Original article
13237
Clinical pattern and progression of ulcerative proctitis in the
Japanese population: a retrospective study of incidence and
risk factors influencing progression
H. Anzai, K. Hata, J. Kishikawa, H. Ishii, T. Nishikawa, T. Tanaka, J. Tanaka, T. Kiyomatsu,
K. Kawai, H. Nozawa, S. Kazama, H. Yamaguchi, S. Ishihara, E. Sunami, J. Kitayama and
T. Watanabe
Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
Received 20 July 2015; accepted 3 November 2015; Accepted Article online 12 December 2015
Abstract
Aim The rate of extension of proctitis in Western coun-
tries has been reported, but no data regarding long-
term follow-up have been described for the Japanese
population. Additionally, patients with long-standing or
extensive ulcerative colitis have an increased risk for
developing colorectal cancer. This study evaluated both
the rate of extension of the disease and the develop-
ment of neoplasia among patients with an initial diag-
nosis of ulcerative proctitis.
Method We retrospectively investigated the medical
charts of patients with proctitis from 1979 to 2014.
The primary focus of this research was the extension of
the inflammatory area. The secondary focus included
risk factors for disease extension and the development
of neoplasia.
Results Sixty-six patients satisfied the inclusion criteria.
Proximal extension of the disease occurred in 34
patients: 19 patients had left-sided colitis and 15 had
pancolitis. According to a multivariate analysis, disease
extension was significantly higher in patients with dis-
Introduction
Ulcerative colitis (UC) is a chronic inflammatory bowel
disease (IBD) of unknown aetiology [1]. The three main
types, proctitis, left-sided colitis and pancolitis, are classi-
fied according to the location and the extent of inflam-
mation. Although proctitis is an inflammation of the
rectal mucosa, long-term epidemiological studies have
revealed that UC always involves the rectum and thence
may extend proximally, ultimately to involve the entire
Correspondence to: Hiroyuki Anzai, MD, Department of Surgical Oncology,
The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
E-mail: anzaih-sur@h.u-tokyo.ac.jp
Colorectal Disease ª 2015 The Association of Coloproctology of Great Britain and Ireland. 18, O97–O102
doi:10.1111/codi.
ease onset before 25 years of age (P-value = 0.043).
The cumulative rates of disease extension at 10 and
20 years were 33.8% and 52.2%, respectively. Three
patients were diagnosed with dysplasia during follow-
up, all of whom experienced disease extension before
the development of dysplasia.
Conclusion The rate of extension of ulcerative colitis in
the Japanese population was comparable to that in Wes-
tern countries. A younger age of disease onset was asso-
ciated with disease extension. Extension of proctitis may
be associated with an increased risk of colorectal cancer.
Keywords Dysplasia, progression of ulcerative colitis,
younger age at symptom onset
What does this paper add to the literature?
This study demonstrates that a younger age at disease
onset was considered to be a risk factor for disease
extension. Patients with disease extension may be at risk
of dysplasia or colorectal cancer even if they previously
had inflammation confined to the rectum.
large bowel (pancolitis). The clinical course of UC varies
from long-term remission to acute illness leading to
urgent surgery. Previous studies from Western countries
have suggested that the disease extension beyond the rec-
tum occurs in 30–60% of patients [2–4], but there have
been no data regarding the clinical characteristics and the
disease extension of ulcerative proctitis in the Japanese
population over the long term. Although IBD has a
worldwide distribution, the prevalence of UC is reported
to be much lower in Asian than in Western countries
[5,6]. Since the number of newly diagnosed cases of UC
has been rising in Asia, it is important to re-evaluate the
clinical characteristics and risk factors for extensive UC.
O97
Progression of proctitis in Japan
Additionally, patients with long-standing or extensive
UC are at an increased risk of colorectal cancer (CRC)
[7] and surveillance colonoscopy is recommended to
detect early mucosal dysplasia. Conversely, patients with
proctitis are believed to be at low risk of CRC, and thus
many guidelines do not include proctitis as an indica-
tion for surveillance colonoscopy. Theoretically, how-
ever, patients with extending proctitis have an increased
risk of CRC and careful follow-up is considered essen-
tial. In this study, we therefore evaluated both the rate
of extension and the outcome of patients with an initial
diagnosis of ulcerative proctitis. These data provide
insight into the incidence and prevalence rates of UC in
Asia.
Method
Selection of patients
The study was carried out in the Department of Surgi-
cal Oncology at the University of Tokyo. Patients were
eligible if, during their first evaluation, UC had been
firmly diagnosed on the basis of clinical, endoscopic and
histological data. The medical charts and colonoscopic
records of patients with UC from 1979 to 2014 were
reviewed. Using the diagnostic criteria of the Montreal
Classification [8], patients were classified into three cat-
egories: (i) pancolitis (inflammation proximal to the
splenic flexure but distal to the caecum), (ii) left-sided
colitis (proximal extent of inflammation distal to the
splenic flexure), and (iii) proctitis (inflammation distal
to the rectosigmoid junction).
Ninety-six patients were diagnosed with proctitis.
Clinical information including gender, age at the onset
of symptoms, smoking habit, extent of the disease and
the presence of extra-intestinal manifestations (EIMs)
was recorded. The diagnosis of UC and the extent of
disease were systematically reassessed at each colono-
scopy to determine whether any disease extension had
occurred. The duration of the disease was defined as
the interval from the date of onset to the date of disease
extension or the last colonoscopy. The primary outcome
of the study was the disease extension rate of proctitis.
Patients who did not exhibit any disease extension were
therefore censored at the date of the last endoscopic
follow-up. The secondary focus of this study included
the risk factors for disease extension and the develop-
ment of neoplasia in patients with proctitis.
Statistical analysis
The cumulative rate of disease extension from proctitis
was calculated using the Kaplan–Meier method. Cox
O98 Colorectal Disease ª 2015 The Association of Coloproctology of Great Britain and Ireland. 18, O97–O102
H. Anzai et al.
regression analysis was used to assess risk factors for UC
disease extension using variables such as the age at
onset of symptoms, use of corticosteroids, presence of
EIMs and smoking habit. Variables were considered sta-
tistically significant at a P-value of < 0.05. The data
were analysed using the JMP PRO 10 software package
(SAS Institute, Inc., Cary, North Carolina, USA).
Results
Characteristics of ulcerative proctitis
During the study period, 96 patients with ulcerative
proctitis were seen at our institution. Thirty were
excluded because colonoscopy was performed only once
at our institution. This left 66 patients who met the
inclusion criteria for ulcerative proctitis and underwent
colonoscopy more than once. Table 1 shows their char-
acteristics. Thirty-six (54.5%) of the patients were men.
The mean age at onset of symptoms was 34.9 years, the
median follow-up period was 14 (1–41) years and the
median number of colonoscopy sessions was 7 (2–27).
There was no significant difference in age or gender
between patients with disease extension and those with-
out. The cumulative rates of disease extension for all
proctitis patients at 5, 10, 15 and 20 years were 17.9,
33.8, 41.9 and 52.2% (Fig. 1).
Risk factors for disease extension
Proximal extension of disease beyond the rectosigmoid
junction occurred in 34 of the 66 patients. In these 34
patients the disease progressed to left-sided colitis in 19
(55.9%) and beyond the splenic flexure (pancolitis) in
15 (45.1%) (Table 1). The median interval from the
onset of symptoms to disease extension was 11.5 (1.7–
29.1) years.
The clinical characteristics of patients with and with-
out disease extension are shown in Table 2. According
Table 1 Demographics and clinical features of patients with
ulcerative proctitis.
Characteristics Patients (n = 66)
Gender male/female 36 (54.5%)/30 (45.5%)
Onset of symptoms 34.9  13.6
(years, mean  SD)
Colonoscopic follow-up 7 (2–27)
(years, range)
Proximal extension of proctitis 34
Extension to left-sided colitis 19 (55.9%)
Extension to pancolitis 15 (45.1%)
H. Anzai et al. Progression of proctitis in Japan

100 Table 3 Risk factors related to proximal disease extension in

ulcerative proctitis according to multivariate analysis.
Cumulative disease

80
Risk factor Hazard ratio 95% CI P-value*
extension (%)

60
40
20
0
5 0 10 15
Years since diagnosis
Number of patients at risk:
66 50 37 27
Figure 1 Cumulative rate of disease extension: rates of proxi-
mal extension after initial diagnosis in 93 patients with ulcera-
tive proctitis.
to univariate analysis, the rate of disease extension was
significantly higher in the group taking corticosteroids
than in those not on this medication (P = 0.002).
Additionally, the cumulative rate of disease extension
was significantly affected by a younger age at onset of
the disease (P = 0.039) (Fig. 2). There was no signifi-
cant relationship between the risk for proximal exten-
sion and the presence of EIMs or smoking.
Data on the risk factors for disease extension anal-
ysed using the Cox regression model are shown in
Table 3. On multivariate analysis, the use of corticos-
teroids and younger age at onset were independent
risk factors for overall proximal extension (hazard
ratio = 3.70, 95% CI 1.45–8.71, P-value = 0.008;
hazard ratio = 2.33, 95% CI 1.03–5.14, P-
value = 0.043). No relationship was found between
the risk of proximal extension and the presence of
EIMs or smoking.
Risk of neoplasia in ulcerative proctitis
Of the 96 patients with proctitis, three were diagnosed
with dysplasia during follow-up. All three developed
Disease onset 2.33 1.03–5.14 0.043
before 25 years
EIMs 1.03 0.27–3.31 0.962
Smoking habit 1.48 0.63–3.92 0.387
Use of corticosteroids 3.70 1.45–8.71 0.008
20
EIMs, extra-intestinal manifestations.
*The P-value is based on the Cox regression model.
18
dysplasia more than 20 years after the onset of symp-
toms. Among these one was diagnosed with high-grade
dysplasia (HGD) and the other two had low-grade dys-
plasia (LGD). The patient with HGD underwent total
colectomy immediately after the diagnosis of HGD and
the final pathological report of surgical specimens
showed no invasive cancer. The two patients who had a
diagnosis of LGD were carefully monitored by colono-
scopy and there has been no evidence of HGD or ade-
nocarcinoma during follow-up.
Discussion
The clinical course of UC has been the subject of many
studies. These have shown that proctitis often extends
proximally and may even develop into pancolitis [3,4].
Although extension rates in patients with proctitis of
32–41% after 10 years have been reported in Western
countries, there have been few studies from Asian coun-
tries demonstrating this trend. Recently, several investi-
gations have shown that the prevalence and incidence of
UC are increasing in Asia, but the exact aetiology and
clinical course are not clear [9–11]. The demographics
of our patients were similar to those in reports from
Western countries in that there was no significant differ-
ence in the gender ratio. In addition the 10-year cumu-
lative rate of disease extension for all proctitis patients

Table 2 Risk factors for proximal exten-

Patients with disease Patients without disease
sion in the 66 patients with ulcerative
Risk factor extension (n = 34) extension (n = 32) P-value*
proctitis.

Disease onset 11 7 0.039

before 25 years
EIMs 5 1 0.401
Smoking habit 8 7 0.990
Use of corticosteroids 10 1 0.002

EIMs, extra-intestinal manifestations.

*The P-value is based on the log-rank test.

Colorectal Disease ª 2015 The Association of Coloproctology of Great Britain and Ireland. 18, O97–O102 O99
Progression of proctitis in Japan H. Anzai et al.

100
P = 0.039

80 onset before
25 years

Cumulative disease
extension (%)
60

40

onset after
20
25 years

0
0 5 10 15 20 Figure 2 Kaplan–Meier cumulative event
rates for the primary outcome in patients
Years since diagnosis
Number of patients at risk: with extension of ulcerative proctitis.
Disease extension was significantly higher
onset before 25 years 18 11 9 6 1
in patients with disease onset before
onset after 25 years 48 39 28 22 15 25 years of age.

in our study (33.8%) was comparable with previous
reports [2,12–15] (Table 4).
It is important to clarify which factors influence dis-
ease extension of proctitis from the clinical point of
view. We found that the use of corticosteroids and a
younger age at disease onset are significant independent
risk factors for disease extension of ulcerative proctitis.
Univariate analysis showed that patients who used corti-
costeroids had a significantly higher risk of disease
extension than patients who did not. Additionally, there
is a significantly higher risk of disease extension with a
younger age at onset. A multivariate analysis demon-
strated that the use of corticosteroids and disease onset
before 25 years of age were significant risk factors. Con-
versely, other factors, such as the presence of EIMs and
smoking, did not show any significant relationship with
disease extension.
Farmer et al. [2] found proctosigmoiditis to be asso-
ciated with disease extension and the early onset of the
disease, which is in line with our results. Furthermore,
our results are consistent with several previous reports
showing that younger age of onset of disease is associated
with a shorter time to relapse of UC [13,16,17]. In con-
trast, Ayres et al. [4] found no significant correlation
with any clinical or demographic features in patients with
proctosigmoiditis. Thomas et al. [18] reported that
patients with an aggressive disease course are more prone
to proximal extension at a later time, and that non-smo-
kers have a more aggressive disease course than smokers.
Although corticosteroids were used before diagnosis of
the extension of proctitis, extension had already occurred
during their use. Therefore, the extension of proctitis
may be influenced by overlapping interactions between
genetic and environmental factors.
Generally, patients with proctitis are believed to be
at low risk of developing CRC, and thus many guideli-
nes do not include proctitis as an indication for surveil-
lance colonoscopy. In this study, three patients were
histopathologically diagnosed to have dysplasia during
follow-up colonoscopy. Of these, one patient had pro-
gressed to pancolitis with HGD in the descending
colon. It is interesting that all the patients with dys-
plasia had experienced disease extension before its
development. Although the risk of CRC does not sig-
nificantly increase in patients with proctitis, there are a
small number of patients who require surgery for HGD.

Table 4 Previous reports of proximal

Cumulative ER
extension of ulcerative proctitis.
Reference Period of study ER (%) at 10 years (%) Nationality

Leijonmark [12] 1955–1984 – 24 Sweden

Farmer [2] 1960–1983 45.9 – US
Sinclair [13] 1967–1976 30 – Scotland
Meucci [14] 1989–1994 16.1 54% Italy
Kim [15] 2000–2007 27.6 – Korea
Present study 1979–2014 49.2 22.6% Japan

ER, extension rate of proctosigmoiditis.

O100 Colorectal Disease ª 2015 The Association of Coloproctology of Great Britain and Ireland. 18, O97–O102
H. Anzai et al.
Additionally, our sample size was small and only three
cases of dysplasia were detected during the surveillance;
this result could be explained by the fact that extensive
colonic involvement is a strong risk factor for UC-asso-
ciated CRC [19], Consequently, surveillance colono-
scopy has been recommended to detect early mucosal
dysplasia and to reduce mortality in patients with exten-
sive colonic involvement [20–22].
Surveillance colonoscopy programmes for patients
with long-standing UC have been established in many
countries [23–25]. Guidelines published by the Ameri-
can College of Gastroenterology (ACG), the British
Society of Gastroenterology (BSG), the European
Crohn’s and Colitis Organisation (ECCO) and also the
Japanese guidelines suggest that screening colonoscopy
should begin 6–10 years after the onset of symptoms.
All guidelines indicate that primary sclerosing cholangi-
tis (PSC) is a risk factor for CRC, and the ECCO and
BSG guidelines indicate disease duration, the severity of
inflammation and family history as influencing the risk
of cancer. Based on the results of this study, disease
extension should be monitored endoscopically in procti-
tis patients, especially those with a younger age at onset,
and if extension occurs the patient should be included
in a surveillance colonoscopy programme.
There are several limitations associated with this study.
First it was retrospective. Secondly it was conducted at
one site and the sample size was small. Thirdly no
histopathological analysis was performed. Therefore,
some of the patients who were classified as having procti-
tis may have had more extensive inflammation.
The rate of disease extension of UC in the Japanese
population was comparable with that in Western coun-
tries. A younger age at onset of the disease was a risk
factor for disease extension in our study, a finding that
has not been reported in previous studies. Those
patients with disease extension may be at risk for the
development of dysplasia or CRC, even if they previ-
ously only had limited colitis confined to the rectum.
Conflict of interest
The first author and co-authors declare that there are
no conflicts of interest.
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