Arch Gynecol Obstet

DOI 10.1007/s00404-016-4227-2

GYNECOLOGIC ONCOLOGY

The impact of total parenteral nutrition on postoperative recovery

in patients treated for advanced stage ovarian cancer
Alberto A. Mendivil1 Mark A. Rettenmaier1 Lisa N. Abaid1 John V. Brown III1
Kristina M. Mori1 Bram H. Goldstein1

Received: 18 August 2016 / Accepted: 2 November 2016

Springer-Verlag Berlin Heidelberg 2016

Abstract
Objectives Total parenteral nutrition (TPN) presumably
benefits cancer patients although reports have disputed the
significance of this nutritional intervention. We sought to
compare the postoperative outcomes of ovarian cancer
patients treated with either TPN or conservative
management.
Methods We retrospectively evaluated the impact of TPN
and conservative management in ovarian cancer patients
who underwent debulking surgery and a bowel resection. The primary study variables encompassed patient time
until restoration of bowel function, number of postoperative complications and duration of hospital stay.
Results There were 147 subjects who were selected for this
study. The patients who were treated with TPN (n = 69)
demonstrated a longer time until restoration of bowel
function (5.77 vs. 4.70 days; P \ 0.001), experienced
lower pre-operative albumin levels (2.22 vs. 2.97 g/dL;
P \ 0.001) and endured a significantly longer hospital stay
(11.46 vs. 7.14 days; P \ 0.001) compared to the conservative management (n = 78) cohort.
Conclusions Postoperative TPN in ovarian cancer patients
may be inadvisable because of the increased risk for
complications. Moreover, in the hypoalbuminemic
patients, TPN may have not only delayed their postoperative recovery and increased hospital stay duration, but
further precipitated the manifestation of nosocomial
sequelae.

& Bram H. Goldstein

bram@gynoncology.com
1

Gynecologic Oncology Associates, 351 Hospital Road, Suite

#507, Newport Beach, CA 92663, USA

Keywords Ovarian cancer
Gynecologic surgery

Intestinal surgery
Total parenteral nutrition

Postoperative recovery

Introduction
A malignancy frequently impairs a patients nutritional
status, contributing to an increased risk for postoperative
morbidity and mortality [1]. Surgical disciplines have
attempted to address this concern by adopting clinical
pathways that advance patient care and attenuate hospital
costs [2]. Ultimately, nutritional protocols have only
intermittently conferred auspicious outcomes, effectuating
significant variation in post-operative care [3].
Total parenteral nutrition (TPN) potentially ameliorates
malnourished oncology patients [4], many of whom are
susceptible to treatment-related adverse events and a protracted hospital stay [57]. Nevertheless, randomized
clinical trials have indicated that TPN does not improve
survival, mitigate toxicity, or enhance tumor response rates
in patients receiving adjuvant therapy [8, 9].
In ovarian cancer, patients are theoretically more vulnerable to developing nutritional deficiency because they
have customarily undergone a significant debulking surgery and a concomitant gastro-intestinal resection
[8, 10, 11]. Additionally, there are, concerns for catheterinduced complications which may occasion increased
readmission rates [6, 7, 11, 12]. Hence, one may conjecture
that TPN is only indicated for patients who are unable to
eat after a week or in severe cases wherein nutritional
intervention is considered palliative [4].
The purpose of this retrospective study was to compare the outcomes of advanced stage ovarian cancer
patients who underwent debulking surgery and a

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clinically defined bowel resection prior to initiating TPN

or conservative management (i.e., physician discretion
that precluded TPN) at a tertiary hospital by a single
group of gynecologic oncologists. We hypothesize that
the ovarian cancer patients who had the most extensive
bowel surgery and received TPN will exhibit a slower
restoration of bowel function, endure higher postoperative complication rates and experience longer hospital
stay than the subjects who were treated with conservative management.

(optimal or sub-optimal cytoreduction and bowel resection)

data.
Bowel resection type
The ovarian cancer patients were grouped into the following, clinically defined intestinal classifications [12]:
1.
2.
3.

Materials and methods

Study inclusionary and exclusionary criteria
Advanced stage epithelial ovarian, fallopian tube and primary peritoneal cancer patients who underwent cytoreductive surgery (optimal = B1 cm, suboptimal = [1 cm)
[13] that incorporated a bowel resection (e.g., sigmoid
resection or rectosigmoid resection with proximal colectomy) from June 2009 until May 2013 were eligible for
study participation. Comprehensive documented records
entailing the subjects intraoperative and postoperative
course (e.g., bowel functioning status, complications) were
required for study inclusion. This investigation received
institutional review board approval prior to the initiation of
any data collection.
Ovarian cancer patients who had an unstaged cancer, a
stage I/II diagnosis of ovarian cancer or a non-ovarian
cancer diagnosis were excluded from study participation.
Moreover, subjects who did not undergo a primary surgical
debulking (i.e., initiated neo-adjuvant chemotherapy) or a
procedure that did not incorporate an intestinal surgery
were precluded. Finally, if adequate patient treatment and
surveillance records were unavailable, the data were
excluded from the study analysis.

4.

Small bowel resection (SBR) or enterectomy.

Proximal colectomy alone (Col), characterized by a
proximal colectomy and reanastomosis.
Rectosigmoid resection (RSR), which encompassed a
sigmoidectomy with reanastomosis.
Rectosigmoid resection with proximal colectomy
(RSR ? Col) comprising a sigmoidectomy with reanastomosis and proximal colectomy with reanastomosis.

Clinical outcomes
The patients pre-operative serum albumin levels, days
until passage of flatus or restoration of bowel function,
postoperative days until initiation of TPN and duration of
TPN, number and severity of postoperative complications
(e.g., fistula, infection, bowel obstruction) [16], length of
hospital stay and number of readmissions were assessed.
Statistical analysis
All statistical analyses were conducted using MedCalc
statistical software for biomedical research (version 9.5.1
for Windows). The initial data analysis was conducted via
multiple regression; additional univariate analyses were
performed using ANOVAs and Chi square. In determining
significance, 2-sided P values with a significance level of
0.05 were utilized to assess any relationships among the
relevant clinicopathologic parameters.

Total parenteral nutrition

Results

In the patients who received TPN, the criteria were based

on a combination of factors, including pre-operative serum
albumin level \2.0 g/dl, significant gastrointestinal toxicity that contraindicated enteral intake, and an anticipated
postoperative resumption of oral intake in excess of 7 days
[14, 15]. Alternatively, conservative nutritional management (watchful waiting or no TPN) was prescribed in
accordance with physician discretion.

We originally identified 271 gynecologic cancer patients

who underwent primary debulking surgery, of whom 124
were summarily excluded because they were diagnosed
with either a non-ovarian (e.g., uterine cancer) malignancy
or did not have a concomitant bowel surgery (n = 95).
Additionally, 29 patients were ineligible because they
either had a stage I/II ovarian cancer or the patient records
were inadequate. Following the completion of patient
chart data, the final study population encompassed 147
subjects.
There were 69 (46.9%) advanced stage ovarian cancer
patients who received postoperative TPN and 78 (53.1%)
who underwent conservative management. Overall mean

Demographic and clinical characteristics

Demographic and clinical data included age, primary
diagnosis, stage and histology of disease, and surgical

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patient age was 61.6 (SD = 10.3) years. The mean age was
62.1 years (SD = 11.2) for the TPN group and 61.2 years
(SD = 8.9) for the conservative management group
(P [ 0.05). In the TPN group, 63 (91.3%) subjects
underwent optimal cytoreduction and 69 (88.5%) conservative management patients had optimal cyto-reductive
surgery (P = 0.573).
In the TPN group, 19 patients underwent an SBR
(27.5%), 14 had an RSR (20.3%), 17 TPN subjects
underwent an RSR ? Col (24.6%) and 19 TPN patients
had a Col (27.5%). Alternatively, in the conservative
management group, 14 had an SBR (17.9%), 17 underwent
an RSR (21.8%), 20 had an RSR ? Col (25.6%) and 27
patients underwent a Col (34.6%). There were no group
differences involving bowel surgery type and the probability of receiving TPN (X2 (3) = 0.523; P = 0.544).
Table 1 illustrates the study groups demographic and
surgical characteristics.
The mean time to restoration of bowel function or flatus
was 5.77 days (SD = 1.27) for the TPN group and
4.70 days (SD = 0.88) in the non-TPN group (P \ 0.001).
The preoperative albumin levels were 2.22 g/dL
(SD = 0.91) for the TPN group and 2.97 g/dL
(SD = 0.57) for the conservative management cohort
(P \ 0.001). In the TPN patients, mean time to initiate the
nutritional intervention was 1.99 (SD = 1.73) days and
duration of treatment was 3.68 (SD = 2.03) days. The
mean duration of hospital stay was 7.14 (2.89) days for the
conservative management group and 11.46 (8.14) days for
the TPN subjects (P \ 0.001).
In the TPN group, a small bowel obstruction was
identified in two subjects. The patients were successfully
treated with either bowel rest and intubation or a nasogastric tube. One TPN patient developed a small bowel
perforation that was effectively remedied with a resection
and reanastomosis. Additionally, one TPN subject suffered
from an entero-cutaneous fistula that was surgically managed with a colon resection and anastomosis. There were
also two TPN subjects who had either a surgical site or
wound infection, both of which were effectively treated
with drainage and anti-biotic therapy.
In the conservative management group, surgical site
infections were diagnosed in two patients, which were
effectively addressed with drainage and anti-biotic therapy.
Moreover, one subject had a minor anastomotic leak that
was appropriately managed with abdominal drainage of the
collected fluid and a stoma formation. In the TPN group,
four of the six patients with postoperative complications
were readmitted, whereas all three of the conservative
management subjects were readmitted.
We utilized multiple logistic regression to analyze the
impact of intestinal surgery type, days until flatus or bowel
restoration, use of TPN, pre-operative albumin levels and

number of postoperative complications on hospital stay

duration. The model (R2 = 0.2355) indicated that lower
albumin levels (P = 0.009), use of TPN (P = 0.013) and a
higher number of complications (P \ 0.001) were prognostic indicators for increased hospital stay.

Discussion
The utility of TPN remains very controversial in the
postoperative treatment of cancer [11, 14] and randomized,
advanced stage cancer studies have indicated that there is
insufficient clinical benefit to warrant the nutritional
intervention [17]. The American College of Physicians has
also declared that TPN is contraindicated for cancer
patients who are undergoing chemotherapy [18]. Contrariwise, select reports have suggested that TPN may
confer advantageous survival benefits, particularly in
ovarian cancer [14]. For example, studies have documented
median survival improvements (e.g., 5389 days) in ovarian cancer patients who received parenteral feeding
[14, 15]. Brard et al. described a group of 55 terminally ill
ovarian cancer patients, 28 of whom received TPN. They
reported significant median survival differences for the
patients who received TPN (74 days) in comparison to the
non-TPN subjects (42 days) [14].
In accordance with our hypothesis, we discerned that the
TPN patients had a significantly prolonged time to
restoration of bowel function, extended hospital stay and a
higher number of complications compared to the conservative management group. Our results coincide with previous investigations indicating that parenteral nutrition was
associated with increased length of hospital stay and a
greater number of complications, namely infection
[57, 19]. Therefore, we speculate that the defining characteristic for the TPN subjects outcomes was the serum
albumin levels [20, 21], which were significantly lower
than what was observed in the conservative management
cohort.
Serum albumin levels may reflect systemic immuneinflammation and hyper-metabolism in response to traumatic injury and sepsis, which can be a significant predictor of operative morbidity [2224]. The patients in the
TPN group were severely hypoalbuminemic (albumin
plasma level B2.5 g/dL), which is a negative prognostic
indicator for surgical outcomes [20, 21, 2325]. Thus,
promptly addressing severe hypoalbuminemia may be
essential to postoperative management, especially since the
condition theoretically contributes to prolonged hospital
stay and delayed bowel functioning [21, 25].
Initially, we had also anticipated that the subjects who
underwent the most extensive bowel surgery (e.g., a rectosigmoidectomy and proximal colectomy) might have

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Table 1 Study population
characteristics for the patients
who received TPN or
conservative management
(n = 147)

Mean age (SD)

TPN (n = 69)

Conservative management (n = 78)

62.1 (11.2)

61.2 (8.9)

Cytoreduction*

0.598
0.573

Optimal

63 (91.3)

69 (88.5)

Sub-optimal

6 (8.7)

9 (11.5)

Disease stage

0.104

III

61 (88.4)

66 (84.6)

IV

8 (11.6)

12 (15.4)

5 (7.2)

8 (10.2)

22 (32.7)

26 (33.3)

42 (60.1)

44 (56.5)

Serous

52 (75.4)

56 (71.3)

Endometrioid

10 (14.5)

13 (16.7)

Mixed
Mucinous

2 (2.9)
2 (2.9)

1 (1.3)
3 (3.8)

Clear Cell

3 (4.3)

3 (4.3)

NOS**

0 (0)

2 (2.6)

10 (14.5)

13 (16.7)

42 (60.8)

50 (64.1)

17 (24.7)

15 (19.2)

SBR

19 (27.5)

14 (17.9)

Col

19 (27.5)

27 (34.6)

RSR

14 (20.4)

17 (21.8)

Disease grade

0.241

Histology

0.181

ECOG***

0.533

Bowel resection****

RSR ? Col

P value

0.544

17 (24.6)

20 (25.7)

Albumin levels

2.22 (0.91)

2.97 (0.57)

\0.001

Days to flatus

5.77 (1.27)

4.70 (0.88)

\0.001
\0.001

Hospital stay (days)

11.46 (8.14)

7.14 (2.89)

Complications
Readmissions

6
4

3
3

0.224
0.368

* Cytoreductive surgery-optimal = B1 cm, suboptimal = [1 cm

** NOS not otherwise specified
*** ECOG Eastern Cooperative Oncology Group
**** SBR small bowel resection or enterectomy, Col proximal colectomy alone, RSR rectosigmoid
resection, RSR ? Col rectosigmoid resection with proximal colectomy

endured a longer hospital stay [12], but ultimately this

hypothesis was not substantiated. We suspect that since all
of our patients underwent a significant, primary debulking
and bowel surgery, distinct postoperative outcomes may
not always be identified within the context of a predefined,
intestinal surgery classification.
There are several limitations to our study, two of which
include the retrospective nature of the investigation and
that only the subjects preliminary outcomes were examined. In particular, we excluded study participants who
underwent interval debulking or did not have bowel

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surgery, both of which are factors that may effectuate

nutritional compromise. Furthermore, since the data were
non-randomized, the observed associations between TPN
and clinical outcomes were potentially the result of patient
characteristics and physician selection. Our specific criteria
to administer TPN were also arguably subjective and differ
from other reported guidelines [26, 27].
The current investigation additionally suggests that TPN
in generally malnourished ovarian cancer patients eventuates prolonged hospital stay although the administration of
postoperative TPN may be subsequent to the development

Arch Gynecol Obstet

of severe hypoalbuminemia, rather than a consequence.

When considering hospital stay, one could also speculate
that if TPN was initiated on the basis of inauspicious
clinical status, then nutritional support cannot be implicated in the patients extended hospital duration. Thus,
when parenteral nutrition is inappropriately employed, the
impact can be considered ineffective or worse, deleterious.
In summary, the use of TPN may have limited value in
advanced stage ovarian cancer patients who underwent
major debulking surgery that incorporated a bowel resection. The utility of TPN, however, remains indeterminate
and the implementation of clinical pathways may be necessary to further elucidate the significance of the intervention during this postoperative juncture. Ultimately,
physician discretion should be used prior to utilizing TPN,
especially because an expeditious transition to enteral
feeding will presumably confer enhanced patient outcomes.
Compliance with ethical standards
Conflict of interest The authors deny any conflicts of interest associated with this manuscript. Additionally, the study received institutional review board approval and with regard to patient consent, the
study qualified for exempt status.
Funding This study was supported by the Nancy Yeary Womens
Cancer Research Foundation.

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