Introduction

Advanced Therapy (AT) should be carefully considered for patients who have both inflammatory bowel disease and a malignancy. The aim of administering AT is to avoid hospitalization and surgery in patients with otherwise intractable inflammatory bowel disease; however, the AT may result in exacerbation or recurrence of the malignancy. After careful consideration, we have been treating patients with both inflammatory bowel disease and a malignancy with AT. We here report the results of AT in patients with ulcerative colitis (UC) and malignant disease.

Aims & Methods

From January 2012 to December 2023, we treated five patients with UC and malignant disease (excluding colitic cancer) at the Ikoma Gastroenterology and Proctology Clinic. Age, sex, disease duration, disease extent, severity, clinical course, intractable or not, use or not of azathioprine, type of AT, duration of AT, curability of malignant disease, type and duration of AT after onset of malignant disease, whether the onset of malignant disease was diagnosed during AT, duration of follow-up after onset of malignant disease, outcome of UC after onset of malignant disease, and outcome of malignant disease.

Results

AT	One drug: UST, ADA (2 patients) Two drugs: GLM→TOF (1 patient)
	Three drugs: IFX→UST→TOF→UST (1 patient)
	Five drugs: ADA→GLM→VED→TOF→UST (1 patient)
Duration AT: range (median) (months)	24–83 (41)
Curability of malignancy: yes/no	5/0
Type and duration of AT after onset of malignant disease (months）	UST　(30), VED　3→TOF　24→UST　36（total 63） UST 30, GLM　1→TOF　59（total 60）
Malignancy first diagnosed during AT: yes/no	Yes: TOF, GLM, ADA (3 patients)/no (2 patients)
Duration of follow-up after onset of malignant disease: range (median)（months）	30–378 (52)
Outcome of UC after onset of malignant disease: remission/relapse	5/0
Outcome of malignant disease: exacerbation or recurrence/no exacerbation or recurrence	0/5

(AT:Advanced Therapy、UST:Ustekinumab、ADA:Adalimumab、GLM:Golimumab、TOF:Tofacitinib、IFX:Infliximab、VED:Vedolizumab)

The results are shown in the Table. Age: range (median) (years) : 45-69(56). Sex:Male/Female: 0/5. Disease duration: range (median）（months）: 114–289 (245) . Extent of UC : total colon/left colon: 1/4. Severity of UC : Severity :severe/moderate : 0/5. Clinical course: chronically persistent/relapsing–remitting: 0/5. Use of azathioprine: yes/no: 0/5.Three patients developed malignant disease during AT (cervical cancer, breast cancer, squamous cell carcinoma of the scalp), the remaining two (breast cancer, thyroid cancer) commencing AT only after the cancer’s onset. Four of the patients continued AT, the exception (a patient with squamous cell carcinoma) received adalimumab. After the onset of malignant disease, UC remained in remission in all patients and no new malignant disease developed.

Conclusion

In patients with UC who develop a malignancy before or during AT and achieve cure of that malignancy, continuing AT can prevent progression of the UC without exacerbation or recurrence of the malignant disease.

Introduction

In recent years, eosinophilic gastrointestinal disorders (EGIDs) have attracted attention due to an increase in their incidence. Although many reports have focused on eosinophilic esophagitis (EoE), there are relatively few reports of eosinophilic enteritis (EoN), which causes eosinophil infiltration of the small intestine. In addition, although the diagnostic criteria for EGID also specify that the number of eosinophils infiltrating the gastrointestinal tract other than the esophagus should be 20 or more, the small intestine has not been clearly defined. Furthermore, not even normal eosinophils have been clearly defined for the small intestine, it is necessary to establish the clinical features of EoN. using double-balloon Enteroscopy (DBE) to differentiate it from other small intestinal diseases such as IBD and IBS, which cause similar symptoms of EoN. Accordingly, we examined both the extent of eosinophilic infiltration in the small intestine using DBE and the associated clinical background in cases which EoN was suspected.

Aims & Methods

Patients who underwent DBE for examination of the small intestine at our hospital from January 2021 to December 2024 and had a biopsy from the small intestine were included. Biopsies were taken from 1 or more of the duodenum, upper jejunum, lower jejunum, upper ileum, lower ileum, or terminal ileum, and the number of eosinophils per 1HPF was counted. By using a × 40 objective and × 10 oculars the number of eosinophils per high power field (EOS / HPF) in up to two HPFs was counted in each biopsy specimens. Five patients who visited our hospital with abdominal symptoms, were suspected of EoN, and underwent DBE‑guided small‑intestinal biopsy revealing more than 50 eosinophils per high‑power field, after other diseases had been ruled out, were classified into the EoN group. (3 males and 2 females, mean age 58.3 years). The non-EoN group (7 males and 6 females, mean age 48.4 years) consisted of 14 patients who underwent small intestinal biopsy by DBE for other reasons during the study period, and the number of eosinophil infiltration in the small intestinal mucosa and clinical background were compared.

Results

All five patients in the EoN group presented to our hospital with a chief complaint of abdominal pain and diarrhea and four cases showed edema of the small intestine on CT. All five had an elevated peripheral blood eosinophil count (median 13%). In contrast, the non-EoN group showed no increase with a median of 2.4%. In total, 80 small intestine biopsy specimens were obtained from 18 patients using DBE, 25 specimens in the EoN group and 55 specimens in the non-EoN group. The median eosinophil count in the EoN group was 77 (15-213), which was elevated and significantly higher than the 23 (3-111) in the non-EoN group. (P < 0.01)(Table 1)(Figure 1)
Table 1. Characteristics of patients and biopsy specimens

	EoN Group (n=5)	Non-EoN Group (n=13)
Patients Male (%) Female (%)	5 3 (50%) 2 (50%)	13 7 (53.8%) 6 (46.2%)
Median age (range, years)	58 (41-75)	46 (13-83)
Median peripheral blood eosinophil (range, %)	13 (10.9-18)	2.4 (0.7-5.5)
Median eosinophil of small intestinal biopsy (EOS/HPF)	77	23

Conclusion

Small intestinal biopsy using DBE may be useful for the diagnosis of EoN, as eosinophil counts are significantly increased in the small intestine in patients with suspected EoN.