Acta Chirurgica Belgica

ISSN: 0001-5458 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/tacb20

Initial Results after Implementation of a

Multimodal Treatment for Peritoneal Malignancies

W. Raue, N. Tsilimparis, C. Langelotz, B. Rau, W. Schwenk & J. Hartmann

To cite this article: W. Raue, N. Tsilimparis, C. Langelotz, B. Rau, W. Schwenk & J. Hartmann
(2011) Initial Results after Implementation of a Multimodal Treatment for Peritoneal Malignancies,
Acta Chirurgica Belgica, 111:2, 68-72, DOI: 10.1080/00015458.2011.11680709

To link to this article: http://dx.doi.org/10.1080/00015458.2011.11680709

Published online: 11 Mar 2016.

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raue_Opmaak 1 14/04/11 09:39 Pagina 68

Original papers

Acta Chir Belg, 2011, 111, 68-72

Initial Results after Implementation of a Multimodal Treatment for Peritoneal

Malignancies
W. Raue1, N. Tsilimparis1, C. Langelotz1, B. Rau1, W. Schwenk2, J. Hartmann1
1
Department of General-, Visceral-, Vascular and Thoracic Surgery, Charité – University Medicine Berlin, Campus Mitte,
Berlin, Germany ; 2Department of General and Visceral Surgery, Asklepios Klinik Altona, Hamburg, Germany.

Abstract. Introduction : Peritoneal carcinomatosis represents a clinical condition with a limited perspective concerning
long term survival. The combination of surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC)
represents a complex multimodal therapeutic management concept with promising results for prolongation of survival.
For the identification of pitfalls during implementation of the HIPEC procedure into clinical practice an observational
study was conducted.
Methods : Between 2005 and 2009 data from all patients treated with cytoreductive surgery and HIPEC for peritoneal
carcinomatosis was prospectively collected and analysed.
Results : During the observational interval a total of 42 patients underwent surgical treatment for peritoneal carcinomato-
sis. In 34 patients the complete procedure with surgical cytoreduction and HIPEC was performed. Perioperative mortal-
ity (6%) and morbidity (35%) was similar to other reported series. Twenty-five patients (76%) survived the 18 months
follow-up period after complete procedure.
Conclusion : The multimodal therapeutic treatment concept of surgical cytoreduction and following HIPEC leads to
promising results for patients suffering from peritoneal carcinomatosis. However this treatment concept is afflicted with
a relevant risk of postoperative complications.

Introduction Patients and Methods

The prognosis for survival is poor for patients with

proven peritoneal carcinomatosis. The mean survival
time is 6 months (1, 2). Frequently only palliative care is
possible. After the development of a combined therapeu-
tical concept including extensive surgical cytoreduction
and the additional intraoperative hyperthermic intraperi-
toneal chemotherapy (HIPEC) curative results could be
demonstrated for the first time (3, 4). These promising
data were confirmed in prospective randomised trials (1,
2). A five-year survival rate of 25% was achieved by sur-
gery and simultaneous HIPEC compared to 0% in the
control group (2).
Based on the newly available clinical evidence, this
multimodal therapy for peritoneal carcinomatosis was
introduced in our department in 2005. A prospective
observational study was conducted to verify the reported
results. Postoperative morbidity and mortality were
meticulously recorded as well as perioperative basic
treatment and vital parameters. Periodical follow up
examinations were begun to assess mid and long term
effects of the HIPEC-procedure on patients’ survival.
Patients
All patients with a histologically proven peritoneal carci-
nomatosis presented at the Department for General-,
Visceral-, Thoracic- and Vascular Surgery, Charité –
University Medicine Berlin Campus Mitte were assessed
for treatment with a combined surgical tumour reduction
and simultaneous heated intraoperative intraperitoneal
chemotherapy.
Patients with extraabdominal tumour manifestations
or proven invasive growth of the peritoneal malignancy
were excluded from further surgical attempt and applied
for palliative therapy. Age > 75 years, concomitant
diseases like myocardial dysfunction (EF < 30%),
pulmonary impairment with a forced expiratory volume
< 1 l/min or ASA class IV (5) also led to exclusion from
scheduling for HIPEC-procedure.
All patients were informed in detail about the status of
the recent knowledge, the therapeutic procedure and the
applied cytostatic medication. Written informed consent
for participation in the present study was obtained from
raue_Opmaak 1 14/04/11 09:39 Pagina 69
Initial Results after HIPEC
every patient in the attendance of the closest relative.
The study was performed in accordance to the
Declaration of Helsinki.
Methods
The present observational clinical trial was conducted to
assess patients’ outcome during implementation of the
concept of surgical cytoreduction and HIPEC for peri-
toneal malignancies into clinical routine.
The surgical procedure was strictly based on the peri-
tonectomy procedure described by SUGARBAKER (3). The
management concept of peritoneal carcinomatosis was
divided into two therapeutic parts : the operative part
with cytoreductive surgery aiming at a complete resec-
tion of all visible tumour mass and the second part :
simultaneous local intraoperative chemotherapy with
hyperthermic lavage of the peritoneal cavity with cyto-
static drugs (HIPEC).
A median laparotomy was performed from the ensi-
form process to the pubis for surgical access. The anteri-
or peritoneum was dissected using the so called „Skin
Traction". Therefore a median abdominal incision was
performed leaving the peritoneum intact beside a small
window for inspection of the abdominal cavity. After that
the peritoneal layer was dissected using electrocautery
under continuous tension of the abdominal wall. A
detailed description of this technique was published else-
where (6, 7, 8). After abdominal exploration the extent of
peritoneal carcinomatosis was documented according to
the peritoneal carcinomatosis index (PCI) to enable bet-
ter comparability. Therefore tumour size was assessed
and accumulated in each of the 13 abdominopelvic
regions. Assessment of tumour size was categorised into
4 groups : 0, no detectable disease ; 1, minimal disease
(tumour thickness < 0.5 cm) ; 2, moderate disease
(tumour thickness ≥ 0.5 cm and ≤ 5 cm) ; and 3, macro-
scopic disease (tumour thickness > 5 cm) (9). The resec-
tion of the affected peritoneum was performed stepwise
if necessary to a complete parietal peritonectomy.
Resection of intraperitoneal organs was necessary in the
case of affected visceral peritoneum. Infiltration of the
small bowel mesentery or of several loops of the small
intestine with symptomatic stenosis represented limiting
factors for curative surgical intention. HIPEC was per-
formed after tumour resection and documentation of the
achieved cytoreduction using the „Completeness of
Cytoreduction Score” (CC score) as described by
Sugarbaker (10).
A half-open coliseum technique was used for the per-
fusion of the abdominal cavity. Thereby a contamination
of the environment was prevented and temperature loss-
es were minimised at the same time. The body core and
blood temperature was simultaneously taken intraab-
dominally, inside the urinary bladder, directly in the
69
descending aorta and in the perfusion machine.
Specialised perfusionists ran a roller pump and heating
unit of a heart lung machine for the hyperthermic
intraperitoneal perfusion to keep a constant flow of
approx. 1-1.2 l/min and to assure the targeted intraab-
dominal temperature of 42°C for 90 min. The surgeon
ensured an even distribution and ‘washing’ of the organs.
Depending on the tumour entity 15 mg/m² body surface
area mitomycin or 25 mg/m² cisplatin diluted in a 1.5%
glucose peritoneal dialysis solution were administered
intraperitoneally and the same dosage of chemotherapeu-
tic agents was repeated after 45min (11).
Intestinal anastomoses were sutured after completion
of HIPEC. Handsewn anastomoses were favoured.
Staplers were used for low rectal or esophagojejunal
anastomosis only. Regularly two 24 Charrière sump
drains (Mallinckrodt Medical GmbH, Hennef, Germany)
were left in place intraabdominally at the end of the pro-
cedure. Early extubation was attempted on our surgical
ICU after completion of the procedure. Oral nutrition
was initiated immediately after stabilisation of the vital
parameters.
Follow up
The further follow up of the patients was conducted in
our outpatient clinic. It included office visits with clini-
cal examination and control of the tumour markers as
well as imaging studies with abdominal CT scan and
chest radiography every six months.
Statistical analysis
A relational database was created and statistical analysis
was performed using SPSS 15.0® for Windows®.
Results
Between October 2005 and February 2009 altogether
42 patients were scheduled to undergo cytoreductive sur-
gery and HIPEC. The complete procedure was accom-
plished in 34 patients. A palliative procedure was per-
formed due to extensive infiltration of the small bowel
(6 patients) or the iliac arteries (further 2 patients). In
two female and one male patient HIPEC without peri-
tonectomy was performed to reduce substantial ascites.
Peritoneal carcinomatosis from ovarian origin repre-
sented the most frequent indication for treatment
(Table I). The median operative time including HIPEC
was 395 min. (range 250-835). The postoperative stay in
the intensive care unit averaged 11 days, while the
duration of postoperative hospitalisation was 26 days
(Table II).
In 56% of the cases (19 patients) complete tumour
resection was achieved (CC score 0). Residual tumour
raue_Opmaak 1 14/04/11 09:39 Pagina 70

70 W. Raue et al.

Table I Table III

Indication for surgical cytoreduction and HIPEC Postoperative course and complications
Tumour entity N = 34 (%) Surgical complications : n (%)
Ovarian carcinoma 10 (29) Anastomotic leakage 2 (6)
Gastric cancer 5 (15) Superficial wound infection 5 (15)
Colorectal Carcinoma 7 (21) Deep wound infection 2 (6)
Pseudomyxoma peritonei 5 (15) Peritonitis / intraabdominal abscess 3 (9)
Mesothelioma 2 (6) Bleeding 5 (15)
Mucinous appendix carcinoma 4 (12) General complications :
Unknown primary 1 (3) Pulmonary 6 (18)
Renal/hepatic 5 (15)
Cardiac 6 (18)
Table II Mental disorder 7 (21)
Catheter associated infection 5 (15)
Patient demographic data and clinical characteristics
Number of patients with complications 12 (35)
N = 34
Age (years) 56 (27-73) Patients with need for surgical revision 7 (21)
Gender female 23 (68) In-hospital mortality 2 (6)

Body mass index (kg/m2) (BMI) 26 (21-31)

ASA score
I / II 27 (79) Table IV
III 7 (21) Treatment related toxicity according
Peritoneal Carcinomatosis Index (PCI) 18 (4-33) to the NCI CTCAE classification
Completeness of cytoreduction score (CCS) Grade III Grade IV Grade V
0 (no remaining tumour) 19 (56%) Infection 7 3 2
1 (remaining tumour < 0,25 cm) 10 (29%) Gastrointestinal tract 2 1 2
2 (remaining tumour 0,25-2,5 cm) 5 (15%) Cardiovascular system 4 2 -
Chemotherapy Bone marrow 1 - -
Neurological system 4 4 -
Mitomycin C 23
Renal / Genitourinary system 4 - -
Cisplatin 11
Haematological system 2 - -
Time for complete surgery/HIPEC (min) 395 (250-835) Pulmonary system 3 2 -
Stay on the Intensive Care Unit (days) 11 (2-42)
Grade 5 refers to toxicity related deaths.
Postoperative hospital stay (days) 26 (8-71) Different complications can occur in one patient.
Data are given as median (range) or number (%).

remained in 15 cases (34%) (Table II). Three patients
with CC score of 1/2 underwent reoperation for tumour
progression to prevent mechanical ileus.
Overall 7 (21%) patients suffered from complications
requiring surgical revision (bleeding : 5, anastomotic
leak : 1, fistula : 1). General complications were seen in
12 (34%) patients. Cardiac failure with need for pro-
longed inotropic support or arrhythmias higher than
Lown III° and pulmonary insufficiency were the most
common general complications that resulted in a pro-
longed time of mechanical ventilation or noninvasive
ventilation support (median 120h, range 4-860h).
Furthermore transient mental disorientation occurred in
21% of all patients after extubation but full recovery was
achieved without specific therapy in all cases (Table III
and IV).
During the early postoperative course two patients
(6%) died from a multi organ failure after anastomotic
leakage. Further 6 patients (18%) died during the follow-
up period from a progression of their underlying malig-
nancy. After a mean follow up of 18 months 76% of all
treated patients were still alive (Fig. 1).
Discussion
The therapeutic concept combining HIPEC and surgical
cytoreduction for peritoneal carcinomatosis offers a
potentially curative treatment for the first time (3).
Success of this approach must be weighed against pallia-
tive conservative treatment including modern systemic
chemotherapy and best supportive care. Acceptable
treatment related mortality and morbidity must be
raue_Opmaak 1 14/04/11 09:39 Pagina 71
Initial Results after HIPEC
Fig. 1
Survival time after surgery and HIPEC for peritoneal carcino-
matosis.
requested. The results of several prospective trials in dif-
ferent tumour entities are promising (2, 12, 13, 14). The
mortality of combined HIPEC and surgical debulking
varies in different studies from 1-12% (2, 12, 15, 16, 17,
18, 19, 20).
The peritoneal carcinomatosis index (PCI) is not only
the most frequently used score comparing the extent of
the peritoneal carcinomatosis between individuals, but
seems to be a relevant prognostic factor (21).
SUGARBAKER demonstrated in a long-term follow up after
treatment for peritoneal carcinomatosis from colonic ori-
gin a 5-year survival rate of 50% in patients with a PCI
< 10 versus 0% in patients with a PCI > 20 (22).
Therefore other authors assume a PCI > 20 to be a con-
traindication for the operation (23). We performed the
complete procedure in cases with a PCI > 20 only if a
complete tumour resection seemed to be achievable.
However finally the major influence of the achieved
completeness of cytoreduction score CCS on the long-
term outcome has been proven in several publications
(14, 15, 19, 24, 25).
General postoperative cardiopulmonary complica-
tions are described as the most common complica-
tions (2, 17, 18, 26, 27). Their incidence in the present
trial is comparable to the data reported in the literature.
Postoperative bleeding and fistulas are frequent com-
plications requiring surgical revision (1, 28, 29, 30, 31).
Especially bleeding is related to the large wound surface
after peritonectomy and the negative effect of HIPEC on
coagulation. Although the rate of surgical revision was
71
comparable to the available data, we noticed a consider-
able lower incidence of fistulas and relevant anastomot-
ic leakages in our trial. One reason for this result might
be consequent creation of a defunctioning ileostomy if a
rectal resection had to be performed. Furthermore a
meticulous preparation including detailed workflows and
close integration of all medical disciplines (e.g. anaes-
thesiology and oncology) helped to improve the learning
curve during for the implementation of the procedure
into clinical routine.
Conclusions concerning the long-term course or the
postoperative survival are limited because of the small
number of treated patients and the short follow up in the
present trial. Nevertheless the preliminary data are prom-
ising. To elucidate further questions, all patients under-
going HIPEC treatment in our hospital will be enrolled in
prospective study protocols. Especially the prevention of
cardiopulmonary complications has not been extensively
studied yet and is in the focus of further investigations.
In conclusion the therapeutical approach of combined
cytoreductive surgery and simultaneous HIPEC offers a
promising attempt for a considerable prolongation of
survival with acceptable morbidity and mortality in cases
of peritoneal carcinomatosis. This procedure can be
safely implemented into clinical practice. However, the
successful introduction of the concept requires accurate
planning, support on multiple administrative and clinical
levels, as well as a preparatory phase for the clinical
implementation.
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Dr. med. W. Raue
Dep. of General, Visceral, Vascular and Thoracic Surgery
Charité - University Medicine Berlin, Campus Mitte
Charitéplatz 1
10117 Berlin, Germany
Tel. : +49/ 30 450 622 325
Fax : +49/ 30 450 522 922
E-mail : wieland.raue@charite.de