Colitis-associated colorectal neoplasia in ulcerative colitis with primary sclerosing cholangitis: a nationwide study

Article information

Intest Res. 2026;.ir.2025.00133

Publication date (electronic) : 2026 February 12

doi : https://doi.org/10.5217/ir.2025.00133

Koichi Komatsu^,1, Takahide Shinagawa¹, Motoi Uchino², Hiroki Ikeuchi², Koji Okabayashi³, Shiro Oka⁴, Kitaro Futami⁵, Michio Itabashi⁶, Kazuhiro Watanabe⁷, Masatsune Shibutani⁸, Yoshiki Okita⁹, Toshifumi Wakai¹⁰, Yusuke Mizuuchi¹¹, Kinya Okamoto¹², Kazutaka Yamada¹³, Yu Sato¹⁴, Takayuki Ogino¹⁵, Hideaki Kimura¹⁶, Kenichi Takahashi¹⁷, Koya Hida¹⁸, Yusuke Kinugasa¹⁹, Fumio Ishida²⁰, Junji Okuda²¹, Koji Daito²², Takayuki Yamamoto²³, Seiichiro Yamamoto²⁴, Fumikazu Koyama²⁵, Tsunekazu Hanai²⁶, Koji Komori²⁷, Dai Shida²⁸, Junya Arakaki²⁹, Yoshito Akagi³⁰, Shigeki Yamaguchi³¹, Hideki Ueno³², Keiji Matsuda³³, Atsuo Maemoto³⁴, Riichiro Nezu³⁵, Shin Sasaki³⁶, Eiji Sunami³⁷, Tatsuki Noguchi¹, Kenichi Sugihara³⁸, Yoichi Ajioka³⁹, Soichiro Ishihara¹, the Study Group for Inflammatory Bowel Disease Associated Intestinal Cancers by the Japanese Society for Cancer of the Colon and Rectum

¹Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan

²Department of Inflammatory Bowel Disease Surgery, Hyogo Medical University, Nishinomiya, Japan

³Department of Surgery, Keio University School of Medicine, Tokyo, Japan

⁴Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

⁵Department of Surgery, Fukuoka University Chikushi Hospital, Chikushino, Japan

⁶Saitama Saiseikai Kazo Hospital, Kazo, Japan

⁷Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan

⁸Department of Gastroenterological Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan

⁹Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Japan

¹⁰Division of Digestive and General Surgery, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan

¹¹Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

¹²Department of Coloproctology, Tokyo Yamate Medical Center, Tokyo, Japan

¹³Department of Surgery, Coloproctology Center Takano Hospital, Kumamoto, Japan

¹⁴Department of Surgery, Toho University Sakura Medical Center, Sakura, Japan

¹⁵Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan

¹⁶Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan

¹⁷Department of Colorectal Surgery, Tohoku Rosai Hospital, Sendai, Japan

¹⁸Department of Surgery, Kyoto University Hospital, Kyoto, Japan

¹⁹Department of Gastrointestinal Surgery, Graduate School of Medicine, Institute of Science Tokyo, Tokyo, Japan

²⁰Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan

²¹Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, Takatsuki, Japan

²²Department of Surgery, Faculty of Medicine, Kindai University, Sayama, Japan

²³Inflammatory Bowel Disease Center, Yokkaichi Hazu Medical Center, Yokkaichi, Japan

²⁴Department of Gastroenterological Surgery, Tokai University School of Medicine, Isehara, Japan

²⁵Department of Surgery, Nara Medical University, Nara, Japan

²⁶Department of Surgery, Fujita Health University, School of Medicine, Kariya, Japan

²⁷Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Kariya, Japan

²⁸Department of Surgery, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

²⁹Center for Gastroenterology, Department of Surgery, Urasoe General Hospital, Urasoe, Japan

³⁰Department of Surgery, Kurume University Hospital, Kurume, Japan

³¹Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka, Japan

³²Department of Surgery, National Defense Medical College, Tokorozawa, Japan

³³Department of Surgery, The Fraternity Memorial Hospital, Tokyo, Japan

³⁴Inflammatory Bowel Disease Center, Sapporo-Higashi Tokushukai Hospital, Sapporo, Japan

³⁵Department of Surgery, Nishinomiya Municipal Central Hospital, Nishinomiya, Japan

³⁶Department of Coloproctological Surgery, Japanese Red Cross Medical Center, Tokyo, Japan

³⁷Department of Surgery, Kyorin University, Tokyo, Japan

³⁸Institute of Science Tokyo, Tokyo, Japan

³⁹Department of Pathology, Niigata University, Niigata, Japan

Correspondence to Koichi Komatsu, Department of Surgical Oncology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail: komatsuk-sur@h.u-tokyo.ac.jp

Received 2025 July 14; Revised 2025 September 4; Accepted 2025 September 21.

Abstract

INTRODUCTION

Primary sclerosing cholangitis (PSC) is associated with inflammatory bowel disease, especially ulcerative colitis (UC) and Crohn’s disease. The prevalence of PSC among patients with inflammatory bowel disease varies by region, being higher in Europe and the United States but lower in East Asia, including Japan [1]. A study reported a lower UC complication rate in the Japanese PSC cohort than in western countries [2]. Although PSC is a significant risk factor for UC-associated colorectal neoplasia (UCAN) [3], there is limited research on patients with UCAN with UC and PSC in Japanese cohorts due to the rarity of such patients. Therefore, this study aims to determine the clinicopathological features and prognosis of UCAN cases with PSC in the largest UCAN cohort in Japan [4].

METHODS

1. Data Collection and Definition

This retrospective cohort study, conducted by the Japanese Society for Cancer of the Colon and Rectum (JSCCR), included 1,222 patients with UC who underwent treatment for UCAN from January 1983 to December 2020 across 43 institutions in Japan. The following patient data were collected from medical records at each institution: age, sex, concomitant PSC diagnosis, UC disease duration, extent of UC, Mayo endoscopic subscore at the most recent endoscopy before UCAN treatment, date of UCAN diagnosis, medications for UC within 1 year before UCAN treatment, diagnostic procedure for UCAN, location of UCAN, pathological findings of UCAN, treatment procedures, prognosis, and other information related to UCAN risk. The follow-up period was determined by the date of the death by any cause or the date of the last visit at each hospital. This study included only patients with UC-associated colorectal cancer and high-grade dysplasia (HGD). Patients with only UC-associated low-grade dysplasia or those with missing data on concomitant PSC, UC disease duration, UCAN histological type or location, pathological stage of UC-associated colorectal cancer, or prognosis were excluded (Fig. 1).

Fig. 1.

Study flowchart. PSC, primary sclerosing cholangitis; UC, ulcerative colitis; UCAN, UC-associated colorectal neoplasia.

The diagnoses of PSC, UC, and UCAN were based on clinical and pathological findings at each institution. The location of UCAN was categorized as the right-sided colon (cecum and ascending and transverse colon), left-sided colon (descending and sigmoid colon), rectum, or other (appendix and anal canal). HGD was defined as neoplastic epithelium that did not invade beyond the basal lamina. Poorly differentiated adenocarcinoma, mucinous adenocarcinoma, and signet ring cell carcinoma were categorized as cancer irrespective of the depth of invasion.

RESULTS

1. Patient Characteristics

Overall, 808 eligible patients with UCAN were divided into PSC-UCAN (n=26) and UCAN-alone (n=782) groups (Fig. 1). Both groups showed a similar age at UC diagnosis (PSC-UCAN: 34.8 years, UCAN-alone: 36.8 years). However, the PSC-UCAN group was younger at UCAN diagnosis (47.8 years) and had a shorter duration of UC (12.8 years) than the UCAN-alone group (53.3 and 16.9 years, respectively) (Table 1). A greater proportion of patients had a disease duration of less than 8 years in the PSC-UCAN group compared with the UCAN-alone group (26.9% vs. 17.7%); however, this difference did not reach statistical significance (P=0.23). Total colitis was the predominant disease extent in both groups (PSC-UCAN: 80.8%, UCANalone: 77.2%), followed by left-sided colitis (PSC-UCAN: 11.5%, UCAN-alone: 17.7%) (Table 1). The most recent endoscopy conducted before UCAN treatment revealed no significant difference in Mayo endoscopic subscore between the 2 groups. Regarding medications used within one year prior to UCAN treatment, there were no significant differences between groups for 5-aminosalicylic acid, prednisolone, immunomodulators, or biologics. Most UCAN cases in both groups were diagnosed via surveillance colonoscopy (PSC-UCAN: 65.4%, UCAN-alone: 67.5%), with approximately one-fourth diagnosed based on symptoms (PSC-UCAN: 23.1%, UCANalone: 26.0%) (Table 1).

Table 1.

Clinicopathological Features of Each Group

3. Treatment and Prognosis

Treatment procedures showed no significant differences between the PSC-UCAN and UCAN-alone groups. Total proctocolectomy was the major procedure in both groups (PSC-UCAN: 73.1%, UCAN-alone: 77.9%) (Table 1), followed by partial colectomy (PSC-UCAN: 15.4%, UCAN-alone: 8.5%) and subtotal colectomy (PSC-UCAN: 7.7%, UCAN-alone: 6.7%).

The 10-year OS (PSC-UCAN: 64.6%, UCAN-alone: 79.3%) and 10-year CSS (PSC-UCAN: 80.8%, UCAN-alone: 83.9%) after treatment were similar between the 2 groups (Fig. 2). In patients with HGD, the 10-year OS rates were 100.0% versus 95.8%, and the 10-year CSS rates were 100.0% versus 99.3% in the PSC-UCAN versus UCAN-alone groups (Fig. 3). In the subgroup analysis restricted to the cases with pStage 1-3, OS was significantly worse in the PSC-UCAN group than in the UCAN-alone group (64.6% vs. 81.0%, P=0.041), whereas CSS did not differ significantly between the 2 groups (80.8% vs. 85.9%, P=0.42) (Supplemental Fig. 1). There were one and two deaths due to biliary tract cancer and liver failure respectively in the PSC-UCAN group.

Fig. 2.

Kaplan-Meier analysis in patients with cancer for (A) 10-year overall survival and (B) 10-year cancer-specific survival. PSC, primary sclerosing cholangitis; UC, ulcerative colitis; UCAN, UC-associated colorectal neoplasia.

Fig. 3.

Kaplan-Meier analysis in patients with high-grade dysplasia for (A) 10-year overall survival and (B) 10-year cancer-specific survival. PSC, primary sclerosing cholangitis; UC, ulcerative colitis; UCAN, UC-associated colorectal neoplasia.

DISCUSSION

This study highlighted the characteristics of patients with PSC-complicated UCAN in Japan. Previous reports of UCAN in patients with PSC from Japan were limited to a few case reports [5-7] and 1 case series study [8]. Although several studies from other East Asian countries have been reported, including 2 reports from Korea [9,10] and 1 report from China [11], none of them described the details of UCAN. The present study included the largest cohort of UCAN cases in patients with UC and PSC in Asia.

In accordance with a previous report from a Dutch cohort, the present study demonstrated that the duration of UC at the time of UCAN diagnosis was significantly shorter in the PSC-UCAN group compared with the UCAN-alone group [12]. The European Crohn’s and Colitis Organisation (ECCO) guidelines recommend initiation of surveillance colonoscopy 8 years after diagnosis in patients with UC without PSC [13]. The present cohort included exclusively PSC-UC cases who had already developed UCAN; consequently, precluding accurate estimation of the absolute cumulative risk of UCAN development in patients with PSC-UC. UC is sometimes diagnosed prior to PSC [14], which suggests that patients with PSC-UC already have a substantial duration of UC by the time PSC is diagnosed [15]. The subclinical course of UC in patients with PSC may provoke apprehension regarding a potential delay in the diagnosis of UC [16]. Moreover, PSC-UCAN cases were characterized by a lower proportion of HGD and a higher proportion of early-stage carcinoma, suggesting that the detection of HGD prior to progression to invasive carcinoma may be inherently difficult in PSC-UC. Taken together, the most appropriate and evidence-based strategy in clinical practice remains adherence to the ECCO guideline recommendation of commencing surveillance immediately following PSC diagnosis in patients with UC. The absence of a difference between the groups in the proportion of cases diagnosed by surveillance may be plausibly explained by the fact that the majority of patients in the UC-alone group (>80%) had a disease duration exceeding 8 years, suggesting that patients, irrespective of concomitant PSC status, may have participated in surveillance programs to a similar extent.

The endoscopic activity of UC was similar between the PSCUCAN and UCAN-alone groups. Moreover, the diagnosis of UCAN was triggered by symptoms in approximately 25% of patients in the PSC-UCAN group. A previous study reported more subclinical endoscopic activity in UC patients with PSC [16]. Although patients with UC and PSC have a milder disease course than patients with only UC in Japan [17], patients with PSC who develop UCAN may experience a greater burden of inflammation in the colon and rectum.

UCAN occurred more frequently in the right-sided colon in the PSC-UCAN group than in the UCAN-alone group. Interestingly, in our Japanese cohort, UCAN occurred in the left-sided colon and rectum with frequencies comparable to those in the right-sided colon in the PSC-UCAN group. Previous reports of UCAN in patients with PSC from Europe [18] and the United States [19,20] have shown that the right-sided colon is the dominant location for UCAN occurrence. This difference between the current study and previous studies may be due to a limited number of cases or geographical variations. Hence, further accumulation of cases is warranted.

No significant differences in OS or CSS were observed between the PSC-UCAN and UCAN-alone groups. Previous reports demonstrated that patients with PSC-UC have a poorer prognosis than those with UC alone [21]. Similar result was also described in a cohort of Japanese patients with PSC [22]. This unfavorable prognosis is likely attributable not only to PSC being a high-risk factor for UCAN but also to its strong association with cholangiocarcinoma and the occurrence of liver failure related to PSC [23]. Liver transplantation is an effective treatment for PSC-related liver failure, and previous reports have suggested that transplantation may reduce the risk of UCAN development in PSC-UC patients [24]; however, information regarding transplantation was not available in our cohort. Liu et al. [20] found no differences in OS between colitis-associated colorectal cancer patients with and without PSC. However, among pStage I-III cases, OS tended to be worse in the PSC group, largely due to deaths related to PSC itself or to sepsis [20]. In accordance with the previous report, our cohort also demonstrated similar results. The discrepancy in OS and CSS among pStage I-III cases was likely explained by deaths from cholangiocarcinoma and liver failure that occurred in the PSC-UCAN group. Moreover, in addition to the recommended initiation of surveillance colonoscopy, ECCO guidelines also suggest the recommended intervals for its implementation [13]. In Japan, however, particularly at academic centers, surveillance colonoscopy is often performed annually or at least every 2 years [25]. In our study as well, among patients with available interval data, approximately 80% had undergone colonoscopy within the 2 years preceding their UCAN diagnosis in both of the 2 groups (data not shown). Such intensive surveillance may have contributed to the reduced proportion of advanced-stage cancer in both groups and might help account for the absence of a significant difference in CSS.

This study highlights the characteristics of UCAN in patients with PSC in Japan. The duration of UC was shorter, and UCAN was diagnosed at a younger age in the PSC-UCAN group than in the UCAN-alone group. Regarding the location of UCAN, the PSC-UCAN group had more than twice the proportion of the right-sided colon than the UCAN-alone group. Early-stage cancer was more frequently observed in the PSC-UCAN group, despite the shorter duration of UC. Our results suggested that it is beneficial for patients with PSC-UC to undergo earlier surveillance colonoscopy than for patients with only UC even in Japan. The 10-year OS and CSS were comparable between the 2 groups.

This study had some limitations. First, detailed information regarding PSC was missing because data collection at registration was focused on UCAN. Second, the diagnosis of PSC, UC, and UCAN was not standardized. Finally, the surveillance strategy for UCAN detection varied depending on the institution. Despite these limitations, this study provides valuable information on the characteristics of UCAN complicated with PSC from the largest cohort of UCAN cases in Asia.

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