{"title":"Surgical strategies and minimal residual disease detection.","authors":"Jürgen Weitz, Christian Herfarth","doi":"10.1002/SSU.1051","DOIUrl":"https://doi.org/10.1002/SSU.1051","url":null,"abstract":"The ultimate goal in the treatment of cancer patients is the elimination of all tumor cells. A cure by surgery alone is possible only if the tumor is still confined locally. Detection of disseminated tumor cells may help to individually tailor the surgical procedure to each patient: extended or limited resections may be indicated depending on the individual state of tumor cell dissemination. In cases of systemic tumor cell dissemination, surgery alone cannot cure the patient. Thus, by detecting disseminated tumor cells, patients with a higher risk for relapse, who might benefit from multimodal therapeutic regimes, could be defined. A second aspect is the possibility of tumor cell shedding induced by manipulation during surgical procedures, which could be demonstrated for several tumor entities. Intraoperative tumor cell dissemination could be prevented by alternative operative strategies. In addition, perioperative antibody or cytotoxic therapy may prevent tumor cell implantation. Well-designed clinical studies are now of major importance to evaluate the clinical impact of individualized patient management and altered surgical procedures.","PeriodicalId":77390,"journal":{"name":"Seminars in surgical oncology","volume":"30 1","pages":"329-33"},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75074695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Minimal residual disease in non-small-cell lung cancer.","authors":"S. Hosch, P. Scheunemann, J. R. Izbicki","doi":"10.1002/SSU.1045","DOIUrl":"https://doi.org/10.1002/SSU.1045","url":null,"abstract":"Early metastatic relapse after complete resection (R0) of apparently localized primary tumors is frequent in patients with non-small-cell lung cancer (NSCLC). This observation indicates an occult tumor cell dissemination already present at the time of primary surgery but undetectable by current tumor staging methods. During the past 10 years ultrasensitive immunohisto-/-cytochemical and molecular assays have been developed that are able to detect single tumor cells and small tumor cell clusters present in lymph nodes classified as tumor-free by conventional histopathologic analysis, bone marrow, or peripheral blood. Here we present an overview of the incidence and prognostic impact of such early disseminated tumor cells in patients with NSCLC.","PeriodicalId":77390,"journal":{"name":"Seminars in surgical oncology","volume":"81 1","pages":"278-81"},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82857667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular detection and characterization of circulating tumor cells and micrometastases in prostatic, urothelial, and renal cell carcinomas.","authors":"R. Ghossein, S. Bhattacharya","doi":"10.1002/SSU.1048","DOIUrl":"https://doi.org/10.1002/SSU.1048","url":null,"abstract":"The detection and molecular characterization of circulating tumor cells (CTCs) and micrometastases in urinary tract and prostatic tumors may have important prognostic and therapeutic implications. In the last decade, numerous groups have attempted the detection of occult tumor cells in renal, prostatic, and urothelial carcinomas using the highly sensitive reverse-transcriptase polymerase chain reaction (RT-PCR). In prostatic carcinoma (PC), tissue-specific transcripts were detected with high specificity in the blood of patients with localized and advanced disease. PCR assays for PC detection were shown to be strong predictors of poorer outcome in some reports, while a lack of prognostic significance was found in other studies. There was a vast difference in the PCR positivity rates between various groups studying PC. This discrepancy could be due to variations in PCR methodology. In urothelial and renal cell carcinoma, the amount of research on the subject is still too limited. Currently, these assays for occult tumor cells are promising but are not yet ready to use in PC and urinary tract tumors. Because of the many limitations of PCR (e.g., false positives), many groups are developing new approaches for the detection of occult tumor cells. The most attractive technique involves immunomagnetic isolation of intact CTC and micrometastases prior to downstream analysis. The tumor-rich magnetic fraction can be subjected to RT-PCR, immunocytochemistry, and in situ hybridization. This will lead to better quantification and molecular characterization of these tumor cells.","PeriodicalId":77390,"journal":{"name":"Seminars in surgical oncology","volume":"2 1","pages":"304-11"},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89948840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Technical aspects of minimal residual disease detection in carcinoma patients.","authors":"J. Lacroix, M. K. Doeberitz","doi":"10.1002/SSU.1042","DOIUrl":"https://doi.org/10.1002/SSU.1042","url":null,"abstract":"The burden of occult malignant cells which remains after a course of treatment that has resulted in clinical remission is referred to as minimal residual disease (MRD). MRD is increasingly considered as a determinant of local or systemic recurrence in cancer patients. During the last 20 years, methods for the detection of rare cancer cells have evolved from mere cytomorphological investigations to a variety of immunological and molecular assays. Since surgical therapy remains the best treatment option for cancer patients with resectable tumors, the first question to address is whether the removal of the tumor was complete or some cancer cells remained from the tumor at the primary site. Several tumor-associated DNA alterations have been identified to solve this diagnostic problem. Assays detecting tumor-associated DNA alterations have been applied to resection margins and body fluids such as bronchoalveolar lavage, sputum, urine, pancreatic juice, colonic lavage, and stool. Due to the higher sensitivity of immunocytochemical and reverse-transcriptase polymerase chain reaction (RT-PCR)-based assays, the second question to be addressed is whether systemic hematogenous or lymphatic spread of cancer cells occurred. Disseminated cancer cells have been detected in bone marrow aspirates, peripheral blood, and lymph node biopsies, and cancer cell dissemination is regarded as a relevant and independent prognostic factor. Thus, sensitive techniques for the detection of MRD are likely to guide indications for surgical or adjuvant therapy protocols in clinical oncology. However, since many of the assays for the detection of MRD are complex, and results are influenced by a variety of technical aspects, the majority of diagnostic applications have not yet been sufficiently standardized. Consequently, quality control and reproducibility of minimal disease detection assays remain unsolved problems. Therefore, well controlled collaborative studies are urgently required to evaluate indications and diagnostic standards for these assays. This review summarizes technical aspects and their implications for the clinical application of presently available assays for MRD detection in carcinoma patients.","PeriodicalId":77390,"journal":{"name":"Seminars in surgical oncology","volume":"9 1 1","pages":"252-64"},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83852446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Minimal residual disease in thyroid carcinoma.","authors":"T. Weber, E. Klar","doi":"10.1002/SSU.1044","DOIUrl":"https://doi.org/10.1002/SSU.1044","url":null,"abstract":"The detection of disseminated tumor cells in differentiated (DTC) and medullary thyroid carcinomas (MTC) is one of the main topics in current thyroid cancer research. Immunocytochemistry and polymerase chain reaction (PCR) provide the tools for the identification of a small number of thyroid cancer cells in peripheral blood and cervical lymph nodes. Thyroid-specific markers, such as thyroglobulin (Tg) mRNA and thyroid peroxidase (TPO) mRNA, have been detected with RT-PCR in blood samples of tumor patients and healthy control subjects. To prevent false-positive results, quantitative PCR systems were established. Tumor-specific markers, such as telomerase activity and cytokeratin 20 (CK20), have been detected in various epithelial tumors. Amplification products of these markers were found in blood samples and in fine-needle aspiration (FNA) biopsies of patients with thyroid carcinomas. Using molecular detection of disseminated tumor cells in cervical lymph nodes with CK20 RT-PCR, a higher percentage of involved lymph nodes was detected compared to immunohistochemistry. The results of the presented studies may help researchers to develop more sensitive methods for early tumor cell dissemination, and refine risk groups that might benefit from more extensive surgical procedures or adjuvant therapy. However, the prognostic value of minimal residual disease (MRD) in thyroid carcinoma has to be confirmed in large or multicenter prospective studies.","PeriodicalId":77390,"journal":{"name":"Seminars in surgical oncology","volume":"34 1","pages":"272-7"},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75022182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Detection of occult metastasis in patients with breast cancer.","authors":"D. Hawes, A. Neville, R. Cote","doi":"10.1002/SSU.1049","DOIUrl":"https://doi.org/10.1002/SSU.1049","url":null,"abstract":"The most important factor affecting the outcome of patients with invasive cancer is whether the tumor has spread, either regionally (to regional lymph nodes) or systemically. However, a proportion of patients with no evidence of systemic dissemination will develop recurrent disease after primary \"curative\" therapy. Clearly, these patients had occult systemic spread of disease that was undetectable by routinely employed methods (careful pathological, clinical, biochemical, and radiological evaluation). In addition, the success of adjuvant therapy is assumed to stem from its ability to eradicate occult metastases before they become clinically evident. Therefore, methods for the detection of occult metastases in patients with the earliest stage of cancer, i.e., prior to detection of metastases by any other clinical or pathological analysis, have received a great deal of attention.","PeriodicalId":77390,"journal":{"name":"Seminars in surgical oncology","volume":"117 1","pages":"312-8"},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76541005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Minimal residual disease in gastrointestinal cancer.","authors":"P. Kienle, M. Koch","doi":"10.1002/SSU.1046","DOIUrl":"https://doi.org/10.1002/SSU.1046","url":null,"abstract":"Tumor progression after curative resection of gastrointestinal carcinomas is probably caused by pre- or intraoperative tumor cell dissemination. Disseminated tumor cells are generally detected by immunohistochemistry- or PCR-based molecular-biology methods. A consensus on which is the most adequate detection method has not yet been found, which makes the comparison of data difficult. The prognostic relevance of disseminated cells has been shown, at least in part, for esophageal, gastric, pancreatic, and colonic cancer. The data regarding hepatocellular cancer is conflicting. This article gives a critical review of tumor cell detection in gastrointestinal cancer.","PeriodicalId":77390,"journal":{"name":"Seminars in surgical oncology","volume":"28 1","pages":"282-93"},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89107513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Observation of the breast cancer patient with a tumor-positive sentinel node: implications of the ACOSOG Z0011 trial.","authors":"B. Grube, A. Giuliano","doi":"10.1002/SSU.1038","DOIUrl":"https://doi.org/10.1002/SSU.1038","url":null,"abstract":"Axillary lymph node status has been the most important prognostic factor for breast cancer throughout the past century. During the past decade, intraoperative lymphatic mapping with sentinel lymph node dissection (SLND) has been investigated as an alternative staging modality. This technique may be as accurate as ALND, and certainly is less invasive. Adjuvant treatment recommendations, which historically were made on the basis of lymph node status alone, now take into account primary tumor features, molecular markers, and patient characteristics. This evolution of current treatment patterns is driven in part by the diminishing size of tumors, the simultaneous decrease in the presence of axillary metastases, and a better understanding of tumor-specific risk factors. How do these trends affect the interpretation of a tumor-positive sentinel node (SN)? Can an axilla with a positive SN be observed? Should it be observed? This review examines the implications of a positive SN in the context of smaller tumor size, decreased nodal disease, and increased reliance on alternative prognostic factors for treatment decisions. The historical data comparing ALND to no ALND in clinically node-negative patients is reviewed and discussed in the context of observation for a positive SN. These are the issues underlying the ACOSOG Z0010 and Z0011 trials.","PeriodicalId":77390,"journal":{"name":"Seminars in surgical oncology","volume":"14 1","pages":"230-7"},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76064660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. J. Diest, H. Torrenga, Sybren L. Meijer, C. Meijer
{"title":"Pathologic analysis of sentinel lymph nodes.","authors":"P. J. Diest, H. Torrenga, Sybren L. Meijer, C. Meijer","doi":"10.1002/SSU.1039","DOIUrl":"https://doi.org/10.1002/SSU.1039","url":null,"abstract":"The sentinel lymph node (SLN) procedure enables selective targeting of the first draining lymph node, where the initial metastases will form. A negative SLN predicts the absence of tumor metastases in the other regional lymph nodes with a high degree of accuracy. This means that in case of a negative SLN, regional lymph node dissection is no longer necessary. Besides saving patients the significant morbidity associated with lymph node dissection, it will also save costs. Crucial for the success of the SLN procedure is the screening of the SLN for metastases by the pathologist. To this end, several techniques are available such as standard histo- and cytopathological techniques, immunohistochemistry, flow cytometry, and molecular biological techniques. In this paper, the value of these methods for detecting SLN metastases is discussed. Some of these techniques have also appeared to be quite useful for intraoperative evaluation of SLNs. The standard protocol for detection of SLN metastases consists of extensive histopathological investigation including stepped sections stained with hematoxylin and eosin (HE) and immunohistochemistry. Intraoperative frozen section analysis and imprint cytology of SLNs have been shown to be reasonably reliable for detecting breast cancer metastases in SLNs. Further studies are necessary to establish the role of multiparameter flow cytometry and sophisticated molecular biological techniques such as reverse transcription polymerase chain reaction (RT-PCR) in detecting SLN metastases.","PeriodicalId":77390,"journal":{"name":"Seminars in surgical oncology","volume":"159 1","pages":"238-45"},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84993177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nipple aspiration in diagnosis of breast cancer.","authors":"Z. Shao, M. Nguyen","doi":"10.1002/SSU.1031","DOIUrl":"https://doi.org/10.1002/SSU.1031","url":null,"abstract":"It has been shown that early detection of breast cancer saves lives. Mammography and physical examination are currently the most commonly utilized screening methods for breast cancer. Research is being carried out to optimize these screening methods, as well as to develop new techniques. This review summarizes the findings of the research focusing on the diagnostic techniques involving the breast ductal system to date. These tests include nipple fluid cytology, nipple fluid tumor markers, ductogram, and ductoscopy.","PeriodicalId":77390,"journal":{"name":"Seminars in surgical oncology","volume":"52 1","pages":"175-80"},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73678158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}