Journal Pre-proof Target region resection in patients undergoing cytoreductive surgery for peritoneal metastases-is it necessary in absence of visible disease? Aditi Bhatt, Yutaka Yonemura, Sanket Mehta, Nazim Benzerdjeb, Praveen Kammar, Loma Parikh, Mita Y. Shah, Sakina Shaikh BHMS, Aruna Prabhu, Suniti Mishra, Snita Sinukumar, Vahan Kepenekian, Naoual Bakrin, Guillaume Passot, Olivier Glehen PII:
S0748-7983(19)31441-6
DOI:
https://doi.org/10.1016/j.ejso.2019.11.495
Reference:
YEJSO 5546
To appear in:
European Journal of Surgical Oncology
Received Date: 25 September 2019 Revised Date:
4 November 2019
Accepted Date: 10 November 2019
Please cite this article as: Bhatt A, Yonemura Y, Mehta S, Benzerdjeb N, Kammar P, Parikh L, Shah MY, Shaikh BHMS S, Prabhu A, Mishra S, Sinukumar S, Kepenekian V, Bakrin N, Passot G, Glehen O, Target region resection in patients undergoing cytoreductive surgery for peritoneal metastases-is it necessary in absence of visible disease?, European Journal of Surgical Oncology (2019), doi: https:// doi.org/10.1016/j.ejso.2019.11.495. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Ltd.
1 2
Target region resection in patients undergoing cytoreductive surgery for
3
peritoneal metastases- is it necessary in absence of visible disease?
4 5
Aditi Bhatt MS MCh. 1, Yutaka Yonemura MD, PhD.2, Sanket Mehta DNB3, Nazim
6
Benzerdjeb MD PhD.4, Praveen Kammar MS, MCh.3, Loma Parikh MD5, Mita Y Shah MD6,
7
Sakina Shaikh BHMS1, Aruna Prabhu MS, MCh.7, Suniti Mishra MD8, Snita Sinukumar9,
8
Vahan Kepenekian MD10, Naoual Bakrin MD, PhD10, Guillaume Passot MD, PhD10, Olivier
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Glehen MD, PhD10
10 11
1
Dept. of Surgical Oncology, Zydus hospital, Ahmedabad, India
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2
Peritoneal Metastases Center, Kishiwada Tokushukai Hospital, Osaka, Japan,
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3
Dept. of Surgical Oncology, Saifee hospital, Mumbai, India
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4
Dept. of Pathology, Centre Hospitalier Lyon-sud, Lyon, France
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5
Dept. of Pathology, Zydus hospital, Ahmedabad, India,
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6
Dept. of Pathology, Saifee hospital, Mumbai, India
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7
Dept. of Surgical Oncology, Thangam Cancer Centre, Nammakkal, India
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8
Dept. of Pathology, Fortis Hospital, Bangalore, India
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9
Dept. of Surgical Oncology, Jehangir hospital, Pune, India
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10
Dept. of Surgical Oncology, Centre Hospitalier Lyon-sud, Lyon, France
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Corresponding author- Prof. Olivier Glehen, MD, PhD.,
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Address- Centre Hospitalier Lyon Sud,
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Hospices Civils de Lyon,
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69495 Pierre Bénite, France
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1 2 3
Phone- (33) 478 86 23 71 E-mail-
[email protected]
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Words-2999
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Pages-17
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Tables- 6
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Figures-0
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The authors have no disclosures or conflict of interests
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The authors received no funding for this study
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Abstract
14
Background
15
The aim was to study the patterns of target region (greater omentum, lesser omentum,
16
falciform and umbilical round ligament) involvement in patients undergoing cytoreductive
17
surgery (CRS) from various primary tumors, factors affecting involvement and implications
18
on surgical practice.
19
Methods
20
All patients undergoing CRS from July 2018 to December 2018 were included in this
21
prospective study. The incidence of target region involvement in presence and absence of
22
visible disease and the impact of primary tumor site, PCI and other variables on target region
23
involvement was evaluated.
24
Results
25
In 191 patients, greater omentum was involved in over 15% of patients irrespective of the
26
primary tumor type and in 15.7 % in absence of visible disease. 75% of these had PCI <20.
2
1
The involvement of the other three target regions was higher than 20% in ovarian cancer,
2
appendiceal tumors and peritoneal mesothelioma. Involvement of these 3 regions was
3
associated with a higher PCI (p<0.001 for all) and omental involvement (p<0.001for all).
4
2.1% of colorectal cancer patients had umbilical round ligament involvement, 4.2% had
5
falciform ligament involvement and none had lesser omentum involvement.
6
Conclusions
7
Target region involvement varies according to primary tumour site and disease extent.
8
Resection of the greater omentum should be performed during CRS for PM arising from all
9
primary sites. Resection of other target organs may be performed for selected patients with
10
ovarian cancer, peritoneal mesothelioma and mucinous appendiceal tumours in absence of
11
visible disease. For other patients, it should be done only in presence of visible disease.
12
Key words- Omental resection, lesser omentum, falciform ligament, ligamentum teres,
13
cytoreductive surgery, target region resection
14 15
Introduction
16
Cytoreductive surgery with or without HIPEC is used as a potentially curative treatment for
17
patients selected patients with peritoneal metastases and comprises of resection of tumor
18
bearing regions of the peritoneum along with the adjacent viscera when involved. [1] The
19
greater omentum, falciform and umbilical round ligaments are often resected in patients
20
undergoing cytoreductive surgery (CRS) for peritoneal metastases (PM) arising from various
21
primary tumors in absence of visible disease. These sites are most likely to harbor occult
22
metastases as the concentration of lymphatic stomata and milky spots is comparatively high
23
in these regions. [2, 3] Such a rationale, however, is borrowed from the principles of
24
treatment of ovarian cancer and appendiceal tumors with peritoneal dissemination. In ovarian
25
cancer, normal peritoneal regions are resected/biopsied in patients undergoing surgery for all
3
1
stages of the disease. [4] The incidence of upstaging is 18% for all stages of epithelial ovarian
2
cancer. [5] The principles of CRS developed by Paul Sugarbaker come largely from those
3
used to treat mucinous appendiceal tumors. [6, 7] The mechanisms of peritoneal
4
dissemination are different for other primary tumors as are the disease distribution and
5
morphology. [8] In some tumors like epithelial ovarian cancer, peritoneal mesothelioma and
6
mucinous appendiceal tumors, there is a higher incidence of occult disease in normal looking
7
peritoneum as compared to others like colorectal and gastric cancer. [9] It may be presumed
8
that ‘target regions’ like the greater omentum, umbilical round ligament and falciform
9
ligament have a greater propensity for harboring occult disease in these patients as compared
10
to others.
11
It is not known in what percentage of patients these structures are involved by disease in
12
patients undergoing CRS. The involvement in relation to the disease extent within the
13
peritoneal cavity is also not known. Similarly, the incidence of lesser omental involvement
14
and factors predicting its involvement are not known.
15
Our goal was to study the patterns of omental, lesser omental, falciform and round ligament
16
involvement in patients undergoing CRS from various primary tumors, factors affecting their
17
involvement and the implications on surgical practice. Secondly, we wanted to look at the
18
necessity of resecting these regions in absence of visible disease on intraoperative inspection.
19
Methods
20
This prospective study was carried out at four peritoneal surface malignancy centers.
21
Institutional permission was obtained. All patients undergoing cytoreductive surgery from
22
various primary tumors were included in the study. The use of intraperitoneal chemotherapy
23
had no bearing on inclusion in the study.
24
Surgical procedures
4
1
The goal of surgery was to obtain a complete cytoreduction (CC-0/1 resection; CC-1
2
resection is acceptable for low grade mucinous carcinoma peritonei and peritoneal
3
mesotheliomia). [10] Intraoperative estimation of peritoneal cancer index was performed for
4
all patients and termed as the surgical PCI (sPCI). [10]
5
Patients taken up for surgery with the intent of complete cytoreduction were included even if
6
an incomplete cytoreduction was performed. Patients undergoing prophylactic and second
7
look surgeries were included in the study. This is because we wanted to study the patterns of
8
involvement in patients with occult disease or no disease. Standard peritonectomy procedures
9
and visceral resections were performed as described previously (Supplement 1). [11] The
10
resection of regions like the greater omentum, lesser omentum, falciform and round ligament
11
in absence of visible disease was at the discretion of the surgeon. The umbilical round
12
ligament (URL) may be covered by varying thickness of the liver parenchyma termed as the
13
‘hepatic bridge’ or ‘pont hepatique’. [12] The URL with its surrounding peritoneum was
14
resected completely as described by Sugarbaker. [12] All surgeons perform a supracolic
15
omentectomy irrespective of the extent of peritoneal disease and presence or absence of
16
greater omental disease. The policy to preserve or sacrifice the Arc of Barkov in presence and
17
absence of disease was different at different centers. Lesser omentectomy was performed
18
preserving the right and left gastric vessels as far as possible.
19
Pathological assessment
20
Each of the 5 peritoneal regions and their sub-regions included in the 5 peritonectomies
21
described by Sugarbaker were marked out by the surgeon and the maximum tumor size in
22
each region mentioned separately. [11]
23
A protocol for pathological evaluation was laid down based on the practices at each
24
institution and has been described elsewhere. [9] It involved assessment of the tumor in each
25
sub-region of the peritoneum, calculation of the pathological PCI (pPCI), evaluation of nodes
5
1
in relation to the primary tumor and peritoneal disease, evaluation of the pathological
2
response to chemotherapy and evaluation of normal regions of the peritoneum in proximity to
3
and at a distance from the tumor nodules. [9] Structures in each region were defined using the
4
PROMISE internet application. [13]
5
The presence of disease on histopathology was considered to be disease in that region. The
6
greater omentum, lesser omentum, umbilical round ligament (URL) and falciform ligament
7
were grouped as ‘target regions’ and the impact of primary tumor site, surgical and
8
pathological PCI, and other variables on target region involvement was evaluated. We looked
9
at correlation between target region involvement and the pathological and surgical PCI both.
10
Our preliminary findings showed a marked difference in the surgical and pathological PCI
11
but intraoperative decision making depends on the surgeons’ evaluation and hence we have
12
considered both. [9]
13
Regions 5, 6, 7 were included in the ‘lower region’, 1,4,8 in the ‘middle region’ and 1,2,3 in
14
the ‘upper region’.
15
Histological sub-types
16
All tumors of appendiceal origin including low and high grade mucinous carcinoma
17
peritonei, mucinous and non-mucinous adenocarcinomas were classified as appendiceal
18
primary tumors. Mucinous peritoneal deposits from other primary tumors (except colorectal
19
cancer) were included in ‘rare primary tumors’.
20
Only patients with stage III-C and above of epithelial ovarian cancer were included in
21
ovarian cancers in this study. Non-epithelial ovarian tumors and mucinous ovarian tumors
22
were included in rare-primary tumors.
23 24
Statistical analysis
25
Categorical data were described as number (%). Abnormally distributed continuous data were
6
1
2 expressed as the median and range. Categorical data were compared with the x test. When
2
multiple variables were being compared, post-hoc analysis was performed and Bonferroni
3
correction applied to determine the impact of each variable separately. For comparison of
4
median values, non-parametric independent sample t test and for means, independent sample
5
t test was used, where in Levene’s test for equality of variance was applied.
6
A p-value of <0.05 was considered statistically significant.
7
Results
8
From July 2018 to Dec 2018, 191 patients were included in the study. The primary tumor site
9
was appendix in 49 (25.6%), colorectal (CRC) in 47 (24.6%), ovary in 44 (23.0%%),
10
stomach in 18 (9.4%), mesothelioma in 15 (7.8%) and rare primary (or unusual indications
11
for CRS; supplementary material 2) in 18 (9.4%). The median sPCI was 11 [range 0-39] and
12
a CC-0/1 resection was obtained in 171 (89.4%). Neoadjuvant chemotherapy was
13
administered to 132 (69.1%) of the patients. The median pathological PCI was 6 [range 0-
14
39]. Lymph nodes were positive in 32.4%. The surgical intervention for PM was the first in
15
143 (74.8%) patients, the second in 43 (22.5%) and the third or more in 7 (3.6%) patients.
16 17
Histological subtypes of various primary tumors
18
In patients with epithelial ovarian cancer, 88.6% had high grade serous tumors. 15.9% of the
19
patients were undergoing a primary CRS, 43.1% interval CRS, 13.6% had a second look
20
surgery for an incomplete first cytoreduction and 27.2% had salvage surgery for recurrent
21
disease.
22
Of the appendiceal tumors, 44.8% had low grade mucinous carcinoma peritonei, 38.7 % had
23
high grade mucinous carcinoma peritonei, 2% had high grade mucinous carcinoma peritonei
24
with signet ring cells and 14.2% had non-mucinous adenocarcinoma.
7
1
Greater omentum
2
The greater omentum was resected in 155 (81.1 %) patients and was involved by tumor in 89
3
(46.5%) (Table 1). In the remaining it had already been removed during a prior surgical
4
intervention. The greater omentum was consistently involved in over 15% of the patients
5
with PM from different primary tumors. It was involved in 80% of the patients with
6
mesothelioma and only 19.1% with colorectal cancer (Table 2). In 14 (15.7%) patients, it
7
was seen in absence of visible disease. In 6 (12.7%) patients with colorectal cancer,
8
involvement of the greater omentum was seen in absence of visible disease. Patients with
9
greater omentum involvement had disease in the lower region in 85.3% as opposed to
10
patients without involvement in 43.9% (p<0.001). In patients whom the lower region was not
11
involved were those who had undergone a prior CRS or incomplete cytoreduction and the
12
lower region had not been evaluated. 34.8% of patients with omental involvement had a
13
pPCI <10 and 73.0% of them had a pPCI <20. There was a significantly higher incidence of
14
URL, falciform and lesser omentum involvement in patients who had disease in the greater
15
omentum as opposed to those that did not (p<0.001 for all, Table 1).
16 17
Umbilical round ligament
18
The umbilical round ligament (URL) was resected in 88 (46.0%) patients. It was positive for
19
malignancy in 36 (18.8%) and negative in 52 (27.2%) (Table 3). The median surgical
20
(p=0.001) and pathological PCI (p<0.001) were both significantly higher in patients with
21
URL involvement. The proportion of patients with a sPCI>20 (p<0.001) and pPCI>20
22
(p<0.001) was also significantly higher in this group. In 22.2% of the patients with URL
23
involvement, pPCI was less than10 and more than 50% had a pPCI<20. In 13.8% it was seen
24
in absence of visible disease.
8
1
Disease in the upper and lower regions was present in all patients with URL involvement and
2
the greater omentum was involved in 88.8% of these patients. Disease in the URL was
3
present in >25% of the patients with ovarian cancer, peritoneal mesothelioma and
4
appendiceal cancer and only in 2.1% with colorectal cancer and none of the patients with
5
gastric cancer. Twenty-three patients with colorectal cancer had resection of the URL of
6
which only one had disease on pathological examination and 8 patients with gastric cancer
7
had resection of which none had disease on pathological examination.
8
Lesser omentum
9
The lesser omentum was resected in 74 (38.7%) patients and positive in 35 (18.3%) (Table
10
4). There were 17.1% in whom involvement was seen in absence of visible disease. Patients
11
with involvement of the lesser omentum had a higher median surgical and pathological PCI
12
compared to those without involvement (p<0.001 for both). There were more patients in this
13
group with a sPCI>20 and pPCI >10 (p<0.001 for both). Only 2 patients (5.4%) with lesser
14
omentum involvement had a pPCI<10 whereas 51.4% had a pPCI<20.
15
Lesser omentum was involved in 46.6% of the patients with peritoneal mesothelioma, 30.6%
16
with appendiceal tumors and 20.4% with ovarian cancer. Only patients with ovarian (9.0%)
17
and appendiceal (4.0 %) tumors had involvement in absence of visible disease. None of the
18
patients with colorectal and only one patient (5.6%) with gastric cancer had lesser omental
19
involvement. All patients with involvement of the lesser omentum had disease in all three
20
regions of the peritoneal cavity.
21
Falciform ligament
22
The falciform ligament was resected in 70 (36.6%) patients and was positive for disease in 22
23
(11.5%) (Table 5). In 13.6%, it was seen in absence of visible disease. Patients with
24
falciform involvement had a significantly higher median surgical and pathological PCI as
25
compared to those that did not (p=<0.001 for sPCI and 0.003 for pPCI). Majority of the
9
1
patients had involvement of the upper, lower and middle regions in these patients and 68.1%
2
of the patients with falciform ligament involvement had a pPCI of more than 10. Falciform
3
involvement was seen in more than 20% of the patients with appendiceal tumors and
4
peritoneal mesothelioma and under 15% in all other tumors (p=0.013).
5
The post-hoc analysis with Bonferroni correction for the above results is provided in
6
supplementary material 3-7.
7 8
Discussion
9
Our results show that involvement of target regions is different in peritoneal metastases
10
arising from different primary tumors and different surgical strategies should be employed
11
for each of these. The clinical implications of these findings are discussed here.
12
Greater Omentum
13
The greater omentum was involved in over 15% of the patients with PM from different
14
primary sites and in 15.7% in absence of visible disease. Hence, it may be inferred that
15
resection of the omentum in all PM from epithelial tumors. Omental involvement in known to
16
occur in absence of visible disease in peritoneal mesothelioma, ovarian cancer and PM from
17
mucinous appendiceal tumors. [9, 14, 15] Our results concur with the findings of a recent
18
study which showed the presence of microscopic disease in the omentum in absence of gross
19
disease in around 15% of the patients with colorectal PM. [16] Thus, the results support
20
performing a greater omentectomy in all patients undergoing CRS for colorectal PM.
21
It was a surgical policy at all institutions to perform a supracolic omentectomy. The patients
22
included in this study all had advanced or recurrent ovarian cancer and none of the surgeons
23
performed an infracolic omentectomy for such patients. However, we cannot derive
24
conclusions on whether to resect the gastroepiploic arch or not in different patients. [17] An
10
1
analysis of the patterns of recurrence would be needed as well as the incidence and pattern of
2
omental lymph node involvement as most of these nodes are along the arc of Barkov.
3
Greater omentectomy may be performed for practical reasons, when HIPEC is given (i.e. to
4
ensure better perfusate circulation throughout the peritoneal cavity.)
5 6
Umbilical Round ligament
7
The URL is a remnant of the fetal umbilical vein that is contained in the inferior border of the
8
falciform ligament and divided the liver into the right and left lobes. [18] The falciform
9
ligament itself is a fold of the peritoneum that connects the anterior part of the liver to the
10
anterior abdominal wall. [19]
11
These regions communicate with the subperitoneal lymphatics and are presumed to harbour
12
occult disease which if not addressed leads to recurrence. [20] There is only one study that
13
describes the round ligament as the sole site of recurrence and this study is for appendiceal
14
tumours. [21] This study largely focuses on dividing the hepatic bridge when it is present to
15
completely resect the URL and its surrounding peritoneum. Our results show a high
16
incidence of URL involvement in patients with ovarian cancer and appendiceal tumours and a
17
low incidence in gastric cancer and colorectal cancer. In both patients with extensive disease
18
and limited disease, involvement of the round ligament was not seen in colorectal cancer
19
(Tables 2 and 3). Hence, resection of this structure in absence of visible disease may not be
20
required in these patients. The same can be concluded for gastric cancer. Another study has
21
shown that it could be involved in absence of gross disease, however, this study included
22
patients from different primary sites and does not look at the impact of primary tumour site
23
on its involvement. [22] Based on these results, the URL should be resected in all patients
24
undergoing CRS for advanced ovarian cancer, peritoneal mesothelioma and PM from
25
mucinous appendiceal tumours. For all others, it may be resected when disease is present. For
11
1
colorectal cancer, second look and prophylactic procedures are performed at some centres,
2
largely as part of clinical trials and some of them include resection of such target regions.
3
[23] Our findings do not support performing such resections. It may be argued that resection
4
of such structures causes little morbidity but some areas can be technically challenging like
5
division of the hepatic bridge. Moreover, there is the risk of tumour implantation in
6
uninvolved regions by disruption of normal tissue planes which should be avoided when
7
there is a miniscule possibility of finding disease in those regions. [24]
8
Lesser omentum
9
Lesser omentum involvement was seen in over 20% of the patients with ovarian cancer,
10
peritoneal mesothelioma and mucinous appendiceal neoplasms and was associated with
11
increased extent of peritoneal disease. The lesser omentum may be resected in patients with
12
PM from these primaries especially when there is disease in the upper and middle regions.
13
For other primary sites, it should be resected only when there is visible disease. But, it may
14
also be discussed to resect it systematically to facilitate the perfusion of omental bursa and of
15
the retro-gastric space when cytoreductive surgery is combined with intraperitoneal
16
chemotherapy.
17
Falciform ligament
18
The recommendations for resection of the lesser omentum can be applied to resection of the
19
falciform ligament as well except for ovarian cancer in which falciform ligament was less
20
commonly involved. It may be argued that the URL and falciform ligament should be
21
considered as one entity however, we noticed a difference in the pattern of involvement in
22
some cancers which could be explained by a differential concentration of lymphatics in some
23
areas of the falciform and the peritoneal fold containing the round ligament.
24
This study is limited by the small numbers and ideally a sample size should have been
25
calculated for the study to have adequate power to predict the probability of involvement of
12
1
each structure in different risk groups. But there is no scientific literature reporting the overall
2
incidence of each target region involvement and incidence according to the disease extent of
3
any of these regions. And because of this, current surgical practices vary from one surgeon or
4
institution to another. The main strength of this study is that it was prospective with a fixed
5
protocol for pathological evaluation. We have provided a set of recommendations in Table 6
6
based on our findings that can be adopted till more evidence is available. Though these
7
findings should be further confirmed in larger series, there are some negative findings which
8
cannot be ignored and may be considered sufficient to derive practice changing conclusions.
9
For e.g. a very low incidence (<5%) of involvement of the target regions (except the greater
10
omentum) in colorectal and gastric cancer indicating that resection of these regions is not
11
required in absence of visible disease. Secondly, greater omental involvement occurred in
12
more than 15% of the patients irrespective of the primary tumour type. Nearly two thirds of
13
the patients had a PCI <20 which is the case with most of the patients undergoing CRS.
14
Hence we recommend extrapolating these findings to all patients and perform resection of the
15
greater omentum even in the absence of visible disease, irrespective of the PCI.
16
It is also important as intraoperative decisions are based on visual inspection that is
17
inaccurate in predicting the presence of absence of disease. [25] There are three ways of
18
determining whether to resect a structure or not- presence of visible disease, high probability
19
of involvement in absence of visible disease and thirdly, impact on survival. We have
20
considered the first two methods in this manuscript to base our recommendations on. It is not
21
possible to determine the impact of resection of a particular peritoneal region on survival
22
since multiple variables are involved in these patients. We also recommend that the impact
23
of neoadjuvant chemotherapy should be studied in future studies.
24
This study can be considered a pilot study to carry out further research in this direction and to
25
the best of our knowledge, this issue has not been address prospectively and in this manner
13
1
before.
2
Conclusions
3
Target region involvement varies according to the primary tumour site and disease extent.
4
Resection of the greater omentum should be performed during CRS for PM arising from all
5
primary sites. Resection of other target organs like umbilical round ligament, falciform
6
ligament and lesser omentum may be performed for selected patients with ovarian cancer,
7
peritoneal mesothelioma and mucinous appendiceal tumours in absence of visible disease.
8
For other patients, it should be done only in presence of visible disease.
9 10 11 12
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Tables Table 1 Clinical and pathological findings in patients with or without resection of the greater omentum Characteristic
Primary tumor site
All patients N=191(%) Appendix Colorectal Ovary Mesothelioma Stomach Rare primary
Surgical PCI (sPCI)
0-9 10-19 20-29 30-39 Pathological PCI (pPCI) 0-9 10-19 20-29 30-39 Median surgical PCI (sPCI) [range]
49 (25.6) 47 (24.6) 44 (23.0) 15 (7.8) 18 (9.4) 18 (9.4)
Greater omentum not resected N=36 (%) 10 (27.7) 11 (30.5) 6 (16.6) 2 (5.5) 3 (8.3) 4 (11.1)
Greater omentum resected Positive for Negative for disease disease N=89 (%) N=66 (%) 29 (32.5) 10 (15.1) 9 (10.1) 27 (40.9) 28 (31.4)) 10 (15.1) 12 (13.4) 1 (1.5) 5 (5.6) 10 (15.1) 6 (6.7) 8 (12.1)
p-value
0.001
88 (46.0) 44 (23.0) 41 (21.4) 18 (9.4) 115 (60.2) 46 (24.0) 28 (14.6) 2 (1.0) 11 [0-39]
29 (80.5) 10 (27.7) 4 (11.1) 3 (8.3) 24 (66.6) 6 (16.6) 5 (13.8) 1 (2.7) 9 [0-39]
20 (22.4) 22 (24.7) 33 (37.0) 14 (15.7) 31 (34.8) 34 (38.2) 23 (25.8) 1 (1.1) 21[0-39]
47 (71.2) 12 (18.1) 4 (6.0) 1 (1.5) 60 (90.9) 6 (9.0) 0 (0.0) 0 (0.0) 5 [0-35]
<0.001
6 [0-39]
5 [0-35]
13 [0-39]
2 [0-15]
<0.001
126 (65.9) 45 (23.5) 20 (10.4) 95 (49.7)
25 (69.4) 6 (16.6) 5 (13.8) 15 (41.6)
45 (50.5) 32 (35.9) 12 (13.4) 66 (74.1)
56 (84.8) 7 (10.6) 3 (4.5) 14 (21.1)
<0.001
Upper region disease
CC-0 CC-1 CC-2/3 Present
Lower region disease
Present
129 (47.5)
25 (69.4)
76 (85.3)
28 (42.2)
<0.001
Middle region disease
Present
119 (62.3)
12(33.3)
89 (100.0)
18 (25.7)
<0.001
Disease in the URL
36 (18.8)
2 (5.5%)
32 (35.9)
2 (3.0)
<0.001
Disease in the falciform ligament
22 (11.5)
1 (2.7)
19 (21.3)
2 (3.0)
<0.001
Disease in the lesser omentum
35 (18.3)
1 (2.7)
33 (37.0)
1 (1.5)
<0.001
Median pathological PCI (pPCI) [range] CC-score
<0.001
<0.001
<0.001
Abbreviations: PCI- peritoneal cancer index; CC-score- completeness of cytoreduction score; URL- Umbilical round ligament
Table 2 Disease distribution and target region involvement according to primary tumor site All patients N=191 (%)
Median sPCI [Range] Median pPCI [Range] CC-score CC-0 CC-1 CC-2/3
Ovarian cancer N=44 19 (43.1) 15 (34.0) 10 (22.7) 0 (0.0) 27 (61.3) 14 (31.8) 3 (6.8) 0 (0.0) 10 [0-31] 6 [0-26] 32 (72.7) 10 (22.7) 2 (4.5)
Appendiceal cancer N=49 12 (24.4) 10 (20.4) 16 (32.6) 11 (22.4) 20 (40.8) 12 (24.4) 16 (32.6) 1 (2.0) 21.5 [0-39] 13.5 [0-39] 24 (48.9) 16 (32.6) 9 (18.3)
Mesothelioma N=15
88 (46.0) 44 (23.0) 41 (21.4) 18 (9.4) 115 (60.2) 46 (24.0) 28 (14.6) 2 (1.0) 11 [0-39] 6 [0-39] 126 (65.9) 45 (23.5) 20 (10.4)
Colorectal cancer N=47 32 (68.0) 8 (17.0) 5 (10.6) 2 (4.2) 37 (78.7) 6 (12.7) 4 (8.5) 0 (0.0) 6 [0-35] 2 [0-23] 41 (87.2) 3 (6.3) 3 (6.3)
Greater omentum resection
Performed Not performed Present Absent Performed Not performed Present Absent Performed Not performed Present Absent
155 (81.1) 36 (28.9)
36 (76.5) 11 (23.5)
38 (86.3) 6 (13.7)
89 (46.5) 66 (34.5) 88 (46.0) 103 (53.9)
9 (19.1)) 27 (57.4) 23 (48.9) 24 (51.1)
36 (18.8) 52 (27.2) 74 (38.7) 117 (61.2)
Surgical PCI (sPCI)
Pathological PCI
(pPCI)
Disease in greater omentum URL resection
Disease in URL Lesser omentum resection Disease in lesser omentum Falciform resected
Disease in falciform
Upper region disease Lower region disease Middle region disease
1 (6.6) 4 (26.6) 7 (46.6) 3 (20.0) 2 (13.3) 9 (60.0) 3 (20.0) 1 (6.6) 26 [0-39] 16.5 [4-35] 4 (26.6) 7 (46.6) 4 (26.6)
Gastric cancer N=18 13 (72.2) 3 (16.6) 2 (11.1) 0 (0.0) 15 (83.3) 3 (16.7) 0 (0.0) 0 (0.0) 3.5 [0-26] 2 [0-15] 15 (83.3) 1 (5.6) 2 (11.1)
Rare primaries N=18 11 (61.1) 4 (22.2) 1 (5.6) 2 (11.1) 14 (77.7) 2 (11.1) 2 (11.1) 0 (0.0) 11 0-33] 8 [0-26] 10 (55.5) 7 (38.8) 1 (5.6)
39 (79.5) 10 (20.5)
13 (86.6) 2 (13.3)
15 (83.3) 3 (16.7)
14 (77.8) 4 (22.2)
0.929
28 (63.6) 10 (22.7) 24 (54.5) 20 (45.5)
29 (59.1) 10 (20.5) 22 (44.8) 27 (55.1)
12 (80.0) 1 (6.6) 7 (46.6) 8 (53.4)
5 (27.7) 10 (55.5) 8 (44.4) 10 (55.5)
6 (33.3) 8 (44.4) 4 (22.2) 14(77.7)
<0.001
1 (2.1) 22 (46.8) 13 (27.6) 34 (72.4)
16 (36.3) 8 (18.1) 20 (45.5) 24 (54.5)
12 (24.4) 10 (20.5) 21 (42.8) 28 (57.1)
6 (40.9) 1 (6.6) 9 (60.0) 6 (40.0)
0 (0.0) 8 (44.4) 2 (11.1) 16 (88.9)
1 (5.6) 3 (16.7) 9 (50.0) 9 (50.0)
<0.001
35 (18.3) 39 (20.4)
0(0.0) 12 (25.5)
15 (30.6) 7 (14.2)
7 (46.6) 2 (13.3)
1 (5.6) 1 (5.6)
3 (16.7) 6 (33.3)
0.010
Performed Not performed Present Absent
70 (36.6) 121 (63.3)
10 (21.2) 37 (78.7)
9 (20.4) 11 (25..0) 24 (54.5) 20 (45.5)
18 (36.7) 31 (63.3)
7 (46.6) 8 (53.4)
4 (22.2) 14 (77.8)
7 (38.8) 11 (61.2)
0.022
22 (11.5) 48 (25.1)
2 (4.2) 45 (95.8)
2 (4.5) 42 (95.5)
11 (22.4) 38 (77.6)
4 (26.6) 11 (73.4)
1 (5.6) 17 (94.4)
2 (11.1) 16 (88.9)
0.013
Present Present Present
95 (49.7) 129 (47.5) 119 (62.3)
13 (27.6) 23 (48.9) 21 (44.6)
28 (63.6) 32 (72.7) 29 (55.7)
32 (65.3) 38 (77.5) 38 (77.5)
10 (66.6) 14 (93.3) 12 (80.0)
3 (16.7) 7 (38.8) 8 (44.4)
9 (50.0) 15 (83.3) 11 (61.1)
<0.001 <0.001 0.004
0-9 10-19 20-29 30-39 0-9 10-19 20-29 30-39
Abbreviations: PCI- peritoneal cancer index; CC-score- completeness of cytoreduction score; URL- Umbilical round ligament
pvalue <0.001
<0.001
<0.001 <0.001 <0.001
0.970
0.037
Table 3 Clinical and pathological findings in patients with and without resection of the umbilical round ligament
Characteristic
Primary tumor site
All patients n=191(%) 49 (25.6) 47 (24.6) 44 (23.0) 15 (7.8) 18 (9.4) 18 (9.4)
URL resected Positive Negative for for disease disease N=36 N=52
p-value
Omental disease
CC-0 CC-1 CC-2/3 Present
12 (33.3) 1 (2.7) 16 (44.4) 6 (16.6) 0 (0.0) 1 (2.7) 8 (22.2) 10 (27.7) 16 (48.4) 2 (5.5) 8 (22.2) 14 (38.8) 13 (36.1) 1 (2.7) 21 [0-39] 17 [2-26] 17 (47.2) 19 (52.7) 0 (0.0) 32 (88.8)
10 (19.2) 22 (42.3) 9 (17.3) 1 (1.9) 7 (13.4) 3 (5.7) 30 (57.6) 13 (25.0) 9 (17.3) 0 (0.0) 37 (71.1) 9 (17.3) 6 (11.5) 0 (0.0) 8 [0-28] 4 [0-35] 47 (90.3) 5 (9.6) 0 (0.0) 17 (32.6)
<0.001
88 (46.0) 44 (23.0) 41 (21.4) 18 (9.4) 115 (60.2) 46 (24.0) 28 (14.6) 2 (1.0) 11 [0-39] 6 [0-39] 126 (65.9) 45 (23.5) 20 (10.4) 89 (46.5)
27 (26.2) 24 (23.3) 19 (18.4) 8 (7.7) 11 (10.6) 14 (13.5) 50 (48.5) 21 (20.3) 16 (15.5) 16 (15.5) 70 (67.9) 23 (22.3) 8 (7.7) 1 (0.9) 10 [0-39] 4.5 [0-39] 62 (60.1) 21 (20.3) 20 (19.4) 40 (38.8)
Upper region disease
Present
95 (49.7)
41 (39.8)
36 (100.0)
18 (34.6)
<0.001
Lower region disease
Present
129 (47.5)
67 (65.0)
36 (100.0)
26 (50.0)
<0.001
Middle region disease
Present
119 (62.3)
59 (57.2)
34 (94.4)
26 (50.0)
<0.001
Surgical PCI (sPCI)
Pathological PCI (pPCI)
Appendix Colorectal Ovary Mesothelioma Stomach Rare primary 0-9 10-19 20-29 30-39 0-9 10-19 20-29 30-39
URL not resected N=103
Median sPCI [Range] Median pPCI [Range]
CC-score
<0.001
<0.001
0.001 <0.001 <0.001
<0.001
Abbreviations: PCI- peritoneal cancer index; CC-score- completeness of cytoreduction score; URL- Umbilical round ligament
Table 4 Clinical and pathological findings in patients with and without resection of the lesser omentum Characteristic
All patients n=191(%)
Primary tumor site
49 (25.6) 47 (24.6) 44 (23.0) 15 (7.8) 18 (9.4) 18 (9.4) 88 (46.0) 44 (23.0) 41 (21.4) 18 (9.4) 115 (60.2) 46 (24.0) 28 (14.6) 2 (1.0) 11 [0-39]
Lesser omentum not resected N=117 28 (23.9) 34 (29.0) 24 (20.5) 6 (5.1) 16 (13.6) 9 (7.6) 68 (56.4) 26 (22.2) 14 (12.8) 10 (8.5) 85 (72.6) 18 (15.3) 13 (11.1) 1 (0.8) 8 [0-39]
6 [0-39]
4 [0-39]
19 [6-35]
4.5 [0-14]
<0.001
CC-0 CC-1 CC-2/3 Present
126 (65.9) 45 (23.5) 20 (10.4) 89 (46.5)
89 (76.0) 18 (15.3) 10 (8.5) 36 (30.7)
12 (34.2) 19 (54.2) 4 (11.4) 33 (94.2)
25 (64.1) 8 (20.5) 6 (15.3) 20 (51.2)
<0.001
<0.001
Present
95 (49.7)
47 (40.1)
35 (100.0)
15 (38.4)
<0.001
Present
129 (47.5)
70 (59.8)
35 (100.0)
26 (66.6)
<0.001
Present
119 (62.3)
60 (51.2)
35 (100.0)
26 (66.6)
<0.001
Appendix Colorectal Ovary Mesothelioma Stomach Rare primary Surgical PCI 0-9 (sPCI) 10-19 20-29 30-39 Pathological PCI 0-9 (pPCI) 10-19 20-29 30-39 Median sPCI [Range] Median pPCI [Range] CC-score
Omental disease Upper region disease Lower region disease Middle region disease
Lesser omentum resected Positive for Negative disease for disease N=35 N=39 15 (42.8) 6 (15.3) 0 (0.0) 13 (33.3) 9 (25.7) 11(28.2) 7 (20.0) 2 (5.1) 1 (2.8) 1 (2.5) 3 (8.5) 6 (15.3) 2 (5.7) 18 (48.7) 10 (28.5) 8 (20.5) 18 (51.4) 9 (23.0) 5 (14.2) 3 (7.6) 2 (5.7) 28 (71.7) 18 (51.4) 10 (25.6) 14 (40.0) 1 (2.5) 1 (2.8) 0 (0.0) 23 [0-39] 11.5 [0-35]
p-value
0.001
<0.001
<0.001
<0.001
Abbreviations: PCI- peritoneal cancer index; CC-score- completeness of cytoreduction score;
Table 5 Clinical and pathological findings in patients with and without resection of the falciform ligament
Characteristic
Primary tumor site
Surgical PCI (sPCI)
Appendix Colorectal Ovary Mesothelioma Stomach Rare primary 0-9 10-19 20-29 30-39 0-9 10-19 20-29 30-39
All patients n=191(%)
Falciform not resected N=121 (%)
49 (25.6) 47 (24.6) 44 (23.0) 15 (7.8) 18 (9.4) 18 (9.4)
31(25.6) 37 (30.5) 20 (16.5) 8 (6.6) 14 (11.5) 11(9.0) 67 (55.3) 27 (22.3) 21(17.3) 6 (4.95) 75 (61.9) 25(20.6) 19(15.7) 2 (1.6) 9 [0-39]
Falciform resected Positive for Negative disease for disease N=22 N=48 11(50.0) 7 (14.5) 2 (9.0) 8 (16.6) 2 (9.0) 22 (45.8) 4 (18.1) 3 (6.2) 1 (4.5) 3 (6.2) 2 (9.0) 5 (10.4) 1(4.5) 20 (41.6) 4 (18.1) 13(27.0) 8 (36.3) 12 (25.0) 9 (40.9) 3 (6.2) 7 (31.2) 33(68.7) 9 (40.9) 12(25.0) 6 (27.2) 3 (6.2) 0 (0.0) 0 (0.0) 28 [8-39] 11.5[0-39]
p-value
<0.001
Median sPCI
[Range]
88 (46.0) 44 (23.0) 41 (21.4) 18 (9.4) 115 (60.2) 46 (24.0) 28 (14.6) 2 (1.0) 11 [0-39]
Median pPCI
[Range]
6 [0-39]
5.5 [0-39]
15 [2-29]
6 [0-27]
0.003
CC-0 CC-1 CC-2/3 Present
126 (65.9) 45 (23.5) 20 (10.4) 89 (46.5)
94(77.6) 21(17.3) 6 (4.9) 44 (36.3)
4 (18.1) 9 (40.9) 9 (40.9) 19 (86.3)
28 (58.3) 14(29.1) 6 (12.5) 26 (54.1)
<0.001
<0.001
Present Present Present
95 (49.7) 129 (47.5) 119 (62.3)
54(44.6) 74(61.1) 69(57.0)
19 (86.3) 20 (90.9) 21(95.4)
22(45.8) 35(72.9) 29(60.4)
0.001 0.041 0.002
Pathological PCI (pPCI)
CC-score
Greater omentum disease Upper region disease Lower region disease Middle region disease
<0.001
0.063
<0.001
Abbreviations: PCI- peritoneal cancer index; CC-score- completeness of cytoreduction score; URL- Umbilical round ligament
Table 6 Recommendations for target region resection in different clinical situations in absence of visible disease* Primary site
Clinical situations
Greater omentum
Colorectal cancer (nonmucinous)
No visible disease Disease in upper region Disease in lower region alone
No visible disease Disease in upper region Disease in lower region alone Appendiceal No visible disease adenocarcinoma (nonDisease in upper region mucinous)* Disease in lower region alone Gastric cancer No visible disease Disease in upper region Disease in lower region alone Epithelial ovarian No visible disease cancer (non-mucinous) Disease in upper region Disease in lower region alone Epithelial ovarian No visible disease cancer (mucinous) Disease in upper region Disease in lower region alone Peritoneal mesothelioma No visible disease Disease in upper region Disease in lower region alone
Appendiceal mucinous tumors
*Are treated like colorectal adenocarcinomas
Yes Yes Yes
Lesser Umbilical omentum round ligament No No No No No No
No No No
Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Yes Yes Uncertain No No No No Uncertain No Yes Yes Uncertain Yes Yes Uncertain Yes Yes Yes
Yes Yes Yes No No No No No No Yes Yes Yes Yes Yes Yes Yes Yes Yes
Yes Yes Yes No No No No No No Yes Yes Yes Yes Yes Yes Yes Yes Yes
Falciform ligament