The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Colon Cancer Jon D

Total Page:16

File Type:pdf, Size:1020Kb

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Colon Cancer Jon D CLINICAL PRACTICE GUIDELINES The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Colon Cancer Jon D. Vogel, M.D. • Cagla Eskicioglu, M.D. • Martin R. Weiser, M.D. Daniel L. Feingold, M.D. • Scott R. Steele, M.D. Prepared by the Clinical Practice Guidelines Committee of The American Society of Colon and Rectal Surgeons he American Society of Colon and Rectal Surgeons STATEMENT OF THE PROBLEM is dedicated to ensuring high-quality patient care by advancing the science, prevention, and manage- In the United States, an estimated 96,000 and 38,000 new T cases of colon and rectal cancer will be diagnosed in 2017.1 ment of disorders and diseases of the colon, rectum, and anus. The Clinical Practice Guidelines Committee is com- Colorectal cancer is the third most common cancer and posed of society members who are chosen because they cause of cancer death in both men and women in the Unit- have demonstrated expertise in the specialty of colon and ed States. The treatment of patients with colon cancer is rectal surgery. This committee was created to lead inter- largely guided by stage at presentation, emphasizing the national efforts in defining quality care for conditions re- importance of a comprehensive strategy of diagnosis, eval- lated to the colon, rectum, and anus. This is accompanied uation, and treatment. Surgery encompasses the primary by developing Clinical Practice Guidelines based on the form of treatment for colon cancer, whereas chemother- best available evidence. These guidelines are inclusive and apy is used most commonly in the adjuvant setting. The 5-year overall survival for patients with localized, regional, not prescriptive. Their purpose is to provide information 2 on which decisions can be made, rather than to dictate a and metastatic colon cancer is 91%, 72%, and 13%. specific form of treatment. These guidelines are intended The scope of this guideline is to address the issues re- for the use of all practitioners, health care workers, and lated to the evaluation and treatment of patients who have patients who desire information about the management been diagnosed with colon cancer. Matters pertinent to colon cancer screening and surveillance after colon cancer of the conditions addressed by the topics covered in these 3 4 guidelines. It should be recognized that these guidelines treatment, as well as rectal cancer, are addressed in sepa- should not be deemed inclusive of all proper methods of rate documents. care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgment regard- METHODOLOGY ing the propriety of any specific procedure must be made by the physician in light of all the circumstances presented This guideline is based on the previous parameter pub- by the individual patient. lished in 2012.5 An organized search of MEDLINE, EM- BASE, and the Cochrane Database of Collected Reviews Supplemental digital content is available for this article. Direct URL ci- was performed for the period of January 1, 1997 to April tations appear in the printed text, and links to the digital files are pro- 21, 2017. The complete search strategy is included as an vided in the HTML and PDF versions of this article on the journal’s Web appendix (http://links.lww.com/DCR/A436). In brief, a site (www.dcrjournal.com). total of 16,925 unique journal titles were identified. Initial Financial Disclosures: None reported. review of the search results resulted in exclusion of 11,204 titles based on either irrelevance of the title or the jour- Correspondence: Scott R. Steele, M.D., Chairman, Department of nal. Secondary review resulted in exclusion of 5,480 titles Colorectal Surgery Cleveland Clinic, Professor of Surgery Case Western considered irrelevant or outdated. A tertiary review of the Reserve University School of Medicine, 9500 Euclid Ave/A30, Cleveland, remaining 241 titles included assessment of the abstract or OH 44195. E-mail: [email protected] full-length article. This led to exclusion of an additional 30 titles for which similar but higher-level evidence was avail- Dis Colon Rectum 2017; 60: 999–1017 DOI: 10.1097/DCR.0000000000000926 able. The remaining 211 titles were considered for grading © The ASCRS 2017 of the recommendations. A directed search of references DISEASES OF THE COLON & RECTUM VOLUME 60: 10 (2017) 999 Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited. 1000 VOGEL ET AL: TREATMENT OF COLON CANCER embedded in the candidate publications was performed. formal evaluation, when possible, and consideration of Emphasis was placed on prospective trials, meta-analyses, genetics testing, because the results may impact surgical systematic reviews, and practice guidelines. Peer-reviewed decision making. Physical examination should include as- observational studies and retrospective studies were in- sessment for an abdominal mass lesion, adenopathy, or cluded when higher-quality evidence was insufficient. The surgical scars, all of which may influence diagnostic and final source material used was evaluated for the method- treatment-related decisions. Selective rather than routine ological quality, the evidence base was examined, and a use of preoperative laboratory testing such as complete treatment guideline was formulated by the subcommittee blood count, liver function tests, and coagulation studies for this guideline. A final grade of recommendation was are recommended for the evaluation of new patients with assigned using the Grades of Recommendation, Assess- colon cancer.8,9 Carcinoembryonic antigen levels should ment, Development, and Evaluation (GRADE) system typically be assessed before elective surgery for colon can- (Table 1).6 When agreement was incomplete regarding the cer to establish a baseline value and during the surveillance evidence base or treatment guideline, consensus from the period to monitor for signs of recurrence. A multivariate committee chair, vice chair, and 2 assigned reviewers de- analysis of over 130,000 patients included in the National termined the outcome. Members of the American Society Cancer Database recently indicated that preoperative CEA of Colon and Rectal Surgeons (ASCRS) practice guidelines is an independent predictor of overall survival in patients committee worked in joint production of these guide- with stage I to III colon cancer.10 Although higher CEA lines from inception to final publication. Recommenda- levels are generally associated with advanced cancer stage, tions formulated by the subcommittee were reviewed by conflicting evidence on the independent predictive value the entire Clinical Practice Guidelines Committee. Final of this test should be acknowledged.11–14 recommendations were approved by the ASCRS Clinical Guidelines Committee and ASCRS Executive Committee. 2. When possible, patients with presumed or proven co- In general, each ASCRS Clinical Practice Guideline is up- lon cancer should undergo a full colonic evaluation dated every 5 years. with histologic assessment of the colonic lesion before treatment. Grade of Recommendation: Strong recom- mendation based on low-quality evidence, 1C. RECOMMENDATIONS When possible, the histologic diagnosis of colon cancer Evaluation and Risk Assessment should be confirmed before elective surgical resection be- cause nonneoplastic processes such as diverticulitis or IBD 1. An assessment of disease-specific symptoms, past may be associated with the endoscopic or radiographic ap- medical and family history, physical examination, and pearance of colon cancer. Lesions concerning for malig- serum CEA level should typically be evaluated in pa- nancy, but without histologic confirmation (eg, possible tients with colon cancer. Grade of Recommendation: sampling error), that are not amenable to endoscopic re- Strong recommendation based on low-quality evi- moval warrant oncologic resection. When feasible, com- dence, 1C. plete evaluation of the colorectal mucosa is typically Sporadic, familial, and hereditary types of colon cancer advised before surgery to detect synchronous cancers, account for approximately 65%, 30%, and <5% of new which were recently reported to be present in 4% of 2400 cancers in the United States.7 Although often asymptom- patients with stages I to III sporadic colon cancer.15 Com- atic, colon cancer may also be heralded by symptoms of plete examination of the colorectal mucosa is also impor- fatigue, blood in the stool, abdominal pain, or obstructive tant to identify synchronous adenomas that are present in symptoms. These symptoms often correlate with more ad- 30% to 50% of patients.16,17 vanced stages of colon cancer and may be used to compli- In patients with colon cancer who have an endo- ment the information that is subsequently gained during scopically obstructing lesion or another reason for which the process of staging the cancer and planning treatment. complete colonoscopy was not performed, complete pre- Comorbid conditions should be assessed to help deter- operative mucosal examination may be accomplished via mine operative risk and to identify opportunities for med- a second attempt at conventional colonoscopy, CT colo- ical optimization before colon surgery. A careful history, nography, or colon capsule endoscopy. When performed including family history and colon cancer-specific history by expert endoscopists, 2 recent studies reported that re- can guide the surgeon to suspect hereditary cancer syn- peat colonoscopy resulted in
Recommended publications
  • The Evolution of Antibodies Into Versatile Tumor-Targeting Agents
    Vol. 11, 129–138, January 1, 2005 Clinical Cancer Research 129 The Evolution of Antibodies into Versatile Tumor-Targeting Agents Michael Z. Lin,1 Michael A. Teitell,2 cancer is an old idea, often credited to Paul Ehrlich and William 1 Coley over 100 years ago, a time that predates our understanding and Gary J. Schiller of the cellular and molecular components of the immune system. 1 2 Departments of Medicine and Pathology and Laboratory Medicine, It was the elucidation of mechanisms of immunity and the David Geffen School of Medicine at University of California at introduction of a theory of cancer immunosurveillance by Lewis Los Angeles, Los Angeles, California Thomas and MacFarlane Burnet in the 1960s, however, that gave rise to the modern concept of using the adaptive immune system ABSTRACT to recognize and eliminate tumor cells whereas sparing normal In recent years, monoclonal antibodies have become tissue. After decades of waxing and waning interest, the idea of important weapons in the arsenal of anticancer drugs, and in immunotherapy has recently achieved widespread acceptance select cases are now the drugs of choice due to their favor- (1), in large part owing to the successful introduction within the able toxicity profiles. Originally developed to confer passive last decade of antibody-based cancer therapies into the clinic. immunity against tumor-specific antigens, clinical uses of Having accumulated several years of experience with anticancer monoclonal antibodies are expanding to include growth fac- antibodies, researchers are now in a position evaluate these first tor sequestration, signal transduction modulation, and tumor- examples of immunotherapeutic drugs, looking back to relate specific drug delivery.
    [Show full text]
  • Does Liver Cirrhosis Affect the Surgical Outcome of Primary Colorectal
    Cheng et al. World Journal of Surgical Oncology (2021) 19:167 https://doi.org/10.1186/s12957-021-02267-6 RESEARCH Open Access Does liver cirrhosis affect the surgical outcome of primary colorectal cancer surgery? A meta-analysis Yu-Xi Cheng†, Wei Tao†, Hua Zhang, Dong Peng* and Zheng-Qiang Wei Abstract Purpose: The purpose of this meta-analysis was to evaluate the effect of liver cirrhosis (LC) on the short-term and long-term surgical outcomes of colorectal cancer (CRC). Methods: The PubMed, Embase, and Cochrane Library databases were searched from inception to March 23, 2021. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of enrolled studies, and RevMan 5.3 was used for data analysis in this meta-analysis. The registration ID of this current meta-analysis on PROSPERO is CRD42021238042. Results: In total, five studies with 2485 patients were included in this meta-analysis. For the baseline information, no significant differences in age, sex, tumor location, or tumor T staging were noted. Regarding short-term outcomes, the cirrhotic group had more major complications (OR=5.15, 95% CI=1.62 to 16.37, p=0.005), a higher re- operation rate (OR=2.04, 95% CI=1.07 to 3.88, p=0.03), and a higher short-term mortality rate (OR=2.85, 95% CI=1.93 to 4.20, p<0.00001) than the non-cirrhotic group. However, no significant differences in minor complications (OR= 1.54, 95% CI=0.78 to 3.02, p=0.21) or the rate of intensive care unit (ICU) admission (OR=0.76, 95% CI=0.10 to 5.99, p=0.80) were noted between the two groups.
    [Show full text]
  • The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Inherited Polyposis Syndromes Daniel Herzig, M.D
    CLINICAL PRACTICE GUIDELINES The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Inherited Polyposis Syndromes Daniel Herzig, M.D. • Karin Hardimann, M.D. • Martin Weiser, M.D. • Nancy Yu, M.D. Ian Paquette, M.D. • Daniel L. Feingold, M.D. • Scott R. Steele, M.D. Prepared by the Clinical Practice Guidelines Committee of The American Society of Colon and Rectal Surgeons he American Society of Colon and Rectal Surgeons METHODOLOGY (ASCRS) is dedicated to ensuring high-quality pa- tient care by advancing the science, prevention, and These guidelines are built on the last set of the ASCRS T Practice Parameters for the Identification and Testing of management of disorders and diseases of the colon, rectum, Patients at Risk for Dominantly Inherited Colorectal Can- and anus. The Clinical Practice Guidelines Committee is 1 composed of society members who are chosen because they cer published in 2003. An organized search of MEDLINE have demonstrated expertise in the specialty of colon and (1946 to December week 1, 2016) was performed from rectal surgery. This committee was created to lead interna- 1946 through week 4 of September 2016 (Fig. 1). Subject tional efforts in defining quality care for conditions related headings for “adenomatous polyposis coli” (4203 results) to the colon, rectum, and anus, in addition to the devel- and “intestinal polyposis” (445 results) were included, us- opment of Clinical Practice Guidelines based on the best ing focused search. The results were combined (4629 re- available evidence. These guidelines are inclusive and not sults) and limited to English language (3981 results), then prescriptive.
    [Show full text]
  • Risk of Colorectal Cancer and Other Cancers in Patients with Gall Stones
    Gut 1996; 39:439-443 439 Risk of colorectal cancer and other cancers in patients with gall stones Gut: first published as 10.1136/gut.39.3.439 on 1 September 1996. Downloaded from C Johansen, Wong-Ho Chow, T J0rgensen, L Mellemkjaer, G Engholm, J H Olsen Abstract Although the relation between cholecystec- Background-The occurrence of gall tomy and colorectal cancer has been con- stones has repeatedly been associated with sidered in many studies, the results are equi- an increased risk for cancer of the colon, vocal"; most of the case-control studies but risk associated with cholecystectomy showed a positive relation, but only the two remains unclear. largest cohort studies showed significantly Aims-To evaluate the hypothesis in a increased risks, which were restricted to nationwide cohort ofmore than 40 000 gall women and to the proximal part of the stone patients with complete follow up colon.'4 15 including information of cholecystectomy These results suggest that gall stones, and and obesity. possibly cholecystectomy, which are done Patients-In the population based study mainly as a result ofgall stones increase the risk described here, 42098 patients with gall for colon cancer, particularly among women stones in 1977-1989 were identified in the and in the proximal part of the colon. One Danish Hospital Discharge Register. hypothesis is that post-cholecystectomy Methods-These patients were linked to changes in the composition and secretion of the Danish Cancer Registry to assess their bile salts affect enterohepatic circulation and risks for colorectal and other cancers exposure of the colon to bile acids,'6 '` which during follow up to the end of 1992.
    [Show full text]
  • Review of Intra-Arterial Therapies for Colorectal Cancer Liver Metastasis
    cancers Review Review of Intra-Arterial Therapies for Colorectal Cancer Liver Metastasis Justin Kwan * and Uei Pua Department of Vascular and Interventional Radiology, Tan Tock Seng Hospital, Singapore 388403, Singapore; [email protected] * Correspondence: [email protected] Simple Summary: Colorectal cancer liver metastasis occurs in more than 50% of patients with colorectal cancer and is thought to be the most common cause of death from this cancer. The mainstay of treatment for inoperable liver metastasis has been combination systemic chemotherapy with or without the addition of biological targeted therapy with a goal for disease downstaging, for potential curative resection, or more frequently, for disease control. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies including hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are alternative treatment strategies that have shown promising results, most commonly in the salvage setting in patients with chemo-refractory disease. In recent years, their role in the first-line setting in conjunction with concurrent systemic chemotherapy has also been explored. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future. Abstract: The liver is frequently the most common site of metastasis in patients with colorectal cancer, occurring in more than 50% of patients. While surgical resection remains the only potential Citation: Kwan, J.; Pua, U. Review of curative option, it is only eligible in 15–20% of patients at presentation. In the past two decades, Intra-Arterial Therapies for Colorectal major advances in modern chemotherapy and personalized biological agents have improved overall Cancer Liver Metastasis.
    [Show full text]
  • Hepatoblastoma and APC Gene Mutation in Familial Adenomatous Polyposis Gut: First Published As 10.1136/Gut.39.6.867 on 1 December 1996
    Gut 1996; 39: 867-869 867 Hepatoblastoma and APC gene mutation in familial adenomatous polyposis Gut: first published as 10.1136/gut.39.6.867 on 1 December 1996. Downloaded from F M Giardiello, G M Petersen, J D Brensinger, M C Luce, M C Cayouette, J Bacon, S V Booker, S R Hamilton Abstract tumours; and extracolonic cancers of the Background-Hepatoblastoma is a rare, thyroid, duodenum, pancreas, liver, and rapidly progressive, usually fatal child- brain.1-4 hood malignancy, which if confined to the Hepatoblastoma is a rare malignant liver can be cured by radical surgical embryonal tumour of the liver, which occurs in resection. An association between hepato- infancy and childhood. An association between blastoma and familial adenomatous hepatoblastoma and familial adenomatous polyposis (FAP), which is due to germline polyposis was first described by Kingston et al mutation of the APC (adenomatous in 1982,6 and since then over 30 additional polyposis coli) gene, has been confirmed, cases have been reported.7-15 Moreover, a but correlation with site of APC mutation pronounced increased relative risk of hepato- has not been studied. blastoma in patients affected with FAP and Aim-To analyse the APC mutational their first degree relatives has been found spectrum in FAP families with hepato- (relative risk 847, 95% confidence limits 230 blastoma as a possible basis to select and 2168).16 kindreds for surveillance. FAP is caused by germline mutations of the Patients-Eight patients with hepato- APC (adenomatous polyposis coli) gene blastoma in seven FAP kindreds were located on the long arm of chromosome 5 in compared with 97 families with identified band q2 1.17-'20The APC gene has 15 exons and APC gene mutation in a large Registry.
    [Show full text]
  • Familial Adenomatous Polyposis Polymnia Galiatsatos, M.D., F.R.C.P.(C),1 and William D
    American Journal of Gastroenterology ISSN 0002-9270 C 2006 by Am. Coll. of Gastroenterology doi: 10.1111/j.1572-0241.2006.00375.x Published by Blackwell Publishing CME Familial Adenomatous Polyposis Polymnia Galiatsatos, M.D., F.R.C.P.(C),1 and William D. Foulkes, M.B., Ph.D.2 1Division of Gastroenterology, Department of Medicine, The Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, Quebec, Canada, and 2Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada Familial adenomatous polyposis (FAP) is an autosomal-dominant colorectal cancer syndrome, caused by a germline mutation in the adenomatous polyposis coli (APC) gene, on chromosome 5q21. It is characterized by hundreds of adenomatous colorectal polyps, with an almost inevitable progression to colorectal cancer at an average age of 35 to 40 yr. Associated features include upper gastrointestinal tract polyps, congenital hypertrophy of the retinal pigment epithelium, desmoid tumors, and other extracolonic malignancies. Gardner syndrome is more of a historical subdivision of FAP, characterized by osteomas, dental anomalies, epidermal cysts, and soft tissue tumors. Other specified variants include Turcot syndrome (associated with central nervous system malignancies) and hereditary desmoid disease. Several genotype–phenotype correlations have been observed. Attenuated FAP is a phenotypically distinct entity, presenting with fewer than 100 adenomas. Multiple colorectal adenomas can also be caused by mutations in the human MutY homologue (MYH) gene, in an autosomal recessive condition referred to as MYH associated polyposis (MAP). Endoscopic screening of FAP probands and relatives is advocated as early as the ages of 10–12 yr, with the objective of reducing the occurrence of colorectal cancer.
    [Show full text]
  • Cancer Treatment and Survivorship Facts & Figures 2019-2021
    Cancer Treatment & Survivorship Facts & Figures 2019-2021 Estimated Numbers of Cancer Survivors by State as of January 1, 2019 WA 386,540 NH MT VT 84,080 ME ND 95,540 59,970 38,430 34,360 OR MN 213,620 300,980 MA ID 434,230 77,860 SD WI NY 42,810 313,370 1,105,550 WY MI 33,310 RI 570,760 67,900 IA PA NE CT 243,410 NV 185,720 771,120 108,500 OH 132,950 NJ 543,190 UT IL IN 581,350 115,840 651,810 296,940 DE 55,460 CA CO WV 225,470 1,888,480 KS 117,070 VA MO MD 275,420 151,950 408,060 300,200 KY 254,780 DC 18,750 NC TN 470,120 AZ OK 326,530 NM 207,260 AR 392,530 111,620 SC 143,320 280,890 GA AL MS 446,900 135,260 244,320 TX 1,140,170 LA 232,100 AK 36,550 FL 1,482,090 US 16,920,370 HI 84,960 States estimates do not sum to US total due to rounding. Source: Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute. Contents Introduction 1 Long-term Survivorship 24 Who Are Cancer Survivors? 1 Quality of Life 24 How Many People Have a History of Cancer? 2 Financial Hardship among Cancer Survivors 26 Cancer Treatment and Common Side Effects 4 Regaining and Improving Health through Healthy Behaviors 26 Cancer Survival and Access to Care 5 Concerns of Caregivers and Families 28 Selected Cancers 6 The Future of Cancer Survivorship in Breast (Female) 6 the United States 28 Cancers in Children and Adolescents 9 The American Cancer Society 30 Colon and Rectum 10 How the American Cancer Society Saves Lives 30 Leukemia and Lymphoma 12 Research 34 Lung and Bronchus 15 Advocacy 34 Melanoma of the Skin 16 Prostate 16 Sources of Statistics 36 Testis 17 References 37 Thyroid 19 Acknowledgments 45 Urinary Bladder 19 Uterine Corpus 21 Navigating the Cancer Experience: Treatment and Supportive Care 22 Making Decisions about Cancer Care 22 Cancer Rehabilitation 22 Psychosocial Care 23 Palliative Care 23 Transitioning to Long-term Survivorship 23 This publication attempts to summarize current scientific information about Global Headquarters: American Cancer Society Inc.
    [Show full text]
  • Sporadic (Nonhereditary) Colorectal Cancer: Introduction
    Sporadic (Nonhereditary) Colorectal Cancer: Introduction Colorectal cancer affects about 5% of the population, with up to 150,000 new cases per year in the United States alone. Cancer of the large intestine accounts for 21% of all cancers in the US, ranking second only to lung cancer in mortality in both males and females. It is, however, one of the most potentially curable of gastrointestinal cancers. Colorectal cancer is detected through screening procedures or when the patient presents with symptoms. Screening is vital to prevention and should be a part of routine care for adults over the age of 50 who are at average risk. High-risk individuals (those with previous colon cancer , family history of colon cancer , inflammatory bowel disease, or history of colorectal polyps) require careful follow-up. There is great variability in the worldwide incidence and mortality rates. Industrialized nations appear to have the greatest risk while most developing nations have lower rates. Unfortunately, this incidence is on the increase. North America, Western Europe, Australia and New Zealand have high rates for colorectal neoplasms (Figure 2). Figure 1. Location of the colon in the body. Figure 2. Geographic distribution of sporadic colon cancer . Symptoms Colorectal cancer does not usually produce symptoms early in the disease process. Symptoms are dependent upon the site of the primary tumor. Cancers of the proximal colon tend to grow larger than those of the left colon and rectum before they produce symptoms. Abnormal vasculature and trauma from the fecal stream may result in bleeding as the tumor expands in the intestinal lumen.
    [Show full text]
  • Soluble Epcam Levels in Ascites Correlate with Positive Cytology And
    Seeber et al. BMC Cancer (2015) 15:372 DOI 10.1186/s12885-015-1371-1 RESEARCH ARTICLE Open Access Soluble EpCAM levels in ascites correlate with positive cytology and neutralize catumaxomab activity in vitro Andreas Seeber1,2,3†, Agnieszka Martowicz1,4†, Gilbert Spizzo1,2,5, Thomas Buratti6, Peter Obrist7, Dominic Fong1,5, Guenther Gastl3 and Gerold Untergasser1,2,3* Abstract Background: EpCAM is highly expressed on membrane of epithelial tumor cells and has been detected as soluble/ secreted (sEpCAM) in serum of cancer patients. In this study we established an ELISA for in vitro diagnostics to measure sEpCAM concentrations in ascites. Moreover, we evaluated the influence of sEpCAM levels on catumaxomab (antibody) - dependent cellular cytotoxicity (ADCC). Methods: Ascites specimens from cancer patients with positive (C+, n = 49) and negative (C-, n = 22) cytology and ascites of patients with liver cirrhosis (LC, n = 31) were collected. All cell-free plasma samples were analyzed for sEpCAM levels with a sandwich ELISA system established and validated by a human recombinant EpCAM standard for measurements in ascites as biological matrix. In addition, we evaluated effects of different sEpCAM concentrations on catumaxomab-dependent cell-mediated cytotoxicity (ADCC) with human peripheral blood mononuclear cells (PBMNCs) and human tumor cells. Results: Our ELISA showed a high specificity for secreted EpCAM as determined by control HEK293FT cell lines stably expressing intracellular (EpICD), extracellular (EpEX) and the full-length protein (EpCAM) as fusion proteins. The lower limit of quantification was 200 pg/mL and the linear quantification range up to 5,000 pg/mL in ascites as biological matrix.
    [Show full text]
  • Monoclonal Antibody Therapy with Edrecolomab in Breast Cancer Patients: Monitoring of Elimination of Disseminated Cytokeratin- Positive Tumor Cells in Bone Marrow1
    Vol. 5, 3999–4004, December 1999 Clinical Cancer Research 3999 Monoclonal Antibody Therapy with Edrecolomab in Breast Cancer Patients: Monitoring of Elimination of Disseminated Cytokeratin- positive Tumor Cells in Bone Marrow1 Stephan Braun,2 Florian Hepp, mor cells in bone marrow and typed EpCAM expression. Christina R. M. Kentenich, Wolfgang Janni, This allowed us to monitor the cytotoxic elimination of such cells after Edrecolomab application. Selection of EpCAM2/ Klaus Pantel, Gert Riethmu¨ller, Fritz Willgeroth, 1 CK tumor clones showed that further antibodies directed and Harald L. Sommer against tumor-associated antigens are warranted to improve I. Frauenklinik, Klinikum Innenstadt [S. B., F. H., C. R. M. K., W. J., the efficacy of monospecific approaches. F. W., H. L. S.], and Institute of Immunology [G. R.], Ludwig- Maximilians-Universita¨t, D-80337 Munich, and Frauenklinik, Universita¨tsklinikum Eppendorf, D-20251 Hamburg [K. P.], Germany INTRODUCTION A reliable indication of the efficacy of adjuvant therapy requires trials with large numbers of patients observed for ABSTRACT several years (1), especially in breast cancer, because residual Despite current advances in antibody-based immuno- tumor cells may exert their influence on survival at 10 years or therapy of breast and colorectal cancer, we have recently later (2). Because adjuvant treatment usually is delivered to shown that the actual target cells (e.g., tumor cells dissem- patients with clinically occult micrometastatic disease after the inated to bone marrow) may express a heterogeneous pat- successful resection of the primary tumor, the efficacy of ther- tern of the potential target antigens. Tumor antigen heter- apy can be only assessed retrospectively from the rate of disease- ogeneity may therefore represent an important limitation of free survival.
    [Show full text]
  • VARYING DEGREES of MALIGNANCY in CANCER of the BREAST Differences in the Degree of Malignancy of Malignant Tumors Have Been Reco
    VARYING DEGREES OF MALIGNANCY IN CANCER OF THE BREAST ROBERT 13. GREENOUGH BOSTON Differences in the degree of malignancy of malignant tumors have been recognized by pathologists for many years. Indeed, Virchow’s original conception of a malignant tumor was one composed of cells, derived from the tissue cells of the individual, but differing from the normal cells in the rapidity and independ- ence of their growth. Hansemann (1) carried this idea somewhat further and intro- duced the word “anaplasia” to indicate the process by which cancer cells came to differ from the normal type cell of the body tissue concerned. Anaplasia involves a loss of differentiation and an increase of reproductive power, so that the anaplastic cell fulfils only in abortive fashion, if at all, its normal function, such as secretion or keratinization; while it shows by increased number of mitotic figures, and especially by the irregularity and abnormality of its nuclear chromatic elements and figures, the increase in rapidity of cell division and of cell growth which is characteristic of malignancy. X number of attempts have been made to grade the malig- nancy of different breast tumors by distinguishing their histo- logical characteristics, such as adenocarcinoma, medullary, scirrhus, colloid, etc. ; but with the exception of adenocarcinoma and colloid, these divisions have proved of little value in prognosis. There the matter rested till 1921, when, under the influence of MacCarty (2) of the Mayo Clinic, Broders published a paper suggesting the classification of cancer tissue according to the degree of malignancy, as estimated by loss of differentiation and increase of reproductive characteristics.
    [Show full text]