ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Ralf Sodian
Roland Hetzer
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Potapov, E. V.
Right arrow Articles by Hetzer, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Potapov, E. V.
Right arrow Articles by Hetzer, R.
Related Collections
Right arrow Extracorporeal circulation

Ann Thorac Surg 2002;74:384-389
© 2002 The Society of Thoracic Surgeons

Original article: cardiovascular

Impact of cardiac surgery using cardiopulmonary bypass on course of chronic lymphatic leukemia: a case-control study

Evgenij V. Potapov, MD*a, Heinz R. Zurbrügg, MD, PhDa, Corinna Herzke, MDa, Stefanie Srock, MDb, Hanno Riess, MD, PhDb, Ralf Sodian, MDa, Sabine Hübler, MDa, Roland Hetzer, MD, PhDa

a Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Germany
b Department of Hematology and Oncology, Humboldt University of Berlin, Charité, Campus Virchow Klinikum, Berlin, Germany

Accepted for publication April 10, 2002.

* Address reprint requests to Dr Potapov, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
e-mail: potapov{at}dhzb.de


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Background. Chronic lymphatic leukemia (CLL) is a common disease among elderly individuals. The number of older patients undergoing operations with cardiopulmonary bypass (CPB) is increasing. The aim of the present study was to evaluate the impact of cardiac surgery using CPB on the long-term course of CLL.

Methods. From 1992 to 2000, a total of 28 patients with CLL underwent heart surgery using CPB at our institution (group I). These patients were compared with 25 patients from the CLL register who were retrospectively matched with regard to preoperative administration of chemotherapy, Binet classification, age, and sex (group II). A time-point was selected for each patient in group II so that the variables for the two groups corresponded in relation to the time of operation of the patients in group I. Midterm follow-up data in both groups were analyzed.

Results. There were no differences between groups regarding matched variables. The mean follow-up time was similar in both groups (2.6 ± 2.2 vs 2.3 ± 1.3 years, p > 0.5). The 30-day mortality in group I was 14.3%. The mean stay in the intensive care unit was 4.2 ± 7.5 days; the median number of units of packed red blood cells transfused was three (range 0 to 17). Compared with group II, in group I significantly fewer patients (11 vs 17, p = 0.049) required chemotherapy significantly later (1.98 ± 2.06 vs 0.84 ± 1.18 years, p = 0.018). During follow-up, no difference was found between groups regarding severe infections (10 vs 14, p = 0.14). Despite postoperative mortality in group I, the long-term mortality was similar in both groups (p = 0.3).

Conclusions. Cardiac surgery using CPB did not have a negative impact on the natural course of CLL. Moreover, this procedure seems to be associated with a decrease in the number of postoperative chemotherapy administrations and with an increase of chemotherapy-free survival time. Although CLL may be a risk factor in the early postoperative period, it is not a contraindication for cardiac surgery using CPB.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Chronic lymphatic leukemia (CLL) is a disease of the elderly, with 70% of patients being more than 60 years of age [1]. The incidence of CLL found in a study in the United States was between 0.6 per 100,000 among Asian individuals and 5.4 per 100,000 among white non-Hispanic individuals, with a tendency that increased with age [2]. The disease is characterized by a malignant proliferation of monoclonal immunologically incompetent lymphocytes with subsequent lymphocytic accumulation in the bone marrow, liver, spleen, and lymph nodes. Chronic lymphatic leukemia causes immune defects with progressive decrease of polyclonal immunoglobulins and a decrease in the number of polynuclear granulocytes, with subsequent death mostly due to infection. Chronic lymphatic leukemia has a variable clinical course: some patients die within 1 year after diagnosis, but a substantial number live longer than 10 years. New therapies have increased the chemotherapy-free survival in patients with CLL [3, 4]. Despite recent advances, CLL still has no established cure. The natural course of CLL has changed in the last 30 years. Currently, CLL patients are much older than in previous years, and a large proportion of them are in the low-risk Binet A clinical stage [3], with estimated survival of 10 to 12.5 years. The estimated survival of patients in clinical stage B (intermediate risk) and C (high risk) is 7 to 8 years and 2.5 to 3.5 years, respectively [4].

Cardiopulmonary bypass (CPB) and surgical trauma have long been known to cause altered activation of the inflammatory response, in part related to blood exposure to the large artificial surfaces [5, 6]. This includes complement activation and consumption along with elevation in levels of interleukin, tumor necrosis factor-{alpha}, and procalcitonin [7]. This results in changes in counts and properties of granulocytes and lymphocytes, as well as their subsets [8]. Furthermore, CPB decreases serum gamma globulin levels and also platelets and red blood cell counts. All of these changes lead to significant immunodepression. Despite significant progress in technique [5, 6], CPB remains a significant factor contributing to morbidity after cardiac surgery.

The aging of the population and the increase in life expectancy in developed countries [9], as well as progress in CLL treatment [3, 10, 11], have led to an increased number of older patients with CLL-related immune deficiency who may require operations using CPB. On the other hand, the improvements in CPB technique [12, 13] and the experience gained with older patients have led to increased acceptance of these patients for cardiac surgery [14]. Some authors have reported good postoperative outcome in CLL patients [15–17]. However, the postoperative course of CLL in these patients is unknown.

The aim of the present study was to evaluate the impact of cardiac surgery using CPB on the mid-term course of CLL.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 Acknowledgments
 References
 
From January 1992 to March 2000, a total of 28 patients with CLL diagnosed preoperatively (group I) underwent cardiac operations using CPB in our institution. Of these, 21 patients underwent isolated coronary artery bypass grafting (in 3 cases a redo operation), 4 patients valve replacement, 1 patient mitral valve replacement, 1 patient closure of a coronary fistula, and 1 patient a heart transplantation. All patients received routine antibiotic prophylaxis perioperatively (Cefazolin 2 g, five times intravenously). For staging the Binet classification was used, which recognizes three stages: low-risk stage (stage A), intermediate-risk stage (stage B), and high-risk stage (stage C) [18].

As a control group (group II), 25 patients from the CLL Register of Humboldt University, Virchow Klinikum, were retrospectively matched to patients from group I. The matching critera (in order of priority) are as follows: administration of chemotherapy preoperatively (group I) and before the matching time-point (group II), Binet classification, age, and sex, based on information from the database and medical records. The modus of chemotherapy (short- or long-term) and type (single drug or multiple drug administration) were taken into consideration. The order of priority was chosen because the need for chemotherapy and the Binet classification are the two variables that correlate with quality of life and prognosis for CLL patients, respectively. The time-point for the beginning of follow-up investigation for each patient in group II was selected so that the variables for paired patients corresponded, taking the time of operation of the patient in group I as the beginning of the follow-up time.

The medical records of patients in both groups were retrospectively analyzed. Follow-up was completed by means of a questionnaire or by telephone contact with general practitioners, hematologists, and, if necessary, the patients themselves.

The indications for chemotherapy were similar in both groups and remained constant throughout the study period; these included symptoms of bone marrow failure, progressive lymphadenopathy or hepatosplenomegaly, progressive lymphocytosis, and development of constitutional symptoms [1, 10, 11].

Infections were classified and defined according to severity. They were included in the analysis if the patient required hospital admission and antibiotic therapy or died due to infection.

To assess the impact of cardiac surgery using CPB on blood cells, the hemoglobin level and platelets and white blood cell (WBC) counts were recorded both preoperatively and on the third postoperative day.

The number of units of packed red blood cells, units of fresh frozen plasma, and platelet concentrates transfused during the hospital stay of patients in group I was recorded. For comparison, the use of blood products during hospital stay in consecutive patients who were more 18 years of age and were undergoing operation with CPB in our institution during the arbitrarily selected period from January 1 through December 31, 1999 (n = 3,078) was calculated using the hospital database. A hemoglobin level of 8 to 9 g/dL, depending on the hemodynamic and clinical situation, was the transfusion trigger point both in these patients and in the CLL patients.

Statistical analysis
Statistical analysis of the data was performed with SPSS software, version 9.0.0 for Windows (SPSS Inc, Chicago, IL). Normally distributed data are presented as means and standard deviations, whereas the non-normally distributed date are given as median, 25th percentile, and 75th percentile. The unpaired t test or Wilcoxon test was used to test for group differences in the case of quantitative data, as appropriate. For qualitative data, frequencies were calculated and the {chi}2 test was used to test for group differences. Freedom from chemotherapy initiated after surgery (group I) or after the matching time-point (group II) and cumulative survival were examined by Kaplan-Meier analysis and compared using a log-rank test. A reference value of p of less than 0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 Acknowledgments
 References
 
There were no significant differences between groups regarding matched criteria (Table 1). The groups were well balanced: 1 patient in group I and 2 patients in group II had anemia (hemoglobin <10 g/dL). In each group, 1 patient presented with thrombocytopenia (<100,000/µg) before the matching time-point and 50% of patients had a WBC count of more than 20,000/µL. There were no significant differences between the groups before the matching time-point for the number of patients receiving chemotherapy, the mode and type of chemotherapy, Binet classification, age, sex, or follow-up time (Table 1). There were also no significant differences between group I and II for median hemoglobin level (12.8 g/dL [25th and 75th percentiles 11.3 and 14 g/dL] vs 14.0 g/dL [25th and 75th percentiles 11.5 and 14.7 g/dL]), median platelet count (177,000 µL-1 [25th and 75th percentiles 142,000 and 276,000 µL-1] vs 166,300 µL-1 [25th and 75th percentiles 131,400 and 205,600 µL-1]), or median WBC count (22,000 µL-1 [25th and 75th percentiles 12,400 and 37,300 µL-1] vs 24,600 µL-1 [25th and 75th percentiles 16,100 and 53,400 µL-1]). The follow-up investigation was completed in 27 patients in group I and in all patients in group II. Follow-up time was similar in both groups (Table 1).


View this table:
[in this window]
[in a new window]
  		Table 1. Patient Data Before Matching Time Point and Follow-up Data in the Study Groups

 
The mean preoperative left ventricular ejection fraction in group I was 51% ± 15%. In 4 patients an emergency operation was performed. Thirty-day mortality occurred in 4 of 28 patients (14.3%). Of 21 patients who received isolated coronary artery bypass grafting, 2 patients died early after surgery from sepsis (caused in 1 by Pseudomonas aeruginosa, Proteus mirabilis, and Enteroccoci; in the other patient, the microorganisms could not be identified). These 2 patients underwent emergency surgery. The third patient died from low cardiac output syndrome caused by preoperative myocardial infarction, and had also required emergency surgery. The transplant patient died from acute graft failure. Of 4 patients in Binet classification stage C, 1 died early postoperatively of sepsis. The mean ICU stay for all patients was 4.2 ± 7.5 days.

The blood cell counts and values for hemoglobin in group I measured preoperatively and early postoperatively (ie, on the third postoperative day) are presented in Table 2. There was a significant decrease in hemoglobin level and platelet number on the third postoperative day. The WBC increased postoperatively, but the difference did not reach a statistically significant level.


View this table:
[in this window]
[in a new window]
  		Table 2. Preoperative and Early Postoperative Blood Cell Counts and Hemoglobin Levels in Group I

 
During follow-up, 7 patients in group I experienced a total of 10 severe infections. Of these 7 patients, 2 died from sepsis early postoperatively and 2 from pneumonia. In 1 patient, herpes zoster infection, a hand abscess, and subsequently phlegmona of the other hand were successfully treated. One patient presented with a local sternal wound infection, which was successfully treated by surgical debridement and administration of systemic antibiotics. In another patient, a respiratory infection was successfully treated with systemic antibiotics. In group II, 8 patients had 14 severe infections. Pneumonia was diagnosed in 6 cases, fever of unknown origin in 4 cases, respiratory infection in 3 cases, and herpes zoster infection in 1 case. In all of these cases, antibiotic therapy was successful. There was no difference between the groups with regard to severe infections (Table 1).

During follow-up, significantly fewer patients in group I required chemotherapy compared with those in group II. The mean period between operation and initiation of chemotherapy in group I or between the selected time-point and the initiation of chemotherapy in group II was also significantly greater in group I (Table 1). Kaplan-Meier analysis results are shown in Figure 1. Despite the inclusion in the analysis of the postoperative mortality rate of 14.3% in group I, the long-term survival was similar in both groups. The Kaplan-Meier analysis is presented in Figure 2.



View larger version (21K):
[in this window]
[in a new window]
  		Fig 1. Kaplan-Meier analysis of midterm freedom from chemotherapy in both groups. There was a significant difference between the two groups.

 


View larger version (21K):
[in this window]
[in a new window]
  		Fig 2. Kaplan-Meier analysis of midterm cumulative survival in both groups. There was no significant difference between the two groups.

 
The median numbers and the 25th and 75th percentiles of packed red blood cell units, units of fresh frozen plasma, and platelet concentrates transfused during the hospital stay in patients in group I and in 3,078 consecutive patients more than 18 years of age (mean age 64.1 ± 11.9 years) who underwent operation using CPB in our institution during 1999 are presented in Table 3. Significantly more units of packed red blood cells were transfused in CLL patients, whereas no differences were found for transfusion frequencies of units of fresh frozen plasma and platelet concentrates.


View this table:
[in this window]
[in a new window]
  		Table 3. Comparison of Blood Products Transfused in Group I and in Consecutive Patients More Than 18 Years of Age Undergoing Operations Using Cardiopulmonary Bypass During 1999, as Calculated From Hospital Database

 

   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
Acknowledgments
 References
 
This study suggests that the immunosuppressive effect of cardiac surgery using CPB does not aggravate the natural course of CLL. Moreover, the significant decrease of the frequency of chemotherapy and the increase of chemotherapy-free survival time (Table 1 and Fig 1) imply that the alterations of the immune system during and immediately after cardiac operations using CPB may have a positive effect on the course of CLL.

Although the patients in group I had cardiac disease as an additional risk factor, their midterm survival was similar to that of patients in group II as well as that reported from the US National Cancer Data Base for CLL patients between 60 and 80 years of age [19]. This fact could be explained by improvement in the natural course of CLL in patients who underwent cardiac surgery using CPB (Fig 1). Diehl and colleagues [19] showed that, in CLL patients, CLL is still a major cause of death with increasing age. Thus, the improved course of CLL may lead to improved survival in CLL patients with additional heart disease who require cardiac surgery.

Despite well-balanced matching, it is possible that preselection of patients in group I as being fit enough to withstand cardiac surgery could be considered to affect our study results; but, in fact, the patients in group I were in general sicker due to the existence of cardiac disease.

Some effects of CPB and cardiac surgery on immunologic response have been described [5–8]. In summary, the proinflammatory role of CPB, surgical trauma and cardioplegic arrest has been demonstrated by an increase of proinflammatory complement factors and cytokine levels in serum [5, 6, 20]. Both CPB and allogenic blood transfusion lead to an increase in the antiinflammatory interleukin-10 serum level, which suppresses T-cell activity, especially that of the cytotoxic T-cells and Th1 cells [8, 21].

Increased apoptosis of CLL cells related to CPB may also have an effect on the course of CLL. The microenvironment plays a prominent role in the apoptotic behavior of CLL cells, as the malignant cells accumulate in vivo with a life span of up to 4 years, whereas they rapidly undergo apoptosis when cultured in vitro [22].

Recently CD4+ T-cells have been identified as interacting with CLL cells by means of the CD40 ligand. Through the stimulation of CD40, survivin is expressed. The stimulated B-CLL cells are also Bcl-2+, thus showing a tendency to survive [23]. As CD4+ lymphocytes are significantly reduced after CPB [24], the reduced costimulatory effects of CD4+ T-lymphocytes may lead to higher sensitivity towards proapoptotic signals.

There is some clinical and biochemical evidence that the impact of CPB on immune response is greater than that of major surgical trauma [5, 25, 26]. However, the interactions between the variables of immune response during and after cardiac surgery remain not clearly understood, and there are still more questions than answers [27].

Another factor that may contribute to the immunosupressive effect of cardiac surgery using CPB is the postoperative transfusions of stored allogenic blood components that were performed in the majority of patients in group I. Alloantigens that are expressed in various blood products can elicit a suppression of the immune response [28]. The immunologic mechanism leading to downregulation of the alloimmune response is not clear. One possible explanation is the induction of a Th2 response by nonprofessional antigen presentation by the transfused blood cells with subsequent increase of the serum interleukin-10 level [21]. On the other hand, evidence is accumulating that the degree of HLA compatibility between donor and recipient is a determining factor [28].

The fact that chemotherapy was continued perioperatively in 2 patients in group I suggests that the postoperative status did not lead to a delay in the initiation of chemotherapy. However, further investigations are necessary to establish whether the significantly longer chemotherapy-free period in group I was related to alterations of the inflammatory response system due to CPB, major surgical trauma, or allogenic blood transfusion.

Chronic lymphatic leukemia remains a risk factor in the early postoperative period after cardiac surgery. The operative mortality in CLL patients is higher [15–17] than in a comparable population as reported in the Registry of The Society of Thoracic Surgeons. In our patients, the early postoperative mortality was strongly related to the need for emergency surgery (all patients who required emergency surgery died), whereas 3 of the 4 patients with advanced disease (Binet stage C) survived over the early postoperative period.

Some risk factors in patients with CLL may contribute to increased postoperative mortality. Thrombocytopenia and abnormal platelet function are risk factors for postoperative bleeding. The normal preoperative median platelet count and thrombocytopenia in only 1 patient in group I may explain the similar frequency of the postoperative use of blood products (with the exception of a slight increase in use of units of packed red blood cells) in CLL patients compared with that calculated from our hospital database for 1999 (Table 3). The small number of patients with advanced disease who underwent cardiac surgery, and the possible preoperative selection of patients without thrombocytopenia for elective procedures, may also contribute to this effect. However, the significant decrease in median postoperative platelet count in our study may enhance the risk for bleeding, especially in the thrombocytopenic patients. This risk may be reduced if the off-pump technique is used [13, 29].

The decreased immune competence of CLL patients is another risk factor contributing to increased incidence of postoperative infections, which remains the major postoperative complication [15, 16]. The immune suppression related to CPB, surgical trauma, and blood transfusion is also a risk factor and may contribute to this phenomenon. Two patients in our series died from sepsis early in the postoperative period. However, both of these patients required emergency surgery, which is known to be associated with increased postoperative mortality. Based on our experience, we use the first generation of cephalosporins for routine perioperative prophylaxis also in CLL patients, but change to therapy with broad spectrum antibiotics early if signs of systemic infection occur, and then to antibiotics specific to the antibiogram. Although all patients in group I underwent major surgery (which is per se a risk factor for infection [5]), whereas only 1 patient in group II had major surgery (in this case, bowel resection) during follow-up, no differences with regard to severe infection during the follow-up period were found between the groups, even when the early postoperative period was included in the analysis (Table 1).

Limitations of the study
The descriptive nature of the study and the relatively small number of patients preclude a definitive answer about the impact on CLL of cardiac surgery using CPB. Another limitation is that the study could not differentiate between the impact of CPB itself and the transfusion of blood components on the natural course of CLL. There was a slightly different distribution of clinical stages in both groups. Nevertheless, stage distribution was similar to that reported by Karmiris and colleagues [4]. Although our study reports the largest population of CLL patients who underwent cardiac surgery using CPB, the relatively small number of patients precluded better matching or differentiation into subgroups. In larger studies tests for paired variables could be used to improve the statistical analysis. The chemotherapy was initiated in both groups based on published recommendations [1, 10, 11]. However, a long period of data collection precluded more rigorous definition. Cellular morphology, patterns of bone marrow involvement, lymphocyte doubling time, drug resistance, cytogenic variables, Ig VH mutational status, and serum markers were not considered as matching criteria because these data were not available for most patients, especially in the early period.

In conclusion, cardiac surgery using CPB probably did not have a negative impact on the natural course of CLL in this study. Moreover, this procedure seems to be associated with a decrease in the number of postoperative chemotherapy administrations and with an increase of chemotherapy-free survival time. Although CLL may be a risk factor in the early postoperative period, especially with regard to infection, it is not a contraindication for cardiac surgery using CPB.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
References
 
We thank Professor Dieter Huhn for advice on hematological aspects, Anne Gale for editorial assistance, and Julia Stein for statistical advice. This article contains data from the doctoral thesis of Corinna Herzke, MD.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Johnson L.E. Chronic lymphocytic leukemia. Am Fam Physician 1988;38:167-176.
  2. Call T.G., Phyliky R.L., Noel P., et al. Incidence of chronic lymphocytic leukemia in Olmsted County, Minnesota, 1935 through 1989, with emphasis on changes in initial stage at diagnosis. Mayo Clin Proc 1994;69:323-328.[Medline]
  3. Rozman C., Bosch F., Montserrat E. Chronic lymphocytic leukemia: a changing natural history?. Leukemia 1997;11:775-778.[Medline]
  4. Karmiris T., Rohatiner A.Z., Love S., et al. The management of chronic lymphocytic leukemia at a single centre over a 24-year period: prognostic factors for survival. Hematol Oncol 1994;12:29-39.[Medline]
  5. Diegeler A., Doll N., Rauch T., et al. Humoral immune response during coronary artery bypass grafting: a comparison of limited approach, "off-pump" technique, and conventional cardiopulmonary bypass. Circulation 2000;102(Suppl 3):III95-III100.
  6. Struber M., Cremer J.T., Gohrbandt B., et al. Human cytokine responses to coronary artery bypass grafting with and without cardiopulmonary bypass. Ann Thorac Surg 1999;68:1330-1335.[Abstract/Free Full Text]
  7. Loebe M., Locziewski S., Brunkhorst F., Harke C., Hetzer R. Procalcitonin in patients undergoing cardiopulmonary bypass in open heart surgery—first results of the Procalcitonin in the Heart Surgery Study (ProHearts). Intensive Care Med 2000;26(Suppl 2):193-198.
  8. Markewitz A., Faist E., Lang S., Hultner L., Weinhold C., Reichart B. An imbalance in T-helper cell subsets alters immune response after cardiac surgery. Eur J Cardiothorac Surg 1996;10:61-67.[Abstract]
  9. Specer G. US Bureau of the Census: Projections of the population of the United States by age, sex and race; 1988 to 2080. Washington, DC: US Government Printing Office, 1989.
  10. Kipps T.J. Chronic lymphocytic leukemia. Curr Opin Hematol 2000;7:223-234.[Medline]
  11. Rai K.R. Chronic lymphocytic leukaemia. Current strategy and new perspectives of treatment. Haematologica 1999;84:94-95.
  12. Belboul A., Akbar O., Lofgren C., Jungbeck M., Storm C., Roberts A. Improved blood cellular biocompatibility with heparin coated circuits during cardiopulmonary bypass. J Cardiovasc Surg 2000;41:357-362.[Medline]
  13. Baumgartner F.J., Yokoyama T., Gheissari A., Capouya E.R., Panagiotides G.P., Declusin R.J. Effect of off-pump coronary artery bypass grafting on morbidity. Am J Cardiol 2000;86:1021-1022.[Medline]
  14. Craver J.M., Puskas J.D., Weintraub W.W., et al. 601 Octogenarians undergoing cardiac surgery: outcome and comparison with younger age groups. Ann Thorac Surg 1999;67:1104-1110.[Abstract/Free Full Text]
  15. Samuels L.E., Kaufman M.S., Morris R.J., Styler M., Brockman S.K. Open heart surgery in patients with chronic lymphocytic leukemia. Leuk Res 1999;23:71-75.[Medline]
  16. Finck S.J., Cockerill K.J., Jeter J.E., Orszulak T.A. Coronary artery bypass grafting in patients with chronic lymphocytic leukemia. Ann Thorac Surg 1993;55:1192-1196.[Abstract]
  17. Ghosh P., Carroll I., Kanhere A., Ng B., Larbalestier R., Edwards M. Cardiac operations in patients with low-grade small lymphocytic malignancies. J Thorac Cardiovasc Surg 1999;118:1033-1037.[Abstract/Free Full Text]
  18. Binet J.L., Auquier A., Dighiero G., et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 1981;48:198-206.[Medline]
  19. Diehl L.F., Karnell L.H., Menck H.R. The American College of Surgeons Commission on Cancer and the American Cancer Society. The National Cancer Data Base report on age, gender, treatment, and outcomes of patients with chronic lymphocytic leukemia. Cancer 1999;86:2684-2692.[Medline]
  20. Brasil L.A., Gomes W.J., Salomao R., Buffolo E. Inflammatory response after myocardial revascularization with or without cardiopulmonary bypass. Ann Thorac Surg 1998;66:56-59.[Abstract/Free Full Text]
  21. Heiss M.M., Fraunberger P., Delanoff C., et al. Modulation of immune response by blood transfusion: evidence for a differential effect of allogeneic and autologous blood in colorectal cancer surgery. Shock 1997;8:402-408.[Medline]
  22. Caligaris-Cappio F., Hamblin T.J. B-cell chronic lymphocytic leukemia: a bird of a different feather. J Clin Oncol 1999;17:399-408.[Abstract/Free Full Text]
  23. Granziero L., Ghia P., Circosta P., et al. Survivin is expressed on CD40 stimulation and interfaces proliferation and apoptosis in B-cell chronic lymphocytic leukemia. Blood 2001;97:2777-2783.[Abstract/Free Full Text]
  24. Diegeler A., Tarnok A., Rauch T., et al. Changes of leukocyte subsets in coronary artery bypass surgery: cardiopulmonary bypass versus "off-pump" techniques. Thorac Cardiovasc Surg 1998;46:327-332.[Medline]
  25. Gu Y.J., Mariani M.A., Boonstra P.W., Grandjean J.G., van Oeveren W. Complement activation in coronary artery bypass grafting patients without cardiopulmonary bypass: the role of tissue injury by surgical incision. Chest 1999;116:892-898.[Abstract/Free Full Text]
  26. McGrory B.J., Trousdale R.T. Total hip arthroplasty in patients who have chronic lymphocytic leukemia. J Arthroplasty 1995;10:758-763.[Medline]
  27. Markewitz A. Tumor necrosis factor-alpha and cardiac surgical procedures: still more questions than answers. Ann Thorac Surg 1999;67:595-596.[Free Full Text]
  28. Roelen D.L., van Rood J.J., Brand A., Claas F.H. Immunomodulation by blood transfusions. Vox Sang 2000;78(Suppl 2):273-275.
  29. Ascione R., Williams S., Lloyd C.T., Sundaramoorthi T., Pitsis A.A., Angelini G.D. Reduced postoperative blood loss and transfusion requirement after beating-heart coronary operations: a prospective randomized study. J Thorac Cardiovasc Surg 2001;121:689-696.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Eur. J. Cardiothorac. Surg.Home page
A. M. Fecher, T. J. Birdas, D. Haybron, P. K. Papasavas, D. Evers, and P. F. Caushaj
Cardiac operations in patients with hematologic malignancies
Eur. J. Cardiothorac. Surg., April 1, 2004; 25(4): 537 - 540.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Ralf Sodian
Roland Hetzer
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Potapov, E. V.
Right arrow Articles by Hetzer, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Potapov, E. V.
Right arrow Articles by Hetzer, R.
Related Collections
Right arrow Extracorporeal circulation

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS