Feasibility of Radical Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy For Pseudomyxoma Peritonei of Appendiceal Origin

Article (PDF Available)inScandinavian journal of surgery: SJS: official organ for the Finnish Surgical Society and the Scandinavian Surgical Society 102(3):145-51 · September 2013with30 Reads
DOI: 10.1177/1457496913490463 · Source: PubMed
Abstract
We analyzed the feasibility of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with pseudomyxoma peritonei. A prospective database comprised 90 consecutive patients with demonstrable pseudomyxoma peritonei collected during 48 months. These patients, referred to our unit for consideration for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, received both cytoreductive surgery and hyperthermic intraperitoneal chemotherapy if possible. We evaluated the factors associated with a successful procedure. Hyperthermic intraperitoneal chemotherapy was successfully delivered to 56 of 90 patients (62%) with demonstrable pseudomyxoma peritonei. Tumor morphology of low grade (p = 0.013), age under 65 years (p = 0.004), and serum carcinoembryonic antigen level under 5.0 µg/L (p = 0.003) were associated with successful administration of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Mean peritoneal cancer index was lower (18.9 vs 32.6, p < 0.001) and age was younger (54.3 vs 61.6, p = 0.003) in patients who underwent hyperthermic intraperitoneal chemotherapy than in patients who did not. Four patients had complete cytoreductive surgery alone, and 20 patients underwent palliative debulking, but 10 were ineligible for this operation. Although the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is currently suggested the standard practice for pseudomyxoma peritonei, not all patients are eligible for this protocol. In this study, hyperthermic intraperitoneal chemotherapy was suitable for 62% of patients with pseudomyxoma peritonei of appendiceal origin.

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Scandinavian Journal of Surgery 102: 145 –151, 2013
FEASIBILITY OF RADICAL CYTOREDUCTIVE SURGERY AND
HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY FOR
PSEUDOMYXOMA PERITONEI OF APPENDICEAL ORIGIN
P. Järvinen
1
, A. Ristimäki
2,3,4
, J. Kantonen
2,3
, A. Lepistö
5,6
1
Department of Surgery, Kanta-Häme Central Hospital, Hämeenlinna, Finland
2
Department of Pathology, HUSLAB, Helsinki University Central Hospital, Helsinki, Finland
3
Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland
4
Genome-Scale Biology, Research Programs Unit, University of Helsinki, Helsinki, Finland
5
Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland
6
Surgical Hospital, Helsinki University Central Hospital, Helsinki, Finland
ABSTRACT
Background and Aims: We analyzed the feasibility of cytoreductive surgery and
hyperthermic intraperitoneal chemotherapy in patients with pseudomyxoma peritonei.
Material and Methods: A prospective database comprised 90 consecutive patients with
demonstrable pseudomyxoma peritonei collected during 48 months. These patients,
referred to our unit for consideration for cytoreductive surgery and hyperthermic
intraperitoneal chemotherapy, received both cytoreductive surgery and hyperthermic
intraperitoneal chemotherapy if possible. We evaluated the factors associated with a
successful procedure.
Results: Hyperthermic intraperitoneal chemotherapy was successfully delivered to 56 of
90 patients (62%) with demonstrable pseudomyxoma peritonei. Tumor morphology of low
grade (p = 0.013), age under 65 years (p = 0.004), and serum carcinoembryonic antigen level
under 5.0 µg/L (p = 0.003) were associated with successful administration of cytoreductive
surgery and hyperthermic intraperitoneal chemotherapy. Mean peritoneal cancer index
was lower (18.9 vs 32.6, p < 0.001) and age was younger (54.3 vs 61.6, p = 0.003) in patients
who underwent hyperthermic intraperitoneal chemotherapy than in patients who did
not. Four patients had complete cytoreductive surgery alone, and 20 patients underwent
palliative debulking, but 10 were ineligible for this operation.
Conclusions: Although the combination of cytoreductive surgery and hyperthermic
intraperitoneal chemotherapy is currently suggested the standard practice for
pseudomyxoma peritonei, not all patients are eligible for this protocol. In this study,
Correspondence:
Anna Lepistö, M.D., Ph.D.
Surgical Hospital
Helsinki University Central Hospital Kasarminkatu 11 – 13
Helsinki
P.O. Box 263
FIN-00029 HUS
Finland
Email: anna.lepisto@kolumbus.fi
490463
SJS102310.1177/1457496913490463Feasibility of HIPEC for pseudomyxoma peritoneiP. Järvinen, A. Ristimäki, J. Kantonen, A. Lepistö
2013
ORIGINAL ARTICLE
P. Järvinen, et al.146
hyperthermic intraperitoneal chemotherapy was suitable for 62% of patients with
pseudomyxoma peritonei of appendiceal origin.
Key words: Appendiceal; mucinous neoplasm; peritoneal; peritonectomy; Sugarbaker procedure;
hyperthermic intraperitoneal chemotherapy
INTRODUCTION
Pseudomyxoma peritonei (PMP) is a rare syndrome
with an estimated incidence of 1 to 2 persons per mil-
lion annually (1). Its diagnosis is clinicopathological,
and it is characterized by accumulation of extracellu-
lar mucin and epithelial mucin-secreting cells within
the abdominal cavity. Movement and absorption of
peritoneal fluid plus gravity result in accumulation of
epithelial cells at specific sites in the abdominal cavity;
this is called a redistribution phenomenon (2). An
omental mass, ovarian masses, and a mucinous bur-
den on the right hemidiaphragm are characteristically
present in PMP and can be explained by this effect.
Eventually, the space-taking disease compromises
organ functioning and causes intestinal obstruction,
dyspnea, and malnutrition. Without surgical interven-
tion, mortality will be the outcome.
The primary origin of PMP has been controversial,
ever since the early description of the syndrome as
being associated with an ovarian tumor. Nowadays, in
the vast majority of cases, the appendix can be identi-
fied as the origin (3, 4). Synchronous ovarian metasta-
ses are not uncommon, and PMP of appendiceal origin
can be confused with primary ovarian neoplasia (5).
Moreover, molecular evidence suggests that PMP is
usually derived from an appendiceal neoplasm (6).
However, PMP is not synonymous with appendiceal
neoplasm with peritoneal spread because other tumor
types may also induce this clinical syndrome (6). In par-
ticular, the classification of PMP has been challenging,
with various classification schemes proposed (7–10). In
this study, we used the World Health Organization
(WHO) 2010 classification, where the tumor is classified
as “high-grade” or “low-grade” tumor (11).
In the past, PMP was treated by iterative debulking
operations. However, relapses occurred in most cases,
and repeated surgeries were more challenging when
the disease progressed and scarring, adhesions, and
distortion of the anatomy developed. A serial debulk-
ing protocol resulted in overall survival figures of 21%–
32% after 10 years’ follow-up (12–14). Currently, the
treatment considered optimal for PMP is aggressive
cytoreductive surgery (CRS), to be followed by hyper-
thermic intraperitoneal chemotherapy (HIPEC) (15). In
case of optimally cytoreduced series of PMP patients,
combination of CRS and HIPEC has been reported to
yield 10-year overall survival of up to 85% (16).
As CRS and HIPEC represent complex surgery,
morbidity and mortality rates are also considerable
(17). The complication rate does, however, decrease
with increasing surgical experience, particularly in a
specialized center. As the Basingstoke center experi-
ence points out, not only does surgical technique
influence the learning curve, but so does the emphasis
on case selection (18). Undoubtedly, not all cases of
PMP are amenable to aggressive surgery and HIPEC.
Some patients are ineligible due to the extent of their
disease. Other patients would, technically, be able to
undergo the surgical procedure, but their general con-
dition would prohibit any attempt at surgery. This
study analyzed the feasibility of CRS and HIPEC in
patients with PMP and then evaluated factors associ-
ated with a successful procedure—using an analysis
of prospectively and consecutively recruited patients
numbering 90.
MATERIAL AND METHODS
This study included 90 patients with histologically
proven and demonstrable PMP of appendiceal origin.
The database of 121 patients with suspected or diag-
nosed PMP, who were referred to the Department of
Colorectal Surgery in Helsinki University Central
Hospital since the establishment of our HIPEC center
in November 2007 up to October 2011, 48 months later,
was collected prospectively. The inclusion criterion
was demonstrable mucinous neoplasm of the appen-
dix and of the peritoneum. The exclusion criteria were
as follows: no extra-appendiceal spread (2 patients),
mixed adenoneuroendocrine carcinomas of appendi-
ceal origin (MANEC) (8 patients), the peritoneal carci-
nomatoses of nonappendiceal origin such as ovarian
(3 patients), colorectal (5 patients), and ileal (1 patient)
and mucinous tumors of unknown origin (2 patients)
as well as peritoneal mesothelioma (two patients).
Seven patients referred to our unit were only moni-
tored as they showed no demonstrable disease after
preceding operation(s) and were not included. One
patient with low-grade PMP who refused any further
surgical treatment was excluded. Thus, a total of 90
patients fulfilled the inclusion criterion for analysis.
The patients referred underwent consecutive evalu-
ation regarding possible surgical intervention. Only
their initial evaluation or initial HIPEC operation in
our unit was included here. One patient with high-
grade disease showed signs of early relapse after the
combined-modality treatment and was offered re-
HIPEC during the timeline, but only the initial HIPEC
operation was included to avoid demographic design
bias. Otherwise, both primary and recurrent PMP
were included in the study, regardless of the preced-
ing treatment strategy. There were 65 patients with
primary disease and 25 patients with recurrent dis-
ease.
Diagnosis of PMP was based on intraoperative
findings confirmed by histopathological sampling.
The diagnosis was established either in our unit (13
patients) or in referring units (77 patients). Every
patient was further evaluated and had her diagnosis
Feasibility of HIPEC for pseudomyxoma peritonei 147
confirmed. A total of 83 patients (92%) were invited to
a clinical meeting and one (1%) was assessed ineligible
for HIPEC during an emergency operation. Six (7%)
were excluded from the complex procedures of CRS
and HIPEC after our consulting the patient records. Of
90 patients, 80 (89%) had undergone at least one major
operation before the clinical meeting. Of those 80
patients who had surgery before the meeting, 73 were
operated on elsewhere, 4 had surgery in our unit, and
3 had undergone operations both in our unit and else-
where. The mean number of preceding operations per
patient was 1.4 ± 0.1 (median = 1, range: 0–8). Three of
the patients evaluated had undergone HIPEC opera-
tions elsewhere before receiving a referral to our unit,
with two of them each having had two HIPEC surger-
ies.
Each patient’s carcinoembryonic antigen (CEA)
was measured in 89 of 90 cases (99%) prior to consid-
eration for surgery. The patient with a missing CEA
measurement had poor overall status and severe
comorbidities and underwent surgery. The nature of
this emergency operation was palliative debulking
surgery. Values of CEA below 5 µg/L were considered
normal. The preoperative tumor-load evaluation
included both computed tomography (CT) and the
surgical result of the preceding operation(s) (81
patients) or included CT only (9 patients). Histological
classification of PMP was based on the WHO classifi-
cation of tumors: low grade or high grade. Histological
samples retrieved underwent review by our patholo-
gists (A.R. and J.K.).
The clinical procedures were as follows: patients
were offered combined treatment with CRS and
HIPEC, conventional surgery, or active follow-up (Fig.
1). Every amenable patient who would seem to benefit
from combined treatment was offered an attempt at
the regimen. Conventional surgery was offered to
patients ineligible for HIPEC, and follow-up was initi-
ated in patients ineligible for any surgery. Conventional
surgery and follow-up were arranged either in our
unit or in the referring hospital. Contraindications for
intraperitoneal chemotherapy were poor overall sta-
tus, high age (1 patient, 77 years), and severe comor-
bidities. Those patients with disseminated disease
without any considerable likelihood for complete CRS
were also excluded from any attempt at combined-
modality therapy. Active follow-up was the choice for
patients of very high age (1 patient, 86 years) with
very poor general status, or with extensively dissemi-
nated disease. Active follow-up included iterative
clinical evaluation, serum CEA measurement, and CT
every 6 or 12 months.
If none of the contraindications existed, an attempt
at CRS and HIPEC was scheduled. Aggressive surgery
with peritonectomy procedures combined with neces-
sary organ resections was attempted, as described by
Sugarbaker (19). After complete exploration of the
abdomen and pelvis, every patient who underwent an
attempt of HIPEC (69 patients) received a peritoneal
cancer index (PCI) score determined intraoperatively
(20). No PCI score was determined routinely for the
group who underwent debulking surgery. The final
decision whether or not to administer intraperitoneal
chemotherapy was based on intraoperative assessment
of cytoreduction. The radicality of surgery was assessed
based on the completeness of the cytoreduction scoring
90 paents with PMP,
Nov. 2007 –Oct. 2011
69 aempts at CRS + HIPEC
-56 by CRS and HIPEC
-13 palliavesurgeries
11 cases with convenonal surgeries
without HIPEC
-7 debulking surgeries
-4 completecytoreducons
10 paents referred backor
transferred to palliave care without
surgery
-7 for palliave treatment
-3 for acve follow-up
Fig. 1. Three clinical pathways of treatment. A total of 90 patients with demonstrable PMP evaluated and considered for surgery in
Helsinki during 4 years.
PMP: pseudomyxoma peritonei; CRS: cytoreductive surgery; HIPEC: hyperthermic intraperitoneal chemotherapy.
P. Järvinen, et al.148
system (21). A surgical result of complete cytoreduc-
tion-0 (CC-0) signified no macroscopical residual
tumor, CC-1 signified residual nodules under 0.25 cm,
CC-2 signified residual nodules between 0.25 cm and
2.5 cm, and CC-3 signified residual tumor over 2.5 cm
in diameter. The scores CC-0 and CC-1 were considered
successful cytoreduction, and CC-2 and CC-3 as pallia-
tive surgery. Intraperitoneal chemotherapy with mito-
mycin C was administered routinely after successful
complete cytoreduction by the modified Coliseum
technique (22). The dosage of chemotherapeutic agent
was calculated by each patient’s clinical oncologist. The
standard dosage was 30 mg/m
2
.
All analyses were performed with SPSS
®
Statistics
software (IBM
®
Version 20.0.0). The data were in
proportions (percentages) or number of patients for
categorical variables and as means ± standard errors
(medians, ranges) for continuous variables.
Associations between patient characteristics and suc-
cessfully administered HIPEC were measured by
Pearson’s χ
2
-analysis. The characteristics tested were
morphology of the tumor (low-grade or high-grade
tumor), age with a cutoff above 64 years, whether or
not the serum CEA value was elevated, and gender.
Age and PCI, when available, were compared by
Student’s t-test for differences in means between
patients who underwent or did not undergo a success-
ful HIPEC operation. The delay, determined in months,
between diagnosis and assessment for feasibility of
HIPEC was compared by Mann–Whitney U-test. Ages
and PCI scores were normally distributed, but the
delay was not (the Kolmogorov–Smirnov test 0.20,
0.20, and <0.01, respectively). The p-value < 0.05 was
considered statistically significant (two-sided). This
study was approved by the local ethics committee
(permission number 265/13/03/02/2011).
RESULTS
Of the 90 cases, 58 were women (64%) and 32 men
(36%); they were assessed for feasibility of CRS and
HIPEC. Mean age at assessment was 57.1 ± 1.19 years
(median = 58, range: 30–87 years). The tumor was a
low-grade carcinoma in 57 patients and high grade in
33. Of 89 cases, serum level of CEA was elevated in 41
(46%). Mean of CEA was 46.7 ± 16.8 (median = 4.4,
range: 1–1325.2).
Of the 90 cases, 69 (77%) underwent an attempt at
delivering combined treatment with CRS and HIPEC.
In 56 (81%) of those 69 surgeries (62% of all patients),
HIPEC was successfully administered after a surgical
score of CC-0 or CC-1 was achieved. Tumor burden
preventing radical surgery was located in the hepatic
hilum (7 patients), in the lesser omentum (4 patients),
and extensively in the abdominal cavity (2 patients,
PCI scores 37 and 39). Conventional surgery with
major laparotomy was offered to 11 (12%) patients in
our unit, as those patients were considered unamena-
ble to intraperitoneal chemotherapy. A radical end
result (CC-0 or CC-1) was achieved in four of those 11
cases, of whom 10 were electively operated but preop-
eratively excluded from combined treatment with
CRS and HIPEC. One of those 11 patients had
Alzheimer’s disease as well as atrial fibrillation and
was operated on as an emergency case; this debulking
surgery was considered definitive treatment. Ten
patients (11%) were not scheduled for surgery and
were referred back to their referral hospitals or were
transferred to palliative care in our unit: 6 patients had
widely disseminated disease, and 4 were ineligible for
surgery because of severe comorbidity or old age
(Table 1). The choices of treatments for the 3 patients
who had undergone HIPEC operation elsewhere
before obtaining a referral to our unit were the follow-
ing: one HIPEC, one conventional surgery, and one
active follow-up.
Analysis of variables associated with a successful
cytoreduction (CC-0 or CC-1) and HIPEC included 90
patients with demonstrable PMP at the time of their
evaluation. Successful combined treatment was associ-
ated with low-grade morphology (p = 0.013), serum
CEA level under 5.0 µg/L (p = 0.003), and age < 65
TABLE 1
Reasons for exclusion from attempt at HIPEC in 21 patients with PMP.
Group Patients in group Reason CC-0 or CC-1
Conventional surgeries 11 Severe comorbidities 5 1
Abstinence from blood
transfusion
1 0
Age (77 years) 1 1
Disseminated disease 1 0
Operation room not
scheduled
1 1
Poor general status 1 0
Very local disease 1 1
Referred back 7 Disseminated disease 4
Severe comorbidities 2
Age (86 years) 1
Active follow-up 3 Disseminated disease 2
Severe comorbidities 1
Total 21
HIPEC: hyperthermic intraperitoneal chemotherapy; PMP: pseudomyxoma peritonei.
CC-0 or CC-1 = complete cytoreduction.
Feasibility of HIPEC for pseudomyxoma peritonei 149
years (p = 0.004). Gender showed no effect on surgical
result (p = 0.385). There was, however, significant over-
lap in some variables, such as morphology and CEA
(Table 2). Patients undergoing successful HIPEC also
had significantly lower PCI values (18.9 vs 32.6, p <
0.001) and were younger (54.3 years vs 61.6 years, p =
0.003) than those with no HIPEC treatment. The high-
est PCI value in the HIPEC group was 29 years, and the
oldest patient was aged 73 years (Table 3). We found no
differences in statistical significance in the means for
delay between diagnosis and assessment for feasibility
of HIPEC, although the mean delay was longer in the
non-HIPEC group (24.1 vs 18.3, p = 0.124).
DISCUSSION
Of the 90 PMP patients with demonstrable disease, 69
(77%) were considered suitable for an attempt at CRS
and HIPEC. Of those 69 patients, eventually, 56 (81%)
also received HIPEC treatment, 62% of the total. In a
series of 203 patients with PMP from Manchester, UK,
69 (34%) underwent CRS, and 32 (16%) had debulking
surgery (23). Their proportion of complete cytoreduc-
tion was 68% of those undergoing laparotomy, similar
to our figure of 75%, even though the number of cases
with no operation was higher. In a series of 38 patients
referred from Milan (24), 31 (82%) received CRS and
HIPEC, but that study included only patients with
favorable histology, that is, disseminated peritoneal
adenomucinosis (DPAM) and peritoneal mucinous
carcinomatosis with intermediate or discordant fea-
tures (PMCA-I/D). In our own series, however, 37%
(33 of 90) belonged to the high-grade group. Moreover,
in our series more patients had undergone previous
debulking surgery than in theirs (90% vs 53%), which
is known to diminish probability for complete CRS.
TABLE 2
Characteristics associated with HIPEC administration.
HIPEC Row
percentage
HIPEC not
administered
Row
percentage
Pearson
χ
2
p
Age <65 48 71% 20 29% 8.28 0.004
≥65 8 36% 14 64%
Total 56 62% 34 38%
CEA <5.0 37 77% 11 23% 8.96 0.003
≥5.0 19 46% 22 54%
Total
a
56 63% 33 37%
Morphology High grade 15 45% 18 55% 6.23 0.013
Low grade 41 72% 16 28%
Total 56 62% 34 38%
Gender Female 38 66% 20 34% 0.75 0.385
Male 18 56% 14 44%
Total 56 62% 34 38%
HIPEC: hyperthermic intraperitoneal chemotherapy; CEA: carcinoembryonic antigen.
a
One case missing CEA value.
TABLE 3
Comparison of means in patients undergoing successful HIPEC and other treatment modalities.
Mean PCI ± SE Median Range Student’s t-value p N
HIPEC 54.3 ± 1.27 54 30–73 0.003 56
no HIPEC 61.6 ± 2.18 61 36–87 3.09 34
Total 90
Mean age ± SE Median Range Student’s t-value p N
HIPEC 18.9 ± 0.83 20 5–29 <0.001 56
no HIPEC 32.6 ± 1.64 34 16–39 7.24 13
Total 69
a
Mean delay
b
± SE
Median Range Mann–Whitney
U
p N
HIPEC 18.3 ± 3.86 7 0–149 0.124 56
no HIPEC 24.1 ± 7.82 3.5 0–191 1136.5 34
Total 90
HIPEC: hyperthermic intraperitoneal chemotherapy; SE: Standard error; PCI: peritoneal cancer index.
a
PCI was determined only in 69 patients who underwent an attempt at combined-modality treatment.
b
Delay between diagnosis and assessment for feasibility of HIPEC is presented in months.
P. Järvinen, et al.150
For the 13 patients in whom complete CRS failed,
tumor load was located in the liver hilus, or in the
lesser omentum or extensively in the abdominal cav-
ity, which is in line with previous findings. Lesser
omentum involvement is especially difficult to evalu-
ate in preoperative CT with adequate accuracy, indi-
cating that even as the best modality for PMP
evaluation (25), CT sensitivity is far from optimal.
The finding of a heavy general tumor burden in pre-
operative CT cannot remain the sole exclusion crite-
rion for an attempt at CRS and HIPEC because for
some of the patients with heavy tumor load but low-
grade histology, radical surgery is possible. Neither
has the Verwaal score (26) proven to adequately
exclude patients from an attempt at CRS and HIPEC.
The lack of a sensitive method for patient exclusion is
nearly entirely the problem of waste of surgical
resources—not the problem of the patient. Nearly
every patient benefits from debulking surgery or
“near to complete CRS without HIPEC” because no
better alternative treatment exists. The only disad-
vantage for patients is the longer wait, when opera-
tive resources reserved on HIPEC are wasted on
palliative treatment.
We noted that patients who underwent nonradical
surgery and thus were more prone to undergo debulk-
ing surgery only with no HIPEC had higher PCI scores
than patients with successful HIPEC. A similar effect
has also occurred (23, 27). This finding is reasonable
and points out the importance of early diagnosis and
consideration for surgery before the tumor bulk accu-
mulates. Although we found no difference in statisti-
cal significance in delay between diagnosis and
(intraoperative or preoperative) assessment for feasi-
bility of HIPEC, the mean delay was shorter in the
HIPEC group. It is not impossible that this effect
would become more apparent in larger patient popu-
lations.
Age under 65 years was associated with successful
HIPEC, and the mean age of patients who underwent
HIPEC was, for obvious reasons, lower. As high age
itself was a contraindication for an attempt at HIPEC
in only 2 cases, the increase in comorbidities by age
explains the figures. However, of 56 patients who
received HIPEC, 19 (34%) were aged 60 years or older
and 4 (7%) were 70 years or older. This suggests that
healthy elderly patients in good overall condition and
with a moderate tumor burden deserve an attempt at
combined-modality treatment, as suggested by Klaver
et al. (28) in cases of peritoneal carcinosis of colorectal
cancer.
Serum markers are predictors of adequate cytore-
duction (29), and this study also showed an associa-
tion between elevated CEA and inadequate
cytoreduction and thus unsuccessful HIPEC. This
finding shows that PMP patients with elevated CEA
are not only more likely to develop recurrent disease
and have a significantly shorter recurrence-free inter-
val, as elsewhere noted (30), but are more likely to
undergo nonradical surgery in the first place.
Considering that elevated CEA levels are correlated
with tumor burden and malignant histological mor-
phologies, the surgical result is understandable.
The predictive value of these findings on PCI and
morphology as associated with successfully delivered
HIPEC is limited. Not all our patients had undergone
a previous operation, and determination of PCI is pos-
sible only intraoperatively. Biopsy specimens for
determining morphology often were lacking before an
attempt at HIPEC. Even with knowledge of factors
associated with successful HIPEC, to determine feasi-
bility of HIPEC before an attempt in a specialized
center is still difficult. Nevertheless, when there is a
diagnosed PMP case or a strong suspicion of one, we
suggest that the initial operation, when possible,
should be undertaken in a center with capability of
performing HIPEC.
As combined-modality treatment of CRS and
HIPEC is widely considered standard practice for
patients with PMP, what must be clear is that not all
patients are eligible for these complex procedures. In
this study, HIPEC was successfully delivered to 62%
of patients with demonstrable PMP who were referred
to our unit for consideration for surgery. This study
suggests that nearly two-thirds of patients with PMP
are amenable to these complex procedures. Indeed,
we have a possible referral bias in this study design, as
patients in very poor condition or with extensive dis-
ease are unlikely to be referred to our unit. This bias is
hard to eliminate. As long as there exists controversy
in management and even in classification of PMP, it is
obvious that not all patients with PMP are gaining
referrals to a specialized center. However, regardless
of location of treatment, a considerable proportion of
the patient population has still to be treated with con-
ventional methods: iterative debulking surgery, active
follow-up, or sometimes even palliation without sur-
gical intervention. When evaluating the use of CRS
and HIPEC in the long term and when comparing it to
the results of previous debulking surgery, comparison
is necessary between entire PMP populations because
comparing the results of HIPEC with the whole group
of patients treated with debulking surgery will lead to
bias in favor of HIPEC.
FUNDING
This study was supported by a grant from the Mary and
Georg C. Ehrnrooth foundation.
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Received: August 27, 2012
Accepted: January 29, 2013
  • [Show abstract] [Hide abstract] ABSTRACT: Purpose: Patients with pseudomyxoma peritonei (PMP) benefit from cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Reports on this modality usually have included only patients with successful HIPEC treatment, which can potentially cause biased results. We report the survival of a PMP population treated by CRS and HIPEC, including patients who were not eligible for HIPEC. Methods: The outcome of the whole population of 87 patients with PMP treated by CRS and HIPEC in Helsinki University Central Hospital between 2008 and 2011 was evaluated. The results of treatment were compared with 33 patients treated by serial debulking in our unit between 1984 and 2008. Results: Of the 87 patients in the HIPEC-era group, 56 received HIPEC, 12 were treated non-radically in an attempt at HIPEC, 9 were debulked and 10 were referred back or transferred to palliative care without surgery. The 5-year overall survival for the debulking-era group and the HIPEC-era group were 67 and 69 %, respectively. The number of patients with no evidence of disease was higher in the HIPEC-era group (47/87) than that in the debulking-era group (8/33) at the end of the follow-up. Overall survival for patients who underwent successful CRS and HIPEC at 2 and 5 years was 95 and 93 %, respectively. Conclusions: The improved survival from using the CRS and HIPEC was not apparent after 5-year follow-up, when the whole patient population was included in the analysis. Even so, patients successfully treated by CRS and HIPEC manage well.
    Article · Jun 2014
  • [Show abstract] [Hide abstract] ABSTRACT: Pseudomyxoma peritonei (PMP) is a relatively rare clinical syndrome characterized by neoplastic epithelial cells growing in the peritoneal cavity and secreting mucinous ascites. Our aim was to explore the molecular events behind this fatal but under-investigated disease. We extracted DNA from 19 appendix-derived PMP tumors and nine corresponding normal tissues, and analyzed the mutational hotspot areas of 48 cancer-related genes by amplicon-based next-generation sequencing (NGS). Further, we analyzed the protein expression of V600E mutated BRAF, MLH1, MSH2, MSH6, and p53 from a larger set of PMP tumors (n = 74) using immunohistochemistry. With NGS, we detected activating somatic KRAS mutations in all of the tumors studied. GNAS was mutated in 63% of the tumors with no marked difference between low-grade and high-grade tumors. Only one (5.3%) tumor showed oncogenic PIK3CA mutation, one showed oncogenic AKT1 mutation, three (15.8%) showed SMAD4 mutations, and none showed an APC mutation. P53 protein was aberrantly expressed in higher proportion of high-grade tumors as compared to low-grade ones (31.3% vs. 7.1%, respectively; p = 0.012) and aberrant expression was an independent factor for reduced overall survival (p = 0.002). BRAF V600E mutation was only found in one (1.4%) high-grade tumor by immunohistochemistry (n = 74). All the studied tumors expressed mismatch repair proteins MLH1, MSH2, and MSH6. Our results indicate that KRAS mutations are evident in all and GNAS mutations in most of the PMPs, but BRAF V600E, PIK3CA, and APC mutations are rare. Aberrantly expressed p53 is associated with high-grade histology and reduced survival. © 2014 Wiley Periodicals, Inc.
    Article · Oct 2014
  • [Show abstract] [Hide abstract] ABSTRACT: Pseudomyxoma peritonei (PMP) is a rare, low-grade, peritoneal malignancy predominated by mucus, with an estimated incidence of two to three cases per million people per year [1]. Werth, in 1884, first described PMP as a rare, unusual reaction of the peritoneum to a jelly-like substance, looking like a myxoma, in relation to an ovarian neoplasm [2]. In 1901, Frankel described PMP associated with an appendiceal cyst [3], but the first description of a benign mucocele of the appendix was reported by Rokitansky in 1842 [4].
    Chapter · Jan 2015 · International Journal of Cancer
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