Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) were performed on 31 patients with peritoneal recurrence of ovarian cancer. Complete cytoreduction was achieved in 90% of patients. Morbidity rates were acceptable and comparable to literature. Organ-preserving cytoreductive surgery, when possible, reduced complications and hospital stay compared to those requiring colon resection. 25% of patients experienced tumor recurrence within a median follow-up period of 798 days, most commonly in the parietal abdominal wall. This multimodal approach shows promise for recurrent ovarian cancer but randomized trials are still needed.

1. ORIGINAL ARTICLE
Cytoreductive surgery and HIPEC in peritoneal recurrent
ovarian cancer: experience and lessons learned
Ingmar Königsrainer & Stefan Beckert & Sven Becker & Derek Zieker & Tanja Fehm &
Eva-Maria Grischke & Olivia Lauk & Jörg Glatzle & Björn Brücher &
Diethelm Wallwiener & Alfred Königsrainer
Received: 15 April 2011 /Accepted: 3 August 2011 /Published online: 13 August 2011
# Springer-Verlag 2011
Abstract
Purpose Peritoneal recurrence of ovarian cancer is frequent
after primary surgery and chemotherapy and has poor long-
term survival. De novo cytoreductive surgery is crucial with
the potential to improve prognosis, especially when
combined with hyperthermic intraperitoneal chemotherapy
(HIPEC).
Methods The sampled data of 40 consecutive patients were
retrospectively analyzed. Thirty-one patients were treated
with cytoreductive surgery combined with hyperthermic
intraperitoneal chemotherapy.
Results No patient was lost in the perioperative period, and
the combined procedure was performed with acceptable
morbidity. Colon-preserving cytoreductive surgery was
associated with reduced morbidity.
Conclusions Patients suffering from peritoneal recurrence
of ovarian cancer should be considered for radical reoper-
ation with HIPEC in a center with expertise in multimodal
therapeutic options. Organ-preserving cytoreductive surgery
allows complete cytoreduction with the goal of decreasing
morbidity.
Keywords Peritoneal carcinomatosis . Ovarian cancer.
HIPEC
Introduction
Median survival in stage III and IV ovarian cancer
ranges from 12 to 25 months [1]. So far, standard
treatment consists of radical cytoreductive surgery (CRS)
followed by platinum/paclitaxel-based adjuvant chemo-
therapy. Even though most patients initially respond well
to this treatment, about 50% develop intraperitoneal
recurrent disease within 5 years [1]. Since a regimen of
combined intraperitoneal and intravenous administration
of chemotherapeutic drugs achieved encouraging results in
primary stage III ovarian cancer in randomized trials [2],
cytoreductive surgery along with hyperthermic intraperi-
toneal chemotherapy (HIPEC) was proposed as new
treatment. Two recent reviews prove this strategy to be a
valuable option in primary advanced stage III–IV disease,
in that it affords complete cytoreduction and has the
greatest impact on 5-year survival, reported to range from
12% to 66% [2, 3].
Because the results were so promising, we proposed this
concept for recurrent ovarian cancer and peritoneal spread at
our center for peritonectomy primarily set up for colorectal
cancer and primary peritoneal malignancies. We herein
present our first experience with cytoreductive surgery and
This manuscript contains original material that has not been
previously published.
I. Königsrainer (*) :S. Beckert :D. Zieker :O. Lauk :
J. Glatzle :B. Brücher :A. Königsrainer
Department of General, Visceral and Transplant Surgery,
Comprehensive Cancer Center, University of Tübingen,
Hoppe-Seyler-Strasse 3,
72076 Tübingen, Germany
e-mail: ingmar.koenigsrainer@med.uni-tuebingen.de
S. Becker :T. Fehm :E.-M. Grischke :D. Wallwiener
Department of Gynecology, Comprehensive Cancer Center,
University of Tübingen,
Calwerstrasse 7,
72076 Tübingen, Germany
Langenbecks Arch Surg (2011) 396:1077–1081
DOI 10.1007/s00423-011-0835-2

2. HIPEC for recurrent ovarian cancer and our first lessons
learned from it.
Methods
Patients
Between February 2007 and February 2010, reoperation
was indicated in 40 patients with peritoneal recurrence of
ovarian cancer. Preoperative workup was done by CT or
PET-CT scan and laparoscopy. The selection algorithm for
PC is described elsewhere [4]. In nine patients HIPEC was
not performed, and thus these patients were excluded from
analysis after explorative laparotomy or nonradical tumor
debulking either because of an extensively high tumor load
with a peritoneal carcinomatosis index (PCI) of more than
35 or because of deep infiltration of the retroperitoneum or
the mesenterial axis.
In 31 patients, cytoreductive surgery followed by
HIPEC was performed. All patients received peridural
anesthesia and close temperature monitoring. Data were
analyzed retrospectively. The study was conducted in
compliance with the regulations of the local ethics
committee.
Surgical procedure
After laparotomy and complete adhesiolysis, PCI was
determined following the criteria described by Sugarbaker
et al. [5], in particular with meticulous exploration of small
bowel, exclusion of retroperitoneal infiltration, or liver
metastases. Then, after meticulous exploration of predilec-
tion areas like ligamentum teres, sulcus rex, sulcus arancii,
bursa omentalis, space between the vena cava and liver
segment 1, and retrosplenic sulcus, where most likely tumor
spread is found, cytoreductive surgery was performed
according to the Sugarbaker technique [6, 7]. In the
majority of cases, a multivisceral resection was necessary
to achieve the aim of complete cytoreduction (CC0, CC1;
CC0 meaning no visible disease, CC1 meaning nodules
smaller than 0.25 cm).
After complete cytoreduction and fashioning of
intestinal anastomoses, if necessary, HIPEC using cis-
platin 50 mg/m2
for 90 min at 42°C was administered to
the open abdomen. To optimally maintain 42°C, intraper-
itoneal temperature was controlled with a probe placed
directly in the abdominal fluid. A rubber drain was then
routinely placed in the pelvis and an additional drain in the
left upper abdominal quadrant if splenectomy was per-
formed. Finally, the abdomen was closed with interrupted
sutures.
Statistics
Data are presented as median (min–max) or n (percent),
unless otherwise stated. Qualitative differences were com-
pared using the chi-square test and quantitative differences
using the Mann–Whitney U test. Survival analysis was
performed with the Kaplan–Meier method. For overall
survival (OS), time to event was calculated as time from
cytoreductive surgery until death or time to last contact if
the patient was alive. A p value less than 0.05 was
considered significant. SPSS version 13.0 software (SPSS,
Chicago, Illinois, USA) was used for all statistical analyses.
Results
Demographic data are given in Table 1. Time from primary
diagnosis of ovarian cancer to peritoneal recurrence was
762 (101–3,160) days. Initially, most patients were classi-
fied as FIGO IIIc and tumor grading was G2 or G3
(Table 2). In three patients, in whom it was originally
deemed possible to eradicate the whole tumor, a radical
resection was not possible and therefore a CC2 status was
achieved.
In 74% of the patients, a colonic or rectal resection was
necessary for eradication of all visible tumors. Two patients
required diverting loop ileostomy, while three patients
Table 1 Clinical characteristics
Patients, n 31
Age, years 60 (28–68)
BMI, cm/kg2
24 (17–39)
ASA, n (%)
1 2 (6)
2 16 (52)
3 13 (42)
Time to primary recurrence, days 762 (101–3,160)
Data are presented as median (min, max)
BMI body mass index
FIGO, n (%)
IIIb 2 (7)
IIIc 28 (90)
IV 1 (3)
Grading, n (%)
0 1 (3)
1 2 (7)
2 15 (48)
3 13 (42)
Table 2 FIGO classification,
grading status
Initial FIGO classification
1078 Langenbecks Arch Surg (2011) 396:1077–1081

3. received a terminal colostomy. More than 50% of the
patients underwent splenectomy. The types of operation and
organ resection are shown in Table 3.
Patients who underwent colonic resection had a signifi-
cantly longer median hospital stay than did those with no
colonic resection [18 vs. 14 days (p=0.026)] and also showed
a greater trend to wound infection [(4 vs. 0; p=0.281)] and a
higher incidence of reoperation [6 vs. 0 (p=0.137)]. Full
details are given in Table 4.
No patient was lost in the immediate postoperative
period (Table 5), 19% had to be reoperated due to
postoperative complications, and an anastomotic leak was
observed in three patients. Full details are given in Table 5.
Median follow-up was 798 (188–1,297) days (Table 6). Of
the 28 patients who underwent complete cytoreduction
(CC0 and CC1), 25% experienced tumor recurrence within
the follow-up period. Ten (32%) patients died during the
follow-up from tumor progression.
Tumor recurrence after redo of cytoreductive surgery
followed by HIPEC was mainly located in the parietal
abdominal wall, where peritonectomy was performed
(10.7%). Full details are reported in Table 6. OS is shown
in Fig. 1a, and time of recurrence is described in Fig. 1b
following CRS and HIPEC.
Discussion
We here present our first experience with cytoreductive
surgery and HIPEC for peritoneal carcinomatosis in
recurrent ovarian cancer. The indication for a “re-tumor
debulking” was prompted by the few available alternatives
for those patients and current data on HIPEC in advanced
ovarian cancer with a potential chance for cure.
The morbidity rates from our data are acceptable and
comparable with those reported in the current literature. In
a large review conducted by Chua et al., mortality ranged
from 0% to 10%. Grade IV morbidity with the need for
reoperation ranged from 0% to 15%, and median length of
hospital stay was comparable with our results, varying
from 8 to 25 days [3]. Median overall survival ranged from
22 to 64 months, which is also comparable with our
experience.
The decision whether or not complete cytoreduction can
be achieved is the most challenging issue here. Broad
infiltration of the retroperitoneum, the mesenterial axis, or
diffuse tumor spread on the small bowel are generally
Table 4 Comparison of data
with and without colonic
resections
Data comparing patients with
and patients without colonic
resection; p<0.05 is considered
significant
Colonic resection No colonic resection p value
Complications, n (%) 10 (44) 3 (38) 0.552
Hospital stay, days 18 (11–93) 14 (3–21) 0.026
Wound infection, n (%) 4 (17) 0 0.281
Reoperation, n (%) 6 (26) 0 0.137
Operation time, min 664 (178–1,070) 527 (441–582) 0.016
PCI 19 (3–34) 13 (6–32) 0.386
Table 3 Type of operation during cytoreduction
Operating time, min 593 (178–1,076)
CC status, n (%)
0 20 (65)
1 8 (25)
2 3 (10)
Colon or rectum resection, n (%) 23 (74)
Small bowel resection, n (%) 9 (29)
Protective enterostomy, n (%) 2 (6.5)
Colostomy terminal, n (%) 3 (10)
Resection of diaphragm, n (%) 10 (32)
Pancreatic resection, n (%) 2 (6.5)
Splenectomy, n (%) 18 (58)
Cholecystectomy, n (%) 9 (29)
Time and type of operation during cytoreduction are reported; data are
presented as median (min, max) or n (%)
Table 5 Complications and mortality, n
Cumulative complications 23
30-day mortality, n 0
90-day mortality, n 0
Cardiac 1 (3%)
Pneumonia 1 (3%)
Sepsis 1 (3%)
Thromobembolic 4 (13%)
Postoperative bleeding 1 (3%)
Ureter injury 1 (3%)
Resuscitation during HIPEC 1 (3%)
Wound infection 4 (13%)
Leukopenia 4 (13%)
Anastomotic leakage 3 of 23 (13%)
Compartment syndrome 1 (3%)
Transient paresthesia in the legs 1 (3%)
Reoperation due to complication 6 (19%)
Complications and perioperative mortality, n (%)
Langenbecks Arch Surg (2011) 396:1077–1081 1079

4. accepted as limitations for complete cytoreductive surgery.
This is also true for liver metastasis. Our median PCI score
was 18 (3–34). We were able to achieve radical cytor-
eduction in 90% of patients (CC0/CC1) who completed the
multimodal concept with HIPEC. In three patients tumor
nodules left behind were between 0.25 and 2.5 cm,
classified as CC2 status. HIPEC in these particular patients
was also performed to treat tumor-related ascites.
Since peritoneal carcinomatosis is a disease that rarely
involves the organs itself, tumor masses can be removed
without resection. The small bowel itself can mostly be
meticulously cleaned of tumor nodules with subsequent
oversewing of partially removed serosal layers. Cleaning
of the mesenterium is much easier, and the nodules can be
removed with electrocautery. In patients with colonic
spread, partial or even complete colectomy was consid-
ered necessary in the past because of the risk of secondary
perforation after local resection. With increasing experi-
ence we learned to also meticulously clean the colon and
rectum of tumor nodules, similar to the small bowel, with
no higher complication rate and with equal radicality. In
fact, in most cases, this can be achieved without
necessitating a colorectal resection. Similarly, serosal
defects are oversewn with vicryl 4-0 single sutures. In
the case of a full-thickness resection, the colon is
oversewn with double-layer sutures.
Interestingly, we observed a trend to a higher rate of
complications and a significantly longer hospital stay in
those patients who underwent colorectal resection. Retro-
spectively, we are convinced that in some patients, colon
resection might have been an overtreatment, and we
therefore changed our policy so as to preserve the large
bowel whenever possible.
Furthermore, tumor recurrence astonishingly was found
most often in the parietal abdominal wall and not on the
bowel. Normally, after peritonectomy of the parietal
abdominal wall, a large wound area is left behind, which
poses a risk for tumor adhesion [8, 9]. However, our patient
number is low and it is too early to make conclusions about
risk factors for recurrence. We therefore immediately
oversew all serosal defects on the small or large bowel to
avoid any exposure of the wound surfaces to potential free
tumor cells.
The management of recurrent ovarian cancer should to
be reconsidered from a standpoint that focuses on radical
reoperation in combination with HIPEC. No mortality and
acceptable morbidity with good overall survival are
promising criteria for further promoting this concept. Using
organ-sparing cytoreduction, complications and hospital
stay were reduced without compromising completeness of
cytoreduction. Concerning the effectiveness of CRS and
HIPEC, no conclusions can be drawn from this study. A
comparison of the “HIPEC group” to a “surgery alone
group” is not possible retrospectively because the exact
exploration of the whole abdomen is mandatory to obtain
the PCI which is crucial for prognosis. To address this
question, a randomized controlled trial is needed to prove
the benefit of CRS and HIPEC on outcome and survival in
patients suffering from recurrent ovarian cancer.
Fig. 1 Kaplan–Meier curves for overall survival (a) and recurrence
(b)
Table 6 Recurrence and mortalities during follow-up
Recurrence, n (%) 7/28 (25)
Mortality during follow-up, n (%) 10 (32)
Follow-up time, days 798 (188–1,297)
Overall, n (%) 7 (25)
Retroperitoneal, n (%) 1 (3.6)
Liver surface/right upper quadrant, n (%) 2 (7.1)
Parietal abdominal wall, n (%) 3 (10.7)
Spleen, n (%) 1 (3.6)
Recurrence data and follow-up time; data are presented as median
(min, max) or n (%)
1080 Langenbecks Arch Surg (2011) 396:1077–1081

5. Conflicts of interest None.
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