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International Journal of Hyperthermia
ISSN: 0265-6736 (Print) 1464-5157 (Online) Journal homepage: http://www.tandfonline.com/loi/ihyt20
Survival difference between mucinous vs.
non-mucinous colorectal cancer following
cytoreductive surgery and intraperitoneal
chemotherapy
Yeqian Huang, Nayef A. Alzahrani, Winston Liauw, Arief Arrowaili & David L.
Morris
To cite this article: Yeqian Huang, Nayef A. Alzahrani, Winston Liauw, Arief Arrowaili & David L.
Morris (2018): Survival difference between mucinous vs. non-mucinous colorectal cancer following
cytoreductive surgery and intraperitoneal chemotherapy, International Journal of Hyperthermia,
DOI: 10.1080/02656736.2018.1496486
To link to this article: https://doi.org/10.1080/02656736.2018.1496486
© 2018 The Author(s). Published with
license by Taylor & Francis Group, LLC.
Published online: 21 Aug 2018.
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Survival difference between mucinous vs. non-mucinous colorectal cancer
following cytoreductive surgery and intraperitoneal chemotherapy
Yeqian Huang
a
, Nayef A. Alzahrani
a,b
, Winston Liauw
c
, Arief Arrowaili
b
and David L. Morris
a
a
Department of Surgery, University of New South Wales, St George Hospital, New South Wales, Australia;
b
College of Medicine, Al Imam
Muhammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia;
c
Department of Medical Oncology, University of New South Wales,
St George Hospital, Sydney, New South Wales, Australia
ABSTRACT
Background: It is believed that the oncologic behavior of mucinous colorectal adenocarcinoma (MC)
is different from non-mucinous adenocarcinoma (NMC). The aim of the study is to compare long-term
survivals between patients with MC and those with NMC following cytoreductive surgery (CRS) and
intraperitoneal chemotherapy (IPC).
Methods: This was a retrospective study of prospectively collected data of patients with peritoneal
metastases of colorectal origin following CRS and IPC. Group I included patients with MC which was
defined as being composed of >50% extracellular mucin. Group II included those with NMC.
Subgroup analysis was performed according to the location of primary tumor.
Results: A total of 213 patients were included in this study. The two groups had similar hospital mor-
tality, high dependency unit stay. MC group had a significantly longer mean intensive care unit (ICU)
stay (p¼.037) and total hospital stay (p¼.037). There was no significant difference in overall survival
(OS) and disease-free survival (DFS) between two groups (p¼.657 and p¼.938, respectively).
Multivariate analysis showed that the presence of mucin was not an independent negative prognostic
factor for OS (p¼.190).
Conclusion: In summary, patients with MC had a similar long-term survival outcome with those with
NMC following CRS and IPC.
ARTICLE HISTORY
Received 16 May 2018
Revised 1 July 2018
Accepted 1 July 2018
Published online 21 August
2018
KEYWORDS
Mucinous colorectal cancer;
cytoreductive surgery;
intraperitoneal chemother-
apy; HIPEC
Introduction
Mucinous colorectal adenocarcinoma (MC) is a histologic
variant of colorectal cancer and accounts for 3.9–19% of
colorectal cancers [1]. It is characterized by abundant extra-
cellular mucin of more than 50% of tumor volume [2]. It is
believed that the oncologic behavior of MC is different from
non-mucinous adenocarcinoma (NMC) [1]. MC is suggested
to be more common in younger patients and proximal colon.
It seems more aggressive and associated with villous adeno-
mas and poor prognosis [2].
Cytoreductive surgery (CRS) combined with intraperitoneal
chemotherapy (IPC) has significantly improved the survival
for those with peritoneal metastases of colorectal origin (PM)
and has become the gold standard therapy for it in last few
decades [3]. CRS involves surgical resection of macroscopic
disease to minimize residual tumor burden within the abdo-
men. After CRS, IPC administers a heated chemotherapy into
the abdomen to achieve a high local concentration of
chemotherapy drug locally, targeting at microscopic residual
diseases [4]. A multicentric French study has shown an
encouraging median survival of 30.1 months with a 1-year,
3-year and 5-year survival of 81%, 41% and 27%, respectively
for PM following CRS and IPC [5,6].
The current hypothesis in the literature is that MC is a dis-
tinct subtype as compared to NMC. However, the evidence is
still limited. These two groups of patients receive the same
first-line treatment at present [7]. The aim of this study is to
compare long-term survivals between patients with MC and
those with NMC following CRS and IPC.
Materials and methods
Settings
This is a retrospective study of prospectively collected data
of patients with peritoneal metastases of colorectal origin,
who underwent CRS and IPC by the same surgical team at St
George hospital, Sydney, Australia between January 1996
and Jan 2018. All the clinical and treatment-related data
were collected and entered into a computerized database to
evaluate the perioperative outcomes of these patients. A
signed informed consent was obtained from all patients.
CONTACT Nayef A. Alzahrani nayefalhariri@hotmail.com Department of Surgery, Hepatobiliary and Surgical Oncology Unit, St George Hospital, University
of New South Wales, Level 3 Pitney Building, Gray Street, Kogarah, Sydney, NSW 2217, Australia
ß2018 The Author(s). Published with license by Taylor & Francis Group, LLC.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits
unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
INTERNATIONAL JOURNAL OF HYPERTHERMIA
https://doi.org/10.1080/02656736.2018.1496486
Patients
Patients had a good performance status (World Health
Organization Performance Status 2), and had a histological
diagnosis of PM. All patients were managed by a standard
treatment protocol combining CRS and PIC. Suitability to
undergo CRS and PIC was evaluated during a regular weekly
meeting attended by a multidisciplinary team (MDT) includ-
ing surgical oncologists, medical oncologists, radiologists,
cancer care nurses and research staff. Exclusion criteria
include synchronous liver metastases at the time of oper-
ation, debulking surgery (i.e., no PIC was given) or incom-
plete cytoreduction.
Patients were divided into two groups. Group I included
patients with MC which was defined as being composed of
>50% extracellular mucin. Group II included those with
NMC. Subgroup analysis was performed according to the
location of primary tumor.
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 portography or primovist mag-
netic reasonance imaging of the liver. Positron emission tom-
ography was performed in all patients in addition to the
stating laparoscopy to assess the PCI if the scans showed
borderline results.
Our current selection criteria for consideration of CRS and
hyperthermic intraperitoneal chemotherapy (HIPEC) included
PCI 15, PCI <10 in the presence of liver metastases (max-
imum of four liver metastases), being able to perform com-
plete cytoreduction, absence of extra-abdominal disease, no
evidence of progressive disease in preoperative chemother-
apy and no severe comorbidity. In early years, PCI was lim-
ited to 20 in patients with colorectal cancer. This was
lowered to 15 in 2012. We would also consider repeat CRS
and HIPEC if PCI <10 and recurrence after 12 months after
primary CRS and IPC.
CRS
An initial assessment of the volume and extent of disease
was recorded using PCI. This assessment combines maximal
diameter of lesion size (LS) (LS 0: no Macroscopic tumor; LS
1: tumor <0.5 cm; LS 2: tumor 0.5–5 cm; and LS3: tumor
>5 cm) with tumor distribution (abdominopelvic region
0–12) to quantify the extent of disease as a numerical score
(PCI 0–39). CRS was performed using Sugarbaker’s tech-
nique [8].
All sites and volumes of residual disease following CRS
were recorded prospectively using CC score (CC0-no
Macroscopic residual cancer remained; CC1-no nodule
>2.5 mm in diameter remained; CC2-nodules 2.5 mm-2.5 cm
in diameter remained; CC3-nodules >2.5 cm in diameter
remained) [9]. In patients with colorectal cancer (CRC), only
complete cytoreduction (i.e., CC0 or CC-1) is considered
appropriate and included in this study. Perioperative compli-
cations in all patients were graded I to IV with increasing
severity based on the Clavien-Dindo classification (Grade I:
no treatment; Grade II: medications only; Grade III: surgical,
endoscopic or radiological intervention; Grade IV: life-threat-
ening complications requiring intensive care unit (ICU)
admission) [10]. Major morbidity was defined as grade III or
grade IV complications.
Hyperthermic intraperitoneal chemotherapy
After complete CRS, but prior to intestinal anastomosis or
repair of seromuscular tears, HIPEC was performed by instal-
lation of a heated chemoperfusate into the abdomen using
the coliseum technique at approximately 42 C. Oxaliplatin
350 mg/m
2
in 500 mL of 5% dextrose was given over 30 min
or mitomycin C 12.5 mg/m
2
in 3 L of 1.5 dextrose peritoneal
dialysis fluid if oxaliplatin in contraindicated.
Early postoperative intraperitoneal chemotherapy
Patients with peritoneal dissemination of low-grade appendi-
ceal mucinous neoplasms (LAMNs) are routinely offered.
Early postoperative intraperitoneal chemotherapy (EPIC) is
not routinely performed in patients with PM. However, in
cases where there was lack of availability of HIPEC (e.g.,
emergency) or where there may have been contraindication
to oxaliplatin or MMC, patients received EPIC. Furthermore,
in instances where the macroscopic appearance suggested
abundant areas of low-grade appendiceal disease or pseudo-
myxoma peritonei, patients were consented to receive EPIC.
5-Fluorouracil (5-FU) (650 mg/m
2
) following CRS/HIPEC was
administered either in ICU or high dependency unit (HDU)
on postoperative days 2–6. The criteria for EPIC have been
previously reported [11].
Follow-up
All patients were followed up at monthly intervals for the
first three months and six-monthly intervals thereafter until
the last time of contact or death. The follow-up review
included clinical examination, measurement of tumor
markers and assessment of CT scans with or without
PET scans.
Statistical analysis
All statistical analyses were performed by using IBM SPSS for
Windows version 22. Comparison of normally distributed var-
iables was performed using analysis of variance (one way-
ANOVA) test. Categorical variables were analyzed using the
Chi-square test or Fisher’exact test where appropriate.
Perioperative morbidity and mortality were the primary out-
comes of this study. Hospital mortality was defined as any
death that occurred during the same hospital admission for
CRS. Median survival was calculated based on the date of
death or last follow-up in the unit of months. Survival ana-
lysis was performed using the Kaplan–Meier curves and Log
2 Y. HUANG ET AL.
Rank test for comparison. A subgroup analysis was further
on presence of liver metastases. Prognostic factors for sur-
vival were evaluated using the Cox proportional hazards
regression model for the multivariate analysis. A significant
difference was defined as pvalues <.05.
Results
Descriptive characteristics
A total of 319 patients were diagnosed with PM. Eight
patients were excluded because of incomplete cytoreduction
(i.e., CC2 and CC3). Five patients were excluded from the
study due to missing information on details of histopath-
ology. Three hundred and six patients formed the cohort of
this study. It includes 213 patients with NMC (69.6%) and 93
patients with MC (30.4%). Table 1 summarized patients’back-
ground characteristics. 42.5% of patients were males
(n¼130). The median age was 57.0 years old (Range 15–84;
Mean 55.4, Standard Deviation (SD) ¼13.5). The overall mean
PCI was 9.6 (SD ¼6.5, Median ¼9.0, Range 0–35).
67 patients had liver metastases (21.9%) whereas lymph
node involvement was present in 209 patients (72.3%). There
were more females who were diagnosed with NMC whereas
more males were diagnosed with MC (p¼.017). Patients with
MC also had a significantly higher mean PCI as compared to
those with NMC (p<.001). There were more patients who
were found to have signet cells in MC group as compared to
those in NMC group (26.2% vs. 1.6%, p<.001). In contrast,
more patients in NMC group had liver metastases at the
time of surgery as compared to patients with MC (27.1% vs.
8.6%, p<.001). In addition, more patients with MC received
HIPEC (p¼.035). There was no statistical difference in mean
age (p¼.776), use of EPIC (p¼.757), site of primary tumor
(p¼.322) and use of preoperative chemotherapy (p¼.744).
Perioperative mortality and morbidity
Table 2 summarized the perioperative mortality and morbid-
ity results. The overall hospital mortality was 0.7% (n¼2) with
an overall major morbidity rate of 33% (n¼101). The overall
mean ICU, HDU, total hospital stay was 3.2 days (SD ¼6.8,
median¼2.0, range ¼0–101), 2.1 days (SD ¼4.1, median ¼
1.0, range ¼0–38) and 22.9 (SD ¼21.6, median ¼17.0,
range ¼3–206). Patients with MC had a significantly longer
mean ICU stay and total hospital stay (p¼.037 and p¼.037,
respectively, Table 2). There was no difference in hospital
mortality (p¼.347), major morbidity rate (p¼.750) and mean
length of HDU stay (p¼.820) (Table 2).
Survival outcomes
The median overall survival (OS) was 37.5 months (95% confi-
dence interval (CI) ¼31.5–43.5) with a 1-year OS, 3-year OS
and 5-year OS of 88.6%, 51.8% and 33.7%, respectively. The
median disease-free survival (DFS) was 13.1 months (95%
CI ¼11.4–14.8). Table 3 summarizes the overall OS, 1-year
OS, 3-year OS and 5-year OS of two groups. There was no
significant difference in OS and DFS between NMC and MC
groups (p¼.657 and p¼.938, respectively) (Table 3,Figures
1and 2). A subgroup analysis was performed on presence of
liver metastases. There were no significant differences in the
long-term survivals of patients with MC (p¼.805, Figure 3)
and those with NMC (p¼.346, Figure 4).
Multivariate analysis using cox-regression model showed
presence of mucin was not an independent negative prog-
nostic factor for OS (HR ¼1.41, 95%CI ¼0.84–2.36, p¼.190),
adjusted for PCI, presence of liver metastases and lymph
node involvement, age, use of HIPEC, tumor grade, use of
preoperative chemotherapy and site of primary tumor
(Table 4).
Discussion
The prognostic significance of presence of secretorymucin
remains controversial. Some studies have reported poor
prognosis with MC [12–15], whereas others failed to demon-
strate the difference in survival outcomes between patients
with MC and those with NMC [16,17]. A recent meta-analysis
performed by Verhulst et al. analyzed 44 studies and sug-
gested that mucinous differentiation results in a 2–8%
increased hazard of death after correction for stage.
However, there was a significant heterogeneity in included
studies [18]. A recent study performed by Yu et al. demon-
strated an improvement in cancer-specific survival for
Table 1. Patient characteristics.
Non-Mucinous
CRC (NMC)
Mucinous
CRC (MC) p
Total n ¼311 (%) 213 (69.6) 93 (30.4)
Sex, n(%) .017
Male 81 (38.0) 49 (52.7)
Female 132 (62.0) 44 (47.3)
Age mean (SD) 55.6 (13.4) 55.1 (13.7) .776
PCI mean (SD) 8.1 (5.2) 12.9 (7.8) <.001
Presence of liver metastases n(%) 59 (27.1) 8 (8.6) <.001
Primary lymph node involvement n(%) 143 (71.1) 66 (75.0) .500
HIPEC n(%) 184 (86.4) 88 (94.6) .035
EPIC n(%) 56 (26.4) 23 (24.7) .757
Site of primary tumor n(%) .322
Right colon 76 (36.9) 44 (47.8)
Left colon 22 (10.7) 9 (9.8)
Transverse colon 14 (6.8) 9 (9.8)
Rectum 23 (11.2) 7 (7.6)
Rectosigmoid 13 (6.3) 6 (6.5)
Sigmoid 58 (28.2) 17 (18.5)
Preoperative chemotherapy n(%) 161 (75.9) 69 (74.2) .744
Grade n(%) <.001
No malignancy 29 (15.5) 3 (3.8)
Well differentiated 2 (1.1) 4 (5.0)
Moderately differentiated 119 (63.6) 45 (56.2)
Poorly differentiated 34 (18.2) 7 (8.8)
Signet cell 3 (1.6) 21 (26.2)
Table 2. Perioperative mortality and morbidity and survival outcomes.
Non-mucinous
CRC
Mucinous
CRC p
Hospital mortality (%) 2 (0.9) 0 (0) .347
Major morbidity (Grade III/IV) n(%) 69 (32.5) 31 (34.4) .750
ICU stay mean (SD) 2.6 (2.8) 4.4 (11.5) .037
HDU stay mean (SD) 2.1 (3.7) 2.2 (5.0) .820
Total stay mean (SD) 21.2 (17.4) 26.8 (28.7) .037
INTERNATIONAL JOURNAL OF HYPERTHERMIA 3
patients with stage III and high-risk stage II NMC after receiv-
ing oxaliplatin in addition to 5-FU, however, it failed to dem-
onstrate a benefit with addition of oxaliplatin for patients
with stage III or stage II MC [19]. It may reflect the oncologic
behaviors between different histological subtypes.
Poorer prognosis associated with MC could be explained
by several mechanisms. It allows tumor cells to gain access
to peritoneal cavity. Also, mucoid material is taken up by
regional lymph nodes, facilitating lymphatic spread [20,21].
In addition, mucin may also interfere with inflammatory
response and immunological recognition of malignant cells
[22]. Another possible reason could be due to poorer respon-
siveness to chemotherapy [7] One study compared the
molecular features between carcinoma with signet ring cell
component and carcinoma with mucinous component but
no signet cell component. They found similar molecular
properties between these two groups, including higher inci-
dence of BRAF mutation, MSI and MLH1 loss [23].
These two groups of patients demonstrated a similar inci-
dence of hospital mortality and major morbidity. However,
patients with NMC had a significantly shorter ICU stay and
total hospital stay. Our findings in this study did not demon-
strate a long-term survival difference between these two
groups in both univariate analysis and multivariate analysis.
One of the recent studies performed by Park et al. analyzed
survival outcomes of 6475 patients with stages I to III who
underwent radical surgery. They identified a 5-year OS sur-
vival difference (81.3% and 87.4% for patients with MC and
those with NMC, respectively p¼.005) [1]. Interestingly, a
recent study performed by Hugen et al. demonstrated the
poor prognosis for MC is only present in rectal cancer. With
adjuvant chemotherapy, there was no difference in efficacy
of chemotherapy between MC and NMC. The reason is
unclear but it could be due to the fact that MCs in the rec-
tum are usually larger and often have a positive margin after
resection [24].
Table 3. Survival outcomes.
Non-mucinous CRC Mucinous CRC p
Overall OS median (months) (95% CI) 38.1 (31.1–45.0) 32.6 (21.3–44.0) .657
1-year OS (%) 87.9 90.4
3-year OS (%) 54.5 43.9
5-year OS (%) 35.2 29.4
DFS median (months) (95% CI) 13.1 (11.5–14.8) 2.3 (7.7–16.7) .938
1-year DFS (%) 55.6 51.8
3-year DFS (%) 11.0 14.3
5-year DFS (%) 0.6 3.6
Subgroup analysis –Median OS (months) (95% CI)
Right colon 43.3 (30.7–55.9) 39.2 (18.4–60.0) .863
Left colon 102.8 (–) 24.9 (0–54.0) .551
Transverse colon 59.8 (3.7–116.0) 44.9 (0–98.4) .277
Rectum 72.8 (–) 18.5 (15.1–22.0) .178
Rectosigmoid 30.7 (17.1–44.3) 40.9 (–) .156
Sigmoid 37.8 (22.0–53.7) 24.6 (11.9–37.4) .814
Figure 1. OS between MC and NMC.
4 Y. HUANG ET AL.
In our study, there was no significant difference in OS
outcomes between MC and NMC, including rectal subgroup.
Thus in patients with PM who underwent CRS and IPC, MC
might not necessarily indicate a poor prognosis and at the
current time should not be considered a contraindication to
treatment. The observation in our sample that synchronous
liver metastasis was more likely in the mucinous tumors war-
rants further investigation. Mucinous tumors may have
molecular characteristics that make liver metastasis less likely
however our observation could also reflect bias introduced
by our local selection criteria for simultaneous liver resection
an cytoreduction being four or fewer liver metastasis and PCI
less than or equal to 10. Mucinous tumors tended to have
higher PCI. Kermanshahi et al. have demonstrated previously
that mucinous tumors are less likely to develop liver metas-
tasis and more likely to develop peritoneal disease [25]. A
recent study of a Dutch cohort has shown colorectal cancer
peritoneal metastases to be enriched for the consensus
molecular subtype (CMS) four or the mesenchymal subtype.
Eight of twenty-four of these patients had mucinous adeno-
carcinoma [26]. In a review of clinical, morphological and
molecular classification of colorectal cancer, Jass notes that
mucinous differentiation is not specific to clinicopathological
subtypes [27]. Therefore, given the distribution of adverse
Figure 2. DFS between MC and NMC.
Figure 3. Subgroup analysis: liver metastases in patients with NMC.
INTERNATIONAL JOURNAL OF HYPERTHERMIA 5
molecular prognostic markers, there are many variables that
would potentially abrogate any effect of mucinous
differentiation.
There are several limitations that need to be taken into
consideration when interpreting the outcomes of this study.
It was a retrospective analysis of a prospectively maintained
patient cohort, leading to selection bias. Also, this study was
conducted in a center with an experience of more than 1200
patients. The learning curve and volume outcome affects
should be considered. Over the time frame of the study pat-
terns of use of systemic therapy including targeted therapies
has also evolved.
Conclusions
In summary, patients with MC had a similar long-term sur-
vival outcome with those with NMC following CRS and IPC.
More studies are warranted to further investigate the survival
differences between patients with MC and those with NMC
following CRS and IPC.
Disclosure statement
No potential conflict of interest was reported by the authors.
ORCID
Yeqian Huang http://orcid.org/0000-0001-5416-1246
References
[1] Park JS, Huh JW, Park YA, et al. Prognostic comparison between
mucinous and nonmucinous adenocarcinoma in colorectal can-
cer. Medicine. 2015;94:e658.
[2] Papadopoulos V, Michalopoulos A, Netta S, et al. Prognostic sig-
nificance of mucinous component in colorectal carcinoma. Tech
Coloproctol. 2004;8:s123–s125.
[3] Smeenk R, Verwaal V, Zoetmulder F. Learning curve of combined
modality treatment in peritoneal surface disease. Br J Surg.
2007;94:1408–1414.
[4] Chua TC, Yan TD, Saxena A, et al. Should the treatment of peri-
toneal carcinomatosis by cytoreductive surgery and hyperthermic
intraperitoneal chemotherapy still be regarded as a highly mor-
bid procedure?: A systematic review of morbidity and mortality.
Ann Surg. 2009;249:900–907.
[5] Elias D, Gilly F, Boutitie F, et al. Peritoneal colorectal carcinoma-
tosis treated with surgery and perioperative intraperitoneal
chemotherapy: retrospective analysis of 523 patients from a mul-
ticentric French study. J Clin Oncol. 2010;28:63–68.
[6] Verwaal VJ, van Ruth S, de Bree E, et al. Randomized trial of
cytoreduction and hyperthermic intraperitoneal chemotherapy
versus systemic chemotherapy and palliative surgery in patients
Figure 4. Subgroup analysis: liver metastases in patients with MC.
Table 4. Univariate and multivariate analysis of prognostic factors for OS.
Univariate (HR, 95%CI) pMultivariate (HR, 95%CI) p
MC 0.92 (0.64–1.32) .657 1.41 (0.84–2.36) .190
PCI 1.07 (1.05–1.10) <.001 1.07 (1.04–1.11) <.001
Presence of liver metastasis 1.12 (0.770–1.64) .562 0.84 (0.49–1.47) .546
Involvement of lymph node 1.51 (1.02–2.23) .040 1.26 (0.79–2.00) .338
HIPEC 0.63 (0.42–0.95) .029 0.62 (0.34–1.14) .126
Age 1.00 (0.98–1.01) .723
Tumor grade 1.48 (1.22–1.79) <.001 1.40 (1.12–1.76) .004
Preoperative chemotherapy 1.40 (0.94–2.08) .100 1.65 (1.06–2.56) .025
Site of primary tumor 1.09 (1.00–1.19) .059 1.13 (1.02–1.26) .025
6 Y. HUANG ET AL.
with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol.
2003;21:3737–3743.
[7] Debunne H, Ceelen W. Mucinous differentiation in colorectal can-
cer: molecular, histological and clinical aspects. Acta Chir Belg.
2013;113:385–390.
[8] Sugarbaker PH. Peritonectomy procedures. Ann Surg. 1995;
221:29–42.
[9] Jacquet P, Sugarbaker PH. Clinical research methodologies in
diagnosis and staging of patients with peritoneal carcinomatosis.
Peritoneal carcinomatosis: principles of management. Boston, MA:
Springer; 1996. 359–374.
[10] Dindo D, Demartines N, 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. 2004;240:205.
[11] Huang Y, Alzahrani NA, Liauw W, et al. Early postoperative intra-
peritoneal chemotherapy for low-grade appendiceal mucinous
neoplasms with Pseudomyxoma peritonei: is it beneficial?. Ann
Surg Oncol. 2017;24:176–183.
[12] Coindre J, Trojani M, Maree D, et al. The prognostic significance
of specific histologic features of carcinoma of the colon and rec-
tum. Surg Gynecol Obstet. 1981;153:511–514.
[13] Symonds DA, Vickery AL. Mucinous carcinoma of the colon and
rectum. Cancer. 1976;37:1891–1900.
[14] Green JB, Timmcke AE, Mitchell WT, et al. Mucinous carcinoma-
just another colon cancer? Dis Colon Rectum. 1993;36:49–54.
[15] Bagante F, Spolverato G, Beal E, et al. Impact of histological sub-
type on the prognosis of patients undergoing surgery for colon
cancer. J Surg Oncol. 2018;117:1355–1363.
[16] Coco C, Magistrelli P, Vecchio F, et al. The prognostic role of ana-
tomo-pathological factors in colorectal cancer: an univariate ana-
lysis. Ann Ital Chir. 1991;62:355–362.
[17] Langner C, Harbaum L, Pollheimer MJ, et al. Mucinous differenti-
ation in colorectal cancer–indicator of poor prognosis?
Histopathology. 2012;60:1060–1072.
[18] Verhulst J, Ferdinande L, Demetter P, et al. Mucinous sub-
type as prognostic factor in colorectal cancer: a systematic
review and meta-analysis. J Clin Pathol. 2012;65:381–388.
[19] Yu D, Gao P, Song Y, et al. The differences on efficacy of oxalipla-
tin in locally advanced colon cancer between mucinous and non-
mucinous adenocarcinoma. Cancer Med. 2018;7:600–615.
[20] Numata M, Shiozawa M, Watanabe T, et al. The clinicopatho-
logical features of colorectal mucinous adenocarcinoma and a
therapeutic strategy for the disease. World J Surg Oncol.
2012;10:109.
[21] Yamamoto S, Mochizuki H, Hase K, et al. Assessment of clinicopa-
thologic features of colorectal mucinous adenocarcinoma. Am J
Surg. 1993;166:257–261.
[22] Glasgow S, Yu J, Carvalho L, et al. Unfavourable expression of
pharmacologic markers in mucinous colorectal cancer. Br J
Cancer. 2005;92:259.
[23] Ogino S, Brahmandam M, Cantor M, et al. Distinct molecular fea-
tures of colorectal carcinoma with signet ring cell component
and colorectal carcinoma with mucinous component. Mod
Pathol. 2006;19:59.
[24] Hugen N, Verhoeven R, Radema S, et al. Prognosis and value of
adjuvant chemotherapy in stage III mucinous colorectal carcin-
oma. Ann Oncol. 2013;24:2819–2824.
[25] Kermanshahi TR, Magge D, Choudry H, et al. Mucinous and signet
ring cell differentiation affect patterns of metastasis in colorectal
carcinoma and influence survival. Int J Surg Pathol. 2017;25:
108–117.
[26] Ubink I, van Eden W, Snaebjornsson P, et al. Histopathological
and molecular classification of colorectal cancer and correspond-
ing peritoneal metastases. Br J Surg. 2018;105:e204.
[27] Jass J. Classification of colorectal cancer based on correlation of
clinical, morphological and molecular features. Histopathology.
2007;50:113–130.
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