J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Review

Volume 12, Number 12, December 2020, pages 773-779

Low Preoperative Serum Albumin Levels Are Associated With Impaired Outcome After Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies

**Table 1.** Detailed Presentation of the Studies’ Key Features and the Significance of Preoperative Serum Albumin Levels With Respect to the Surgical and Oncological Outcome
Authors	PSM origin and study sample	Postoperative morbidity and mortality (entire cohort)	Survival (entire cohort)	Significance of hypoalbuminemia
OS: overall survival; PFS: progression-free survival; DFS: disease-free survival; DSM: death and serious morbidity; PM: peritoneal metastases; PSM: peritoneal surface malignancies; PMP: pseudomyxoma peritonei; LOS: length of stay; ICU: intensive care unit; HDU: high dependency unit; N.S.: non-significant; pts: patients.
Graziosi et al, 2016 [19]	N = 64 pts with PM of various primary origins (34.4% colorectal, 32.8% gastric, 14.1% ovarian and 10.9% other origin)	5.1% major postoperative morbidity (grades III/IV)	Median follow-up was 26.5 months (range 4 - 120 months)	With 3.8 g/dL as preoperative albumin cut-off value, 5-year OS of 70% vs. a 5- year OS of 38% in the high vs. low albumin group.
5.1% postoperative mortality	5-year OS was 55 % for entire cohort	Preoperative albumin level was identified as an independent prognostic factor for OS in multivariate analysis.
No data regarding albumin as predictor of postoperative morbidity/mortality.
Cascales-Campos et al, 2016 [20]	N = 85 pts (> 75 years) with PM of various primary origins (42% colorectal, 31% ovarian, 20% appendiceal-PMP, 7% other origin)	43.5% overall morbidity (grades I - IV)	No survival data	Preoperative albumin level < 3 g/dL was associated with overall morbidity (grades I - IV) in univariate analysis.
23.5% and 14.4% minor (grades I/II) and major (grades III/IV) morbidity
5.1% 90-day mortality (2/5 of the deceased died of complications not related to CRS and PIC)	Preoperative albumin level < 3.5 g/dL was associated with major morbidity (grades III/IV) in multivariate analysis.
No survival data.
Huang et al, 2016 [21]	N = 591 pts with PM of various primary origins (31.3% appendiceal 23.4% colorectal, 29.3% PMP, 11.5% mesothelioma, ovarian 4.7%)	41.8% overall major morbidity (grades III/IV)	62.2 months median OS	Preoperative albumin was 3.7 ± 0.55 g/dL for entire cohort; albumin value of 3.5 g/dL used as cut-off of hypoalbuminemia.
Hypoalbuminemic group had statistically significant higher PCI than the normoalbuminemic one.
0.8% post-operative mortality	N.S. differences in mortality between normo- and hypoalbuminemic groups (2 vs. 3 pts).
Hypoalbuminemic group had statistically significant higher rates of major morbidity (grades III/IV), as well as LOS, ICU and HDU hospitalization duration (twice median stay).
In multivariate analysis, preoperative serum albumin < 3.5 g/dL was an independent prognostic factor for a poor perioperative outcome (grades III - V - 1.5-fold risk of a poor perioperative outcome when preoperative serum albumin < 3.5g/dL)).
Hypoalbuminemic group had statistically significant poorer OS (49.3 months (32.0 - 66.6) vs. 65.8 months (48.5 - 83.1)).
Peters et al, 2015 [22]	N = 1,085 pts with PM of various primary origins	44% and 37% overall and major morbidity	No survival data	Preoperative albumin < 3 g/dL and weight loss were the only preoperative factors significantly associated with DSM in the multivariate model.
1.8% postoperative mortality
overall 30-day DSM rate of 37.4%	No survival data.
Winer et al, 2013 [23]	N = 67 pts with PM of appendiceal (AP, n = 37) or colorectal origin (CRC, n = 30) with signet cell histology	22% vs. 29% major morbidity (grade III/IV) in the CRC vs. AP group	Median follow-up of CRC and AP groups was 4.4 and 4.1 years, respectively	In univariate analysis, preoperative albumin level < 3.5 g/dL was significant predictor of poor survival in the CRC group and marginally in the AP group.
5.4% vs. 6.7% 60-day mortality for AP vs. CRC group	Preoperative albumin was not independent survival predictor in multivariate analysis in any of the groups.
PFS and OS were 9 and 12 months in CRC and 12 and 21 months in AP pts	No data regarding albumin as predictor of postoperative morbidity/mortality.
Votanopoulos et al, 2013 [24]	N =13 pts with PM from rectal primary; N = 204 pts with PM from colonic primary	30-day mortality for colon and rectal group was 5.7% and 0%, respectively	Median follow-up was 40.1 and 88.1 months for rectal and colonic group, respectively	In univariate analysis, preoperative albumin level was not statistically significant in predicting survival in the pts groups.
Overall morbidity for the colon and rectal groups was 51% and 46 %, respectively	Median survival was 14.6 months for the rectal group and 17.3 months for the colon group
3-year survival was 28.2% and 25.1 % for the rectal and colon groups, respectively	Albumin was not independent survival predictor in multivariate analysis in any of the groups.
No data regarding albumin as predictor of postoperative morbidity/mortality.
Votanopoulos et al, 2013 [25]	N = 81 patients (> 70 years) with PM of various primary origins (39.5% appendiceal, 24.7% colorectal, 12.3% mesothelioma, 9.9% ovarian, 7.4% gastric, 6.2% other primaries)	Minor morbidity (grade I/II) was 28 %, while major morbidity (grade III/IV) was 38 %	Median follow-up was 48.1 months	Average albumin level of the entire cohort was 3.6 g/dL, while for patients with complications was 3.7 g/dL; average albumin level of those patients who suffered mortality was 3.2 g/dL.
13.6% 30-day mortality for the entire cohort	Median survival stratified by primary cancer: 31.8 months for appendiceal, 41.5 months for mesothelioma, 54 months for ovarian, 13.2 months for colonic, and 7.6 months for gastric	Preoperative albumin was a significant predictor of survival in both univariate and multivariate analysis in absence of complications.
27.4% 90-day mortality for the entire cohort	Mortality risk was reduced by 40% for each additional gram of albumin.
Deraco et al, 2012 [26]	N = 56 pts with PM from recurrent ovarian cancer	5.3% procedure-related mortality	23.1 months median follow-up time	Preoperative serum albumin (cut-off for hypoalbuminemia was 3.5 g/dL) was identified as independent prognostic factor of PFS and OS in multivariate analysis.
Overall DSM rate of 26.3%	Median OS and PFS were 25.7 and 10.8 months, respectively
5-year OS and PFS were 23% and 7%, respectively	No data regarding albumin as predictor of postoperative morbidity/mortality.
Banaste et al, 2018 [27]	N = 214 patients with PM from colorectal primary	50% major postoperative complication rate	Median follow-up was 24 months (range 0 - 82 months)	Preoperative serum albumin (cut-off for hypoalbuminemia was 3.5 g/dL) was identified as independent prognostic factor of PFS and OS in multivariate analysis.
No mortality data	Median OS and PFS were 58.9 and 13 months, respectively	Hypoalbuminemia was not a predictor of postoperative morbidity.
3- and 5-year OS were 63% and 46%, respectively
3- and 5-year PFS survival were 17% and14%, respectively

Table 1. Detailed Presentation of the Studies’ Key Features and the Significance of Preoperative Serum Albumin Levels With Respect to the Surgical and Oncological Outcome

Authors

PSM origin and study sample

Postoperative morbidity and mortality (entire cohort)

Survival (entire cohort)

Significance of hypoalbuminemia

OS: overall survival; PFS: progression-free survival; DFS: disease-free survival; DSM: death and serious morbidity; PM: peritoneal metastases; PSM: peritoneal surface malignancies; PMP: pseudomyxoma peritonei; LOS: length of stay; ICU: intensive care unit; HDU: high dependency unit; N.S.: non-significant; pts: patients.

Graziosi et al, 2016 [19]

N = 64 pts with PM of various primary origins (34.4% colorectal, 32.8% gastric, 14.1% ovarian and 10.9% other origin)

5.1% major postoperative morbidity (grades III/IV)

Median follow-up was 26.5 months (range 4 - 120 months)

With 3.8 g/dL as preoperative albumin cut-off value, 5-year OS of 70% vs. a 5- year OS of 38% in the high vs. low albumin group.

5.1% postoperative mortality

5-year OS was 55 % for entire cohort

Preoperative albumin level was identified as an independent prognostic factor for OS in multivariate analysis.

No data regarding albumin as predictor of postoperative morbidity/mortality.

Cascales-Campos et al, 2016 [20]

N = 85 pts (> 75 years) with PM of various primary origins (42% colorectal, 31% ovarian, 20% appendiceal-PMP, 7% other origin)

43.5% overall morbidity (grades I - IV)

No survival data

Preoperative albumin level < 3 g/dL was associated with overall morbidity (grades I - IV) in univariate analysis.

23.5% and 14.4% minor (grades I/II) and major (grades III/IV) morbidity

5.1% 90-day mortality (2/5 of the deceased died of complications not related to CRS and PIC)

Preoperative albumin level < 3.5 g/dL was associated with major morbidity (grades III/IV) in multivariate analysis.

No survival data.

Huang et al, 2016 [21]

N = 591 pts with PM of various primary origins (31.3% appendiceal 23.4% colorectal, 29.3% PMP, 11.5% mesothelioma, ovarian 4.7%)

41.8% overall major morbidity (grades III/IV)

62.2 months median OS

Preoperative albumin was 3.7 ± 0.55 g/dL for entire cohort; albumin value of 3.5 g/dL used as cut-off of hypoalbuminemia.

Hypoalbuminemic group had statistically significant higher PCI than the normoalbuminemic one.

0.8% post-operative mortality

N.S. differences in mortality between normo- and hypoalbuminemic groups (2 vs. 3 pts).

Hypoalbuminemic group had statistically significant higher rates of major morbidity (grades III/IV), as well as LOS, ICU and HDU hospitalization duration (twice median stay).

In multivariate analysis, preoperative serum albumin < 3.5 g/dL was an independent prognostic factor for a poor perioperative outcome (grades III - V - 1.5-fold risk of a poor perioperative outcome when preoperative serum albumin < 3.5g/dL)).

Hypoalbuminemic group had statistically significant poorer OS (49.3 months (32.0 - 66.6) vs. 65.8 months (48.5 - 83.1)).

Peters et al, 2015 [22]

N = 1,085 pts with PM of various primary origins

44% and 37% overall and major morbidity

No survival data

Preoperative albumin < 3 g/dL and weight loss were the only preoperative factors significantly associated with DSM in the multivariate model.

1.8% postoperative mortality

overall 30-day DSM rate of 37.4%

No survival data.

Winer et al, 2013 [23]

N = 67 pts with PM of appendiceal (AP, n = 37) or colorectal origin (CRC, n = 30) with signet cell histology

22% vs. 29% major morbidity (grade III/IV) in the CRC vs. AP group

Median follow-up of CRC and AP groups was 4.4 and 4.1 years, respectively

In univariate analysis, preoperative albumin level < 3.5 g/dL was significant predictor of poor survival in the CRC group and marginally in the AP group.

5.4% vs. 6.7% 60-day mortality for AP vs. CRC group

Preoperative albumin was not independent survival predictor in multivariate analysis in any of the groups.

PFS and OS were 9 and 12 months in CRC and 12 and 21 months in AP pts

No data regarding albumin as predictor of postoperative morbidity/mortality.

Votanopoulos et al, 2013 [24]

N =13 pts with PM from rectal primary; N = 204 pts with PM from colonic primary

30-day mortality for colon and rectal group was 5.7% and 0%, respectively

Median follow-up was 40.1 and 88.1 months for rectal and colonic group, respectively

In univariate analysis, preoperative albumin level was not statistically significant in predicting survival in the pts groups.

Overall morbidity for the colon and rectal groups was 51% and 46 %, respectively

Median survival was 14.6 months for the rectal group and 17.3 months for the colon group

3-year survival was 28.2% and 25.1 % for the rectal and colon groups, respectively

Albumin was not independent survival predictor in multivariate analysis in any of the groups.

No data regarding albumin as predictor of postoperative morbidity/mortality.

Votanopoulos et al, 2013 [25]

N = 81 patients (> 70 years) with PM of various primary origins (39.5% appendiceal, 24.7% colorectal, 12.3% mesothelioma, 9.9% ovarian, 7.4% gastric, 6.2% other primaries)

Minor morbidity (grade I/II) was 28 %, while major morbidity (grade III/IV) was 38 %

Median follow-up was 48.1 months

Average albumin level of the entire cohort was 3.6 g/dL, while for patients with complications was 3.7 g/dL; average albumin level of those patients who suffered mortality was 3.2 g/dL.

13.6% 30-day mortality for the entire cohort

Median survival stratified by primary cancer: 31.8 months for appendiceal, 41.5 months for mesothelioma, 54 months for ovarian, 13.2 months for colonic, and 7.6 months for gastric

Preoperative albumin was a significant predictor of survival in both univariate and multivariate analysis in absence of complications.

27.4% 90-day mortality for the entire cohort

Mortality risk was reduced by 40% for each additional gram of albumin.

Deraco et al, 2012 [26]

N = 56 pts with PM from recurrent ovarian cancer

5.3% procedure-related mortality

23.1 months median follow-up time

Preoperative serum albumin (cut-off for hypoalbuminemia was 3.5 g/dL) was identified as independent prognostic factor of PFS and OS in multivariate analysis.

Overall DSM rate of 26.3%

Median OS and PFS were 25.7 and 10.8 months, respectively

5-year OS and PFS were 23% and 7%, respectively

No data regarding albumin as predictor of postoperative morbidity/mortality.

Banaste et al, 2018 [27]

N = 214 patients with PM from colorectal primary

50% major postoperative complication rate

Median follow-up was 24 months (range 0 - 82 months)

Preoperative serum albumin (cut-off for hypoalbuminemia was 3.5 g/dL) was identified as independent prognostic factor of PFS and OS in multivariate analysis.

No mortality data

Median OS and PFS were 58.9 and 13 months, respectively

Hypoalbuminemia was not a predictor of postoperative morbidity.

3- and 5-year OS were 63% and 46%, respectively

3- and 5-year PFS survival were 17% and14%, respectively