|Year : 2016 | Volume
| Issue : 1 | Page : 146-149
The role of perioperative blood transfusion on postoperative outcomes and overall survival in patients after laparoscopic radical cystectomy
Juan Gómez Rivas1, Sergio Alonso y Gregorio1, Jesús Cisneros Ledo1, Ángel Tabernero Gómez1, Jesús Díez Sebastián2, JJ de la Peña Barthel1
1 Department of Urology, La Paz University Hospital, Madrid, Spain
2 Department of Statistics, La Paz University Hospital, Madrid, Spain
|Date of Web Publication||13-Apr-2016|
Juan Gómez Rivas
Department of Urology, Paseo la Castellana 261, Madrid-28034
Source of Support: None, Conflict of Interest: None
Introduction: There are different studies in the last decades focused on general surgery patients and the impact of perioperative blood transfusion (PBT) in cancer patients' survival, and most of them have supported an independent association between PBT and worse survival in those with solid tumor malignancies. The aim of this study is to evaluate the impact of perioperative blood transfusion on the postoperative outcomes and survival of patients after LRC.
Materials and Methods: We performed a retrospective study analyzing our series of 218 patients surgically treated with LRC form 2005 to 2012. One-way analysis of variance test was used. Survival was estimated using the Kaplan - Meier method and was compared with log – rank and the Cox regression model was used to evaluate the association of PBT with the outcomes.
Results: The PBT rate of LRC series was 16%. Patients' age, comorbidities and pathological stage were not related to the PBT rate. A statistically significant relationship was found between the PBT rate and the appearance of infectious complications. Overall 3 years survival estimated with the Kaplan-Meier method was significantly worse in the transfused group: 41.38% versus 63.57% for non-transfused patients. PBT was not a significant independent predictor factor in the survival of patients after LRC. The main independent factor was the TNM classification.
Conclusions: Many studies including ours have reported a lower survival rate in patients who receive PBT after oncological surgery. There was a relationship between infectious complications and PBT. We have to make efforts to limit the use of blood products in patients surgically treated with radical cystectomy for bladder cancer.
Keywords: Laparoscopic radical cystectomy, perioperative blood transfusion, survival
|How to cite this article:|
Rivas JG, Gregorio SA, Ledo JC, Gómez ÁT, Sebastián JD, de la Peña Barthel J J. The role of perioperative blood transfusion on postoperative outcomes and overall survival in patients after laparoscopic radical cystectomy. J Can Res Ther 2016;12:146-9
|How to cite this URL:|
Rivas JG, Gregorio SA, Ledo JC, Gómez ÁT, Sebastián JD, de la Peña Barthel J J. The role of perioperative blood transfusion on postoperative outcomes and overall survival in patients after laparoscopic radical cystectomy. J Can Res Ther [serial online] 2016 [cited 2021 Jan 19];12:146-9. Available from: https://www.cancerjournal.net/text.asp?2016/12/1/146/146125
| > Introduction|| |
During the last years, the comprehension of clinical oncology, tumor biology and immunology has advanced impressively. Nowadays, is known that several mechanisms might promote metastasis after surgery including the postoperative immunosuppression; this issue has been well analyzed by Shakhar et al., also the immunosuppressive effect of blood transfusion has been described in the 70s decade in a report of enhanced renal allograft survival among patients receiving a transfusion.,,,,,
There are different studies in the last decades focused on general surgery patients and the impact of perioperative blood transfusion (PBT) in cancer patients' survival, and most of them have supported an independent association between PBT and worse survival in those with solid tumor malignancies. PBT has been independently associated with mortality in patients after surgery for gastric cancer, hepatocellular carcinoma, lung cancer, and colorectal cancer.,,,
Open radical cystectomy (ORC) is associated with a high rate of transfusion, ranging around 30% in different series, but there are a few studies evaluating the relationship between transfusion and survival after this procedure,, furthermore there are no studies regarding laparoscopic radical cystectomy (LRC) as a minimally invasive procedure and its impact on perioperative transfusion rate and survival.
The aim of this study is to evaluate the impact of perioperative blood transfusion (PBT) on the postoperative outcomes and overall survival of patients after LRC.
| > Materials and Methods|| |
Institutional review board approved this study, the principles of the Helsinki declaration were followed and all human subjects provided written in formed consent prior surgery with guarantees of confidentiality. We performed a retrospective study analyzing our series of 218 patients surgically treated with LRC from 2005 to 2012. LRC was performed by three experienced surgeons using the procedure described by Cansino et al. The PBT rate was defined as the requirement of concentrate (s) of red blood cells packing during 1) the intra-operatory by decision of the anesthesiologist in charge or 2) in the post-operatory in patients who had a low hemoglobin in the post operatory (< gr/dL or <9 gr/dL with symptoms). Transfusions of other blood products, including fresh frozen plasma or platelets, were not included in this analysis.
Thirty-fivepatients requiring PBT were identified for this study. Covariates including age, comorbidities, pathologic stage using the TNM classification of 2010, estimated blood loss and complications wereobtained through patient charts. Relation between PBT and these aspects were investigated rate using a one-way analysis of variance test.
Survival was estimated using the Kaplan-Meier method and was compared with log –rank and the Cox regression model was used to evaluate the association of PBT with the outcomes, controlling various clinical and pathological variables. P < 0.05 were considered statistically significant. Data have been analyzed statistically at the biostatistics section in our hospital with the SPSS 20 program. The results are expressed in absolute values, percentages, median, standard deviation (SD), and confidence interval (CI) 95%.
| > Results|| |
The PBT rate of the LRC series performed at our department was 16% (35 patients). Clinical and pathologic demographics for the patients are shown in [Table 1]. Patients age, comorbidities and pathological stage (TNM) and other oncological featureswere not related to the PBT rate with P > 0.05 [Table 1]. Astatistically significant relationship (P < 0.05) was found between the PBT rate and the appearance of postoperative complications especiallyinfectious ones like pneumonia and others, the details are shown in [Table 2].
Overall 3-years survival estimated with the Kaplan-Meier method wassignificantly worse (P = 0.03) in the transfused group: 41.38% (SD: 13.02, CI 95% 10.26-61.33) versus 63.57% for non-transfused patients (SD: 14.8, CI 95%: 30.86-80.09) [Figure 1].
|Figure 1: Kaplan-Meier estimate of overall survival in patients with PTB vs no PTB after LRC|
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We wanted to assess for an independent association between PBT and overall survival, so the Cox regression modelwas applied and it showed that the PBTwas not a significant independent factor in the overall survival of patients after LRC. The main independent factor in the overall survival after LRC was the TNM classification. The T-stage had an independent association with P < 0.0001 and positive lymphatic nodes (N) with P = 0.044. The results are shown in [Table 3].
| > Discussion|| |
Nowadays, ORC is the standard treatment for localized muscle invasive bladder cancer. LRC and robot-assisted laparoscopic radical cystectomy (RRC) are feasible but they are currently considered experimental therapies because of the limited number of cases reported, the absence of long-term oncologic and functional outcome data, and a possible selection bias. Despite of this fact, the numbers of series reporting perioperative outcomes and survival of LRC and RRC is increasing in the last decade and the benefits of the minimal invasive approaches have been demonstrated in decreased length of stay, decreased intraoperative blood loss, less postoperative pain and faster patient recovery.,,,,
Major surgery frequently causes blood loss and needs PBT. The hypovolemic shock seems to cause immunosuppression that is correlated with the volume of lost blood and also PBT is known to interfere with several aspects of cell-mediated immunity, including cytokine levels, NK-cell activity, and T-cell blastogenesis., The mechanism implicit in the causes ofimmunosuppression remains unknown, but it is suggested that cellular interactions with transfused leukocytes and possibly accumulation of immunosuppressive cytokines in stored blood are main factors, so following this mechanisms PBT may reduce survival in oncological patients.
To our knowledge, this is the first study evaluating the impact of PBT on the postoperative outcomes and survival of patients after a minimally invasive procedure (laparoscopic radical cystectomy) in muscle invasive bladder cancer. From the oncologic point of view, we estimated overall survival with the Kaplan-Meier method and the three years overall survival was significantly worse in the transfused group: 41.38% versus 63.57% for non- transfused patients with a P value of 0.038. The majority of reports in the general surgery literature evaluating patients with solid tumor malignancies undergoing radical surgery have found an independent adverse effect of PBT on survival.,,,
The theoretical and probable impact on survival of PBT on radical cystectomy has been described in two recent studies. Linder et al., in a single center study over a total of 1279 patients who received PBT after radical cystectomy found an association of PBT with significantly increased risks of tumor recurrence and mortality following Morgan et al., in a retrospective cohort study of 323 consecutive patients who underwent PBT after RC found an increased mortality risk associated with PBT in increased overall mortality and additionally, an independent association was demonstrated in a non-transformed Cox regression model, but they concluded that the relationship between transfusion and its influence on overall survival in patients with solid tumor malignancies including bladder cancer, is complex and remains controversial.
The main independent factor that predicts overall survival of patients after LRC in our study is the TNM classification. PBT was not a significant independent predictor factor in the survival of patients after LRC in our study but it remained close to signification (P = 0.07), this is probably because different factors: (1) our low PBT rate (16%), (2) the low number of patients in the series (only 35 over 218 required PBT) and (3) Carter et al. in a study published in 2001 said thatminimally invasive surgeries are markedly less immunosuppressive than standard oncological operations. Animal models additionally showed that laparoscopy results in less metastasis than does comparable laparotomy, presumably through less disruption of cell-mediated immunity.
Regarding postoperative complications, we found an increase of infectious complications in the PBT group especially pneumonia and infections related with catheters (P = 0.007 and P = 0.006, respectively). The contribution of the natural and acquired immunity in the protection against infections is well known, so this fact may be explained due the immunosuppression caused by PBT. Others infectious complications like sepsis and surgical wound infections are not significant probable because the low number of patients in our LRC series as is shown in [Table 2].
There are several limitations in this study: (1) is a retrospective, single center and short cohort study, (2) estimated blood loss is an inexact measure of blood loss, due to the sum of different factors such as: Blood, lymph coming from the lymph node dissection and washing liquid, (3) The decision to administer a PBT was made on a case-by-case basis without any transfusion guidelines and (4) we only assessed overall survival on patients and not cancer-specific survival or others oncological factors due to the low number of patients to archive an accurate oncological specific findings, but as we said before this is to our knowledge the first study evaluating the impact of PBT on the postoperative outcomes and survival of patients after a minimally invasive procedure (LRC) in oncological urology. Efforts should be targeted to make multi-centric, experimental and prospective studies in order to validate these findings.
| > Conclusions|| |
Many studies including ours have reported a lower survival rate in patients who receive PBT after oncological surgery butPBT was not an independent factor in the survival of patients after LRC. The main independent factor was the TNM classification. There was a relationship between infectious postoperative complications and PBT, these findings are explained because the immunosuppression caused by blood loss and PBT. We have to make efforts to limit the use of blood products in patients surgically treated with radical cystectomy for bladder cancer.
| > References|| |
Buinauskas P, McDonald GO, Cole WH. Role of operative stress on the resistance of the experimental animal to inoculated cancer cells. Ann Surg 1958;148:642-5.
Weese JL, Ottery FD, Emoto SE. Do operations facilitate tumor growth? An experimental model in rats. Surgery 1986;100:273-7.
Sietses C, Beelen RH, Meijer S, Cuesta MA. Immunological consequences of laparoscopic surgery, speculations on the cause and clinical implications. Langenbecks Arch Surg 1999;384:250-8.
Carter JJ, Whelan RL. The immunologic consequences of laparoscopy in oncology. Surg Oncol Clin N
Shakhar G, Ben-Eliyahu S. Potential prophylactic measures against postoperative immunosuppression: Could they reduce recurrence rates in oncological patients? Ann Surg Oncol 2003;10:972-92.
Opelz G, Terasaki PI. Poor kidney-transplant survival in recipients with frozen-blood transfusions or no transfusions. Lancet 1974;2:696-8.
Busch OR, Hop WC, Hoynck van Papendrecht MA, Marquet RL, Jeekel J. Blood transfusions and prognosis in colorectal cancer. N Engl J Med 1993;328:1372-6.
Zhou HY, Yi W, Wang J, Zhang J, Wang WJ, Hu ZQ. Association of perioperative allogeneic blood transfusions and prognosis of patients with gastric cancer after curative gastrectomy. Am J Surg 2014;208:80-7.
Shiba H, Ishida Y, Wakiyama S, Iida T, Matsumoto M, Sakamoto T, et al
. Negative impact of blood transfusion on recurrence and prognosis of hepatocellular carcinoma after hepatic resection. J Gastrointest Surg 2009;13:1636-42.
Wang CC, Iyer SG, Low JK, Lin CY, Wang SH, Lu SN, et al
. Perioperative factors affecting long-term outcomes of 473 consecutive patients undergoing hepatectomy for hepatocellular carcinoma. Ann Surg Oncol 2009;16:1832-42.
Chang SS, Smith JA Jr, Wells N, Peterson M, Kovach B, Cookson MS. Estimated blood loss and transfusion requirements of radical cystectomy. J Urol 2001;166:2151-4.
Linder BJ, Frank I, Cheville JC, Matthew KT, Thompson RH, Tarrell RF, et al
. The Impact of perioperative blood transfusion on cancer recurrence and survival following radical cystectomy. Eur Urol 2013;63:839-45.
Morgan TM, Barocas DA, Chang SS, Phillips SE, Salem S, Clark PE, et al
. The relationship between perioperative blood transfusion and overall mortality in patients undergoing radical cystectomy for bladder cancer. Urol Oncol 2013;31:871-7.
Cansino JR, Cisneros J, Alonso S, Martínez-Piñeiro L, Aguilera A, Tabernero A, et al
. Laparoscopic radical cystectomy: Initial series and analysis of results. Eur Urol Suppl 2006;5:956-61.
Edge SB, Compton CC. The American Joint Committee on Cancer: The 7th
edition of the AJCC Cancer Staging Manual and the future of TNM. Ann Surg Oncol 2010;17:1471-4.
Witjes JA, Compérat E, Cowan NC, De Santis M, Gakis G, Lebret T, et al
.; European Association of Urology. EAU guidelines on muscle-invasive and metastatic bladder cancer: Summary of the 2013 Guidelines. Eur Urol 2014;65:778-92.
Chade DC, Laudone VP, Bochner BH, Parra RO. Oncological outcomes after radical cystectomy for bladder cancer: Open versus minimally invasive approaches. J Urol 2010;183:862-9.
Li K, Lin T, Fan X, Xu K, Bi L, Duan Y, et al
. Systematic review and meta-analysis of comparative studies reporting early outcomes after robot-assisted radical cystectomy versus open radical cystectomy. Cancer Treat Rev 2012;39:551-60.
Ng CK, Kauffman EC, Lee MM, Otto BJ, Portnoff A, Ehrlich JR, et al
. A comparison of postoperative complications in open versus robotic cystectomy. Eur Urol 2010;57:274-81.
Styn NR, Montgomery JS, Wood DP, Hafez KS, Lee CT, Tallman C, et al
. Matched comparison of robotic-assisted and open radical cystectomy. Urology 2012;79:1303-8.
Johar RS, Hayn MH, Stegemann AP, Ahmed K, Agarwal P, Balbay MD, et al
. Complications after robot-assisted radical cystectomy: Results from the International Robotic Cystectomy Consortium. Eur Urol 2013;64:52-7.
Xu YX, Ayala A, Chaudry IH. Prolonged immunodepression after trauma and hemorrhagic shock. J Trauma 1998;44:335-41.
Klein HG. Immunomodulatory aspects of transfusion: A once and future risk? Anesthesiology 1999;91:861-5.
Blajchman MA. Transfusion-associated immunomodulation and universal white cell reduction: Are we putting the cart before the horse? Transfusion 1999;39:665-70.
[Table 1], [Table 2], [Table 3]