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Background Although laparoscopic hepatectomy (LH) is associated with improved short-term outcomes compared to open hepatectomy (OH), it is unknown whether frail patients also benefit from LH. The aim of this study was to evaluate the impact of frailty on post-operative outcomes after LH and OH. Patients and methods Consecutive patients who underwent LH and OH between January 2011 and December 2018 were identified from a prospective database. Frailty was assessed using the modified Frailty Index (mFI), with patients scoring mFI ≥ 1 deemed to be frail. Results Of 1826 patients, 34.7% ( N = 634) were frail and 18.6% ( N = 340) were elderly (≥ 75 years). Frail patients had significantly higher 90-day mortality (6.6% vs. 2.9%, p < 0.001) and post-operative complications (36.3% vs. 26.1%, p < 0.001) than those who were not frail, effects that were independent of patient age on multivariate analysis. For those undergoing minor resections, the benefits of LH vs. OH were similar for frail and non-frail patients. Length of hospital stay was 53% longer in OH (vs. LH) in frail patients, compared to 58% longer in the subgroup of non-frail patients. Conclusions Frailty is independently associated with inferior post-operative outcomes in patients undergoing hepatectomy. However, the benefits of laparoscopic (compared to open) hepatectomy are similar for frail and non-frail patients. Frailty should not be a contraindication to laparoscopic minor hepatectomy in carefully selected patients.
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ORIGINAL SCIENTIFIC REPORT
Impact of Frailty on Short-Term Outcomes After Laparoscopic
and Open Hepatectomy
D. Osei-Bordom
1,2
L. Hall
3
J. Hodson
4
K. Joshi
5
L. Austen
6
D. Bartlett
5
J. Isaac
5
D. F. Mirza
5
R. Marudanayagam
5
K. Roberts
5
B. V. Dasari
5
N. Chatzizacharias
5
R. P. Sutcliffe
5
Accepted: 6 June 2022 / Published online: 9 July 2022
ÓThe Author(s) 2022
Abstract
Background Although laparoscopic hepatectomy (LH) is associated with improved short-term outcomes compared
to open hepatectomy (OH), it is unknown whether frail patients also benefit from LH. The aim of this study was to
evaluate the impact of frailty on post-operative outcomes after LH and OH.
Patients and methods Consecutive patients who underwent LH and OH between January 2011 and December 2018
were identified from a prospective database. Frailty was assessed using the modified Frailty Index (mFI), with
patients scoring mFI C1 deemed to be frail.
Results Of 1826 patients, 34.7% (N= 634) were frail and 18.6% (N= 340) were elderly (C75 years). Frail patients
had significantly higher 90-day mortality (6.6% vs. 2.9%, p\0.001) and post-operative complications (36.3% vs.
26.1%, p\0.001) than those who were not frail, effects that were independent of patient age on multivariate
analysis. For those undergoing minor resections, the benefits of LH vs. OH were similar for frail and non-frail
patients. Length of hospital stay was 53% longer in OH (vs. LH) in frail patients, compared to 58% longer in the
subgroup of non-frail patients.
Conclusions Frailty is independently associated with inferior post-operative outcomes in patients undergoing hep-
atectomy. However, the benefits of laparoscopic (compared to open) hepatectomy are similar for frail and non-frail
patients. Frailty should not be a contraindication to laparoscopic minor hepatectomy in carefully selected patients.
D. Osei-Bordom and L. Hall have contributed equally.
&R. P. Sutcliffe
robert.sutcliffe@uhb.nhs.uk
1
Department of General Surgery, Queen Elizabeth Hospital
Birmingham, University Hospitals Birmingham NHS
Foundation Trust, Birmingham B15 2TH, UK
2
Institute of Immunology and Immunotherapy, College of
Medical and Dental Sciences, University of Birmingham,
Birmingham B15 2TH, UK
3
College of Medical and Dental Sciences, University of
Birmingham, Birmingham B15 2TH, UK
4
Department of Medical Statistics, Institute of Translational
Medicine, University Hospitals Birmingham NHS Foundation
Trust, Birmingham B15 2TH, UK
5
The Liver Unit, Nuffield House, Queen Elizabeth Hospital
Birmingham, University Hospitals Birmingham NHS
Foundation Trust, Birmingham B15 2TH, UK
6
Department of Anaesthesia, Birmingham Heartlands
Hospital, University Hospitals Birmingham NHS Foundation
Trust, Birmingham B9 5SS, UK
123
World J Surg (2022) 46:2444–2453
https://doi.org/10.1007/s00268-022-06648-0
Introduction
Hepatectomy is a potentially curative treatment for patients
with primary and secondary hepatic malignancies, and a
laparoscopic approach, when feasible, is associated with
less morbidity, lower mortality and faster recovery than
open surgery [1,2]. In an increasingly ageing population
[3], there is a growing number of frail and elderly patients
with comorbidity who are being considered for major
surgery, including hepatectomy [4]. Although the risks of
surgery are known to increase with advancing age, the
short-term advantages of laparoscopic hepatectomy (LH)
compared to open hepatectomy (OH) appear to be retained,
at least in selected patients undergoing minor hepatectomy
[5,6]. However, the benefits of LH appear to diminish with
increasing age amongst elderly cohorts [7], and it is not
known whether similar benefits of LH are observed in frail
patients.
Frailty is a condition that is characterised by reduced
physiological reserve and is associated with an increased
risk of post-operative complications, prolonged hospital-
ization, increased readmission rates and loss of indepen-
dence following general surgical procedures [8]. Frailty is
also common in patients undergoing hepatectomy, with a
reported incidence of 14–29% in recently published studies
[9,10], although there is currently limited data to support
an association with worse post-operative outcomes [10].
Available data on the impact of frailty in minimally inva-
sive surgery is also limited and conflicting. In two recent
studies of the ACS-NSQIP database, Kothari et al.
demonstrated that the benefits of laparoscopic colectomy
over open colectomy were preserved in frail patients [11],
whilst Lo et al. reported possible worse outcomes after
robotic compared to open colectomy [12]. The effects of
frailty on the short-term outcomes of LH are unknown, and
it is unclear whether frail patients should preferentially
undergo LH or OH.
Various clinical scores have been developed and vali-
dated to measure frailty in surgical patients, and typically
include an assessment of functional status combined with
the presence and severity of comorbidity, such as diabetes
mellitus, hypertension and cardiovascular disease [13]. The
modified Frailty Index (mFI) [14] consists of 11 variables
that were adapted from the original 70-item Frailty Index
[15] and has been shown to be significantly associated with
poor surgical outcomes, including after hepatectomy [8].
The primary aim of this study was to evaluate the effects
of age and frailty on short-term post-operative outcomes
after hepatectomy. The secondary aim was to evaluate the
relationship between age, frailty and post-operative out-
comes in patients undergoing laparoscopic and open
hepatectomy.
Methods
Consecutive patients who underwent laparoscopic or open
hepatectomy at a single centre between 2011 and 2018
were identified from a prospectively maintained database.
Repeat hepatectomy (N= 152) and emergency hepatec-
tomy for trauma (N= 4) patients were excluded. The type
of hepatectomy was defined as minor, major or extra major
according to the Tokyo 2020 terminology of liver anatomy
and resections which is an update of the Brisbane 2000
system [16]. Frailty was defined as a modified Frailty Index
(mFI) C1 and was calculated for all patients. Patients aged
75 years and over were considered elderly, and the effects
of both frailty and age on hepatectomy outcomes were
compared. Data were collected regarding comorbidity,
indications for surgery, post-operative complications,
length of hospital (LOS) and 90-day mortality. Post-oper-
ative complications were graded according to the Clavien–
Dindo classification [17].
Statistical analysis
Continuous variables were reported as median (interquar-
tile range; IQR), and associations with age and mFI were
assessed using Mann–Whitney U tests. Ordinal variables
were analysed using the same approach, whilst nominal
variables were assessed using Fisher’s exact tests. To
assess the interplay between age and frailty with respect to
dichotomous patient outcomes, binary logistic regression
models were produced with age, frailty and the age*frailty
interaction as independent variables. These models were
then evaluated to produce odds ratios for frail vs. non-frail
patients within each age subgroup, with the p-value of the
interaction term representing the comparison between these
two odds ratios. Length of stay was then analysed using a
similar approach, but using an ANOVA model. Lengths of
stay were log
10
-transformed, prior to this analysis, in order
to normalise the distribution; hence were summarised using
geometric means, with differences between groups repor-
ted as percentages. Multivariable models were then pro-
duced, to assess whether age and frailty were independent
predictors of the primary outcomes. This used binary
logistic regression models for 90-day mortality and com-
plication rates, with a general linear model used for length
of stay, which was log
10
-transformed for analysis. Age and
frailty were entered into the models as continuous covari-
ates, and a backwards stepwise approach was used to select
other potentially confounding factors for inclusion in the
models. Analyses were then performed to compare the
effect of operative approach (open vs. laparoscopic)
between subgroups of age and frailty, which used a similar
approach to that previously described. All analyses were
World J Surg (2022) 46:2444–2453 2445
123
performed using IBM SPSS 24 (IBM Corp. Armonk, NY),
with p\0.05 deemed to be indicative of statistical sig-
nificance throughout.
Results
Cohort characteristics
Data were available for a total of N= 1826 patients (56.6%
male), with a median age of 65.3 years (IQR: 56.0–73.1).
The most common indication for surgery was colorectal
liver metastases (58.8%), with the majority of patients
undergoing open surgery (86.0%). The extent of resection
was minor in 53.1% of cases, with 33.3% major and 13.6%
extra-major resections. Major (Clavien–Dindo grade III-V)
complications developed in 10.7% of patients, and patients
surviving to discharge had a median length of stay of
6 days (IQR: 5–8). In-hospital, 30-day and 90-day mor-
tality rates were 2.2% (N= 40), 1.9% (N= 35) and 4.2%
(N= 76), respectively.
Age and frailty of the cohort
The majority of patients scored 0 on the mFI (65.3%), with
25.9%, 8.5%, and 0.3% scoring 1, 2 and 3 points, respec-
tively. The hypertension and diabetes mellitus components
were the main contributors to the mFI scores, being present
in 26.1% and 13.3% of patients, respectively. Only 0.3%
(N= 5) of patients were non-independent with their
activities of daily living. A significant correlation between
age and mFI was observed (rho: 0.304, p\0.001), with
the median age increasing from 62.1 (IQR: 52.2–70.9) to
71.7 (64.4–76.7) years, for those with an mFI of 0 vs. 2–3.
Table 1 Cohort characteristics by age and frailty
NAge at surgery mFI Score
\75 years C75 years p-value mFI = 0 mFI C1p-value
Age at surgery (years) 1826 62.2
(53.4–68.7)
78.6
(76.6–80.8)
N/A 62.1
(52.2–70.9)
69.7
(63.2–75.6)
< 0.001
Gender (% male) 1826 812 (54.6%) 222 (65.3%) < 0.001 615 (51.6%) 419 (66.1%) < 0.001
BMI (kg/m
2
) 1825 27.1
(24.3–30.9)
27.2
(24.7–30.0)
0.840 26.6
(23.9–29.8)
28.4
(25.5–31.8)
< 0.001
ASA grade (% [2) 1826 421 (28.3%) 103 (30.3%) 0.466 345 (28.9%) 179 (28.2%) 0.786
Hypertension 1826 333 (22.4%) 144 (42.4%) < 0.001 0 (0.0%) 477 (75.2%) N/A
Diabetes mellitus 1826 177 (11.9%) 65 (19.1%) < 0.001 0 (0.0%) 242 (38.2%) N/A
Congestive heart failure 1826 2 (0.1%) 0 (0.0%) 1.000 0 (0.0%) 2 (0.3%) N/A
COPD/pneumonia 1826 52 (3.5%) 22 (6.5%) 0.021 0 (0.0%) 74 (11.7%) N/A
Non-independent in ADL 1826 4 (0.3%) 1 (0.3%) 1.000 0 (0.0%) 5 (0.8%) N/A
mFI (% C1) 1826 456 (30.7%) 178 (52.4%) < 0.001 ––
Indication for surgery 1826 < 0.001 < 0.001
Colorectal liver metastases 848 (57.1%) 226 (66.5%) 705 (59.1%) 369 (58.2%)
Hepatocellular carcinoma 115 (7.7%) 49 (14.4%) 75 (6.3%) 89 (14.0%)
Gallbladder
cancer/cholangiocarcinoma
149 (10.0%) 31 (9.1%) 102 (8.6%) 78 (12.3%)
Other malignant 145 (9.8%) 18 (5.3%) 123 (10.3%) 40 (6.3%)
Benign 229 (15.4%) 16 (4.7%) 187 (15.7%) 58 (9.1%)
Extent of resection 1826 0.042** 0.200**
Minor 774 (52.1%) 196 (57.6%) 623 (52.3%) 347 (54.7%)
Major 501 (33.7%) 107 (31.5%) 397 (33.3%) 211 (33.3%)
Extra-major 211 (14.2%) 37 (10.9%) 172 (14.4%) 76 (12.0%)
Operative approach (% open) 1826 1285 (86.5%) 286 (84.1%) 0.260 1034 (86.7%) 537 (84.7%) 0.229
Operative duration (hours) 1790 4.6 (3.6–5.8) 4.2 (3.4–5.2) < 0.001 4.5 (3.5–5.7) 4.4 (3.5–5.6) 0.451
Blood transfusion* 1826 147 (9.9%) 43 (12.6%) 0.140 119 (10.0%) 71 (11.2%) 0.422
Continuous variables are reported as median (interquartile range), with p-values from Mann–Whitney U tests. Categorical variables are reported
as N(column %), with p-values from Fisher’s exact tests, unless stated otherwise. Bold p-values are significant at p\0.05. *Within 24 h post-
operatively. **p-Value from Mann–Whitney U test, as the factor is ordinal. ADL activities of daily living; BMI body mass index; COPD Chronic
obstructive pulmonary disease; mFI modified frailty index
2446 World J Surg (2022) 46:2444–2453
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This was largely as a result of the comorbidity components
of the mFI, with rates of hypertension, diabetes mellitus
and COPD/pneumonia all increasing significantly with age
(all p\0.001).
Characteristics and outcomes by age and frailty
For the initial analyses, both age and mFI were dichot-
omised, with age C75 years classified as ‘elderly’
(18.6%; N= 340), and mFI C1 classified as ‘frail’
(34.7%; N= 634). Of the demographic factors considered
(Table 1), both elderly and frail patients were found to be
significantly more likely to be male, and to have malignant
tumours. Elderly patients were additionally found to have
significantly less extensive resections, compared to the
non-elderly (p= 0.042; minor resections: 57.6% vs.
52.1%), with a corresponding reduction in the average
operative duration (median: 4.2 vs. 4.6 h; p\0.001); no
such significant differences were observed for the analysis
of frailty (p= 0.200, p= 0.451, respectively). Rates of
open (vs. laparoscopic) surgery were not found to differ
significantly by age (p= 0.260) or frailty (p= 0.229).
Table 2 Post-operative complications by patient age and modified Frailty Index
Age at surgery mFI Score
\75 years C75 years p-value mFI = 0 mFI C1p-value
Any complications 425 (28.6%) 116 (34.1%) 0.048 311 (26.1%) 230 (36.3%) < 0.001
Highest Clavien–Dindo grade 0.032** < 0.001**
No complication 1061 (71.4%) 224 (65.9%) 881 (73.9%) 404 (63.7%)
Grade I–II 270 (18.2%) 75 (22.1%) 201 (16.9%) 144 (22.7%)
Grade III–V 155 (10.4%) 41 (12.1%) 110 (9.2%) 86 (13.6%)
Length of stay (days)* 6 (5–8) 7 (5–9) < 0.001 6 (5–8) 6 (5–9) 0.060
30-day mortality 22 (1.5%) 13 (3.8%) 0.008 14 (1.2%) 21 (3.3%) 0.002
90-day mortality 53 (3.6%) 23 (6.8%) 0.015 34 (2.9%) 42 (6.6%) < 0.001
In-hospital mortality 25 (1.7%) 15 (4.4%) 0.006 17 (1.4%) 23 (3.6%) 0.004
Details of surgical complications
PHLF 45 (3.0%) 7 (2.1%) 0.468 28 (2.3%) 24 (3.8%) 0.103
PHLF Grade 0.335** 0.079**
No PHLF 1441 (97.0%) 333 (97.9%) 1164 (97.7%) 610 (96.2%)
Grade A 24 (1.6%) 3 (0.9%) 14 (1.2%) 13 (2.1%)
Grade B 8 (0.5%) 2 (0.6%) 7 (0.6%) 3 (0.5%)
Grade C 13 (0.9%) 2 (0.6%) 7 (0.6%) 8 (1.3%)
Bile leak 65 (4.4%) 9 (2.6%) 0.170 41 (3.4%) 33 (5.2%) 0.081
Post-operative haemorrhage 25 (1.7%) 8 (2.4%) 0.372 23 (1.9%) 10 (1.6%) 0.713
Wound infection 45 (3.0%) 10 (2.9%) 1.000 37 (3.1%) 18 (2.8%) 0.886
Re-operation for bleeding 10 (0.7%) 5 (1.5%) 0.175 11 (0.9%) 4 (0.6%) 0.597
Radiological drainage of collection 42 (2.8%) 6 (1.8%) 0.348 28 (2.3%) 20 (3.2%) 0.357
Other surgical complication 32 (2.2%) 5 (1.5%) 0.526 20 (1.7%) 17 (2.7%) 0.164
Any of the above 226 (15.2%) 43 (12.6%) 0.270 162 (13.6%) 107 (16.9%) 0.061
Details of medical complications
Pneumonia 85 (5.7%) 20 (5.9%) 0.897 62 (5.2%) 43 (6.8%) 0.171
AKI (requiring RRT) 4 (0.3%) 2 (0.6%) 0.311 3 (0.3%) 3 (0.5%) 0.424
Respiratory failure (requiring vent.) 12 (0.8%) 5 (1.5%) 0.342 10 (0.8%) 7 (1.1%) 0.613
Myocardial infarction 5 (0.3%) 3 (0.9%) 0.173 6 (0.5%) 2 (0.3%) 0.722
Dysrhythmia 35 (2.4%) 20 (5.9%) 0.001 30 (2.5%) 25 (3.9%) 0.113
Other medical complication 120 (8.1%) 40 (11.8%) 0.034 84 (7.0%) 76 (12.0%) < 0.001
Any of the above 247 (16.6%) 84 (24.7%) < 0.001 182 (15.3%) 149 (23.5%) < 0.001
Continuous variables are reported as median (interquartile range), with p-values from Mann–Whitney U tests. Categorical variables are reported
as N(column %), with p-values from Fisher’s exact tests, unless stated otherwise. Bold p-values are significant at p\0.05. *Excludes patients
that died in hospital prior to discharge. **p-Value from Mann–Whitney U test, as the factor is ordinal. AKI acute kidney injury; mFI modified
frailty index; PHLF Post hepatectomy liver failure; RRT renal replacement therapy; Vent. ventilation
World J Surg (2022) 46:2444–2453 2447
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Univariable analysis of post-operative outcomes found
overall complication rates to be significantly higher in both
elderly (34.1% vs. 28.6%, p= 0.048) and frail (36.3% vs.
26.1%, p\0.001) patients (Table 2). Further assessment
of complication types found that this was largely a result of
higher rates of medical complications (p\0.001 for both),
with surgical complication rates not found to be signifi-
cantly higher in either elderly (p= 0.270) or frail
(p= 0.061) patients. Elderly patients also had significantly
longer lengths of stay (median: 7 vs. 6 days, p\0.001),
with no such difference observed for frail patients (median:
6 vs. 6 days, p= 0.060). Mortality rates were also signif-
icantly higher in the elderly and the frail, with 90-day
mortality of 6.8% vs. 3.6% (p= 0.015) for elderly vs. non-
elderly, and 6.6% vs. 2.9% (p\0.001) for frail vs. non-
frail.
Interplay between age and frailty
Comparisons of outcomes between frail and non-frail
patients were then performed within the elderly and non-
elderly patient subgroups. Analysis of mortality, compli-
cation rates and length of stay found the effect of frailty to
be similar in non-elderly and elderly patients (Table 3). For
example, for non-elderly patients, frailty (vs. non-frailty)
was associated with odds ratio for 90-day mortality of 2.25
(5.7% vs. 2.6%), which was similar to the 2.19 (9.0% vs.
4.3%) observed in elderly patients (p= 0.961).
Associations with primary outcomes
The associations between both age and frailty, and the
primary outcomes of 90-day mortality, post-operative
complications and length of stay were then assessed in
further detail. Age and mFI were treated as continuous
covariates in these analyses and were found to be signifi-
cantly associated with all three outcomes on univariable
analysis (Fig. 1). On multivariable analysis, both age and
mFI were found to be significant independent predictors of
90-day mortality, with odds ratios of 1.71 (95% CI:
1.32–2.22, p\0.001) per decade of age and 1.45
(1.04–2.03, p= 0.029) per point on the mFI (Table 4). Age
and mFI were found to be significant independent predic-
tors of post-operative complications (p\0.001, p= 0.002,
respectively). Whilst age was found to be significantly
associated with length of stay (p\0.001), mFI narrowly
missed statistical significance in this analysis (p= 0.056).
Effect of operative approach by age and frailty
in minor resections
The operative approach was found to vary significantly by
the extent of the resection (p\0.001), with 22.3% of
minor resections being laparoscopic, compared to 6.1% of
major and 0.8% of extra-major resections. As such, to
negate the confounding effect of the extent of resection,
only the subgroup of minor resections were considered in
Table 3 Interplay between age and frailty
Age: \75 years Age: C75 years Interaction term
p-value
mFI = 0
(N= 1030)
mFI C1
(N= 456)
Odds ratio
(95% CI)
mFI = 0
(N= 162)
mFI C1
(N= 178)
Odds ratio
(95% CI)
Any complications 265 (25.7%) 160 (35.1%) 1.56
(1.23–1.98)
46 (28.4%) 70 (39.3%) 1.63
(1.04–2.58)
0.860
Any surgical
complication
143 (13.9%) 83 (18.2%) 1.38
(1.03–1.86)
19 (11.7%) 24 (13.5%) 1.17
(0.62–2.23)
0.652
Any medical
complication
151 (14.7%) 96 (21.1%) 1.55
(1.17–2.06)
31 (19.1%) 53 (29.8%) 1.79
(1.08–2.97)
0.628
Length of stay
(days)*
6.3 (6.1, 6.5)* 6.5 (6.2, 6.9)* 4% (-3%,
10%)
6.9 (6.3, 7.6)* 7.8 (7.0, 8.6)* 12% (-2%,
28%)*
0.276*
In-hospital
mortality
13 (1.3%) 12 (2.6%) 2.11
(0.96–4.67)
4 (2.5%) 11 (6.2%) 2.60
(0.81–8.34)
0.773
30-day mortality 10 (1.0%) 12 (2.6%) 2.76
(1.18–6.43)
4 (2.5%) 9 (5.1%) 2.10
(0.64–6.97)
0.718
90-day mortality 27 (2.6%) 26 (5.7%) 2.25
(1.30–3.89)
7 (4.3%) 16 (9.0%) 2.19
(0.88–5.46)
0.961
For binary outcomes, odds ratios are from binary logistic regression models within each age subgroup, with mFI (C1 vs. 0) as the independent
variable. The p-values relate to the interaction terms of binary logistic regression models with age, frailty and the age*frailty interaction as
independent variables, hence represent a comparison between the reported odds ratio for each subgroup. *Analysis of length of stay excluded
those patients who died in hospital prior to discharge. For the remainder, the average lengths of stay are reported as geometric mean (95% CI).
Lengths of stay were then log
10
-transformed, and analysed using an ANOVA model, parameterised as previously described, with the com-
parisons between groups reported as percentage differences. CI confidence interval; mFI modified frailty index
2448 World J Surg (2022) 46:2444–2453
123
the analysis (N= 970). Within this subgroup, neither
complication nor mortality rates were found to differ sig-
nificantly by the operative approach (Table 5). However,
open surgery was associated with a significantly longer
operative duration (median: 4.1 vs. 3.6 h, p\0.001) and
length of stay (median 6 vs. 4 days, p\0.001), compared
to laparoscopic surgery. The effects of operative approach
were then compared between elderly vs. non-elderly and
frail vs. non-frail patients (Table 6). We found no evidence
to suggest that the effect of operative approach varied
significantly by age or frailty for any of the outcomes
considered. For example, open (vs. laparoscopic) surgery
was associated with a 53% (geometric mean: 6.5 vs.
4.2 days) longer length of stay in frail patients, which was
similar to the 58% (6.1 vs. 3.8 days) longer length of stay
after open (vs. laparoscopic) surgery in non-frail patients
(p= 0.699). As such, the relative benefits of laparoscopic
vs. open surgery appeared to be similar, regardless of the
age or frailty of the patient. However, these analyses were
limited by the small number of outcomes occurring within
some subgroups of patients, with no events being observed
for some of the outcomes considered. This will have
Fig. 1 Associations between
age/mFI and the primary
outcomes. Points represent the
observed
mortality/complication rates, or
the geometric mean lengths of
stay, with whiskers representing
95% confidence intervals. For
age, each point corresponds to a
quintile of the age distribution,
and is plotted at the mean of the
interval, whilst points for mFI
correspond to values of 0, 1 and
2; mFI = 3 was not plotted, due
to the small sample size
(N= 5). Trend lines are from
univariable binary logistic
regression models for the
dichotomous outcomes, with a
univariable log-linear regression
model used for length of stay, as
per Table 4
World J Surg (2022) 46:2444–2453 2449
123
resulted in very low statistical power, meaning that only
large differences will have been detectable. As such, this
analysis will be subject to an inflated false-negative rate,
and the results must be interpreted with this in mind.
Discussion
Frailty is increasingly recognised as being an important
determinant of post-operative outcomes in surgical patients
[18], and our data have shown that frailty is an independent
predictor of morbidity and mortality after hepatectomy.
Over one third of patients in this large cohort were con-
sidered frail, and despite acceptable short-term outcomes,
were exposed to an increased risk of medical complica-
tions, prolonged recovery and post-operative mortality
compared to non-frail patients, which is consistent with
published data [9,19,20]. Importantly, frailty was asso-
ciated with worse outcomes for both elderly and non-
elderly patients undergoing hepatectomy. Data from meta-
analyses and randomized trials have shown that laparo-
scopic hepatectomy is associated with improved short-term
outcomes compared to open hepatectomy [2,21]. Our
analysis has indicated that the short-term benefits (e.g.
reduced hospital stay) of laparoscopic surgery are retained
in frail patients undergoing minor hepatectomy, and sug-
gests that in carefully selected patients, frailty is not a
contraindication to laparoscopic minor hepatectomy. This
Table 4 Associations between age/frailty and primary outcomes
Univariable analysis Multivariable analysis
Coefficient (95% CI) p-value Coefficient (95% CI) p-value
90-day mortality
Age at surgery (per decade) 1.75 (1.39–2.22) < 0.001 1.71 (1.32–2.22) < 0.001
mFI (per point) 1.72 (1.28–2.32) < 0.001 1.45 (1.04–2.03) 0.029
Any post-operative complications
Age at surgery (per decade) 1.24 (1.14–1.35) < 0.001 1.26 (1.14–1.39) < 0.001
mFI (per point) 1.40 (1.21–1.62) < 0.001 1.30 (1.10–1.53) 0.002
Length of stay
Age at surgery (per decade) 4.5% (2.4%, 6.7%) < 0.001 5.9% (3.7%, 8.1%) < 0.001
mFI (per point) 5.5% (1.4%, 9.9%) 0.009 3.8% (-0.1%, 8.0%) 0.056
Analyses of 90-day mortality and complications were performed using binary logistic regression models, with coefficients representing odds
ratios. Analysis of length of stay was performed using general linear models, with the log
10
[length of stay] as the dependent variable; coefficients
represent percentage differences. For all outcomes, age and mFI were initially treated as continuous covariates in separate univariable models,
with coefficients representing the change in the outcome per decade or per point, respectively. Multivariable models were then produced, which
considered gender, BMI, ASA grade, indication for surgery, extent of resection, operative approach and duration of surgery for inclusion, with a
backwards stepwise approach to variable selection. The full models are reported in Supplementary Table 1–3. Bold p-values are significant at
p\0.05. CI confidence interval; mFI modified frailty index; OR odds ratio
Table 5 Outcomes by operative approach in minor resections
Operative approach
Laparoscopic (N= 216) Open (N= 754) p-value
Operative duration (hours) 3.6 (3.0–4.4) 4.1 (3.3–5.2) < 0.001
Any complications 37 (17.1%) 175 (23.2%) 0.062
Any surgical complication 13 (6.0%) 74 (9.8%) 0.104
Any medical complication 24 (11.1%) 110 (14.6%) 0.219
Length of stay (days)* 4 (3–5) 6 (5–7) < 0.001
In-hospital mortality 2 (0.9%) 7 (0.9%) 1.000
30-day mortality 2 (0.9%) 6 (0.8%) 1.000
90-day mortality 3 (1.4%) 19 (2.5%) 0.441
Only those patients with minor resections (N= 970) are included in the analysis. Data are reported as N(column %), with p-values from Fisher’s
exact tests, or as median (interquartile range), with p-values from Mann–Whitney U tests. Bold p-values are significant at p\0.05. *Analysis of
length of stay excluded those patients who died in hospital prior to discharge
2450 World J Surg (2022) 46:2444–2453
123
finding is not unexpected, since the benefits of laparoscopic
surgery are primarily due to reduced medical complica-
tions, which occur as a result of less post-operative pain,
improved respiratory function and earlier ambulation. It is
unknown whether frail patients undergoing major
hepatectomy would also benefit from a laparoscopic
approach. A recent patient blinded randomized trial
demonstrated a faster recovery in patients undergoing
laparoscopic major hepatectomy compared to open [22],
but there is currently no data specifically evaluating the
Table 6 Interplay between operative approach and age/frailty in minor resections
Age: \75 years Age: C75 years
Laparoscopic
(N= 172)
Open
(N= 602)
Odds ratio
(95% CI)
Laparoscopic
(N= 44)
Open
(N= 152)
Odds ratio
(95% CI)
Interaction term
p-value
Operative duration
(hours)*
3.7 (3.5, 3.9)* 4.2 (4.1,
4.4)*
15% (8%,
22%)*
3.8 (3.5, 4.2)* 3.9 (3.8,
4.1)*
3% (-6%,
14%)*
0.096*
Any complications 29 (16.9%) 132
(21.9%)
1.38
(0.89–2.16)
8 (18.2%) 43 (28.3%) 1.78
(0.76–4.13)
0.610
Any surgical
complication
11 (6.4%) 60 (10.0%) 1.62
(0.83–3.16)
2 (4.5%) 14 (9.2%) 2.13
(0.47–9.75)
0.747
Any medical
complication
18 (10.5%) 79 (13.1%) 1.29
(0.75–2.22)
6 (13.6%) 31 (20.4%) 1.62
(0.63–4.18)
0.683
Length of stay
(days)*
3.9 (3.6, 4.2)* 6.0 (5.8,
6.3)*
54% (41%,
67%)*
4.4 (3.7, 5.1)* 7.1 (6.5,
7.7)*
61% (34%,
92%)*
0.632*
In-hospital mortality 0 (0.0%) 4 (0.7%) NC** 2 (4.5%) 3 (2.0%) 0.42
(0.07–2.61)
NC**
30-day mortality 0 (0.0%) 3 (0.5%) NC** 2 (4.5%) 3 (2.0%) 0.42
(0.07–2.61)
NC**
90-day mortality 1 (0.6%) 15 (2.5%) 4.37
(0.57–33.3)
2 (4.5%) 4 (2.6%) 0.57
(0.10–3.21)
0.134
mFI = 0 mFI C1
Laparoscopic
(N= 130)
Open
(N= 493)
Odds ratio
(95% CI)
Laparoscopic
(N= 86)
Open
(N= 261)
Odds ratio
(95% CI)
Interaction term
p-value
Operative duration
(hours)*
3.6 (3.4, 3.8)* 4.2 (4.1,
4.3)*
17% (10%,
25%)*
3.9 (3.6, 4.2)* 4.1 (4.0,
4.3)*
6% (-2%,
15%)*
0.066*
Any complications 21 (16.2%) 97 (19.7%) 1.27
(0.76–2.13)
16 (18.6%) 78 (29.9%) 1.86
(1.02–3.41)
0.345
Any surgical
complication
8 (6.2%) 42 (8.5%) 1.42
(0.65–3.10)
5 (5.8%) 32 (12.3%) 2.26
(0.85–6.01)
0.465
Any medical
complication
13 (10.0%) 61 (12.4%) 1.27
(0.68–2.39)
11 (12.8%) 49 (18.8%) 1.58
(0.78–3.19)
0.656
Length of stay
(days)*
3.8 (3.5, 4.2)* 6.1 (5.8,
6.3)*
58% (43%,
73%)*
4.2 (3.8, 4.8)* 6.5 (6.1,
6.9)*
53% (34%,
74%)*
0.699*
In-hospital mortality 1 (0.8%) 3 (0.6%) 0.79
(0.08–7.66)
1 (1.2%) 4 (1.5%) 1.32
(0.15–12.00)
0.749
30-day mortality 1 (0.8%) 3 (0.6%) 0.79
(0.08–7.66)
1 (1.2%) 3 (1.1%) 0.99
(0.10–9.63)
0.891
90-day mortality 1 (0.8%) 9 (1.8%) 2.40
(0.30–19.1)
2 (2.3%) 10 (3.8%) 1.67
(0.36–7.79)
0.785
Only those patients with minor resections (N= 970) are included in the analysis, with analysis of length of stay additionally excluding those
patients who died in hospital prior to discharge. For the analysis by age, odds ratios are from binary logistic regression models within each age
subgroup, with the operative approach (open vs. laparoscopic) as the independent variable. The p-values relate to the interaction terms of binary
logistic regression models with age, operative approach and the age*operative approach interaction as independent variables, hence represent a
comparison between the reported odds ratio for each subgroup. The analysis was repeated similarly for mFI. *Operative duration and length of
stay followed skewed distributions, hence were log
10
-transformed, and analysed using an ANOVA model, parameterised as previously described;
averages are reported as geometric means (95% CI), and comparisons between groups are reported as percentage differences. **Hazard ratios
were not calculable, as there were no events in one of the subgroups
World J Surg (2022) 46:2444–2453 2451
123
outcomes of laparoscopic major hepatectomy in frail
patients. Laparoscopic major hepatectomy is a complex
procedure associated with significantly longer operating
times and longer hepatic inflow occlusion times compared
to open surgery, and it is unknown whether these factors
may negate the potential benefits of laparoscopic surgery in
frail patients. It was not possible to evaluate the effect of
laparoscopic approach in frail patients undergoing major
hepatectomy in our study due to small numbers in this
subgroup (Supplementary Table 4), and it is likely that a
multi-centre study would be required.
Detection of frailty prior to major surgery is important,
since it may allow risk stratification, facilitates preopera-
tive counselling, and guides perioperative management
including choice of post-operative destination (i.e. critical
care or surgical high dependency). Frail patients may also
benefit from preoperative interventions to address rever-
sible deficits (e.g. aerobic fitness and nutrition) [23], and
the concept of prehabilitation is likely to become a central
component of perioperative care for patients being con-
sidered for hepatectomy in the near future [24,25]. Post-
operative functional recovery following hospital discharge
and return to baseline function is an under-researched,
patient-centred outcome that may also be influenced by
frailty. A recent Japanese study of over 65-year-old
patients undergoing hepatectomy found that frailty,
advanced age (C76 years) and open hepatectomy were
independent risk factors for post-operative loss of inde-
pendence [9].
This study has several limitations. Due to its retro-
spective nature, the effect of selection bias on the operative
approach may have affected the results, and it was also not
possible to ascertain how many patients were deemed
unsuitable for hepatectomy due to severe frailty. As dis-
cussed above, the small number of laparoscopic major
hepatectomy patients precluded analysis of the impact of
frailty and outcome in this subgroup.
In conclusion, frailty is a common finding in patients
undergoing hepatectomy, and is an independent risk factors
for post-operative morbidity and mortality. The short-term
benefits of laparoscopic hepatectomy appear to be pre-
served in frail patients. As such, frailty is not contraindi-
cated in patients being considered for laparoscopic minor
hepatectomy. Further study is needed to determine if frail
patients would also benefit from laparoscopic major
hepatectomy.
Declarations
Conflict of interest The authors declare that the research was con-
ducted in the absence of any commercial or financial relationships
that could be construed as a potential conflict of interest.
Open Access This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use, sharing,
adaptation, distribution and reproduction in any medium or format, as
long as you give appropriate credit to the original author(s) and the
source, provide a link to the Creative Commons licence, and indicate
if changes were made. The images or other third party material in this
article are included in the article’s Creative Commons licence, unless
indicated otherwise in a credit line to the material. If material is not
included in the article’s Creative Commons licence and your intended
use is not permitted by statutory regulation or exceeds the permitted
use, you will need to obtain permission directly from the copyright
holder. To view a copy of this licence, visit http://creativecommons.
org/licenses/by/4.0/.
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... Ten studies containing surgical data after liver surgery between frail versus nonfrail patients were included (Table 1). [13][14][15][16][17][18][19][20][21][22] The initial search found 1027 studies. After excluding duplicates and unrelated studies based on abstract triage, 18 full texts were assessed for eligibility, of which ten matched the inclusion criteria and were systematically reviewed. ...
... Eight studies were retrospective, whereas two were designed prospectively. [13][14][15][16][17][18][19][20][21][22] The total number of included patients was 71,102, split into two groups: study group/frail group (F, n = 17,167) and control group/nonfrail group (NF, n = 53,928). Frailty was defined by using one of the already known scores: the 11-factor modified frailty index (mFI-11, n = 3), the 5-factor modified frailty index (mFI-5, n = 1), the clinical frailty scale (CFS, n = 3), the Johns Hopkins frailty assessment calculator (Johns Hopkins score, n = 2), and the Kihon checklist (KCL, n = 1). ...
... Eight studies, describing 45,014 patients, included data on mean age. 14,15,[17][18][19][20][21][22] Nonfrail patients were significantly younger with a mean difference of 0.54 years, with significant interstudy variance (mean difference 0.540, 95% CI 0.055-1.024, p = 0.02, Q = 661.067, ...
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... Be that as it may, the laparoscopic approach is generally accepted as a superior approach in terms of postoperative recovery and return to normal life function [78]. As frailty did not alter the benefits of laparoscopic surgery in a hepatectomy population [79], it seems unlikely that it will do so in the case of cholecystectomy. Our subgroup analysis showed no difference between studies including open and laparoscopic surgeries and studies using laparoscopic approaches only for cholecystectomy in terms of how well frailty can predict their outcomes, but it is worth mentioning that there are few studies in this matter and this non-superiority may be due to this limitation. ...
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... Osei-Bordom et al. showed that patients with frailty had significantly higher 90-day mortality (6.6% vs. 2.9%, p < 0.001) and postoperative complications (36.3% vs. 26.1%, p < 0.001) following liver resection [64]. Frailty can also impact long-term outcomes, with frail patients showing significantly worse 3-year survival post-resection for CRLM than patients without frailty (69.3% vs. 91%, p < 0.01) [65]. ...
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Background and aim Favorable outcomes of laparoscopic hepatectomy (LH) over open hepatectomy (OH) have been demonstrated. LH offers less postoperative morbidity, less blood loss and shorter hospital stay, while maintaining oncological safety. Only limited evidence about outcomes of LH in elderly is currently available. Therefore, this study aimed to compare short term outcomes of LH to OH for patients >65 years. Methods A systematic review and meta-analysis were performed according to Cochrane guidelines. Embase, PubMed, Cochrane Library, and Google Scholar were searched to identify eligible studies. Studies were included if they compared LH to OH, and focused on an elderly population, or had a majority of patients >65 years. Perioperative and postoperative outcomes were analyzed. Results Thirteen studies with 1 174 patients (LH:532, OH:642) were included for analysis. When compared to OH, elderly undergoing LH had significantly less postoperative complications (relative risk [RR]0.52; 95% confidence interval(CI):0.43-0.63), less blood loss (mean difference[MD]-198.58; 95% CI:-299.88 to -97.28), and shorter length of stay (MD-4.83; 95%CI:-7.91 to -1.84), while oncological safety was non-inferior (RR1.04; 95%CI:1.00-1.08). Conclusions Within the elderly population LH seems to be superior to OH, concerning short-term outcomes. However, for broader applicability more trials are needed including more difficult and major resections.
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To evaluate comparative outcomes of laparoscopic versus open hepatectomy for malignant liver tumours in elderly patients. A systematic online search was conducted using the following databases: PubMed, Scopus, Cochrane database, The Virtual Health Library, Clinical trials.gov, and Science Direct. Comparative studies comparing laparoscopic (LH) versus open hepatectomy (OH) for both primary and metastatic malignant liver tumours in the elderly were included. Total operative time (minutes), need to perform Pringle's manoeuvre, blood loss (ml), the requirement for blood transfusion intra-operatively/post-operatively, post-operative complications, r0 resection rate, specimen resection margin (mm), re-operation rate, length of hospital stay (LOS), and 90-day mortality were the evaluated outcome parameters. Twelve studies reporting a total number of 1762 patients who underwent laparoscopic (n = 831) or open (n = 931) hepatectomy were included. OH group was associated with a significantly higher overall number of post-operative complications compared to LH (P = 0.00001). Complications such as post-operative liver failure (P = 0.02), ascites formation (P = 0.002), surgical site infection (P = 0.02), blood loss (P = 0.03), blood transfusion rate (P = 0.05), and LOS (P = 0.00001) were significantly higher in the OH group when compared to LH. There was no significant difference between the two groups in terms of total operative time (P = 0.53), bile leak (P = 0.12), r0 resection rate (P = 0.36), re-operation (P = 0.70), and 90-day mortality (P = 0.11). Laparoscopic liver resections are safe with at least equal or superior peri-operative outcomes in the elderly population, although available data regards mainly the results of minor resections. Laparoscopic major resections in the elderly population should be carefully evaluated and preferably performed in expert centres.
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Objective: To assess four measures of the accumulating deficits model of frailty for postoperative mortality and readmissions including their stability over time. Background: Frailty has been assessed by multiple methods. It is unclear whether variation in how frailty is measured is important and would be stable over time. Methods: Rockwood's 57-item frailty index (FI) was mapped onto 14,568 ICD9 diagnosis codes from Healthcare Cost and Utilization Project State Inpatient Database for the state of Florida (HCUP-SID-FL) for calendar years 2011-2015, inclusive, with 962 ICD9 codes matching onto 42 items. This became the modified frailty index (mFI) used. Three measures of the mFI were differentiated: the number of admission diagnoses, number of chronic conditions upon admission, and number of increased deficits accumulated during the admission. The Charlson Co-Morbidity Index was a fourth measure of frailty. The mFI of patients who survived or died and were readmitted or not were compared. Results: Across all years, 4,796,006 patient observations were compared to the number of diagnoses matched on the 42 items of the mFI. The median mFI scores for each method was statistically significantly higher for patients who died compared those that survived and for patients readmitted compared to patients not re-admitted for all years. There was little-to-no variation in the year to year median mFI scores. Conclusions: The four methods of calculating frailty performed similarly and were stable. The actual method of determining the accumulated deficits may not be as important as enumerating their number.
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Background: Prehabilitation encompasses multidisciplinary interventions to improve health and lessen incidence of surgical deterioration by reducing physiologic stress and functional decline. This study presents an interim analysis to demonstrate prehabilitation for hepatopancreatobiliary (HPB) surgical patients. Methods: In 2018, a structured prehabilitation pilot program was implemented. Eligibility required HPB malignancy, neoadjuvant chemotherapy, and residence within hour drive. Patients were enrolled into the 4-month program. The fitness component was composed of timed up and go test and grip strength with exercise recommendations. Nutrition involved evaluation of sarcopenic obesity, glucose management, and smoking and alcohol counseling. Psychological services included psychosocial assessments and advanced care planning, with social work referrals. Component were evaluated monthly by a physician using laboratory results, nutritional data and questionnaires, psychological assessments, and validated fitness tests. Nurse navigators spoke with patients weekly to monitor compliance. Results: At 12 months, nineteen patients were enrolled. Ten completed prehabilitation, neoadjuvant chemotherapy and underwent their surgical procedure. There were no differences found after prehabilitation in functional status, physical performance, psychosocial assessments, or nutrition. Frailty, as assessed by Fried frailty criteria, improved significantly after prehabilitation ( P < .0001). Symptom severity and laboratory values did not change. Length of stay was 6.5 days and all patients were discharged to home. There was 1 readmission for transient ischemic attack and 90-day mortality rate was 0%. Discussion: Prehabilitation to improve recovery is a promising concept encompassing a wide array of multidisciplinary assessments and interventions. It may demonstrate a protective effect on physiologic decline from chemotherapy and may reverse frailty phenotypes.
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Background: Liver resection is commonly performed among patients at risk of being frail. Frailty can be used to assess perioperative risk. Thus, we evaluated frailty as a predictor of postoperative complications following liver resection using a validated modified frailty index (mFI). Materials and Methods: Retrospective cohort of consecutive patients undergoing liver resection (2011-2018). mFI consisting of 11 variables was used to stratify patients into groups: high (≥0.27) and low mFI (<0.27). The effect of mFI on postoperative complications (Clavien-Dindo) was evaluated using multiple logistic regression, expressed as odds ratios (OR) and 95% confidence intervals (CI). Results: Of 409 patients, 58 (14%) had high mFI. There were no differences in type of liver resection (laparoscopic: 57% vs. 55%, p=0.766), number of segments resected (3 vs. 4, p=0.417) or operative time (257 vs. 293 min, p=0.097) between the high and low mFI groups, respectively. High mFI patients had a longer median length of hospital stay (9.5 vs. 5 days, p<0.001), higher proportion of postoperative complications (79% vs. 46%, p<0.001); including minor complications (69% vs. 42%, p<0.001), major complications (50% vs. 13%, p<0.001), and 90-day postoperative mortality (12% vs. 3.4%, p=0.04). On multivariable analysis, longer operating time (OR 1.15, 95%CI, 1.03 to 1.27), higher number of segments resected (OR 1.43, 95%CI, 1.12 to 1.82), and high mFI (OR 6.74, 95%CI, 2.76 to 16.51) were independent predictors of major postoperative complications. Discussion: mFI predicts postoperative outcomes following liver resection and can be used as a risk stratification tool for patients being considered for surgery.
Article
Background Preoperative phase can be effectively used by multidisciplinary teams to optimize the surgical candidate to improve perioperative outcomes. The aim of our study was to evaluate the impact of prehabilitation program (PP) in patients undergoing elective liver resection (LR). Methods This was a prospective study including patients undergoing elective LR from February 2016 to October 2017. Outcomes of patients enrolled into PP were compared with patients receiving standard care. PP involved physiotherapist, dietitian, and case managers along with surgical and anesthetic services. Postoperative morbidity, length of stay, 90-day mortality, readmission rate, quality of life, and cost were measured. Results Seventy patients were enrolled into PP and compared with 34 patients receiving standard care. Median Charlson comorbidity index was higher in PP group (4 versus 3, P = 0.03). PP showed reduction in overall morbidity (30% versus 52.9%, P = 0.02) and social issues (nil versus 3, P = 0.03). Quality of life survey showed improved social well-being. A tendency to cost savings was observed in prehabilitation group with 16.5% (1359)costreduction(mediancost1359) cost reduction (median cost 6892 versus $8251, P = 0.07). Conclusions PP improves outcomes in patients undergoing elective LR.
Article
Background: Minimally invasive surgical techniques are routinely promoted as alternatives to open surgery because of improved outcomes. However, the impact of robotic surgery on certain subsets of the population, such as frail patients, is poorly understood. Objective: The purpose of our study was to examine the association between frailty and minimally invasive surgical approaches to colon cancer surgery. Design: This is a retrospective study of prospectively collected outcomes data. 30-day surgical outcomes were compared by frailty and surgical approach using doubly robust multivariable logistic regression with propensity score weighting, and testing for interaction effects between frailty and surgical approach. Setting: Patients undergoing an open, laparoscopic, or robotic colectomy for primary colon cancer, 2012 to 2016, were identified from the American College of Surgeons National Surgical Quality Improvement Program database. Patients: Patients undergoing a colectomy with an operative indication for primary colon cancer were selected. Main outcome measures: 30-day postoperative complications. Results: After propensity score weighting of colectomy patients, 33.8% (N = 27,649) underwent an open approach versus 34.3% (N = 28,058) laparoscopic versus 31.9% (N = 26,096) robotic. Robotic (OR 0.53, 95% CI 0.42-0.69, p<0.001) and laparoscopic (OR 0.58, 95% CI 0.52-0.66, p<0.001) surgeries were independently associated with decreased rates of major complications. Frailer patients had increased complication rates (OR 1.56, 95% CI 1.07-2.25, p=0.018). When considering the interaction effects between surgical approach and frailty, frailer patients undergoing robotic surgery were more likely to develop a major complication (combined adjusted OR 3.15, 95% CI 1.34-7.45, p=0.009) compared to patients undergoing open surgery. Limitations: Using the modified Frailty Index as an associative proxy for frailty. Conclusions: While minimally invasive surgical approaches have decreased post-operative complications, this effect may be reversed in frail patients. These findings challenge the belief that robotic surgery provides a favorable alternative to open surgery in frail patients. See Video Abstract at http://links.lww.com/DCR/B163.