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14
L. Xia and S. Daneshmand
that some of the principles or protocols discussed here apply to other major pelvic surgeries, such as colorectal and gynecologic
oncologic surgeries.
The University ofSouthern
California ERAS Protocol
The original 22 items published in 2013 RC
ERAS guidelines were mainly based on
colorectal literature [8]. Since the publication
of the guidelines and formation of the Urology
chapter, evidence supporting the use of ERAS
after RC has grown rapidly, including our
University of Southern California (USC)
experience [7, 14–23]. Our institutional experience with ERAS for RC has extended from
2012 when we first implemented a multidisciplinary evidence-based ERAS protocol.
Table 2.1 lists the modern protocols we use
for RC/PLND/UD at USC [14, 17]. Our initial
reports showed significantly shortened LOS
without increased risks of readmissions after
we started to implement the ERAS pathway
[14, 17].
Preoperative Considerations
Preoperatively, an educational class for patients
and caregivers is completed with an emphasis on
expectations for hospitalization and discharge
planning. For patients with RC, education about
urinary diversions is extremely important since it
may affect early discharge [8]. Carbohydrate loading is encouraged as it has been demonstrated to
facilitate improved recovery after various surgeries
and potentially decrease infection rates [24, 25].
It has been well established that preoperative
mechanical bowel preparation (MBP) can be
safely omitted in both urologic and colorectal literature [26, 27]. Slim etal. [27] included 14 randomized controlled trials (RCTs) with a total of
4859 patients before colorectal surgery in a metaanalysis: 2452in the MBP group and 2407in the
no MBP group. The results showed the use of different MBP regimes did not inuence primary
and secondary outcomes (complications). Deng
etal. [26] included two RCT and ve cohort studies in a meta-analysis focusing on the role of
MBP before ileal UD. The meta-analysis suggested that MBP did not reduce the incidence of
perioperative complications in UD.
Table 2.1 The USC ERAS protocol
Preoperative Precystectomy educational class
Carbohydrate loading
No bowel preparation
Alvimopan 12mg oral rst dose 12h before operation
No epidural
Intraoperative Opioid sparing anesthesia
Minimize intravenous uid based on stroke volume/central venous pressure
Postoperative No nasogastric tube
Nausea and vomiting prophylaxis
Prokinetics (metoclopramide 10mg intravenously every 6h as needed)
Alvimopan (12mg twice daily until bowel activity for maximum of 7days)
Neostigmine (0.5mg subcutaneously twice daily starting on POD 1 until bowel activity for
maximum of 72h)
H2 blocker and proton pump inhibitor
Early enteral feeding (cystectomy/regular diet—POD 1)
Nonnarcotic pain control
24-h perioperative prophylactic antibiotics
Prophylactic antibiotics until catheter/stent removal
Home intravenous hydration
Oral sodium bicarbonate at time of discharge if needed
PODpostoperative day
2 Modern-Enhanced Recovery After Surgery (ERAS) forMajor Pelvic Surgery
15
The impact of narcotic pain medications on
slowing bowel function is well known.
However, adequate pain control following any
surgical intervention is essential for appropriate recovery. Regional anesthesia has been
advocated for patients undergoing
RC.Retrospective studies have shown that epidural anesthesia may be associated with
increased postoperative complications [28,
29]. Another alternative is the rectus sheath
catheter, and a recent RCT has shown noninferiority of rectus sheath catheter insertion
compared to epidural for opiate usage and satisfaction with pain control [30]. We do not routinely place epidural catheters for RC at USC,
but we do use rectus sheath catheter analgesia
with an elastomeric pump, along with around
the clock acetaminophen and nonsteroidal
anti- inammatory drugs (NSAIDs) for pain
control and minimize opioid usage in patients.
Intraoperative Considerations
We emphasize opioid-sparing anesthesia and
goal-directed uid therapy for the surgery [31].
Goal-directed uid therapy aims to decrease
complications associated with uid excess or
hypovolemia. The original 2013 ERAS society
guidelines suggested uid balance should be
optimized by targeting cardiac output using the
esophageal Doppler system or other systems for
this purpose and avoiding overhydration.
Judicious use of vasopressors was recommended
with arterial hypotension [8]. Fluid monitoring in
cystectomy patients can be challenging as urine
output is not reliable.
Another consideration worth discussing is
robot-assisted RC (RARC). Most of the RCTs
showed decreased blood loss but longer operative
time with the RARC compared to open RC
(ORC) [32–35]. No convincing evidence suggests that RARC enhances recovery in terms of
LOS or rates of complications when compared
with modern open series applying ERAS care
pathways. Current data seem to indicate that clinical outcomes are impacted more by perioperative care patterns (ERAS) than by surgical
approaches [20, 36]. Indeed, our series suggested
that the surgical approach was not a determinant
of readmission or major complications following
RC in the context of an ERAS protocol [20]. We
believe smaller incisions, less bowel manipulation, efcient/expeditious surgery, minimization
of blood loss/transfusion, and consistency play
important roles in ERAS for RC.
Postoperative Considerations
Gastrointestinal (GI) complications such as ileus
are very common after RC, and they are associated with prolonged LOS, increased morbidity,
and increased cost [16]. Therefore, interventions
to address GI complications are among the most
closely studied [3, 7]. As we can see from
Table 2.1, most of the postoperative items are
used to target GI complications, especially postoperative ileus.
are removed at the end of surgery and not routinely continued postoperatively. A Cochrane
analysis for RCTs comparing groups with and
without nasogastric tubes for major abdominal
surgeries showed patients without NG tubes had
earlier return to bowel function [37]. Bowel preps
and prolonged use of NG tubes are no longer
recommended.
using antiemetics and/or prokinetics. The most
notable medication is Alvimopan, a peripheral
μ-opioid receptor agonist in the GI tract. Its usage
is supported by the highest level of evidence
[38–40]. A multicenter double-blinded RCT that
included RCs performed in 31 high-volume centers from the United States showed that the perioperative use of Alvimopan was associated with
1.3days decrease in GI recovery time and almost
2.7days decrease in LOS compared to placebo
[38]. Ileus-related morbidity was only 8.4% in
the Alvimopan group compared to 29.1% in the
placebo group. The need for postoperative NG
tubes and prolonged LOS due to ileus-related
morbidity were also signicantly lower in the
Alvimopan group. FDA approved Alvimopan for
perioperative use in patients undergoing RC
Nasogastric tubes (or orogastric tubes if used)
We tend to be very aggressive in terms of
16
L. Xia and S. Daneshmand
based on this trial, and Alvimopan has become an
essential part of modern ERAS protocols. Of
note, there is a difference between the duration of
Alvimopan between our institution and the protocol used in the trial. We typically discontinue the
medication after the rst few bowel movements
while it was continued for 7days or until the time
of discharge in the trial. It is unclear whether
resuming Alvimopan after the return of regular
bowel movements would have any additional
benets. One major disadvantage of Alvimopan
is the cost, and our modied administration protocol could potentially relieve some of the concerns regarding the cost of this medication while
still ensuring a signicant reduction in GI
complications.
As part of our USC protocol, we have used
neostigmine to further stimulate bowel recovery.
All patients who receive low-dose neostigmine
postoperatively remain on cardiac monitoring for
at least 24–48h given the potential risk of cardiac
arrhythmias reported with this medication.
Neostigmine is typically discontinued after the
rst bowel movement [14]. With previously mentioned protocols to accelerate bowel recovery,
early feeding is well tolerated in our RC patients.
Early feeding is also well supported in the literature [41, 42]. Patients at USC start a regular diet
on the rst postoperative day.
In our recent series of 292 patients who underwent RC under ERAS protocol, the GI complication rate was only 15.4% with ileus being the
most common one at 11.6% [43]. When compared to non-ERAS perioperative care, the
30-day GI complication rate in the ERAS group
was signicantly lower (13% versus 27%). The
most signicant reduction in GI complications
was noted for ileus (7% versus 23%). The median
time from surgery to rst atus was 2d (range
1–6) in the ERAS cohort and 5d (range 2–8) in
the control group. The median time to rst bowel
movement was 2 d (range 1–7) in the ERAS
cohort and 5d (range 2–13) in the control group.
Median LOS was signicantly shorter in the
ERAS cohort (4 d, range 3–16) than in the control group (9d, range 5–23).
Infectious complications, especially urinary
tract infections (UTIs), are also very common
after RC and are associated with signicant morbidity and risk of readmission [17, 44]. One
study reported a UTI rate of approximately 36%
and the urosepsis rate of 7.2% within 90days of
surgery in a large cohort of RC patients even
with ERAS protocol [44]. UTIs are common in
RC because of the nature of urinary diversion
(using bowel segments, reuxing ureteroenteric
anastomosis, using catheters and ureteral stents).
As a standard procedure, all patients undergoing
RC receive 24-h perioperative antibiotics.
Although there is no high level of evidence to
support prolonged prophylactic antibiotic usage,
some retrospective data suggested the potential
benets [45, 46]. However, the use of prophylactic antibiotics beyond 24h after surgery to prevent UTI is still debatable, and its duration is
widely variable among different institutions
[45]. In our institution, all patients are placed on
prophylactic oral antibiotics after the rst 24h
until the time of the stent removal which varies
based on the type of UD (10days for ileal conduit and 21days for orthotopic neobladder). The
antibiotic of choice in our institution is currently
nitrofurantoin (100mg daily) based on our internal review of antimicrobial sensitivity analysis
of urine culture results and institutional
antibiogram.
Finally, all patients are arranged to receive
home intravenous hydration following discharge
to prevent complications of dehydration and acidosis [10, 47]. For acidosis, oral sodium bicarbonate will also be prescribed if needed. At our
institution, a comparatively high volume of continent urinary diversions is performed in eligible
patients. It is our experience that these patients
are particularly prone to dehydration in the early
postoperative period, and the provision of intravenous uid can limit this complication.
Future Directions
ERAS continues to evolve and improve as comprehensive multidisciplinary approaches to the
care of complex surgical patients. Several important issues remain to be answered with more or
higher levels of data.
2 Modern-Enhanced Recovery After Surgery (ERAS) forMajor Pelvic Surgery
17
Thromboembolic Events
Patients undergoing pelvic surgery of signicant
length are at an increased risk for VTE [48–50].
Neoadjuvant chemotherapy, older age, PLND,
and malignancy put RC patients at even higher
risk. The incidence of symptomatic venous
thromboembolism in short-term follow-up after
RC is 3%–11.6%, of which more than 50% of
cases will occur after hospital discharge [49, 50].
Meta-analyses of clinical trials in patients undergoing major abdominal or pelvic cancer
surgeries suggest a decreased risk of venous
thromboembolisms for patients receiving
extended (4 weeks) venous thromboembolism
prophylaxis [51, 52]. Literature on RC also suggested extended prophylaxis (most commonly
Enoxaparin) should be considered in all RC cases
[49, 53]. Most recent data showed that oral anticoagulants (e.g., apixaban, rivaroxaban) are
acceptable alternatives to enoxaparin with similar safety and efcacy proles [54, 55]. For other
pelvic surgeries, one RCT showed oral apixaban
is comparable to subcutaneous enoxaparin for
thromboembolism prophylaxis after surgery for
gynecologic cancer [56].
Prehabilitation
There is emerging evidence supporting multimodal prehabilitation as a strategy to reduce the
risk of complications and improve functional
recovery after major surgery [57–59]. There are a
few studies that investigated the impact of single
modal or multimodal prehabilitation programs on
functional recovery following RC [60–62]. The
program in one study included only 4-week
supervised preoperative exercise training [60].
Successful compliance, dened as adherence to
>70% of sessions, was achieved by 80% of
patients. A multimodal preoperative conditioning
intervention in one study included aerobic and
resistance exercise, diet therapy, and relaxation
techniques [62]. Four weeks postoperatively, the
prehabilitation group had signicantly improved
functional capacity as measured by a 6-min walk
test compared to the standard group. Despite
these studies, the role of prehabilitation in the
ERAS pathway and its benets in surgical outcomes are not well understood. No adequately
powered trial has been performed, but several
larger multi-centered RCTs are being conducted,
including PREPARE-ABC trial, Prehab4cancer
trial, and ENHANCE trial [63–65].
Immunonutrition
It is well known that nutritional status is associated with postoperative outcomes, and ERAS
society has incorporated some of the nutritional
care into their guidelines [24]. In recent years,
studies have shown the use of immunonutrition
in patients who have undergone oncological surgery decreases the levels of inammatory markers and infectious postoperative complications
[66, 67]. More studies about the use of immunonutrition in ERAS protocols for different types
of surgeries are still needed. SWOG 1600, a randomized phase III double-blind clinical trial,
was designed to evaluate the effect of a specialized immunonutritional supplement containing
arginine, omega-3 fatty acids, dietary nucleotides, and vitamin A on outcomes after RC [68].
The study is expected to be completed by
December 2023 and will answer some of the
pending questions in terms of its role in ERAS
protocol.
Summary
ERAS has been well studied in various surgical
specialties and has been rmly established as an
effective care to improve outcomes. ERAS represents a patient-centered and evidence-based
approach to providing high-quality care to surgical patients and should be embraced at all levels of care. Most of the major pelvic surgeries
such as colorectal and gynecologic oncologic
surgeries should benet from ERAS. Ongoing
research and future studies will continue to
rene care pathways for each operation and
reveal the best methods for improving the care
of these patients.
18
L. Xia and S. Daneshmand
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Frailty
ArminShahrokni
3
Frailty
Frailty is dened as the reduced ability of the
body to tolerate stress [1]. It argues that if you
apply the same level of distress to the bodies of
two persons of the same age through, for example, surgery, the person who is more frail will
experience a poorer outcome compared to the
person who is more t. However, as we age, the
likelihood and degree of frailty increase [2]. This
is the reason that many studies based on realworld datasets which include the typical community dwelling older adults have found that older
age is associated with poorer outcomes, while in
randomized control trials with restrictive exclusion criteria such as the patient’s performance
status, kidney or liver function, the relationship
between older age and poorer outcomes becomes
less pronounced. Frailty is also dynamic rather
than static [3]. Patients can experience improvements or worsening of their frailty over time,
depending on medical events and/or other stressors. For example, a systematic review showed
that among nonfrail patients who survived at
least 3 years, about 14% of them became frail
during that time period [4]. Hence the need for
reassessing frailty, especially after major healthrelated events.
A. Shahrokni (*)
Department of Medicine, Jersey Shore University
Medical Center, Neptune, NJ, USA
e-mail: armin.shahrokni@hmhn.org
Biological age is also associated with signicant molecular and physiological changes [5].
Some have argued that a combination of nine factors, namely telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient
sensing, mitochondrial dysfunction, cellular
senescence, stem cell exhaustion, and altered
intercellular communication, could lead to the
aging process and/or its acceleration [6]. Aging is
also associated with signicant physiological
changes [5]. Aging affects all organs, but its association is different from one patient to another, and
in one patient, one organ may be affected more
than others. An example of a major physiological
change is decreased compliance of large vessels
such as the aorta. Stiff arteries can lead to an
increase in systolic blood pressure and a decrease
in diastolic blood pressure, leading to a widening
of pulse pressure. In the same line, the left ventricle compliance decreases, and its relaxation is
delayed. These and other changes predispose the
heart to the aging process, leading to an increase in
blood pressure, aortic stenosis, heart failure, and
nerve conduction abnormalities. Decreased lung
function remains one of the hallmarks of the aging
process. Peak aerobic exercise capacity falls by
about 20% for every 10 years after age 70.
Respiratory compliance decreases and as a result
functional residual capacity decreases. The aging
process is also associated with decreased ability of
respiratory muscles in response to issues like
hypoxia. Aging is also associated with diffuse glo-
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2025
M. Hoffman et al. (eds.), Major Complications of Female Pelvic Surgery,
https://doi.org/10.1007/978-3-031-66772-5_3
23
24
A. Shahrokni
merulosclerosis. While serum creatinine may
remain constant during aging, the glomerular ltration rate will fall. The immune system, both
adaptive and innate, also declines with aging. As
we age, our bone marrow is more inltrated with
fat which results in a decrease in bone marrow
hematopoietic tissue. Other organs also experience
changes with aging. For example, liver mass
decreases by about 20–40%. Age-related muscle
loss is a result of inltration of muscles by fat and
connective tissues.
Assessing Frailty
The gold standard for assessing frailty is the geriatric assessment, which is usually performed by
geriatricians [7]. This is a comprehensive assessment of older adults that typically starts by
assessing cognitive function through tools such
as the Mini-Cog [8] or Mini-Mental State Exam
[9]. It then proceeds to assess patients for the
presence and severity of various comorbidities,
nutritional status, polypharmacy, gait and balance, history of falls, social support and activity,
and emotional well-being. However, a comprehensive geriatric assessment may take up to
60min to complete, making it unfeasible in fastpaced clinics. Despite this, many argue that the
value of the geriatric assessment is so high that
healthcare institutions should make every effort
to perform it routinely [10]. Alternatively, some
have explored other solutions to increase the likelihood of this assessment being performed as
routine care. For example, instead of using paper
questionnaires and hiring personnel to administer
the assessment, some have developed web-based
geriatric assessment tools. These tools have been
shown to be feasible in patients older than age 75
going for surgery, older patients who are receiving even toxic treatment such as chemotherapy,
and minority patients [11–14]. Some have
explored innovative approaches such as voiceassisted solutions [15]. These solutions, which
some might be familiar with names like Alexa or
Siri, automatically read the questions to the
patients and then register patients’ responses
without any involvement from personnel.
There are various frailty assessment tools
available for patients and healthcare providers
who may not have the time, resources, or necessary skills to perform a full geriatric assessment.
These tools can be categorized into two models:
the phenotype model and the cumulative agingimpairment model [16].
The Fried Frailty Index [17] is one of the most
commonly used frailty assessment tools based on
the phenotype model. It assesses ve factors,
including involuntary loss of 10 pounds or more
in the past 6months, reduced grip strength, difculty initiating movements, reduced walking
speed, and fatigue. Patients with no impairments
are considered t, those with one or two impairments are pre-frail, and those with a higher number of impairments are considered frail. On the
other hand, the cumulative aging-impairment
model is based on the theory that as we age, we
accumulate various aging-related impairments
[18]. The more we accumulate these impairments, the more frail we become and, consequently, we become more susceptible to adverse
outcomes during and after cancer treatment. In
one study, researchers used a web-based geriatric
assessment tool called electronic rapid tness
assessment to assess the frailty of cancer patients
[19]. The study found that the number of agingrelated impairments was associated with a sixmonth survival rate following cancer surgery.
Even after adjusting for factors such as age and
American Society of Anesthesiologists-Physical
Status classication, each additional agingrelated impairment was associated with a 14%
increase in six-month mortality following cancer
surgery. Other studies have also shown that the
accumulation of aging-related impairments is
associated with mortality, chemotherapy toxicity,
and the risk of institutionalization [20–24].
In addition to instruments based on frailty
phenotype or cumulative decits, there are also
many frailty screening tools that are shorter and
take much less time to complete. An umbrella
review of frailty screening tools reviewed 26
questionnaires aimed at detecting frailty and
eight frailty indicators [25]. Huisingh-Scheetz
and colleague described some of these frailty
screening tools and provided guidance on how to