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Abstract. Aim: The aims of this study were to explore
clinical outcomes and assess the learning curve for
cytoreductive surgery and perioperative intraperitoneal
chemotherapy (PIC) for patients with a high peritoneal
cancer index (PCI). Patients and Methods: This was a
retrospective study of patients with a PCI of 20 or more
following CRS and PIC. Outcomes in five successive groups
based on the operation date were analyzed. Results: Three
hundred and five patients were included in the study. The
median overall survival (OS) was 89.3 months (95%
confidence interval=58.9-107.6 months). OS at 1, 3 and 5
years of our study cohort was 89.4%, 70.4% and 57.5%,
respectively. In terms of the learning curve, the mean
duration of operation and hospital mortality decreased
(p<0.001 and p=0.006 respectively). A trend for decreasing
intensive care unit stay (p=0.497), high dependency unit stay
(p=0.042) and total hospital stay (p=0.202) were also
recorded. Conclusion: A high PCI alone should not be a
contraindication for cytoreductive surgery and PIC in
specialized centres.
Peritoneal carcinomatosis occurs in 10% to 30% of patients
with gastrointestinal cancer at the time of their initial surgery
or at a site of disease recurrence (1). In the past, peritoneal
carcinomatosis was considered to be a terminal condition,
associated with a median survival of about 6 months (2). In
the 1990s, Sugarbaker introduced an innovative technique
combining cytoreductive surgery (CRS) and perioperative
intraperitoneal chemotherapy (PIC) (3). Following a long
period of follow-up and acquisition of clinical data of treated
patients, this combined approach is considered as a standard
for selected patients with peritoneal carcinomatosis from
colorectal carcinoma (CRC), low-grade appendiceal
pseudomyxoma peritonei (PMP), diffuse malignant
peritoneal mesothelioma (DMPM) and appendiceal
carcinoma (4).
The peritoneal cancer index (PCI) grades the extent of
peritoneal deposits within the abdominal cavity and
comprises an aggregate score incorporating the distribution
of the tumour deposits and size of the lesions. PCI is
recognised to be an important prognostic factor in
appendiceal cancer, CRC and DMPM (5-7). The leading
surgeons from high-volume centres have worked towards
to establishing criteria for CRS through a consensus
statement published through the American Society of
Peritoneal Surface Malignancies (8). The consensus
statement recommended that patients should undergo a
thorough diagnostic workup and the PCI be used as a
scoring system to guide their further management. Patients
without distant disease should be offered further
assessment for completeness of cytoreduction. However,
those with distant dissemination should be only offered
systemic therapy (8). High-volume peritoneal disease does
entail more major surgery, which is associated with greater
morbidity, and some have considered this a relative
contraindication (4).
With almost 20 years of experience in CRS, we have
acquired a small sub-group of patients treated off protocol
under the auspices of a multidisciplinary team consensus
who have had extensive peritoneal carcinomatosis. The
primary aim of this study was to explore the clinical
outcomes of patients with peritoneal carcinomatosis and a
high PCI (PCI ≥20). The secondary aim was to assess the
learning curve for CRS and PIC for those patients.
1033
Correspondence to: Dr. Nayef A. Alzahrani, Hepatobiliary and
Surgical Oncology Unit, Department of Surgery, St George Hospital,
University of New South Wales, Level 3 Pitney Building, Gray
Street, Kogarah, Sydney, NSW 2217, Australia. Tel: +61 291132590,
Fax: +61 291133997, e-mail: nayefalhariri@hotmail.com
Key Words: Peritoneal cancer index, cytoreductive surgery,
perioperative intraperitoneal chemotherapy.
ANTICANCER RESEARCH 36: 1033-1040 (2016)
Clinical Outcomes of Patients with Extensive Peritoneal
Carcinomatosis Following Cytoreductive Surgery and
Perioperative Intraperitoneal Chemotherapy
YEQIAN HUANG1, NAYEF A. ALZAHRANI1,2, TERENCE C. CHUA3, YA RUTH HUO1and DAVID L. MORRIS1
1Department of Surgery, University of New South Wales, St George Hospital, Sydney, NSW, Australia;
2College of Medicine, Imam Muhammad ibn Saud Islamic University, Riyadh, Kingdom of Saudi Arabia;
3Department of Gastrointestinal Surgery, Royal North Shore Hospital, St Leonards, NSW, Australia
0250-7005/2016 $2.00+.40
Patients and Methods
Setting. This was a retrospective study of prospectively collected
data of patients with peritoneal carcinomatosis who underwent CRS
and PIC by one surgical team at the St George Hospital in Sydney,
Australia between Jan 1996 and Sep 2015.
Patients. Inclusion criteria included patients who had a good
performance status (World Health Organisation Performance Status
≤2), and a histological diagnosis of peritoneal carcinomatosis from
CRC, PMP, DMPM and appendiceal carcinoma. Patients with a
PCI≥20 were included in this study. Exclusion criteria included
histological diagnoses of peritoneal carcinomatosis from other
primary types of cancer and debulking surgery. PCI was further
divided into three groups for comparison (group A: 20-24; group B:
25-29; group C: ≥30).
In order to assess the learning curve, a total of 937 patients who
underwent CRS and PIC at our Centre during the study period were
divided into five groups according to the date of their operation:
Group I: Jan 1996-Aug 2006; group II: Feb 2007-Feb 2010; group
III: Feb 2010-Mar 2012; group IV: Nov 2012-Jun 2014; group V:
Jul 2014-Sep 2015. The first four groups included 200 patients each;
the fifth group include 137 patients. Patients with a PCI ≥20 were
selected from each group for comparison in order to assess learning
curves for CRS and PIC for patients with extensive peritoneal
carcinomatosis. The learning curve assessment method was based
on the learning curve at our Centre, which showed clinical outcomes
improved after the first 200 cases (9).
Preoperative management. All patients underwent standard
preoperative investigations which included physical examination;
double contrast-enhanced computed tomography (CT) scans of the
chest, abdomen and pelvis; and CT pontography of the liver or
primovist (a hepatospecific paramagnetic gadolinium-based contrast
agent) magnetic resonance imaging for PMP and CRC and
appendiceal carcinoma. Positron-emission tomography was
routinely performed in patients with CRC, appendiceal carcinoma
and DMPM. Staging laparoscopy was considered in some patients
with borderline PCI.
CRS. An initial assessment of the volume and extent of disease was
recorded using PCI, as described by Jacquet and Sugarbaker (10).
CRS was performed using Sugarbaker’s technique (3). All sites and
volumes of residual disease following CRS were recorded
prospectively using completeness of cytoreductive (CC) score:
CC0: no macroscopic residual cancer remaining; CC1: no nodule
>2.5 mm in diameter remaining; CC2: nodules between 2.5 mm and
2.5 cm in diameter remaining; CC3: nodules >2.5 cm in diameter
remaining (10). CC0 or CC1 was considered as complete
cytoreduction, whereas CC2 and CC3 were considered as
incomplete cytoreduction. In the early part of our series, PCI was
limited to 20 in patients with CRC; this was lowered to 15 in 2012.
Hyperthermic intraperitoneal chemotherapy (HIPEC). After CRS,
HIPEC was performed by installation of a heated chemoperfusate
into the abdomen using the coliseum technique at approximately
42°C for 30 or 90 min during CRS, depending on tumour type. For
PMP, mitomycin C (12.5 mg/m2) was used for 90 min. For DMPM,
cisplatin (100 mg/m2) and mitomycin C (12.5 mg/m2) in 1,000 ml
normal saline were given over 90 min. For CRC and appendiceal
carcinoma, 350 mg/m2oxaliplatin in 500 ml of 5% dextrose was
given over 30 min.
Early postoperative intraperitoneal chemotherapy (EPIC). EPIC
was only offered to patients with PMP or lack of availability of
HIPEC in emergency surgeries. The criteria for EPIC include
absence of leakage of the intraperitoneal chemotherapy system,
absence of major organ failure, and the ability of the patient to
tolerate increased intra-abdominal fluid volume and intra-abdominal
pressure with adequate urine output.
The sump drains were clamped during the EPIC infusion via the
peritoneal catheter port. For patients with PMP, 650 mg/m25-
fluorouracil i.p. combined with 50 mEq sodium bicarbonate was
administered from day 2 to 6. Normally EPIC was administered
either in intensive care unit (ICU) or high dependency unit (HDU).
ANTICANCER RESEARCH 36: 1033-1040 (2016)
1034
Table I. Background characteristics and perioperative outcomes of the
whole study cohort.
Total n=305 patients
Gender, n (%)
Male 152 (49.8)
Female 153 (50.2)
Mean age (SD), years 53.6 (13.1)
Mean PCI (SD) 30.1 (6.4)
HIPEC, n (%)
Yes 302 (99.0)
No 3 (1.0)
EPIC, n (%)
Yes 150 (49.2)
No 152 (49.8)
Unknown 3 (1.0)
Pathology, n (%)
CRC 17 (5.6)
PMP 130(42.6)
DMPM 36 (11.8)
Appendiceal carcinoma 122 (40.0)
CC, n (%)
0/1 294 (96.4)
2/3 10 (3.3)
Unknown 1 (0.3)
Transfusion units, mean (SD), n 8.7 (6.4)
Duration of surgery, mean (SD), hours 11.1 (2.9)
Hospital mortality, n (%) 7 (2.3)
Morbidity grade, n (%)
0/1/2 128 (42.0)
3/4 174 (57.0)
Unknown 3 (1.0)
ICU stay, mean (SD), days 6.3 (11.9)
HDU stay, mean (SD), days 5.1 (4.9)
Total hospital stay, mean (SD), days 37.0 (30.3)
SD: Standard deviation; PCI: peritoneal cancer index; HIPEC:
hyperthermic intraperitoneal chemotherapy; EPIC: early postoperative
intraperitoneal chemotherapy; CRC: colorectal cancer; PMP:
pseudomyxoma peritonei; DMPM: diffuse malignancy peritoneal
mesothelioma; CC: completeness of cytoreduction score; ICU: intensive
care unit; HDU: high dependency unit.
Postoperative management. Perioperative complications in all patients
were graded based on the Clavien-Dindo Classification (CDC) of
surgical complications: Grade I: no treatment; grade II: medications
only; grade III: surgical, endoscopic or radiological intervention;
grade IV: life-threatening complications requiring ICU admission
(11). Major morbidity was defined as CDC grade III or IV.
All of patients with aggressive tumour were then followed-up at
3-monthly intervals for the first 12 months and 6-month intervals
thereafter until the last time of contact or death. Patients with PMP
were seen at 3, 6 and 12 monthly thereafter. The follow-up review
included clinical examination, measurement of relevant tumour
markers, and assessment of abdominopelvic CT scans.
Statistical analysis. All statistical analyses were performed using
SPSS for Windows version 22 (IBM Corporation, New York, NY,
USA). Comparison of normally distributed variables was performed
using analysis of variance (one way-ANOVA) test. Categorical
variables were analysed using the Chi-square test or Fisher’s exact
test where appropriate. Hospital mortality was defined as any death
that occurred during the same hospital admission for CRS. Median
overall survival (OS) in months was calculated based on last time
of contact or death. Survival analysis was performed using the
Kaplan–Meier curves and log-rank test for comparison. Due to lack
of survival data for group V at the time of analysis, this group was
excluded from the survival analysis. A significant difference was
defined as a p-value of less than 0.05.
Results
Descriptive characteristics and perioperative outcomes of the
whole study cohort. Of a total of 937 patients, 305 patients
had a PCI ≥20 and were included in the study. A total of 115
patients with peritoneal carcinomatosis from other primaries
were excluded from the study. A total of 32 patients were
excluded from the study because they did not receive PIC;
another 488 patients with a PCI <20 were also excluded.
Table I summarizes the background characteristics and
perioperative outcomes of patients with a high PCI.
Survival outcomes. The median OS was 89.3 months [95%
confidence interval (CI)=58.9-107.6]. OS at 1, 3 and 5 years
of our study cohort was 89.4%, 70.4% and 57.5%,
respectively. Table II summarizes survival outcomes of whole
study cohort. There was no statistical difference in OS
among PCI groups and by CC score (CC0/1 vs. CC2/3).
However, patients who experienced major perioperative
morbidity (i.e. CDC grade 3/4) had a significantly lower OS
compared to those who did not experience any complication
or only experienced non-major complications (p=0.010)
(Table II).
Table III summarizes the survival outcomes by each
histological diagnosis. In the CRC group, patients who
experienced a major morbidity perioperatively had a
significantly lower OS (p=0.041) (Table III and Figure 1).
In the PMP group, patients with an extremely high PCI (i.e.
≥30) had a significantly lower OS than the other two PCI
groups (Table III and Figure 2). There was no statistical
difference in OS among PCI groups for patients with CRC,
DMPM and appendiceal carcinoma. All patients with CRC,
PMP or DMPM underwent complete cytoreduction. The
difference in OS between major morbidity grade and non-
major morbidity grade did not reach a statistical significance
in PMP, DMPM and appendiceal carcinoma groups.
Assessment of learning curve. Table IV compares the
background characteristics of patients and clinical outcomes
according to the date of surgery. The mean duration of
operation decreased significantly with increasing experience
(p<0.001). There was also a statistical increase in the use of
HIPEC, whilst EPIC was used less among the five groups
(p<0.001 and p<0.001 respectively). The difference in the
rate of major morbidity among the five groups did not
achieve a statistical significance (Table IV). However,
hospital mortality was significantly lower (0%) in the most
Huang et al: High PCI and Outcomes After CRS and PIC
1035
Table II. Survival outcomes for the whole study cohort.
Survival data
Variable N Median overall (95% CI), months 1-Year (%) 3-Year (%) 5-Year (%) p-Value
PCI 0.153
20-24 62 96.0 (40.6-151.4) 93.5 72.5 64.6
25-29 49 125.5 (61.0-190.1) 87.5 74.7 67.0
≥30 121 58.5 (43.9073.1) 88.1 67.2 48.6
CC score 0.849
0/1 228 83.3 (58.0-108.5) 89.3 70.6 57.7
2/3 3 23.1 (-) 100 50.0 NR
Morbidity 0.010*
0-2 95 125.5 (-) 93.5 76.4 68.8
3&4 137 58.5 (47.2-69.8) 86.6 66.2 48.2
CI: Confidence interval; PCI: peritoneal cancer index; CC: completeness of cytoreduction score.
recent two groups (i.e. groups IV and V) (p=0.006). The
mean HDU stay in group V was almost half of that of group
I (3.6 vs. 6.9 days). The difference in the mean ICU stay and
total hospital stay among the five groups did not reach a
statistical difference, however, a trend for decreasing mean
ICU and total hospital stay were also observed with the
increasing experience (Table IV).
Table V summarises the survival outcomes of the first four
groups (i.e. groups I to IV). The median OS of group III was
not reached yet but it was shown to be greater than 66.2
months. Thus the median OS, and 1-, 3-and 5-year OS in
group II and III were much higher than those of group I,
although these differences did not achieve statistical
significance (p=0.344) (Table V and Figure 3).
Discussion
The combination of CRS and PIC has provided optimal
survival outcomes for patients with peritoneal
carcinomatosis. CRS and PIC complement each other,
whereby CRS aims to remove macroscopic disease and PIC
is used to attempt to eradicate any residual microscopic
tumour (12). Multiple prognostic factors for peritoneal
carcinomatosis have been extensively explored in the past
two decades (13-17). One of the important prognostic factors
is PCI. It allows the estimation of completeness of
cytoreduction and thus survival at the time of surgical
exploration of the abdomen and pelvis (13).
The most recent systemic review by Chua et al. (2009)
assessed morbidity and mortality outcomes of CRS and
HIPEC from all tertiary Institutions located in the cities of
Amsterdam, Lyon, Milan, Pittsburgh, Shizuoka, Sydney,
Uppsala, Washington, Winston-Salem and Villejuif
performing this procedure (4). They showed a morbidity rate
ranging from 12% to 52% and a mortality rate ranging 0.9%
and 5.8% across tertiary institutions (4). The rate of major
morbidity in our study cohort was slightly higher than the
range given in this review. However, the mortality rate for
patients with a high volume of disease was good (2.3%) and
consistent with the mortality rate found in the review. The
review also showed the mean length of ICU stay ranged
from 1 to 5 days (4). Our finding in this study cohort is
slightly higher than this range. This could be attributed to
the fact that patients in our study cohort had more extensive
peritoneal disease, as demonstrated by a high PCI. However,
our mean total hospital stay is within the range found
reported in this review (7-48 days).
Our survival analyses of the whole study cohort suggest
that complications affect negatively survival of patients with
CRC. This is consistent with the previous study by Ung et
al. They analyzed clinical outcomes of 211 patients with
peritoneal carcinomatosis from lower gastrointestinal tract
origin. They also found major morbidity as a prognostic
ANTICANCER RESEARCH 36: 1033-1040 (2016)
1036
Table III. Survival outcomes by diagnosis.
CRC PMP DMPM Appendiceal Carcinoma
Variable N Median 5-Year p-Value N Median 5-Year p-Value N Median 5-Year p-Value N Median 5-Year p-Value
(95% CI), (%) (95% CI), (%) (95% CI), (%) (95% CI), (%)
months months months months
Overall 17 18.3 (16.0-20.5) 17.3 105 103.6 (86.0-121.1) 78.4 25 43.2 (22.2-64.2) 43.8 85 58.4 (46.4-70.4) 45.2
PCI 0.250 0.001 0.702 0.561
20-24 7 19.2 (0-40.1) NR 29 NR 88.8 8 43.2 (-) 50.0 18 27.6 (0-65.3) 47.7
25-29 4 3.9 (0-13.4) 25.0 28 125.5 (73.7-177.3) 96.3 3 23.4 (1.2-45.5) NR 14 58.4 (23.6-93.3) 26.2
≥30 6 10.9 (0-22.2) 0 48 83.3 (51.9-114.6) 60.0 14 44.3 (12.7-75.9) 41.3 53 58.5 (41.4-75.6) 46.6
CC score - - - 0.910
0/1 17 18.3 (16.0-20.5) 17.3 104 103.6 (86.0-121.1) 78.4 25 43.2 (22.2-64.2) 43.8 82 58.4 (46.4-70.4) 45.4
2/3 0 - - 0 - - 0 - - 3 23.1 (-) NR
Morbidity 0.041 0.303 0.113 0.235
0-2 8 18.3 (0-44.1) 33.3 47 125.5 (-) 84.4 12 NR 58.9 28 NR 58.9
3/4 9 10.9 (4.9-17.0) 0 58 103.6 (87.4-119.7) 72.6 13 43.2 (0-64.2) 32.3 57 57.1 (35.8-78.5) 36.3
CRC: Colorectal cancer; PMP: pseudomyxoma peritonei; DMPM: diffuse malignancy peritoneal mesothelioma; CI: confidence interval; PCI: peritoneal cancer index; CC: completeness of
cytoreduction; NR: not reached.
factor for survival of patients with CRC (18). As did a
multicentric study by Chua et al. analyzing clinical outcomes
of 2,298 patients from 16 specialised centres who underwent
CRS and HIPEC for peritoneal carcinomatosis from
appendiceal origin (6). They found major postoperative
complications to be a negative prognostic factor associated
with OS (p<0.001).
Importantly, our findings suggest that patients with a high
tumor volume for certain diagnoses could still achieve good
outcomes. Although a high PCI is associated with poorer
survival in patients with PMP, a median survival of 83.3
months, with a 5-year survival of 60% for patients with a
PCI≥30 is still encouraging. Similarly, for patients with
appendiceal carcinoma, the 5-year survival rate of 46.6%
may still be achieved in the context of a high volume of
disease. Our results were slightly poorer than the findings in
the study by Chua et al. (6). They found an encouraging 5-
year survival rate of 73% and 56% in their patients with
high-volume PMP and appendiceal carcinoma (i.e. PCI 31-
39), respectively. Such differences in 5-year survival rates
between our study and theirs could be due to the learning
curves associated with this procedure and variations in
protocols in different specialised centres.
A large multi-institutional study by Yan et al. analyzed 405
patients with diffuse malignant peritoneal mesothelioma (7).
The 5-year OS for our DMPM cohort is slightly lower than
the finding in their study cohort (43.2% vs. 47%). However,
they also included patients with a low PCI (i.e. <20) in their
study. It is also important to emphasise that we included
multicystic mesothelioma in our study because malignant
transformation of benign multicystic mesothelioma has been
Huang et al: High PCI and Outcomes After CRS and PIC
1037
Figure 1. Kaplan–Meier curve of survival for patients according to
morbidity grade (i.e. grade 0/1/2 vs. 3/4) (p=0.041).
Figure 2. Kaplan–Meier curve of survival for patients with
pseudomyxoma peritonei according to peritoneal cancer index group
(p=0.001).
Figure 3. Kaplan–Meier curves for patients with high peritoneal cancer
index according to date of operation (p=0.344) (group I: Jan 1996-Aug
2006; group II: Feb 2007-Feb 2010; group III: Feb 2010-Mar 2012;
group IV: Nov 2012-Jun 2014; group V: Jul 2014-Sep 2015).
reported (14). One of our patients had malignant
transformation from benign cystic mesothelioma to
epithelioid and then subsequently to sarcomatoid type. Yan et
al. did not include multicystic mesothelioma in their study.
Although it is difficult to compare our findings of OS of
mesothelioma with the literature, a 5-year survival rate of
43.2% with a median OS of 43.2 (95% CI=22.2-64.2) months
is still promising.
Our findings of a poor survival outcome for patients with
high volume of peritoneal carcinomatosis from colorectal
origin are in accordance with the consensus in the literature
that a PCI of greater than 20 should be considered as a relative
contraindication for surgery (5, 17, 19). A multicentric study
by Elias et al. reviewed clinical outcomes of 523 patients with
peritoneal carcinomatosis from colorectal origin and showed
a 5-year survival rate of less than 10% in patients with a PCI
>20. Our result is slightly higher, 17.3% 5-year OS is perhaps
quite surprising. Whether to offer CRS and PIC to patients
with a high-volume of peritoneal carcinomatosis of colorectal
origin should be carefully considered.
In the literature, a learning curve associated with CRS and
PIC has been well-established (12, 20-22). Our results also
ANTICANCER RESEARCH 36: 1033-1040 (2016)
1038
Table IV. Comparison of background characteristics and clinical outcomes according to operation date (group I: Jan 1996-Aug 2006; group II:
Feb 2007-Feb 2010; group III: Feb 2010-Mar 2012; group IV: Nov 2012-Jun 2014; group V: Jul 2014-Sep 2015).
Group I Group II Group III Group IV Group V p-Value
Total n 38 (12.5) 80 (26.2) 74 (24.3) 72 (23.6) 41 (13.4)
Age (years) 52.7 (12.5) 51.7 (11.2) 54.7 (12.8) 54.7 (14.4) 54.6 (15.0) 0.534
Diagnosis, n (%) <0.001
CRC 3 (7.9) 4 (5.0) 7 (9.5) 3 (4.2) 0 (0)
PMP 27 (71.1) 42 (52.5) 26 (35.1) 27 (37.5) 8 (19.5)
DMPM 1 (2.6) 12 (15.0) 10 (13.5) 6 (8.3) 7 (17.1)
Appendiceal carcinoma 7 (18.4) 22 (27.5) 31 (41.9) 36 (50.0) 26 (63.4)
PCI mean (SD) 27.8 (6.3) 30.2 (6.3) 30.7 (6.6) 30.4 (6.7) 30.6 (6.0) 0.207
CC score 0.613
0/1 36 (94.7) 78 (98.7) 70 (94.6) 70 (97.2) 40 (97.6)
2/3 2 (5.3) 1 (1.3) 4 (5.4) 2 (2.8) 1 (2.4)
Duration of surgery, mean (SD), hours 13.5 (4.6) 10.3 (2.3) 11.3 (2.1) 11.0 (2.6) 10.1 (2.0) <0.001
HIPEC, n (%) 35 (92.1) 80 (100) 74 (100) 72 (100) 41 (100) <0.001
EPIC, n (%) 24 (63.2) 56 (70.9) 30 (40.5) 30 (41.7) 12 (30.8) <0.001
Transfusion units mean (SD) 11.3 (9.3) 8.7 (7.4) 9.2 (8.9) 8.0 (9.3) 6.7 (6.1) 0.155
Hospital mortality, n (%) 4 (10.5) 1 (1.3) 2 (2.7) 0 (0) 0 (0) 0.006
Major morbidity, n (%) 24 (63.2) 43 (43.8) 39 (52.7) 46 (63.9) 22 (57.9) 0.581
ICU stay, mean (SD), days 7.7 (13.6) 7.3 (12.5) 4.4 (6.5) 7.0 (16.0) 5.6 (7.7) 0.497
HDU stay, mean (SD), days 6.9 (5.5) 4.8 (4.6) 4.7 (4.6) 5.5 (5.7) 3.6 (3.4) 0.042
Total hospital stay, mean (SD), days 47.6 (44.1) 37.7 (29.5) 34.4 (27.3) 34.5 (25.9) 34.6 (27.2) 0.202
CI: Confidence interval; CRC: colorectal cancer; PMP: pseudomyxoma peritonei; DMPM: diffuse malignancy peritoneal mesothelioma; PCI:
peritoneal cancer index; SD: standard deviation; CC: completeness of cytoreduction score; HIPEC: hyperthermic intraperitoneal chemotherapy;
EPIC: early postoperative intraperitoneal chemotherapy; ICU: intensive care unit; HDU: high dependency unit.
Table V. Survival outcomes according to operation date (group I: Jan 1996-Aug 2006; group II: Feb 2007-Feb 2010; group III: Feb 2010-Mar 2012;
group IV: Nov 2012-Jun 2014; group V: Jul 2014-Sep 2015).
Group I Group II Group III Group IV p-Value
Total=233
No of patients n (%) 31 (13.3) 72 (30.9) 61 (26.2) 69 (29.6)
Overall survival
Median (95% CI), months 58.4 (26.4-90.5) 89.1 (-) NR NR 0.344
1-Year, % 80.6 94.4 85.1 92.2
3-Year, % 58.1 80.8 67.3 67.4
5-Year, % 44.6 68.2 55.0 NR
CI: Confidence interval; NR: not reached.
demonstrate a learning curve for this combined procedure for
patients with high volume of peritoneal carcinomatosis. A
trend for decreasing duration of surgery with increasing
experience in CRS for patients with a high volume of disease
and an important fall in was shown in our study mortality.
The significant differences in the use of HIPEC and EPIC
can be explained by the fact that we used EPIC more
frequently in the early period due to limited evidence for
EPIC use. However, with increasing evidence and our
experience, we have improved our protocols over the years.
Most importantly, it was encouraging to observe a
reduction in hospital mortality to 0% in our last two study
cohorts of 113 patients with PCI ≥20 with more experience
in CRS. In addition, there was a trend for a decrease in the
mean HDU stay and total hospital stay over the past two
decades (from 6.9 to 3.6 days and from 46.6 to 34.6 days,
respectively). Although the difference of survival outcomes
among the four groups did not reach statistical significance,
the 5-year survival rate and median OS were improved in
recent groups (group II: 68.2%, 89.1 months; group III:
55.0%, >66.2 months) compared to those who underwent
CRS and PIC in the early period (group I: 44.6%, 58.4
months). It is also important to put these outcomes into
perspective. It is worth noting that 71.1% of patients in group
I were diagnosed with PMP compared to 52.5% in group 2
and 35.1% in group 3. The survival outcomes in group I may
have been skewed by the large proportion of patients with
PMP. Thus the actual survival differences among groups I, II
and III may have been even larger. Similarly, relatively better
outcomes for group II compared to group II could be
attributed to the different proportions of primary tumor sites.
More patients in group III had appendiceal carcinoma and
CRC (41.9% vs. 27.5% and 9.5% vs. 5.0%, respectively).
There exist several limitations in this study that need to be
considered when interpreting our results. Firstly, the
retrospective nature of this study undoubtedly led to selection
bias. Our study is also limited by the small sample size of the
DMPM group. Another limitation is that there was still an
uncertainty regarding the exact reasons for improved outcomes
for patients with extensive peritoneal carcinomatosis.
Furthermore, suitability of patients for CRS and PIC are
strictly assessed during our weekly multidisciplinary team
meeting. This combined approach requires a high level of
training and expertise. Centralization of experience in
anaesthetic care, medical oncology and nursing in order to
provide better perioperative care is often necessary (12, 23).
Conclusion
Our study found encouraging survival results for patients
with a high PCI, and an optimal perioperative mortality of
0% in recent years at our Centre. Thus patients with
extensive peritoneal disease may still achieve a good survival
outcome. In addition, our results also demonstrated a
learning curve associated with CRS and PIC for extensive
peritoneal disease. Therefore, a high PCI alone should not be
a contraindication for CRS and PIC at specialised centres.
Patients with extensive peritoneal carcinomatosis should be
referred to a specialized centre for a thorough assessment to
determine their suitability for CRS and PIC.
Acknowledgements
We express our special thanks to Jing Zhao, MD, for maintaining
the peritonectomy database
References
1 Harmon RL and Sugarbaker PH: Prognostic indicators in
peritoneal carcinomatosis from gastrointestinal cancer. Int Semin
Surg Oncol 2: 3, 2005.
2 Glehen O, Mohamed F and Gilly FN: Peritoneal carcinomatosis
from digestive tract cancer: new management by cytoreductive
surgery and intraperitoneal chemohyperthermia. Lancet Oncol
5(4): 219-228, 2004.
3 Sugarbaker PH: Peritonectomy procedures. Ann Surg 221(1): 29-
42, 1995.
4 Chua TC, Yan TD, Saxena A and Morris DL: Should the
treatment of peritoneal carcinomatosis by cytoreductive surgery
and hyperthermic intraperitoneal chemotherapy still be regarded
as a highly morbid procedure?: a systematic review of morbidity
and mortality. Ann Surg 249(6): 900-907, 2009.
5 Elias D, Gilly F, Boutitie F, Quenet F, Bereder J-M, Mansvelt B,
Lorimier G, Dubè P and Glehen O: Peritoneal colorectal
carcinomatosis treated with surgery and perioperative
intraperitoneal chemotherapy: retrospective analysis of 523
patients from a multicentric French study. J Clin Oncol 28(1):
63-68, 2010.
6 Chua TC, Moran BJ, Sugarbaker PH, Levine EA, Glehen O,
Gilly FN, Baratti D, Deraco M, Elias D and Sardi A: Early-and
long-term outcome data of patients with pseudomyxoma
peritonei from appendiceal origin treated by a strategy of
cytoreductive surgery and hyperthermic intraperitoneal
chemotherapy. J Clin Oncol 30(20): 2449-2456, 2012.
7 Yan TD, Deraco M, Baratti D, Kusamura S, Elias D, Glehen O,
Gilly FN, Levine EA, Shen P and Mohamed F: Cytoreductive
surgery and hyperthermic intraperitoneal chemotherapy for
malignant peritoneal mesothelioma: multi-institutional
experience. J Clin Oncol 27(36): 6237-6242, 2009.
8 Esquivel J, Sticca R, Sugarbaker P, Levine E, Yan T, Alexander R,
Baratti D, Bartlett D, Barone R and Barrios P: Cytoreductive
surgery and hyperthermic intraperitoneal chemotherapy in the
management of peritoneal surface malignancies of colonic origin:
a consensus statement. Ann Surg Oncol 14(1): 128-133, 2007.
9 Huang Y, Alzahrani NA, Liauw W and Morris DL: Learning
curve for cytoreductive surgery and perioperative
intraperitoneal chemotherapy for peritoneal carcinomatosis.
ANZ J Surg 2015.
10 Jacquet P and Sugarbaker PH: Clinical research methodologies in
diagnosis and staging of patients with peritoneal carcinomatosis.
Peritoneal carcinomatosis: principles of management; Springer
359-374, 1996.
Huang et al: High PCI and Outcomes After CRS and PIC
1039
11 Dindo D, Demartines N and Clavien P-A: Classification of
surgical complications: a new proposal with evaluation in a
cohort of 6336 patients and results of a survey. Ann Surg 240(2):
205, 2004.
12 Moradi BN and Esquivel J: Learning curve in cytoreductive
surgery and hyperthermic intraperitoneal chemotherapy. J Surg
Oncol 100(4): 293-296, 2009.
13 Harmon RL and Sugarbaker PH, editors. Prognostic indicators
in peritoneal carcinomatosis from gastrointestinal cancer. Int
Semin Surg Onco; BioMed Central Ltd., 2005.
14 Glehen O, Kwiatkowski F, Sugarbaker P, Elias D, Levine E, De
Simone M, Barone R, Yonemura Y, Cavaliere F and Quenet F:
Cytoreductive surgery combined with perioperative
intraperitoneal chemotherapy for the management of peritoneal
carcinomatosis from colorectal cancer: a multi-institutional
study. J Clin Oncol 22(16): 3284-3292, 2004.
15 Sadeghi B, Arvieux C, Glehen O, Beaujard AC, Rivoire M,
Baulieux J, Fontaumard E, Brachet A, Caillot JL and Faure JL:
Peritoneal carcinomatosis from non-gynecologic malignancies.
Cancer 88(2): 358-363, 2000.
16 Glehen O, Mithieux F, Osinsky D, Beaujard A, Freyer G,
Guertsch P, Francois Y, Peyrat P, Panteix G and Vignal J:
Surgery combined with peritonectomy procedures and
intraperitoneal chemohyperthermia in abdominal cancers with
peritoneal carcinomatosis: a phase II study. J Clin Oncol 21(5):
799-806, 2003.
17 Cashin PH, Graf W, Nygren P and Mahteme H: Cytoreductive
surgery and intraperitoneal chemotherapy for colorectal
peritoneal carcinomatosis: prognosis and treatment of
recurrences in a cohort study. Eur J Surg Oncol 38(6): 509-515,
2012.
18 Ung L, Chua TC and Morris DL: Peritoneal metastases of lower
gastrointestinal tract origin: a comparative study of patient
outcomes following cytoreduction and intraperitoneal chemo-
therapy. J Cancer Res Clin Oncol 139(11): 1899-1908, 2013.
19 da Silva RG and Sugarbaker PH: Analysis of prognostic factors
in seventy patients having a complete cytoreduction plus
perioperative intraperitoneal chemotherapy for carcinomatosis
from colorectal cancer. J Am Coll Surg 203(6): 878-886, 2006.
20 Smeenk R, Verwaal V and Zoetmulder F: Learning curve of
combined modality treatment in peritoneal surface disease. Brit
J Surg 94(11): 1408-1414, 2007.
21 Elias D, Gilly F, Quenet F, Bereder J, Sidéris L, Mansvelt B,
Lorimier G and Glehen O: Pseudomyxoma peritonei: a French
multicentric study of 301 patients treated with cytoreductive
surgery and intraperitoneal chemotherapy. Eur J Surg Oncol
36(5): 456-462, 2010.
22 Kusamura S, Baratti D, Virzì S, Bonomi S, Iusco DR, Grassi A,
Hutanu I and Deraco M: Learning curve for cytoreductive
surgery and hyperthermic intraperitoneal chemotherapy in
peritoneal surface malignancies: analysis of two centres. J Surg
Oncol 107(4): 312-319, 2013.
23 Yan TD, Links M, Fransi S, Jacques T, Black D, Saunders V and
Morris DL: Learning curve for cytoreductive surgery and
perioperative intraperitoneal chemotherapy for peritoneal surface
malignancy – a journey to becoming a Nationally Funded
Peritonectomy Center. Ann Surg Oncol 14(8): 2270-2280, 2007.
Received December 21, 2015
Revised January 28, 2016
Accepted February 1, 2016
ANTICANCER RESEARCH 36: 1033-1040 (2016)
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