Dose-Dependent Effect of Red Blood Cells Transfusion on Perioperative and Long-Term Outcomes in Peritoneal Surface Malignancies Treated with Cytoreduction and HIPEC

Our plain-English summary of Dose-Dependent Effect of Red Blood Cells Transfusion on Perioperative and Long-Term Outcomes in Peritoneal Surface Malignancies Treated with Cytoreduction and HIPEC, by E. Nizri, S. Kusamura, G. Fallabrino, et al (Annals of Surgical Oncology, 2018).

The study

• Authors: E. Nizri, S. Kusamura, G. Fallabrino, M. Guaglio, D. Baratti, M. Deraco
• Journal: Annals of Surgical Oncology
• Published: 2018;25(11):3264-3270
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are associated with increased red blood cell transfusion (RBT) demand. Although the deleterious effects of RBT are documented in various settings, its effect in this setting is obscure. In this study, we evaluated the effects of different-grade RBT on the short- and long-term outcomes of CRS and HIPEC.

Methods: We analyzed 231 patients with diffuse malignant peritoneal mesothelioma (DMPM) and 273 patients with pseudomyxoma peritonei (PMP) operated in our unit. RBT was categorized according to the amount of packed red blood cell units (PRBCs) administered (0, 1-2, 3-5, > 6). The effects of RBT on long-term oncological outcomes [progression-free survival (PFS) and overall survival (OS)] were assessed by using multivariate analysis.

Results: Overall, 74% of the patients were transfused with a median of 2 PRBCs (range 0-37). Transfusion level correlated with operative time, surgical extent (as measured by the peritoneal carcinomatosis index), and age. Postoperatively, patients with major transfusion (> 6 PRBCs) had increased mortality rate (11.1%, p = 0.01) and length of hospital stay (31.2 ± 16.8 days, p = 0.01) compared with other levels of RBT. RBT was dose-dependently associated with oncological outcomes in both DMPM and PMP for both PFS [hazard ratio (HR) = 1.40, 95% confidence interval (CI) 1.12-1.74, p = 0.003; HR = 1.44, 95% CI 1.15-1.81, p = 0.001, respectively] and OS (HR = 1.57, 95% CI 1.21-2.03, p = 0.001; HR = 1.43, 95% CI 1.15-1.90, p = 0.01, respectively).

Conclusions: Our data show a dose-dependent relationship between RBT and oncological outcomes. Further research to develop transfusion sparing protocols is needed in this extensive surgical procedure.

In plain English

This study asked whether red blood cell transfusion during cancer surgery was linked to worse outcomes. The authors analyzed records from an institutional database of 504 patients treated with cytoreductive surgery and heated abdominal chemotherapy (HIPEC) in their unit between August 1995 and October 2017: 231 with diffuse malignant peritoneal mesothelioma and 273 with pseudomyxoma peritonei. Patients were grouped by units of packed red cells received (0, 1–2, 3–5, more than 6). In total, 372 patients (74%) were transfused. Death after surgery occurred in 11.1% of those given more than 6 units, compared with 1.7% of those given none. In mesothelioma patients, median progression-free survival was 49.3 months (with the article printing 0–104.9 beside it) with no transfusion, and 7.7 months (3.2–12.2) with more than 6 units. After adjustment for other factors, transfusion class remained associated with worse overall survival in mesothelioma (hazard ratio 1.57, 95% CI 1.21–2.03). The authors concluded that even minimal transfusion had adverse effects. They cautioned that transfusion may reflect more aggressive disease rather than cause harm. The article does not discuss asbestos.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective analysis of a single institution's prospectively maintained clinical database
• Who was studied: 504 patients treated with cytoreductive surgery and HIPEC in the authors' unit between August 1995 and October 2017. The author affiliations give the unit as the Peritoneal Surface Malignancies Unit, Istituto Nazionale dei Tumori, Milan. 231 patients had diffuse malignant peritoneal mesothelioma (DMPM) and 273 had pseudomyxoma peritonei (PMP). 267 were female (53%), and median age was 56 years (range 21–81).
• Exposure: Red blood cell transfusion during or around surgery, grouped by number of packed red blood cell units: 0, 1–2, 3–5, and more than 6 units. Asbestos exposure is not studied.
• Main results:
  • All 504 patients: 372 (74%) received any transfusion. The median was 2 units (range 0–37).
  • All 504 patients: after stepwise elimination, only operative time, peritoneal cancer index and age predicted transfusion amount. This model explained about 28% of the variation (R2 = 0.28).
  • Postoperative mortality by transfusion group was 3 (1.7%) with 0 units, 3 (2.5%) with 1–2, 4 (3.2%) with 3–5, and 7 (11.1%) with more than 6 units. The more-than-6 group differed significantly from the 0 group (p less than 0.01). Mean hospital stay was 31.2 plus or minus 16.8 days in the more-than-6 group, versus 21.8 plus or minus 12.1 days with no transfusion.
  • Severe (grade 3–5) infections occurred in 42 (22%) with 0 units, 27 (22%) with 1–2, 36 (29%) with 3–5, and 24 (38.1%) with more than 6 units. The 3–5 and more-than-6 groups differed significantly from the 0 group (p less than 0.05).
  • DMPM patients, median progression-free survival (with the figures printed in parentheses): 49.3 (0–104.9) months with 0 units, 21.9 (10.4–33.3) months with 1–2, 14.4 (10.2–18.6) months with 3–5, and 7.7 (3.2–12.2) months with more than 6 units. Median overall survival was not reached with 0 units. It was 76, 35 and 22 months for the 1–2, 3–5 and more-than-6 groups.
  • PMP patients: median progression-free survival was not reached in the 0 and 1–2 unit groups. It was 38.5 months with 3–5 units and 16.5 months with more than 6. Median overall survival was not reached for 0 and 1–2 units. It was 141 and 93 months for the 3–5 and more-than-6 groups.
  • DMPM patients, multivariate analysis: transfusion class was associated with worse overall survival (HR 1.57, 95% CI 1.21–2.03, p = 0.001) and worse progression-free survival (HR 1.40, 95% CI 1.12–1.74, p = 0.003).
  • PMP patients, multivariate analysis: transfusion class was associated with worse progression-free survival (HR 1.44, 95% CI 1.15–1.81, p = 0.001). It was also associated with worse overall survival (HR 1.43, 95% CI 1.08–1.9, p = 0.01, per Table 3).
• The authors' conclusion: The authors concluded that transfusion, even minimal, had a significant adverse effect on both short- and long-term outcomes of cytoreductive surgery. They called for research on transfusion-sparing protocols and evidence-based transfusion triggers.
• Limitations the authors state:
  • The study was retrospective, so transfusion is tied to disease severity and the extent of the operation.
  • Transfusion triggers were not standardized across anesthesiology teams.
  • Factors that influenced the decision to transfuse were not systematically recorded.
  • Transfusion may be a marker of more aggressive disease rather than a cause of worse outcomes. The authors said multivariate analysis only partially addresses this.

Topics

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, HIPEC, Peritoneal Mesothelioma, Progression-Free Survival, Overall Survival, Multivariate Analysis, Hazard Ratio, confidence interval.

Related studies

• The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — S. Kusamura, P.A. Torres Mesa, et al. (2016)
• Impact of Combination Chemotherapy in Peritoneal Mesothelioma Hyperthermic Intraperitoneal Chemotherapy (HIPEC): The RENAPE Study — B. Malgras, E. Gayat, et al. (2018)
• Multicystic peritoneal mesothelioma: outcomes and patho-biological features in a multi-institutional series treated by cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — D. Baratti, M. Vaira, et al. (2010)
• Is Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Justified for Biphasic Variants of Peritoneal Mesothelioma? Outcomes from the Peritoneal Surface Oncology Group International Registry — K.I. Votanopoulos, P. Sugarbaker, et al. (2018)
• Long-term survival outcomes of cytoreductive surgery and perioperative intraperitoneal chemotherapy: Single-institutional experience with 1225 cases — L.S. Kyang, N.A. Alzahrani, et al. (2019)
• Long-term Survival and Propensity Score Matched Outcomes of Bilateral vs. Unilateral Diaphragm Interventions in Cytoreductive Surgery plus Intra-peritoneal Chemotherapy — B. Singh, G. Singh, et al. (2018)

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