Presence Of Micrometastases Research Articles

Micrometastases in cervical lymph nodes from patients with squamous carcinoma of the head and neck: should they be actively sought? Maybe

Techniques are now being developed, which allow ever smaller metastatic deposits in regional lymph nodes to be detected; the question is, should they be sought, or does their presence convey no additional information for treatment of head and neck carcinoma patients at this time? Preliminary findings have suggested that the presence of micrometastases may carry with it some prognostic information, and as a consequence, the search for micrometastases would, for the foreseeable future, appear to be a fertile ground for investigation. To bring some uniformity to this project, it is suggested that these definitions be adopted: a micrometastasis measures greater than 0.2 mm but less than 2.0 mm in diameter, and smaller deposits should be designated as isolated tumor cells, which, in turn, are subdivided into those isolated tumor cells detected by light microscopy, immunohistochemistry, or molecular methods. At this juncture, the import of such micrometastases remains in the realm of the clinical investigator—it remains an open question whether the identification of micrometastases (however they may ultimately come to be defined) will prove to have an impact on the care of head and neck cancer patients.

Absence de valeur prédictive des signes de régression histologique sur l’envahissement du ganglion sentinelle

The predictive value of regression in melanoma is debated. A retrospective single-centre study to evaluate the correlation between regression in primary skin tumor and the presence of micrometastases in sentinel lymph nodes. Histological signs of regression in 84 melanomas (>1 mm) with corresponding sentinel lymph nodes were studied by two independent pathologists. Regression was seen in 40 skin melanoma tumors while micrometastasis was seen in 24. Of the tumors with micrometastasis, only 10 were regressive (RR: 0.47, p=0.49). Breslow value>2 mm and male sex were predictive for node micrometastasis (RR: 4.6, p=0.03 and RR: 7.6, p=0.006, respectively). On multivariate analysis, these two factors were independent. These data suggest that regression in primary cutaneous melanoma is not predictive for lymph node metastasis.

Prognostic significance of histopathological parameters in sentinel nodes of melanoma patients

The presence of micrometastases in the sentinel lymph node (SLN) is an important prognostic parameter for melanoma patients. The aim was to determine the prognostic relevance of histopathological characteristics of micrometastases in the SLN, which has not been adequately addressed thus far. In 169 melanoma patients with positive SLN, histopathological features of the SLN were correlated with overall survival (OS) and relapse-free survival (RFS). Tumour burden, expansion of melanoma cells in the periphery (infiltration of capsule) and towards the centre of the SLN [tumour penetrative depth (TPN)] were of prognostic significance for OS and RFS on univariate analysis. Multivariate analysis revealed three independent significant parameters which predict a poor prognosis: presence of infiltration of the SLN capsule, TPN > or = 2 mm and size of the largest tumour deposit > or = 30 cells. Histopathological analysis of SLN allows the identification of patients with a poor prognosis depending on the location of melanoma cells and tumour burden.

Quantitative Detection of Micrometastases in Pelvic Lymph Nodes in Patients with Clinically Localized Prostate Cancer by Real-time Reverse Transcriptase-PCR

Routine pathologic examination can miss micrometastatic tumor foci in the lymph nodes of patients with prostate cancer, resulting in confusion during tumor staging and clinical decision-making. The objective of this study was to clarify the significance of micrometastases in pelvic lymph nodes in patients who underwent radical prostatectomy for prostate cancer. The expression of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in 2,215 lymph nodes isolated from 120 patients with clinically localized prostate cancer was assessed by a fully quantitative real-time reverse transcriptase-PCR. We regarded specimens in which either PSA or PSMA mRNAs were positive as proof of the "presence of micrometastasis." Immunohistochemical staining of lymph node specimens with an antibody against PSA was also done. Pathologic examinations detected tumor cells in 29 lymph nodes from 11 patients, and real-time reverse transcriptase-PCR further identified micrometastasis in 143 lymph nodes from 32 patients with no pathologic evidence of lymph node involvement. The presence of micrometastatic cancer cells was confirmed by immunohistochemical staining in 61 lymph nodes from 17 patients with pathologically negative lymph nodes. The presence of micrometastases was significantly associated with other conventional prognostic variables, including serum PSA value, pathologic stage, Gleason score, and tumor volume. Biochemical recurrence was detected in 32 patients, 17 of whom were negative for lymph node metastasis by pathologic examination (including 4 patients with pathologically organ-confined disease), but were diagnosed as having micrometastasis. Biochemical recurrence-free survival rate in patients without micrometastasis was significantly higher than in those with micrometastasis irrespective of the presence of pathologically positive nodes. Furthermore, only the presence of micrometastasis was independently associated with biochemical recurrence regardless of other factors examined. These findings suggest that approximately 30% of clinically localized prostate cancers shed cancer cells to the pelvic lymph nodes, and that biochemical recurrence after radical prostatectomy could be explained, at least in part, by micrometastases in pelvic lymph nodes.

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 therapy

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). 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. 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. 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.

Breast Cancer–Specific mRNA Transcripts Presence in Peripheral Blood After Adjuvant Chemotherapy Predicts Poor Survival Among High-Risk Breast Cancer Patients Treated With High-Dose Chemotherapy With Peripheral Blood Stem Cell Support

To study the prognostic significance of the presence of breast cancer-specific mRNA transcripts in peripheral blood (PB), defined by serial analysis of gene expression, in high-risk breast cancer (HRBC) patients undergoing high-dose chemotherapy after receiving adjuvant chemotherapy. From 1994 to 2000, 84 HRBC patients (median age, 44 years; > 10 nodes; 74%) received adjuvant chemotherapy (fluorouracil, epirubicin, and cyclophosphamide for six cycles [83%] or doxorubicin and cyclophosphamide followed by paclitaxel) before undergoing one course of cyclophosphamide plus thiotepa plus carboplatin (STAMP V). Radiotherapy or hormone therapy was administered whenever indicated. Aliquots of apheresis-mononuclear blood cells were frozen from each patient. mRNA was isolated using an automatic nucleic acid extractor based on the magnetic beads technology; reverse transcription was performed using random hexamers. Cytokeratin 19, HER-2, P1B, PS2, and EGP2 transcripts were quantified to B-glucuronidase by real-time polymerase chain reaction (RT-PCR) using a linear DNA probe marked with a quencher and reporter fluorophores used in RT-PCR. Presence of PB micrometastases, estrogen receptor and progesterone receptor status, tumor size, age, tumor grade, number of nodes affected, and treatment with paclitaxel were included in the statistical analysis. Median follow-up was 68.3 months (range, 6 months to 103 months). Forty-seven relapses (56%) and 35 deaths (41.7%) were registered. Both tumor size and presence of micrometastases reached statistical significance according to the Cox multivariate model. Relapse hazard ratio (HR) for those patients with PB micrometastases was 269% (P = .006); death HR, 300% (P = .011). Time relapse was 53 months longer for patients without micrometastases: 31.3 v 84.2 months (P = .021). PB micrometastases presence after adjuvant chemotherapy predicts both relapse and death more powerful than classical factors in HRBC patients undergoing high-dose chemotherapy. Micrometastases search using a gene panel appears to be a more accurate procedure than classical approaches involving only one or two genes.

Cyclooxygenase-2: possible predictor related to micrometastasis in breast cancer patients

Blood and lymphatic circulation are the major routes during metastatic spread of breast cancer cells. Despite the predictive and prognostic value of bone marrow (BM) micro-metastasis, repeated and frequent BM aspirations may not be easily accepted by patients. We try to establish the role of circulating tumor cells as a predictor for micro-metastasis in BM and sentinel lymph node (SLN) as well as to identify the association between micro-metastasis in blood and lymphatic circulation. We prospectively studied 47 breast cancer patients without overt metastasis. Bilateral BM samples and blood samples were obtained before surgery and subsequently handled using magnetic-activated cell separation (MACS) followed by immunocytochemistry (ICC). SLN was examined by hematoxylin and eosin (H and E) staining and ICC.Blood and BM micro-metastasis were detected in 16 (35%) and 25 (54%) of 47 patients. SLN micro-metastasis were detected in 13 (27.7%) and 22 (46.8%) patients using H and E and ICC, respectively. All the patients with circulating tumor cells had micro-metastasis in BM, whereas 9 of 25 (36%) patients with micro-metastasis in BM had no circulating tumor cells (P < 0.001). On the other hand, there is no correlation between circulating tumor cells and micro-metastasis in SLNs detected by either H and E (P = 0.52) or ICC (P = 0.36). We found that the presence of circulating tumor cells might predict BM micro-metastasis but not SLN micro-metastasis. It is also interesting to find that the presence of SLN micro-metastasis does not necessarily correlate with the presence of micro-metastasis in BM and blood.

Circulating tumor cells in patients with breast cancer: possible predictor of micro-metastasis in bone marrow but not in sentinel lymph nodes

Background. - Blood and lymphatic circulation are the major routes during metastatic spread of breast cancer cells. Despite the predictive and prognostic value of bone marrow (BM) micro-metastasis, repeated and frequent BM aspirations may not be easily accepted by patients. We try to establish the role of circulating tumor cells as a predictor for micro-metastasis in BM and sentinel lymph node (SLN) as well as to identify the association between micro-metastasis in blood and lymphatic circulation. We prospectively studied 47 breast cancer patients without overt metastasis. Bilateral BM samples and blood samples were obtained before surgery and subsequently handled using magnetic-activated cell separation (MACS) followed by immunocytochemistry (ICC). SLN was examined by hematoxylin and eosin (H and E) staining and ICC. Results. - Blood and BM micro-metastasis were detected in 16 (35%) and 25 (54%) of 47 patients. SLN micro-metastasis were detected in 13 (27.7%) and 22 (46.8%) patients using H and E and ICC, respectively. All the patients with circulating tumor cells had micro-metastasis in BM, whereas 9 of 25 (36%) patients with micro-metastasis in BM had no circulating tumor cells (P < 0.001). On the other hand, there is no correlation between circulating tumor cells and micro-metastasis in SLNs detected by either H and E (P = 0.52) or ICC (P = 0.36). We found that the presence of circulating tumor cells might predict BM micro-metastasis but not SLN micro-metastasis. It is also interesting to find that the presence of SLN micro-metastasis does not necessarily correlate with the presence of micro-metastasis in BM and blood.

Quantitative Real-time Polymerase Chain Reaction Detection of Lymph Node Lung Cancer Micrometastasis Using Carcinoembryonic Antigen Marker

The survival of patients with surgically resected stage I non-small cell lung cancer (NSCLC) is not optimal, probably because of unsuspected systemic occult tumor dissemination. The current applied technologies and methods for scanning the body and examining lymph nodes for tumor cells have broadly recognized limitations. Several studies have reported that it is possible to detect occult lymph node metastases (micrometastases) using more sensitive methods such as immunohistochemistry or molecular technology. The aim of our study was to evaluate the utility of quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR) for carcinoembryonic antigen (CEA) messenger RNA (mRNA) for detection of lymph node micrometastases and its impact on disease-free interval. Quantitative real-time RT-PCR for CEA mRNA was performed on primary lung tumors and regional lymph nodes from 44 surgically resected NSCLC patients classified as clinical stage I. Fourteen lymph nodes from five patients without malignancy were used as controls. The end point of clinical analysis was cancer recurrence. Average follow-up was 22.5 months. CEA mRNA was detected in all but four lymph nodes used as controls. All primary tumors were positive for CEA mRNA. Of 261 lymph nodes analyzed, 35 lymph nodes (13.4%) showed CEA mRNA levels higher than those detected in control lymph nodes and were considered positive for micrometastasis. Survival analysis by micrometastases showed less cancer recurrences in patients with lymph nodes negative for CEA mRNA (log rank, 5.3; p = 0.021). Among tumor type, tumor grading, age, sex, and molecularly detected lymph node micrometastases, the most powerful predictor of cancer recurrences was the presence of micrometastases (Cox proportional hazard, 3.3; p = 0.027). Quantitative real-time RT-PCR for CEA mRNA can be applied for detection of micrometastases in lymph nodes. This technique may be an appropriate tool in predicting cancer recurrences, and further studies are warranted to determine the most useful clinical applications.

MMP-21 is upregulated at early stages of melanoma progression but disappears with more aggressive phenotype

The expression of matrix metalloproteinases (MMPs) is frequently altered during malignant transformation. We examined the profile of three recently cloned MMPs, MMP-21, MMP-26, and MMP-28, in melanomas in vivo and in culture. Immunohistochemistry for MMPs-21, -26, -28, and -13 in melanoma specimens (27 nonmetastatic, 26 with nodal micrometastases, and 10 in situ melanomas) from 63 patients was performed. MMP-21 was expressed in melanoma cells in 29/53 cases, being more frequent in melanoma samples without micrometastases. Six out of ten in situ melanomas were positive, while five nevus samples were negative. MMP-26 and -28 were not generally expressed in melanoma cells. MMP-13 was detected in melanoma cells in 36/53 samples. MMP-21 was not found in sentinel nodes with metastases, while MMP-13 was seen in all of them. MMP-21 messenger RNA was variably expressed in all five melanoma cell lines investigated using reverse transcriptase-polymerase chain reaction. Our results suggest that expression of MMP-21 may serve as a marker of malignant transformation of melanocytes and does not associate with the presence of micrometastases.

Neoadjuvant chemotherapy does not effect presence of micrometastases in bone marrow of breast cancer patients

867 Background: The idea of adjuvant systemic therapy in breast cancer patients is to eliminate occult tumor cells which may already disseminate at a very early stage. The presence of occult tumor cells in bone marrow of breast cancer patients without evidence for clinically relevant metastatic disease is associated with worse overall and disease-free survival. However, it is unclear whether cytostatics may eliminate those occult tumor cells. Methods: Bone marrow aspirates obtained during surgery in breast cancer patients with locally resticed disease without evidence of a metastatic tumor cell spread were immunohistochemically stained with anti-cytokeratin antibodies in order to detect disseminated tumor cells. In a matched pair analysis bone marrow results of patients receiving neoadjuvant chemotherapy were matched with patients undergoing surgery first followed by adjuvant therapy. Results: Thirtyfour patients receiving neoadjuvant CTx were included into the analysis and matched for clinical stage and age with 34 breast cancer patients undergoing primary surgery. Detection rate of micrometastases was 23 out of 34 in the neoadjuvant group compared to 13 out of 34 in patients receiving surgery first followd by adjuvant therapy. Both groups did not significantly differ in clincal stage, age or bone marrow status. Interestingly, in 2 patients receiving trastuzumab in a neoadjuvant setting, no disseminated tumor cells were detected after systemic therapy. Conclusions: Our results suggest, that bone marrow status - which is highly correlated to survival - is not affected by cytostatic therapy. Therefore, adjuvant therapies in patients with micrometastases in bone marrow may include additional strategies in order to specifically target cells of a minimal residual disease. No significant financial relationships to disclose.

Detection of Micrometastases in Pelvic Lymph Nodes in Patients Undergoing Radical Cystectomy for Focally Invasive Bladder Cancer by Real-time Reverse Transcriptase-PCR for Cytokeratin 19 and Uroplakin II

The objective of this study was to clarify the significance of micrometastases in pelvic lymph nodes in patients who underwent radical cystectomy for bladder cancer. We included 40 patients with locally invasive bladder cancer who underwent radical cystectomy and pelvic lymphadenectomy. Expression of cytokeratin 19 (CK19), uroplakin II (UP II), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in 760 lymph nodes were assessed by a fully quantitative real-time reverse transcription-PCR (RT-PCR) assay. The quantification value of CK19 or UP II mRNA was described as each value relative to GAPDH mRNA. In this study, we regarded specimen in which either CK19 or UP II mRNA was positive as "presence of micrometastasis." Routine pathologic examinations detected tumor cells in 29 lymph nodes from six patients. Real-time RT-PCR identified positive expression of CK19 and UP II mRNAs in 49 lymph nodes from 10 patients and 98 lymph nodes from 16 patients, respectively. Of 633 lymph nodes from 34 patients with no pathologic evidence of nodal involvement, 13 nodes from five patients and 58 nodes from 10 patients were diagnosed as positive for CK19 and UP II mRNAs expression, respectively, by real-time RT-PCR. Presence of micrometastases was significantly associated with other conventional prognostic variables, including pathologic stage and microvascular invasion. Disease recurrence was occurred in eight patients, among whom four patients were negative for lymph node metastasis by routine pathologic examination and diagnosed as having micrometastasis by real-time RT-PCR assay. Furthermore, cause-specific survival rate in patients without micrometastasis was significantly higher than that in those with micrometastasis, irrespective of the presence of pathologic-positive nodes. Approximately 30% of locally invasive bladder cancer shed cancer cells to pelvic lymph nodes, and disease recurrence after radical cystectomy could be explained, at least in part, by micrometastases in pelvic lymph nodes.

Utilizing prognostic and predictive factors in breast cancer

In order to make optimal treatment recommendations for patients with early-stage breast cancer, it is essential to accurately determine the patient's underlying risk of disease recurrence and choose a therapy to which the individual is most likely to respond. Lymph node status, tumor size, histopathologic features including tumor type and grade, and hormone receptor status are well-accepted prognostic factors related to breast cancer. In addition, hormone receptor status is a very strong predictor of response to hormonal therapy. However, our currently accepted prognostic and predictive factors fall short and there is a critical need to more accurately identify those most likely to require or benefit from particular therapies. Attention has therefore focused on the determination of novel prognostic and predictive factors. The most promising new factor is the level of urokinase plasminogen activator and its inhibitor plasminogen activator inhibitor. Other putative factors include proliferative rate, the presence of lymphatic or vascular invasion, human epidermal growth factor receptor 2 (HER-2/neu or erbB-2) positivity, the presence of micrometastases in lymph nodes or bone marrow, and gene expression profile by microarray analysis, and by RNA-based methodology. Data regarding potential new prognostic factors are constantly emerging. These studies are frequently challenging to interpret as they are often retrospective, based on relatively small numbers of patients, include a mix of treated and untreated women, and often do not control for other known prognostic factors. Therefore, new data must be interpreted with caution.

Non‐sentinel lymph node metastases in breast cancer patients with metastatic sentinel nodes

Sentinel lymph node biopsy (SLNB) has been shown to be relatively accurate in axillary nodal staging in breast cancer. In more than half of the patients with metastatic sentinel lymph node (SLN), the SLN was the only lymph node involved in the axilla. A retrospective analysis was performed for those female Chinese breast cancer patients who underwent SLNB. All patients had axillary dissection after SLNB. Those patients with metastatic SLN were selected for analysis. Various tumour factors and SLN factors were analysed to study the association with residual lymph node metastasis. A total of 139 SLNB was performed. The success rate of SLN localization, false negative rate and accuracy were 92%, 9% and 95%, respectively. Fifty-five patients had metastases in the SLN. In 38 patients (69%), SLN was the only lymph node involved in the axilla. Tumours <3 cm, a single metastatic SLN, presence of micro metastases and the absence of extracapsular spread in the SLN were associated with the absence of metastasis in the non-sentinel lymph nodes. Sentinel lymph node biopsy is accurate in the nodal staging of Chinese breast cancer patients. Several factors such as tumour <3 cm, a single metastatic SLN, micro metastases and the absence of extracapsular spread in the sentinel node(s) are useful predictors for the absence of residual disease in the axilla. With further studies and verification, these factors may prove to be important in determining which patients with metastatic SLN will require further axillary treatment. Until such information is available, axillary dissection should be performed when positive sentinel nodes are found.

Immunohistochemical detection of cervical lymph node micrometastases from T2N0 tongue cancer

ConclusionsThese results indicate that extensive, multiple cervical micrometastases occurred from an early stage in patients with T2N0 tongue cancer. The presence of micrometastases suggests the necessity of preventive neck dissection for Level I–IV nodes as a radical treatment.ObjectiveCervical lymph node metastases occur with a relatively high frequency in patients with T2N0 squamous cell carcinoma of the tongue, and control of the metastases greatly influences the prognosis of patients. In this study, micrometastases in the cervical lymph nodes were investigated to clarify the necessity and required extent of preventive neck dissection.Material and methodsWe investigated micrometastases in 24 subjects who had previously been diagnosed with T2N0 tongue cancer. We performed immunostaining with anti-cytokeratin antibody cocktail AE1/AE3 of sections of 401 paraffin-embedded lymph nodes obtained from these patients.ResultsMicrometastases were observed in 14 patients (58%) and were most abundant in Level II nodes (n=11; 46%). Micrometastases were observed in the Level IV nodes of 3 patients (13%), and upstaging to pN2b occurred in 7 patients (29%).

Preoperative imaging in renal cell cancer

Renal cell cancer (RCC) represents the fifth most common cancer in men, with a rising incidence. Radical cancer surgery remains the only curative treatment in localized and advanced RCC. Therefore, preoperative imaging is most important for the planning of the surgical approach and strategy. The aim of any preoperative imaging in RCC is to differentiate benign from malignant lesions, to adequately assess tumor size, localization and organ confinement, to identify lymph node and/or visceral metastases, and to reliably predict the presence and extent of any thrombus of the vena cava. It is our aim to review the current status of preoperative imaging modalities in RCC. Computed tomography (CT) remains the most appropriate imaging modality to differentiate benign from malignant lesions. Although RCC can appear as iso-, hyper- or hypodense lesions on native CT scans, it usually demonstrates a significant contrast enhancement of about 115 HU and intratumoral areas of necrosis following the intravenous application of contrast medium. Benign masses such as renal oncocytoma are most often homogenous lesions exhibiting hypodensity compared to the normal renal parenchyma following the i.v. application of contrast dye. CT accurately predicts the tumor size with only a 0.5 cm difference as compared to the pathological size of the lesion. The identification of lymph node metastases still remains a problem since the limiting size is 4 mm and CT will result in a false negative rate of about 10%, especially in the presence of micrometastases; the false positive rate of 3-43% is mainly due to reactive hyperplasia. New technologies, such as the multidetector CT with thin collimation and multiplanar reformatting, might result in a diagnostic improvement. The involvement of the adrenal gland can be accurately predicted by CT scans or MRI, allowing an adrenal sparing approach in the case of unsuspicious findings. The detection of visceral metastases appears to be crucial since it has been shown that even patients with metastatic disease might benefit from radical nephrectomy followed by systemic immunotherapy in the case of a good performance status, and the presence of lymph node and pulmonary metastases only. Involvement of the renal vein and the vena cava with tumor thrombus formation will change the surgical strategy. Preoperatively, the presence and the cranial extent of the thrombus need to be known in order to plan the surgical approach. With regard to the extent of renal vein thrombi, a three phase helical CT scan is most appropriate; for vena caval thrombi only a MRI examination is able to accurately identify any infra- or suprahepatic as well as intracardial extension of the thrombus. The identification of multifocal lesions remains another unsolved problem in preoperative imaging techniques for RCC. Compared to the pathohistological analysis of nephrectomy specimens, neither ultrasonography, color duplex sonography nor regular CT scans are able to identify multifocal lesions with acceptable sensitivity and specificity. The evaluation of unenhanced CT scans together with the enhanced corticomedullary and the nephrogenic phase result in a 100% sensitivity and might represent a valuable option. Angiography has basically been abandoned from the armory of routine imaging techniques. It has, however, a current role in terms of the embolization of large tumors to reduce intraoperative blood loss, and in the palliative management of pain and bleeding due to RCC not amenable to surgery. Finally, we present a diagnostic algorithm for the most informative imaging techniques in the evaluation of RCC.

Fas expression in pancreatic adenocarcinoma is related to prognosis

9695 Background: Based on the histopathological assessment of pancreatic cancer resection specimens, prognostically relevant factors are known. However, the knowledge of additional factors associated with the prognosis might be helpful in planning the therapy for an individual patient. Methods: We investigated paraffin-embedded specimens of 25 patients undergoing surgical treatment for adenocarcinoma by immunohistochemistry to assess the expression and the prognostic impact of p53, Ki-67, Bcl-2, Fas and MMP-9. The number of positive neoplastic cells and the intensity of staining were scored semiquantitatively. The presence of micrometastases in locoregional lymph nodes was studied by staining for low molecular weight-cytokeratins. Neither survival time nor disease-free survival time were known at the time of the investigation. Results: No correlation was established between immunohistochemically detected micrometastases and prognosis.The expression of p53, Ki-67, Bcl-2 and MMP-9 did not influence the survival or disease-free survival. Expression of Fas, however, was associated with longer disease-free survival (P=0.014). Conclusions: Fas exerts an influence on prognosis in adenocarcinoma of the pancreas. However, further investigations in larger patient samples are required to confirm these results. No significant financial relationships to disclose.

Predictors of nonsentinel node metastasis in patients with breast cancer after sentinel node metastasis.

The presence of nonsentinel lymph node (NSLN) metastasis after having a positive sentinel lymph node dissection finding is associated with tumor size and stage, the presence of lymphovascular invasion, micrometastasis, and extranodal extension. Retrospective case series. University hospital. Four hundred seven consecutive patients at a single institution who underwent sentinel lymph node dissection as part of breast conservation or mastectomy with biopsy-proved cancer. Completion axillary lymph node dissection and definitive therapy. Sentinel node metastasis, NSLN metastasis, tumor size and stage, lymphovacular invasion, micrometastasis, extronodal extension, histological tumor characteristics, and number of sentinel nodes removed. In a univariate analysis, size of the primary tumor and extranodal extension were associated with having positive NSLN findings. The presence of micrometastasis was associated with negative NSLN findings. When all factors were included in a logistic regression analysis, the significant predictor of NSLN metastasis was extranodal extension (P =.002). Lymphovascular invasion was not associated with positive NSLN findings (P =.11). The number of sentinel nodes removed also had no bearing on the status of the NSLNs (P =.37). Although primary tumor size and micrometastases correlate with the status of the NSLNs, extranodal extension is the most important independent predictor of NSLN metastasis. These findings may ultimately spare patients a full axillary lymph node dissection. However, pending results of larger clinical trials, full axillary lymph node dissection is still recommended for patients with sentinel lymph node metastases.

Detection of lymphatic micrometastases in patients with stages I and II colorectal cancer: impact on five-year survival.

Despite having removed the whole macroscopic disease (curative intent surgery), one of five patients with Stages I and II colorectal cancer will develop recurrence. Lymphatic micrometastases detected by immunohistochemistry could be one of explanation for recurrence and cancer-related death in patients without lymph node involvement at light microscopy. However, the biologic importance of micrometastases remains unclear. This study was designed to determine the impact of micrometastases in five-year survival in patients with Stages I and II colorectal cancer. This retrospective study included patients operated on between May 1989 and January 1999 for colorectal cancer without histopathologic lymph node involvement. Patients who received any adjuvant therapy were excluded. Immunohistochemical staining of the lymph nodes was performed with antipancytokeratin antibodies. Follow-up data were obtained from the clinical database and death certificates. Survival was estimated by the Kaplan-Meier method and compared by the log-rank test. Micrometastases were observed in 26 of 90 patients (28.9 percent). The mean follow-up time was 90.7 (range, 11-160) months. Seventeen cancer-related deaths occurred during follow-up (18.9 percent), 6 of them in patients with micrometastases (23.1 percent) and 11 in patients without micrometastases (17.2 percent; P = 0.559). Cancer-specific five-year survival was 87 percent in the whole group and 81 percent in patients positive for micrometastases vs. 90 percent in negative patients ( P = 0.489). The presence of micrometastases in patients with Stages I and II colorectal cancer seems not to have any impact on cancer-specific survival.

Occult micrometastases in axillary lymph nodes predict subsequent distant metastases in stage I breast cancer: a case-control study with 15-year follow-up.

The prognostic significance of occult axillary metastases was evaluated in patients with stage I breast cancer. Ninety-six patients with pT1 breast carcinoma who underwent axillary lymph node dissection had negative nodes in routine microscopic examination. Forty-eight patients developed distant metastases within 15 years after surgery (M group) and are compared to 48 age-matched patients who were disease-free for 15 years (NM group). We reexamined 1539 lymph nodes from these patients, using three levels and cytokeratin immunostain. Occult metastases were detected in 21 patients: 16 of 48 (34%) in the M group and 5 of 48 (11%) in the NM group (P =.007). All metastases measured 2.0 mm or less and were classified as micrometastases (>0.2 mm to 2.0 mm) in 11 cases and as individual tumor cells (individual cells or clusters measuring < or =0.2 mm) in 10 cases. Micrometastases were 10 times more frequent in the M group than in the NM group (10/48 vs. 1/48; P =.004). Although there was no difference in tumor size, histologic type, estrogen receptor status, or type of treatment between the two patient groups, tumors in the M group were of a higher grade, had higher mitotic index and showed lymphovascular invasion. In multiple logistic regression, only high mitotic index and presence of micrometastases showed an independent significant correlation with the subsequent occurrence of distant metastases. The presence of micrometastases (>0.2 to 2.0 mm) in axillary nodes is significantly associated with the development of distant metastases in patients with T1 breast cancer.