T. Matsumoto Background: Autonomic nerve preservation has been advocated as a means of preserving urinary and sexual function after surgery for rectal cancer, but may compromise tumour clearance. The aim of this study was to determine the incidence of micrometastasis in the connective tissues surrounding the pelvic plexus. Methods: The study included 20 consecutive patients who underwent rectal surgery with bilateral lymph node dissection for advanced cancer. A total of 78 connective tissues medial and lateral to the pelvic plexus and 387 lymph nodes were sampled during surgery. All connective tissue samples and 260 lymph nodes were examined for micrometastases by reverse transcriptase,polymerase chain reaction (RT,PCR) after operation. All patients were followed prospectively for a median of 36·0 months. Results: Of 245 histologically negative lymph nodes, 38 (15·5 per cent) were shown by RT,PCR to harbour micrometastases. However, micrometastases to tissues surrounding the pelvic plexus were detected in only two (3 per cent) of 78 tissues, that is in two of 20 patients. Clinical follow-up showed that the two patients had a poor prognosis owing to distant metastases. Conclusion: Autonomic nerve-preserving surgery may be feasible for advanced rectal cancer, but study of more patients positive for micrometastases is required. Copyright © 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Detection of micrometastases in lymph nodes from patients with breast cancerBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 1 2002G. Branagan Background: Sentinel node biopsy affords the opportunity of focused examination of lymph nodes, including the use of the reverse transcriptase,polymerase chain reaction (RT-PCR). The mammaglobin gene is expressed by breast cancers but has not been detected in histologically normal lymph nodes. This study compared mammaglobin RT-PCR with routine histology in the sentinel and non-sentinel nodes of patients with breast cancer. Methods: Patients with breast cancer underwent tumour excision, sentinel node biopsy and axillary dissection. All nodes were bisected and half of each node was sent for routine histological examination. The other half underwent RNA extraction and mammaglobin RT-PCR. Results: Sentinel node biopsy was successful in 50 (96 per cent) of 52 patients. Mammaglobin expression was detected in nine (8 per cent) of 119 histologically negative sentinel nodes (Clopper,Pearson 95 per cent confidence interval (c.i.) 4 to 14 per cent) and in 13 (5 per cent) of 247 histologically negative non-sentinel nodes (95 per cent c.i. 3 to 9 per cent). Mammaglobin expression was detected in four (13 per cent) of 31 patients with histologically negative sentinel nodes (95 per cent c.i. 4 to 30 per cent) and in six (14 per cent) of 44 patients with histologically negative non-sentinel nodes (95 per cent c.i. 5 to 27 per cent). The false-negative rate for sentinel node biopsy was zero using histology results and 10 per cent using RT-PCR. Conclusion: RT-PCR screening of axillary nodes for mammaglobin expression increased the detection of breast cancer metastases compared with routine histology. © 2002 British Journal of Surgery Society Ltd [source] Clinical outcome of patients with lymph node-negative breast carcinoma who have sentinel lymph node micrometastases detected by immunohistochemistryCANCER, Issue 8 2005Mesult Tez M.D. No abstract is available for this article. [source] Clinical outcome of patients with lymph node-negative breast carcinoma who have sentinel lymph node micrometastases detected by immunohistochemistry,CANCER, Issue 8 2005Anees Chagpar M.D., M.Sc. Abstract BACKGROUND The ideal pathologic assessment of sentinel lymph nodes (SLNs) in patients with breast carcinoma remains controversial. The authors evaluated how detailed assessment of SLNs using immunohistochemistry (IHC) and serial sectioning would affect treatment decisions and outcomes in patients with breast carcinoma who had negative SLNs on standard hematoxylin and eosin staining. METHODS The SLNs from patients who were treated between June 1998 and June, 1999 and who had negative lymph node status determined by hematoxylin and eosin staining (n = 84 patients) were evaluated further with serial sectioning and cytokeratin IHC. Patients were offered adjuvant therapy based on primary tumor factors. RESULTS The median patient age was 57 years, and the median tumor size was 1.2 cm. At a median follow-up of 40.2 months, 81 patients (96%) were alive with no evidence of disease, 1 patient was alive with disease, 1 patient had died of disease, and 1 patient had died of other causes. Fifteen patients (18%) had micrometastases identified on IHC. Of the total 84 patients, information regarding adjuvant therapy was not available for 5 patients. Of the remaining 79 patients, 10 patients (13%) were not offered adjuvant chemotherapy but had positive SLN status determined by IHC. SLN status based on IHC evaluation did not correlate with age (P = 0.077), tumor size (P = 0.717), grade (P = 0.148), estrogen receptor status (P = 1.000), or lymphovascular invasion (P = 0.274). Furthermore, IHC-detected positive SLN status did not correlate with distant metastasis (P = 0.372) or overall or distant metastasis-free survival (P = 0.543 and P = 0.540, respectively). CONCLUSIONS Although the finding of SLN micrometastases by IHC may change management in > 12% of patients, preliminary results suggested that such micrometastases do not affect outcomes significantly. Cancer 2005;103:1581,6. © 2005 American Cancer Society. [source] Improving the reproducibility of diagnosing micrometastases and isolated tumor cells,CANCER, Issue 2 2005Gábor Cserni M.D., Ph.D. Abstract BACKGROUND The latest edition of the tumor-lymph node-metastasis (TNM) classification of malignant tumors distinguishes between isolated tumor cells (pN0) and micrometastases (pN1mi). The reproducibility of these categories has not been assessed previously. METHODS Digital images from 50 cases with low-volume lymph node involvement from axillary sentinel lymph nodes were circulated twice for evaluation (Evaluation Rounds 1 and 2) among the members of the European Working Group for Breast Screening Pathology, and the members were asked to categorize lesions as micrometastasis, isolated tumor cells, or something else and to classify each case into a pathologic lymph node (pN) category of the pathologic TNM system. Methods for improving the low reproducibility of the categorizations were discussed between the two evaluation rounds. , Statistics were used for the assessment of interobserver variability. RESULTS The , value for the consistency of categorizing low-volume lymph node load into micrometastasis, isolated tumor cells, or neither of those changed from 0.39 to 0.49 between Evaluation Rounds 1 and 2, but it was slightly lower for the pN categories (0.35 and 0.44, respectively). Interpretation of the definitions of isolated tumor cells (especially with respect to their localization within the lymph node), lack of guidance on how to measure them if they were multiple, and lack of any definitions for multiple simultaneous foci of lymph node involvement were listed among the causes of discordant diagnoses. CONCLUSIONS The results of the current study indicated that the definitions available have minor contradictions and do not permit a reproducible distinction between micrometastases and isolated tumor cells. Refinement of these definitions, therefore, is required. One refinement that may improve reproducibility is suggested in this report. Cancer 2005. © 2004 American Cancer Society. [source] | |||||||||||||||||||||||||||||||