Introduction
Familial adenomatous polyposis (FAP) is strongly associated with the occurrence of
colorectal cancer [1]. The specificities of FAP are management at young age; the specific prophylactic
surgical treatment including total colectomy with ileorectal anastomosis (IRA) or
proctocolectomy with ileoanal anastomosis and J pouch (IAA). Recent guidelines report
a mean age at surgery of 20 years [2]. Rectal preservation is usually recommended when preoperative workup finds fewer
than five rectal adenomas; proctectomy remains the gold standard when > 20 adenomas
are found.
Proctocolectomy is justified by relatively old series that found secondary rectal
cancer rates of 11.2 % at 15 years and 13 % to 59 % at 25 years [3]
[4]. However, in this young population who will undergo mutilating procedures, postoperative
quality of life is a major issue. To date, the main difference between these two strategies
is poorer quality of life with social impairment related to IAA, such as incontinence
and an increased number of stools per day. Thanks to the technical improvements of
endoscopy, a different approach has been adopted in the Lyon university hospital and
relies on systematic endoscopic destruction or resection of residual adenomas in the
rectal stump, allowing for a more conservative attitude. This was possible because
of the development of Nd-Yag laser coagulation in the 1980s, then the development
of argon plasma coagulation in the 1990s, and cold snare resection today. In the context
of this new aggressive endoscopic approach, the main objective of our study was to
describe the long-term risk of rectal/pouch cancer. Secondary objectives were to describe
morbidity related to surgery or to endoscopy and long-term quality of life according
to functional results.
Patients and methods
Databases
Data were extracted from a dedicated national database (plateforme d’échange entre personnels de santé; clinicaltrials.gov NCT01987518) created in January 2011, and included genetic identification
and prospectively-recorded endoscopic follow-up [5]. Data for patients followed before 2011 were retrospectively entered using surgical
and endoscopic databases.
Study population
All patients with FAP diagnosis who underwent prophylactic and/or curative surgery
in three university hospitals of the Rhône-Alpes region of France (Lyon, Grenoble,
and Saint Etienne) between January 1965 and November 2015 were retrospectively (before
2011) or prospectively (2011 and later) included. Endoscopic follow-up was performed
until 2020. Diagnosis of FAP was based on genetic identification of known mutations:
exons 1, 4, 5, 6, 7, 9, 10, 11, 13, 14, 15; introns 6, 7, 9, 10, 14; locus DP1, delq15q23,
and total deletion. When genetic analysis and/or patients refused genetic analysis,
or when genetic analysis failed to identify any mutation, the diagnosis of FAP was
based on classical clinical criteria: diffuse polyposis of the colon and/or rectum,
confluent adenomas in patients aged < 20 years. Patients for whom endoscopic/pathological
data were not available during follow-up, synchronous metastases, or who benefited
from abdominoperineal resection (APR), were excluded from the analysis.
Data collection
Demographic information (age, sex, tumor location when present at diagnosis: colic
and/or rectal, comorbidities, previous surgical history, and known pathogenic variants)
was recorded. As recommended by the French guidelines [2], clinical staging included endoscopic colorectal examination to evaluate colon/rectum
adenoma number to determine surgical indication. For patients without detailed colonic
adenoma count, as endoscopic descriptions were standardized in the three centers,
profuse polyposis in each segment was interpreted as > 100 adenomas, moderate as 50,
and poor as five polyps. Total colectomy with IRA and coloproctectomy with IAA and
J pouch were performed. Surgery consisted of laparoscopic or open en bloc total colectomy
or proctocolectomy, with nodal resection when surgery was performed in case of primary
cancer, or high-grade dysplasia/intramucosal carcinoma; no nodal resection in case
of low-grade adenomas [1]
[2]. Operative techniques were open and laparoscopic approaches.
Surgical indications
Current guidelines recommend that prophylactic surgery be performed according to age
and endoscopic findings [1]
[2]. Guidelines are quite unclear (up to 20 for Sinha and al) regarding the upper limit
of the rectal polyp number justifying proctectomy. In accordance to international
practices and local guidelines (based on clinical observation), rectal preservation
was preferred, independently of adenoma number if endoscopic treatment of rectal adenomas
was estimated to be feasible and safe by a trained endoscopist (expert in FAP management).
This included biopsies revealing benign adenomas with low- or high-grade dysplasia
(Vienna 3 or 4.1), and/or intra mucosal cancer (Vienna 4.2 to 4.4) if complete and
carcinologic resection was achieved. When expert endoscopists estimated that the rectal
disease was not accessible to endoscopic treatment or if patients were not willing
to undergo close follow-up, proctectomy was performed. In cases of advanced primary
cancer, oncological surgery was proposed. In case of colonic cancer, total colectomy
with IRA was performed, and for rectal cancer, proctocolectomy with IAA or perineal
resection was performed.
Follow-up, endoscopic treatment, and secondary cancer occurrence
A follow-up regimen of clinical examination and postoperative lower endoscopy was
recommended 6 months after surgery then at least annually in case of IRA, and biennially
in case of IAA. In case of excellent control in the rectal stump (few residual adenomas
and low-grade dysplasia), the follow-up interval could be extended to every 2 years
in IRA patients [6]. During endoscopy, systematic treatment of remaining or newly developed adenomas
([Fig. 1], [Fig. 2]) was performed (supplementary materials). Small lesions (≤ 5 mm) were treated using
argon plasma coagulation (40 W) [6]. Alternatives were cold-snare biopsy, endoscopic mucosectomy, and submucosal dissection
([Fig. 3] and [Video 1]). In cases of diffuse polyposis (> 100 lesions) in the rectal stump or pouch, a
multistep treatment was proposed with therapeutic lower endoscopies at an interval
of 2 to 3 weeks. When completely treated, follow-up endoscopies were performed every
6 months until rectal adenoma clearance. Further endoscopic follow-up was progressively
extended from every 6 months to yearly surveillance to reach the standard follow-up
frequency. Diagnosis of secondary cancer was based on histologically proven relapse
of cancer within the rectum or the J pouch, including local anastomotic sites. As
this represents standards of care in our center, there was no need for an ethical
committee approval.
Fig. 1 Ileal pouch with multiple flat adenomas without chromoscopy.
Fig. 2 Same ileal pouch with multiple flat adenomas and indigo-carmine dye showing numerous
large flat adenomas.
Fig. 3 Rectal aspect after APC treatment of numerous polyps.
Video 1 This video shows endoscopic treatment of numerous adenomas (most visible lesions
after indigo-carmine dye) in the rectal stump of a polyposis patient using Argon Plasma
Coagulation (APC).
Study endpoints
The primary objective was to describe the impact of a preferred rectal preservation
strategy, associated with systematic endoscopic treatment of the remnant, on secondary
rectal or J pouch cancer occurrence. In this setting, the number of lesions detected
and treated during surveillance (i. e. polyp count) was reported and compared between
IRA and IAA groups. Histological staging used the Union Internationale Contre le Cancer/TNM
classification, seventh edition [7]. Secondary objectives included the description of 15 and 25 years overall and cancer-free
survival. The description of morbidity related to surgery or to endoscopy. Morbidity
was assessed according to surgical classifications [8]. Long-term morbidity was also evaluated through surgical complications: poor nutrition,
sepsis, stenosis, and short bowel syndrome. Regarding Quality of life, we used indirect
comparison of quality-of-life through mean number of stools per day and incontinence
(Jorge & Wexner score ≥ 5 of 20 [9] and nocturnal leakage occurrence); values of the last available visit were considered.
Statistical analysis
The Student’s t-test was used for intergroup comparisons of quantitative variables, and the χ2 test
or the Fisher tests to compare categorical data. Survival description was performed
using Kaplan-Meier. All tests were 2-sided. For multiple tests, Bonferroni adjustment
was applied to all tests and the interpretation of results were performed according
to this adjustment for all datas. Statistical analyses were performed using Statistical
Package for the Social Sciences v19.0 (SPSS, Chicago, Illinois, United States).
Results
Characteristics
Between January 1965 and November 2015, 316 patients underwent prophylactic and/or
curative surgery for FAP in Lyon Grenoble, and Saint Etienne University hospital.
Two patients were excluded because of synchronous metastases, 18 because of the lack
of endoscopic follow-up data. Among the remaining 296 patients, procedures consisted
of proctocolectomy with IAA and J pouch (n = 92; 31.1 %), total colectomy with IRA
(n = 197; 66.5 %), and proctocolectomy with abdominoperineal resection (APR) and definitive
ileostomy (n = 7; 2.3 %). The seven patients with APR were excluded because no lower
endoscopic follow-up was performed. The study population, therefore, included a total
of 289 patients (92 with IAA and 197 with IRA). The sex ratio was 0.9:1. The mean
(SD) age was 29.5 (16.3) years ( [Table 1]). Ninety-five patients (32.9 %) had a previous history of digestive disease (surgical
history and/or medical history n = 58; 20.1 %), metabolic disease (n = 70; 24.2 %),
and cardiovascular disease (n = 51; 17.6 %). All comorbidities were balanced between
groups, except for metabolic comorbidities that were more frequent among patients
in the IRA group than in the IAA group (P = 0.001). The most frequent genetic mutation was found on Exon 15 of the APC gene (n = 96; 34.1 %; [Table 1]).
Table 1
Patient characteristics
|
Sample population
|
IRA
|
IAA
|
P value
|
|
n = 289
|
n = 197
|
n = 92
|
|
Age, (mean (SD))
|
29.5 (16.3)
|
31.9 (18)
|
24.3 (9.6)
|
0.0001
|
|
Sex, n (%)
|
|
|
|
|
|
Male
|
138 (47.8)
|
95 (48.2)
|
43 (46.7)
|
0.81
|
|
Female
|
151 (52.2)
|
102 (51.8)
|
49 (53.3)
|
|
Mutation, n (%)
|
|
|
|
|
|
Exon 15
|
96 (33.2)
|
55 (27.9)
|
41 (44.6)
|
0.005
|
|
Other mutations
|
86 (29.7)
|
57 (28.9)
|
29 (31.5)
|
0.69
|
|
Missing
|
107 (37.1)
|
85 (43.2)
|
22 (23.9)
|
|
|
Comorbidities, n (%)
|
|
|
|
|
|
Smoking
|
|
|
|
|
|
Never
|
221 (76.5)
|
148 (75.1)
|
73 (79.3)
|
0.28
|
|
Previous
|
53 (18.3)
|
13 (6.6)
|
2 (2.2)
|
|
Current
|
15 (5.2)
|
36 (18.3)
|
17 (18.5)
|
|
Pulmonary
|
31 (10.7)
|
21 (10.7)
|
10 (10.9)
|
0.96
|
|
Cardiovascular
|
51 (17.6)
|
39 (19.8)
|
12 (13.0)
|
0.16
|
|
Neurologic
|
30 (10.4)
|
19 (9.6)
|
11 (12.0)
|
0.55
|
|
Hematologic
|
7 (2.4)
|
6 (3.0)
|
1 (1.1)
|
0.31
|
|
Desmoid tumor, n (%)
|
38 (13.1)
|
22 (11.2)
|
16 (17.4)
|
0.14
|
|
Number of preoperative colic adenomas (mean (SD))
|
316.5 (278.7)
|
303.5 (269.6)
|
334.4 (294.9)
|
0.82
|
|
Number of preoperative rectal adenomas (mean (SD))
|
34.1 (34.6)
|
24.7 (33.9)
|
52.8 (27.8)
|
0.0001
|
|
Adenocarcioma at diagnosis, n (%)
|
|
|
|
|
|
Colorectal
|
28 (9.7)
|
21 (10.7)
|
7 (7.6)
|
0.41
|
|
Rectal
|
9 (3.1)
|
3 (1.5)
|
6 (6.5)
|
0.02
|
|
Operative technique, n (%)
|
|
|
|
|
|
Laparoscopy
|
97 (34.6)
|
89 (45.2)
|
8 (8.7)
|
0.0001
|
|
Open
|
192 (65.4)
|
108 (54.8)
|
84 (91.3)
|
IRA, ileorectal anastomosis; IAA, ileoanal anastomosis.
Rectal adenoma count was detailed for most patients. A minority (n = 10; 3.3 %) did
not have a detailed colonic adenoma count. In preoperative workup, the mean (SD) number
of colonic adenomas was 303.5 (269.6) in the IRA group and 334.4 (294.9) in the IAA
group, (P = 0.82). The mean (SD) number of rectal adenomas was 24.7 (33.9) in the IRA group
vs. 52.8 (27.8) in the IAA group (P = 0.0001). Before surgery, primary colorectal cancer was found in 28 patients (9.7 %);
21 (10.7 %) in the IRA group, 7 (7.6 %) in the IAA group (P = 0.19; [95 %CI 0.1–0.91]). In those 28 patients, the repartition of primary cancers
was as follows: primary rectal cancer was found in nine patients (3.1 %): 3 (1.5 %)
in the IRA group (for these three patients, the rectum was preserved as the cancer
was intramucosal and completely treated at endoscopy) and six (6.5 %) in the IAA group
(P = 0.0001).
Secondary cancer on rectal stump or ileal J pouch.
The median follow-up was 17.1 [0–38.1] years. Secondary cancer characteristics are
listed in [Table 2]. Secondary cancer occurred in 13 patients: 12 patients (6.1 %) in the IRA group
and one (1.1 %) in the IAA group (Vienna 4.2). Ten of 12 rectal cancers were diagnosed
at first endoscopy in our center. The 2 other rectal cancers occurred during the follow
up: one despite regular follow-up (intramucosal cancer, Vienna 4.2) and the second
was a T1 cancer diagnosed after a large interruption of follow up (Vienna 4.2). Three
cancers in the IRA group were classified T1 but after pathological examination, one
was T1 and Two Tis (2 intramucosal adenocarcinomas Vienna 4.2) which were exclusively
treated by an endoscopic R0 resection. The mean interval between surgery and rectal
or pouch secondary cancer was 272 months (22.6 years; [Table 3]). Ten of 12 rectal cancers underwent secondary proctectomy (5 IAA and 5 APR). The
mean (SD) number of rectal/pouch adenomas found at each endoscopy was of 22.7 (27.7)
in those with secondary cancer vs. 22.1 (29.8) in those without. The mean (SD) number
of adenomas treated at each endoscopy was of 16.9 (14.4) in those with secondary cancer
vs. 16.1 (20.4) in those without.
Table 2
Description of secondary cancers
|
Patient no.
|
Age at primary surgery
|
Group
|
Age at diagnosis of secondary cancer
|
Number of pretreatment endoscopy reports available
|
Time since last endoscopy
(mo)
|
Findings in previous procedures
|
Endoscopic/surgical treatment
|
Pathology
|
Vienna classification
|
|
1
|
13
|
IAA
|
30
|
1
|
1
|
|
Endoscopic mucosectomy
|
T is
|
4.2
|
|
2
|
49
|
IRA
|
70
|
0
|
|
|
Abdominoperineal resection
|
Not available
|
|
|
3
|
28
|
IRA
|
50
|
4
|
36
|
High-grade dysplasia
|
Abdominoperineal resection
|
T is
|
4.2
|
|
4
|
15
|
IRA
|
50
|
1
|
0
|
Adenocarcinoma
|
Abdominoperineal resection
|
T3N0M0
|
|
|
5
|
21
|
IRA
|
24
|
5
|
6
|
High-grade dysplasia
|
Ileoanal pouch
|
Not available
|
|
|
6
|
54
|
IRA
|
54
|
0
|
|
|
Abdominoperineal resection
|
Not available
|
|
|
7
|
41
|
IRA
|
70
|
0
|
|
|
Abdominoperineal resection
|
Not available
|
|
|
8
|
24
|
IRA
|
44
|
0
|
|
|
Abdominoperineal resection
|
T4N1M0
|
|
|
9
|
38
|
IRA
|
54
|
0
|
|
|
Abdominoperineal resection
|
Not available
|
|
|
10
|
20
|
IRA
|
48
|
0
|
|
|
Abdominoperineal resection
|
T2N0M0
|
|
|
11
|
39
|
IRA
|
56
|
0
|
|
|
Ileoanal pouch
|
Not available
|
|
|
12
|
27
|
IRA
|
50
|
0
|
|
|
Ileoanal pouch
|
Not available
|
|
|
13
|
27
|
IRA
|
71
|
3
|
6
|
High-grade dysplasia
|
Abdominoperineal resection
|
T is
|
4.2
|
IRA, ileorectal anastomosis.
Table 3
Postoperative data
|
IRA
|
IAA
|
P value
|
|
n = 197
|
n = 92
|
|
Mean length of stay, (mean (SD))
|
8.7 (4.8)
|
7.9 (2.8)
|
0.14
|
|
Postoperative morbidity, n (%)
|
29 (14.7)
|
15 (16.3)
|
0.72
|
|
Long-term morbidity, n (%)
|
48 (24.4)
|
37 (40.2)
|
0.006
|
|
Poor nutrition
|
8 (4.1)
|
3 (3.3)
|
0.74
|
|
Short bowel length
|
3 (1.5)
|
4 (4.3)
|
0.21
|
|
Prolapse
|
0
|
1 (1.1)
|
0.31
|
|
Deep abcess
|
1 (0.5)
|
0
|
1
|
|
Ascitis
|
1 (0.5)
|
0
|
1
|
|
Chronic leakage
|
0
|
6 (6.5)
|
0.001
|
|
Bowel perforation related to desmoid tumor
|
0
|
3 (3.3)
|
0.03
|
|
Peritonitis
|
1 (0.5)
|
1 (1.1)
|
0.53
|
|
Bleeding
|
2 (1.0)
|
3 (3.3)
|
0.17
|
|
Occlusion
|
28 (14.2)
|
17 (18.5)
|
0.35
|
|
Anatomotic stenosis
|
9 (4.6)
|
12 (13.0)
|
0.01
|
|
Anal fissure
|
1 (0.5)
|
0
|
1
|
|
Pouchitis
|
0
|
1 (1.1)
|
0.49
|
|
Event rate
|
10 (5.1)
|
5 (5.4)
|
0.89
|
|
Secondary rectal/pouch cancer, n (%)
|
12 (6.1)
|
1 (1.1)
|
0.06
|
|
Surgical treatment
|
10 (5.1)
|
0
|
|
|
IAA
|
5 (2.5)
|
0
|
|
|
APR
|
5 (2.5)
|
0
|
|
|
Endoscopic treatment mucosectomy
|
2 (1.0)
|
1 (1.1)
|
|
|
Pathology of secondary cancer, n (%)
|
|
|
|
|
Intramucosal
|
2 (1.0)
|
1 (1.1)
|
0.71
|
|
T1
|
1 (0.5)
|
0
|
|
T2
|
2 (1.0)
|
0
|
|
T3
|
2 (1.0)
|
0
|
|
T4
|
0
|
0
|
|
N1
|
1 (0.5)
|
0
|
|
M
|
1 (0.5)
|
0
|
|
Carcinomatosis
|
1 (0.5)
|
0
|
0.20
|
|
Pelvic recurrence
|
0
|
1 (1.1)
|
0.21
|
|
Quality of life, n (%)
|
|
|
|
|
Number of stools per day (mean (SD))
|
4.4 (2.5)
|
5.5 (2.6)
|
0.001
|
|
Incontinence
|
14 (7.1)
|
16 (17.4)
|
0.03
|
|
Nocturnal leakage
|
13 (6.6)
|
20 (23.5)
|
0.0001
|
IAA, ileoanal anastomosis; APR, abdominoperineal resection.
Survival
The 15-year cancer-free survival was of 99.5 % in the IRA group and 100 % in the IAA;
the 25-year cancer-free survival was of 96.3 % in the IRA group and 98 % in the IAA
group.
The mean cancer-free survival in the IRA group was 46.55 years (95 %CI 48.12–51.1)
and 46.5 years (95 %CI 43.4–49.7) in the IAA group (P = 0.16). The 15-year overall survival was 98.9 % in IRA group and 98.8 % in IAA group;
the 25-year overall survival was 97.8 % in the IRA group and 98.8 % in the IAA group. The
mean overall survival in the IRA group was 50 years (95 %CI 47.5–80.8) and 49 years
(95 %CI 48.6–52.1) in the IAA group (P = 0.69).
Postoperative morbidity
Postoperative morbidity occurred in 44 patients (15.2 %); 29 patients (14.7 %) of
the IRA group and 15 (16.3 %) of the IAA group (P = 0.72 (95 %CI 0.5–0.79); [Table 3]). The majority of complications were low-grade complications. Severe post-operative
complications were observed in 3 patients (1.5 %) in the IRA group vs. 2 patients
(2.2 %) in the IAA group (P = 0.65 [95 %CI 0.05–0.85]). Redo surgery was performed in 4.1 % of the IRA group
vs. 4.3 % of the IAA group (P = 0.91 (95 %CI 0.34–0.94). Long-term morbidity occurred in 48 patients (24.4 %) in
the IRA group vs. 37 (40.2 %) in the IAA group (P = 0.006 [95 %CI 0.001–0.02]). There was no case of chronic leakage in the IRA group
vs. 6.5 % (n = 6) in the IAA group (P = 0.001 [95 %CI 0.001–0.01]) ( [Table 3]).
Endoscopic follow-up, treatment, and induced morbidity
Endoscopic follow-up was complete for 179 patients (90.9 %) in the IRA group and 84
(91.3 %) in the IAA group (P = 0.90). The mean (SD) number of lower endoscopies performed was respectively 4.4
(3.5) and 4.4 (3.5; P = 0.91). The mean (SD) number of treated adenomas at each endoscopic session was
of 17.8 (20.8) in the IRA group vs. 12.9 (18.8) in the IAA group (P = 0.06). At least one endoscopic complication occurred in 90 patients (45.7 %) in
the IRA group vs. 52 (56.5 %) in the IAA group (P = 0.08) during this long-term follow-up. In case of post-procedural complication,
conservative treatment was possible in 98.8 % of patients in the IRA group vs. 100 %
of the IAA group; surgery was required in 0.5 % of patients in the IRA group vs. none
in the IAA group, and a redo endoscopy for complication treatment was required in
0.5 % of patients in the IRA group vs. 2.2 % in the IAA group ( [Table 4]). The percentage of patients presenting with at least on episode of bleeding related
to endoscopic treatment during the follow-up was 16.8 % in the IRA group and 15.2 %
in the IAA group.
Table 4
Endoscopic follow-up and induced morbidity.
|
IRA
|
IAA
|
P value
|
|
n = 197
|
n = 92
|
|
Endoscopic follow-up, n (%)
|
|
|
|
|
Yes
|
179 (90.9)
|
84 (91.3)
|
|
|
No
|
18 (9.1)
|
8 (8.7)
|
0.90
|
|
Number of lower endoscopy (mean (SD))
|
4.4 (3.5)
|
4.4 (3.5)
|
0.91
|
|
Total number of adenomas per patient
|
95.6±140.3
|
84.8±139.9
|
0.56
|
|
Total number of treated adenomas per patient
|
74±103.8
|
55.1±97.7
|
0.15
|
|
Mean number of adenomas per endoscopy
|
23.7±32.2
|
19.2±23.9
|
0.20
|
|
Mean number of treated adenomas per endoscopy
|
17.8±20.8
|
12.9±18.8
|
0.06
|
|
Endoscopic morbidity, n (%)
|
90 (45.7)
|
52 (56.5)
|
0.08
|
|
Anesthesia
|
8 (4.1)
|
4 (4.3)
|
0.90
|
|
Perforation
|
3 (1.5)
|
2 (2.2)
|
0.65
|
|
Pain
|
14 (7.1)
|
7 (7.6)
|
0.33
|
|
Acute bleeding
|
33 (16.8)
|
14 (15.2)
|
0.74
|
|
Treatment for endoscopic complication, n (%)
|
|
|
|
|
Transfusion
|
3 (1.5)
|
4 (4.3)
|
0.21
|
|
Surgery
|
1 (0.5)
|
0 (0)
|
1
|
|
Redo endoscopy
|
1 (0.5)
|
2 (2.2)
|
0.29
|
IRA, ileorectal anastomosis; IAA, ileoanal anastomosis.
Quality-of-life
At the end of follow-up, the median age in the IRA group was 52 years [35.1–68.9]
and 42.5 [30.4–54.6] in the IAA group. The mean (SD) number of stools per day (including
night-time) was 4.4 (2.5) in the IRA group vs. 5.5 (2.6) in the IAA group (P = 0.001). Fecal incontinence occurred in 14 patients (7.1 %) in the IRA group vs.
16 (17.4 %) in the IAA group (P = 0.03); 13 patients (6.6 %) suffered from nocturnal leakage in the IRA group vs.
20 (23.5 %) in the IAA group (P = 0.0001; [Table 3]).
Discussion
The main limit of the extended rectal preservation strategy is the difficulty to treat
patients curatively without increasing long-term oncological risk. Guidelines for
prophylactic surgery in FAP patients [1]
[2] were defined using thresholds for secondary rectal cancer risk reported in observational
population-based studies [2]
[3]
[10]
[11]
[12]
[13]. The latter did not include intensive interventional follow-up, and, although the
concept of systematic endoscopic treatment of rectal or pouch adenomas is reported,
thresholds are undefined [9]. Furthermore, it is suggested in guidelines that a higher number of lower endoscopies
will be required after rectal preservation, as compared to patients with IA anastomosis
and J pouch, and that the constraints of repeated intrusive investigation mean that
treatment success will be determined by patient willingness to submit to a close follow-up
[1]
[2]. Nevertheless, recent guidelines regarding endoscopic follow up defined surveillance
interval according to phenotype, and proposed to increase these intervals in patients
with a slower evolution [14]
[15]. Furthermore, each cancer occurred in patients who were not willing to accept close
endoscopic follow up. With regard to oncological outcomes, it is of note that in the
present study, the incidence of secondary rectal cancer after extended indications
for rectal preservation were much lower than that previously reported (i. e.13 % to
59 % at 25 years of follow-up [3]
[16]
[17]). Furthermore, the factors reported to be associated with rectal secondary cancer
occurrence in the literature are a longer length of conserved rectum (> 7 cm), age
> 44 years, and profuse preoperative polyposis (> 500 colonic adenomas and > 20 rectal
adenomas) [3]
[4]. In the present cohort, however, neither increased age nor the number of preoperative/postoperative
adenomas during follow-up was found to be associated with secondary rectal cancer
(length of conserved rectum was not systematically reported). These results are in
keeping with the therapeutic strategy proposed, whereby a large number of even small
adenomas was systematically treated during endoscopy, which also impacts the risk
of secondary proctectomy that was far lower than previously reported in the literature
(35 % when > 20 rectal adenomas are found at diagnosis [18], and 70 % 40 years after first surgery) [19].
Herein, only one case of secondary cancer in the ileal J pouch was found. The risk
of pouch cancer was formerly underrecognized, but is now described and accepted [1]
[2]. According to guidelines [1]
[2], this number of lower endoscopies was justified by the need of pouch follow-up due
to the risk of secondary pouch cancer development [9]
[20]
[21]
[22]
[23]
[24]. For instance, in a systematic review that included 18 papers, six studies reported
newly-developed adenocarcinomas of the ileal J pouch, and half were advanced tumors
(T4) [23]. Furthermore, Tonelli et al. reported a low incidence of pouch adenocarcinoma (2
of 66) in a prospective cohort of IAA patients, but noted faster pathophysiological
development compared to adenomas [25]. This underscores the importance of endoscopic follow-up for IAA patients. One of
the arguments against extensive rectal preservation has been the more frequent endoscopy
required, but it is of note that in our experience the mean number of indicated lower
endoscopies was the same in the IRA and IAA groups. The respective bleeding rate after
endoscopic treatment were 16.8 % in the IRA group and 15.2 % in the IAA group. Those
bleeding rate can appear higher than usual morbidity described especially since laser/APC
development. This relatively frequent event may be explained by the frequent use of
APC with relatively frequent immediate and delayed bleeding in this situation.
It is usually accepted that quality of life is higher after IRA than after IAA [2]. These findings are based on several studies and systematic reviews [15]
[26]
[27]
[28]
[29]
[30]
[31]
[32], which considered the mean number of stools per day, developed incontinence to gas
or feces, and social life impairment. The results of the present study are consistent
with previous findings: a significantly lower mean number of stools per day and less
frequent fecal incontinence in patients of the IRA group compared to those in the
IAA group. These results also favor rectal preservation when feasible. Combined with
the positive oncological outcomes induced by aggressive and intense endoscopic treatment
of remaining/newly-developed rectal adenomas, the evolution towards systematic rectal
preservation appears to be a safe and feasible alternative to improve quality of life
without compromising outcomes.
The strengths of the present study include its large sample size for this rare disease,
and the inclusion of patients from a national collaborative network with comparable
modalities of endoscopic follow-up and treatment. It does, however, have potential
limitations related to its (partly) retrospective nature. As with all such cohorts,
the present results would have been exposed to selection bias, yet the impact of this
is likely to have been limited as all patients with available data were analyzed.
In addition, owing to its retrospective nature, no power calculation was performed
but the study does represent a large dedicated series to evaluate the oncological
outcomes of this rare disease. Finally, although no definitive conclusions can be
made, this study provides interesting results on which to base future collaborative,
multicentric controlled trials.
Conclusions
The combination of aggressive endoscopic treatment and extended rectal preservation
appears to be a safe alternative to ileoanal anastomosis and J pouch, which may modify
surgical choices and quality of life in FAP patients. Further prospective studies
evaluating this combined therapeutic strategy are needed to validate these results
and to revise guidelines.
