With advances in the treatment of Crohn's disease (CD), the number of long-term cases is increasing, along with the incidence of CD-related cancers. Here, we discuss the clinical features, diagnosis, treatment, prognosis, and surveillance of CD-related cancers. There are regional differences in the common sites and histological types of CD-related cancers, with right-sided colon cancer accounting for 40% of cases in Europe and the US, and squamous cell carcinoma being common. In Japan, rectal and anal cancers account for 80% of cases, and mucinous carcinoma is common. The prognosis of CD-associated colon cancer and sporadic colon cancer is the same; however, the prognosis of CD-associated rectal cancer is clearly worse than that of sporadic rectal cancer. Early diagnosis is important to improve the prognosis of CD-associated rectal cancer, and it is necessary to establish a surveillance method for CD-associated cancer that combines colonoscopy, anesthetic proctoscopy, and imaging, as appropriate. The basic treatment for CD-related cancer is surgical resection; however, the criteria for selecting the surgical procedure are unclear, and there is no clear evidence for multidisciplinary perioperative treatment including chemotherapy and radiotherapy. Additionally, CD-related rectal and anal cancers have a higher local recurrence rate than that of sporadic rectal cancers; therefore, thorough local control is important. Furthermore, CD-related cancers have different epidemiologies in different regions; therefore, unique diagnostic and treatment strategies must be established for each region.

This letter discusses the incidence of anal cancer among Crohn's disease (CD)-related malignancies. Patients with CD have been demonstrated to be at a higher risk of developing small bowel and colorectal cancers than healthy individuals. Although CD-associated anal cancer is relatively rare, patients with CD accompanied by anal or perianal lesions are at increased risk of anal cancer. Additionally, compared to ulcerative colitis, which is also an inflammatory disease, CD-related anal cancer is often detected at an advanced stage owing to the complexity of CD and is associated with a poor prognosis with frequent local recurrences. Therefore, the detection of early-stage cancer is crucial for improving the prognosis. However, the surveillance methods recommended for CD-related malignancies in the United States and Europe are similar to those for ulcerative colitis. They are not appropriate for detecting CD-related malignancies in the recto-anal region. Therefore, there is an urgent need for surveillance programs aimed at the early detection of malignant anorectal lesions in patients with CD.

The radiological diagnosis of Crohn's disease (CD)-related anorectal cancer is difficult; it is often found in advanced stages and has a poor prognosis because of the difficulty of curative surgery. However, there are no studies on predicting the diagnosis of CD-related cancer. The present study aimed to develop a predictive model to diagnose CD cancerous lesions more accurately in a way that can be interpreted by clinicians. Patients with CD who developed anorectal CD lesions at Hyogo Medical University (Nishinomiya, Japan) between March 2009 and June 2022 were included in the present study. T2-weighted and T1-weighted magnetic resonance (MR) images were utilized for our analysis. Images of anorectal lesions were segmented using open-source 3D Slicer software, and radiomic features were extracted using PyRadiomics. Six machine learning models were investigated and compared: i) Support vector machine; ii) naive Bayes; iii) random forest; iv) light gradient boosting machine; v) extremely randomized trees; vi) and regularized greedy forest (RGF). SHapley Additive exPlanations (SHAP) values were calculated to assess the extent to which each radiomic feature contributed to the model's predictions compared to baseline, represented as the average of the model's predictions for all test data. The T2-weighted images of 28 patients with anorectal cancer and 40 non-cancer patients were analyzed and the contrast-enhanced T1-weighted images of 22 cancer and 40 non-cancer patients. The model with the highest area under the curve (AUC) was the RGF-based model constructed using T2-weighted image features, achieving an AUC of 0.944 (accuracy, 0.862; recall, 0.830). The SHAP-based model explanation suggested a strong association between the diagnosis of CD-related anorectal cancer and features such as complex lesion texture; greater pixel separation within the same coronal cross-section; larger, randomly distributed clumps of pixels with the same signal intensity; and a more spherical lesion shape on T2-weighted images. The MRI radiomics-based RGF model demonstrated outstanding performance in predicting CD-related anorectal cancer. These results may affect the diagnosis and surveillance strategies of CD-related colorectal cancer.

The perianal disease affects up to one-third of individuals with Crohn's disease (CD), causing disabling symptoms and significant impairment in quality of life, particularly for those with perianal fistulising CD (PFCD). The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing. Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents, endoscopic procedures and surgical techniques that show promising results. Among these, mesenchymal stem cells injection is a particularly hopeful therapy. In addition to the burden of fistulas, individuals with perianal CD may face an increased risk of developing anal cancer. This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes. Currently, there is no established formal anal screening programme. In this review, we provide an overview of the current state of the art in managing PFCD, including novel medical, endoscopic and surgical approaches. The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD, intending to propose a risk-based surveillance algorithm. The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes.

Crohn's disease (CD)-associated intestinal cancers are characterized by their high incidence, particularly at the anorectal site in the Japanese population. Accumulating evidence revealed that younger-onset sporadic colorectal cancer may exhibit unique biological features. To the best of our knowledge, few previous articles reported clinicopathological features in patients with CD-associated anorectal cancer (CDAAC). Therefore, we aimed to clarify the relationship between the younger onset of cancer and clinicopathological characteristics and prognosis, and the efficacy of cancer surveillance in patients with CDAAC.

CD patients who had been diagnosed with intestinal cancers from 1983 to 2020 were collected from 39 Japanese institutions in this study. Of 316 patients with CD-associated intestinal cancers, we analyzed 211 patients with CDAAC. We divided the patients into two groups according to the median age at cancer diagnosis (45 years old).

Younger-onset CDAAC (YO-CDAAC) patients were significantly more likely to have a poor outcome than those with older-onset CDAAC (OO-CDAAC) in terms of both disease-free survival (DFS) (p = 0.0014) and overall survival (OS) (p = 0.023). Multivariate analysis showed that age under 45 years old at diagnosis of cancer was one of the independent factors for poor DFS and OS (hazard ratios: 2.15, 95% confidence interval: 1.09-4.26, p = 0.028, hazard ratios: 1.95, 95% confidence interval: 1.05-3.60, p = 0.033, respectively). Patients detected via surveillance showed significantly better DFS and OS rates than symptomatic patients in YO-CDAAC (p = 0.012 and 0.0031, respectively).

YO-CDAAC may have a poorer prognosis compared with OO-CDAAC. Surveillance could be important to improve cancer prognosis, especially in young CD patients with anorectal disease.

Anorectal fistula cancer is often diagnosed in an advanced state, and radical resection is difficult when invasion of the pelvic wall is observed. In addition, there is currently no clear evidence for perioperative treatment of locally advanced cases. We report a case of anorectal fistula cancer with widespread infiltration diagnosed during the course of Crohn's disease, which was curatively resected after preoperative chemoradiotherapy.

A 49-year-old man who had been diagnosed with Crohn's disease (ileocolonic type) at the age of 25 and was found to have an anorectal fistula and perianal abscess at the age of 44 was referred to our department with complaints of abdominal pain and diarrhea. Computed tomography (CT) showed anal stenosis due to a pelvic mass. Pathological analysis of a biopsy taken under general anesthesia indicated mucinous carcinoma. Magnetic resonance imaging (MRI) revealed infiltration into the prostate, seminal vesicles, levator ani muscle, and left internal obturator muscle, and the patient was diagnosed with cT4N0M0 cStage IIIB anorectal fistula cancer (UICC TNM classification 8th edition). After performing a laparoscopic sigmoid colostomy, chemoradiation therapy (capecitabine + oxaliplatin, 50.4 Gy/28fr) was initiated. The patient then underwent laparoscopic total pelvic exenteration, colonic conduit diversion, extensive perineal resection, and reconstruction using bilateral gluteus maximus flaps and a right rectus abdominis musculocutaneous flap. The pathological diagnosis was mucinous adenocarcinoma, pT4, and all margins were negative. No recurrence was evident 6 months after the operation without adjuvant chemotherapy.

We described a case of curative resection after preoperative chemoradiotherapy for anorectal fistula cancer with extensive invasion that was diagnosed during the course of Crohn's disease.An accumulation of cases is needed to determine the usefulness of preoperative chemoradiation therapy for local control of anorectal fistula cancer associated with Crohn's disease.

Colorectal cancer (CRC) is one of the major life-threatening complications in patients with Crohn's disease (CD). Previous studies of CD-associated CRC (CD-CRC) have involved only small numbers of patients, and no large series have been reported from Asia. The aim of this study was to clarify the prognosis and clinicopathological features of CD-CRC compared with sporadic CRC.

A large nationwide database was used to identify patients with CD-CRC (n = 233) and sporadic CRC (n = 129,783) over a 40-year period, from 1980 to 2020. Five-year overall survival (OS), recurrence-free survival (RFS), and clinicopathological characteristics were investigated. The prognosis of CD-CRC was further evaluated in groups divided by colon cancer and anorectal cancer (RC). Multivariable Cox regression analysis was used to adjust for confounding by unbalanced covariables.

Compared with sporadic cases, patients with CD-CRC were younger; more often had RC, multiple lesions, and mucinous adenocarcinoma; and had lower R0 resection rates. Five-year OS was worse for CD-CRC than for sporadic CRC (53.99% vs 71.17%, P < 0.001). Multivariable Cox regression analysis revealed that CD was associated with significantly poorer survival (hazard ratio 2.36, 95% confidence interval: 1.54-3.62, P < 0.0001). Evaluation by tumor location showed significantly worse 5-year OS and RFS of CD-RC compared with sporadic RC. Recurrence was identified in 39.57% of CD-RC cases and was mostly local.

Poor prognosis of CD-CRC is attributable primarily to RC and high local recurrence. Local control is indispensable to improving prognosis.

As the number of patients with inflammatory bowel disease (IBD) increases, the incidence of IBD-related colorectal cancer (CRC) is also on the rise. Crohn's disease (CD)-related CRC has been reported to have a poorer prognosis than sporadic CRC, and the early detection of CD-related CRC is difficult. Japanese patients with CD are reported to have a higher frequency of anorectal cancer than the Western population; however, methods for early diagnosis have not yet been established because of perianal pain during the examination.

We report a case of CD-related anal fistula cancer that was detected early by surveillance examination under anesthesia (EUA). The patient was a 37-year-old man, diagnosed with CD at the age of 15 years and started medical treatment. However, due to poor disease control, the intestinal tract remained highly inflamed and the patient continued to have over 10 bowel movements per day. He was referred to our hospital for surgical treatment after a colonoscopy (CS), which revealed multiple active ulcers and stenoses. Since three perianal seton drainage tubes had been placed around his anus since the age of 33 years, we decided to perform an EUA to rule out cancer coexistence in the anorectal region. After a random biopsy of the rectum by CS under general anesthesia, we resected and curetted multiple perianal fistulas as much as possible and reinserted the seton drainage tubes. Pathological examination of the fistula tract revealed adenocarcinoma in one tract, indicating the coexistence of anal fistula cancer. Based on the diagnosis of multiple intestinal stenoses and anal fistula cancer due to CD, we performed hand-assisted laparoscopic total colectomy, rectal amputation, extensive perineal resection, and reconstruction using a left rectus abdominis flap.

In a long-term CD patient with anorectal lesions, we performed an EUA to diagnose the coexistence of anal fistula cancer at an early stage, and surgical resection was achieved. EUA is effective for the early detection and treatment of CD-related CRC and may contribute to an improved prognosis.

The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set.

The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC.

In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P < 0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [-] 24.5% vs [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% confidence interval, 0.034-0.356], P < 0.001).

Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.

A series of workshops entitled "Advanced endoscopy in the management of inflammatory digestive disease" was held at the 97^th to 100^th biannual meeting of the Japan Gastroenterological Endoscopy Society. During these core sessions, research findings concerning various endoscopic practices in the field of inflammatory bowel disease (IBD) were presented, and meaningful discussions were shared on the evolving role and future challenges of endoscopy in IBD. This article reviews these core sessions and discusses current topics on the role of endoscopy, focusing on the diagnosis, disease monitoring, mucosal healing assessments, cancer surveillance, and therapeutic interventions in IBD.

Although surveillance colonoscopy is recommended by several guidelines for Crohn's disease (CD), the evidence is insufficient to support the validity of this recommendation. Moreover, the efficacy of surveillance colonoscopy for anorectal cancer remains unclear. Therefore, we performed a systematic review of cancer in patients with CD before considering the proper surveillance methods.

We conducted a systematic review and meta-analysis examining the incidence of intestinal cancer and a literature review to clarify the characteristic features of cancer in CD. We performed the systematic literature review of studies published up to May 2019.

Overall, 7344 patients were included in eight studies. The standardized incidence ratios (95% confidence intervals) of colorectal cancer (CRC) and small bowel cancer (SBC) were 2.08 (1.43-3.02) and 22.01 (9.10-53.25), respectively. The prevalence of CRC and SBC was 57/7344 (0.77%) and 17/7344 (0.23%), respectively, during a median follow-up of 12.55 years. Additionally, 54 studies reporting 208 anorectal cancer cases were identified. In patients with anorectal cancer, the prognosis for survival was 2.1 ± 2.3 years, and advanced cancer greater than stage T3 occurred in 46/74 patients (62.1%). Many more reports of anorectal cancer were published in Asia than in Western countries.

Although we were unable to state a recommendation for surveillance for SBC, we should perform cancer surveillance for CRC in patients with CD. However, the characteristics of cancer may differ according to geography or race. We must establish proper and effective surveillance methods that are independently suitable to detect these differences.