The influence of laparotomy and laparoscopy on tumor growth in a
rat model
C. A. Jacobi,
1
J. Ordemann,
1
B. Bo¨hm,
1
H. U. Zieren,
1
C. Liebenthal,
2
H. D. Volk,
2
J. M. Mu¨ller
1
1
Department of Surgery, Humboldt-University of Berlin, Charite´, Schumann Strae 20/21, 10098 Berlin, Germany
2
Institute of Medical Immunology, Humboldt-University of Berlin, Charite´, Schumann Strae 20/21, 10098 Berlin, Germany
Received: 7 November 1996/Accepted: 3 December 1996
Abstract
Background: The effects of laparotomy and laparoscopy
with different gases on subcutaneous and intraperitoneal
tumor growth have not been evaluated yet.
Methods: Tumor growth of colon adenocarcinoma DHD/
K12/TRb was measured in rats after laparotomy, laparos-
copy with CO
2
or air, and in control group. Cell kinetics
were determined after incubation with carbon dioxide or air
in vitro and tumor growth was measured subcutaneously
and intraperitoneally after surgery in vivo.
Results: In vitro, tumor cell growth increased significantly
after incubation with air and CO
2
. In vivo, intraperitoneal
tumor weight was increased after laparotomy (1,203 ± 780
mg) and after laparoscopy with air (1,085 ± 891 mg) and
with CO
2
(718 ± 690 mg) compared to control group (521
± 221 mg) (p < 0.05). Subcutaneous tumor growth was
promoted after laparotomy (71 ± 35 mg) and even more
after laparoscopy with air (82 ± 45 mg) and CO
2
(99±55
mg) compared to control group (36 ± 33 mg).
Conclusions: Insufflation of air and CO
2
promote tumor
growth in vitro. In vivo, intraperitoneal tumor growth seems
to be promoted primarily by intraperitoneal air and subcu-
taneous tumor growth by CO
2
.
Key words: Laparotomy — Laparoscopy — Tumor growth
— Air — Carbon dioxide
Laparoscopic techniques are still discussed controversially
for treatment of malignancies because port site recurrences
and peritoneal tumor seeding after laparoscopic cholecys-
tectomy, colectomy, and gastric resection have been re-
ported [3, 4, 6, 7, 11, 12, 15]. Apparently tumor seeding and
development of subcutaneous metastases appear more often
after laparoscopic than after open resections of malignant
tumors. The mechanism of this phenomen is still hypotheti-
cal [2, 8, 14]. In contrast to these clinical observations,
Allendorf et al. have demonstrated that subcutaneous tu-
mors were more easily established and grew more aggres-
sively after laparotomy than after insufflation with CO
2
in a
mice model [1]. It was suggested that the difference in
tumor growth is due to postoperative immune advantage in
the laparoscopic group compared to open surgery. Since
immunologic changes have not been evaluated in this study
the hypothesis remains theoretical and has not been con-
firmed yet. Another important factor in tumor growth,
which has not been evaluated until now, may be the influ-
ence of the gas used to establish pneumoperitoneum.
Whether carbon dioxide, commonly utilized in laparoscopic
surgery, causes subcutaneus port site recurrences has to be
evaluated. The influence of air on tumor cell growth has
also not been investigated.
Therefore, we investigated the influence of different
gases commonly used in laparotomy and laparoscopy on
tumor cell growth in vitro, ex vivo, and in vivo.
Methods
In the first experiment the influence of carbon dioxide and air on tumor
cells was investigated in vitro in order to evaluate the influence of different
gases on the cell lines without immunological interaction of the host. Air
was chosen to duplicate the situation during laparotomy. The hypothesis of
the study was that there is a difference in tumor growth between the
different gases.
Colonic carcinoma cell line DHD/K12/TRb cells (ECACC) were cul-
tured in Dulbecco’s MEM (Biochrom, Germany) and Ham’s F10 medium
(Biochrom, Germany) 1:1 supplemented with 10% fetal bovine serum
(Gibco BRL, Germany), 2 mmol/l Gluthamin (Biochrom, Germany), and
penicillin-streptomycin (Gibco, Germany) 1,000 IU/ml.
Cells (5 × 10
6
) were suspended in 10 ml of culture medium. They were
incubated either with pure carbon dioxide or air or underwent no further
manipulation in the control group. The gases were insufflated into the
culture flasks (75 cm
2
/250 ml) through a sterile filter and drawn out
through a control valve. Pressure during incubation was 0.5 (0–1.0) mmHg
in each experiment. Gas analyses of the ‘‘atmosphere’’ in the flasks de-
tected absence of oxygen during the incubation with carbon dioxide. Partial
pressure of oxygen was 20.8 ± 0.7 kPa after air incubation and 20.5 ± 0.4
Correspondence to: C. A. Jacobi
Surg Endosc (1997) 11: 618–621
Surgical
Endoscopy
© Springer-Verlag New York Inc. 1997