Efficacy of Dose Escalation of Oral 5-Aminosalicylic Acid for Ulcerative Colitis With a Mayo Endoscopic Subscore of 1: An Open Label Randomized Controlled Trial.

BACKGROUND: Endoscopic healing is generally defined as Mayo endoscopic subscore (MES) ≤1 in ulcerative colitis (UC). However, patients with an MES of 1 are at higher relapse risk than those with an MES of 0. This study evaluated the therapeutic efficacy of proactive dose escalation of oral 5-aminosalicylic acid (5-ASA) in UC patients with an MES of 1. METHODS: An open-label, randomized controlled trial was conducted in 5 hospitals between 2018 and 2022. Ulcerative colitis patients in clinical remission under oral 5-ASA therapy and diagnosed as having an MES of 1 were enrolled. Patients receiving maintenance therapy other than 5-ASA and immunomodulator were excluded. Patients were randomly assigned in a 1:1 ratio to receive either a dose-escalated (intervention) or constant dose (control) of 5-ASA. Concomitant immunomodulator was used as the stratification factor in the randomization. The primary end point was relapse within 1 year. The subgroup analysis was stratified for the use of immunomodulators. RESULTS: The full analysis set included 79 patients (39 intervention and 40 control). Immunomodulators were used in 20 (25.3%) patients. Relapse was less in the intervention group (15.4%) than the control group (37.5%; P = .026). In the subgroup with concomitant immunomodulators, relapse was also less in the intervention group (10.0%) than the control group (70.0%; P = .020). In patients without immunomodulators, the difference was not significant between 2 groups (intervention, 17.2%; control, 26.7%; P = .53). CONCLUSIONS: Dose escalation of 5-ASA reduced relapse within 1 year in UC patients in clinical remission with an MES of 1.

Dose escalation of 5-aminosalicylic acid for ulcerative colitis reduced relapse rate in patients in clinical remission with a Mayo endoscopic subscore of 1. The therapeutic efficacy was more evident in those whom immunomodulators were used.

Medical treatment selection and outcomes for hospitalized patients with severe ulcerative colitis as defined by the Japanese criteria.

BACKGROUND: Hospitalization for ulcerative colitis (UC) is potentially life-threatening. Severe disease in the Japanese criteria which modifies the Truelove-Witts' criteria might encompass more fulminant cases than the definition for acute severe UC. However, few studies have investigated the predictive factors for clinical remission (CR) after medical treatments for severe hospitalized patients by Japanese criteria. METHODS: Medical treatment selection, CR rates, and factors contributing to CR on day 14 were assessed in severe patients by Japanese criteria. We also investigated whether the reduction rate in patient-reported outcome 2 (PRO2) on day 3 could predict short-term prognosis. RESULTS: Eighty-five severe hospitalized patients were selected. Corticosteroids, tacrolimus, and infliximab were mainly selected as first-line treatments (76/85; 89.4%). The CR rates on day 14 were 26.8%, 21.4%, and 33.3% in patients receiving corticosteroids, tacrolimus, and infliximab, respectively. Extensive disease (odds ratio [OR] 0.022; 95% confidence interval [CI] 0.002-0.198), higher PRO2 (OR 0.306; 95% CI 0.144-0.821), and higher reduction rate in PRO2 on day 3 (OR 1.047; 95% CI 1.019-1.075) were independent factors predicting CR on day 14. If the cutoff value for the reduction rate in PRO2 on day 3 was 18.3%, sensitivity was 0.714 and specificity was 0.731 to predict CR on day 14. A higher reduction rate in PRO2 on day 3 (OR 0.922; 95% CI 0.853-0.995) was a negative factor to predict surgery within 28 days. CONCLUSIONS: Tacrolimus and infliximab in addition to corticosteroids were used as first-line treatment in severe hospitalized patients. PRO2 on day 3 is a useful marker for switching to second-line therapy or colectomy.

[A Case of Fournier's Gangrene during Second-Line IRIS plus Bevacizumab Chemotherapy for Rectal and Anal Canal Cancer].

A 52-year-old man diagnosed with Stage ⅢA rectal and anal canal cancer underwent abdominal perineal resection using Miles's method. Two years later, local recurrence and lung metastases were detected using contrasted CT imaging. First-line chemotherapy of XELOX was administered for 4 months until the disease progressed and lung metastases developed. After 4 courses of second-line IRIS plus bevacizumab chemotherapy, fever and swelling of the right buttock appeared; he visited and was admitted to our hospital. A CT scan revealed a pelvic abscess which resulted in septic shock. Swelling and pain extended to the right scrotum, and acute necrotizing fasciitis was suspected, and emergency surgery was performed. An incision was made from the right buttock to the right scrotum, bloody purulent drainage with a foul odor was observed, and a diagnosis of Fournier's gangrene was made. Although typical CT findings such as emphysema due to gas-producing bacteria were not observed in this case, early diagnosis and intervention of systemic management including early surgical drainage and operation were effective. For pelvic infections occurring during bevacizumab chemotherapy, Fournier's gangrene should considered for differential diagnosis, even if CT findings are atypical.

Factors associated with SARS-CoV-2 antibody titers and prognosis of breakthrough infection in hemodialysis patients.

BACKGROUND: The mortality rate of Coronavirus disease 2019 (COVID-19) is extremely high in hemodialysis patients (HDP). These patients also develop lower antibody titers after vaccination. Therefore, factors associated with antibody titers and vaccine efficacy in HDP with breakthrough infection need to be investigated. METHODS: We measured anti-S1 antibody titers in HDP (n = 104) and controls (n = 35), evaluating the influence of background on HDP by multivariable regression analysis. We classified 26 HDP patients admitted with COVID-19 into the unvaccinated (n = 15) and breakthrough infection group (n = 11), performing between-group comparisons of laboratory findings and prognosis. Vaccinated COVID-19 patients were classified into HDP and non-HDP controls, and compared the relationship between antibody titer and severity, and the prognosis of breakthrough infection. RESULTS: The antibody titer was significantly lower in the HDP group than in the control group. Among HDP, age and smoking history were significantly independent factors associated with antibody titer. The breakthrough infection group had significantly better laboratory findings (KL-6 and LDH), severity, and hospitalization period than the unvaccinated group even if antibody titers were lower than the known threshold for neutralization (p < 0.05). There was no significant difference in prognosis between the HDP and non-HDP with breakthrough infection. Severity of COVID-19 tended to be higher with lower antibody titer in non-HDP, but not in HDP. CONCLUSION: Vaccines improved the severity of COVID-19 and hospitalization period of breakthrough infection in HDP, although HDP, especially in elderly smokers had lower antibody titers than control. There was no significant association between antibody titer and severity in HDP.

Identification of diverticular bleeding needs early colonoscopy rather than preparation.

Background and study aims When patients present with acute colonic diverticulum bleeding (CDB), a colonoscopy is performed to identify stigmata of recent hemorrhage (SRH), but valuable time can be lost in bowel preparation. This study retrospectively examined groups of patients who either had a standard pre-colonoscopy regimen or no preparation. Patients and methods This study compared data from 433 patients who either followed a lengthy regimen of bowel preparation (prepared group, 266 patients) or had no preparation (unprepared group, 60 patients). We compared the association between time (hours) between admission before starting a colonoscopy (TMS) and identification of SRH using a chi-square test. Results In 48 of 60 cases (80.0 %) in the unprepared group, a total colonoscopy was performed and the time to identify SRH was decreased. The respective rates of SRH identification in the unprepared and prepared groups were 55.2 % (16/29) vs. 46.7 % (7/15) if the TMS was < 3 hours; 47.1 % (8/7) vs. 36.8 % (35/95) in 3 to 12 hours; 0 % (0/3) vs. 22.0% (13/59) in 12 to 18 hours; and 21.8 % (3/11) vs. 20.6% (42/204) in > 18 hours. There were no significant differences between the two groups. However, the SRH identification rates before and after 12 hours were 42.3 % (66/156) and 20.9 % (58/277) ( P  < 0.001). Conclusions Our data suggest that the bowel preparation method before colonoscopy is an independent variable predicting success in identifying SRH among patients with CDB. Decreasing the time before colonoscopy to no more than 12 hours after admission played an important role in identifying SRH.

[Incidence of Secondary Malignancy of Chronic Myeloid Leukemia during Treatment of Breast Cancer with Hormone Therapy].

It is expected that the number of long-term breast cancer survivors will increase owing to the improvements in chemotherapy and irradiation, while the risk of double cancers, including secondary malignancy, may become an issue. There are many unclear points in the treatment policy with regard to when a secondary malignancy occurs or the primary cancer relapses during the management of a secondary malignancy. A 54-year-old woman who was diagnosed with ER/PgR-positive HER2 negative breast cancer Stage ⅢB received neoadjuvant chemotherapy FEC and docetaxel followed by breast surgery, adjuvant hormone therapy, and radiation therapy. Chronic myeloid leukemia diagnosed by the abnormal findings of leukocytosis and bone marrow aspiration emerged after 3 years of the diagnosis of the first breast cancer. After 3 years of imatinib therapy that achieved a major molecular response(MMR)of CML, a recurrence of sacral metastasis of breast cancer was revealed by MRI. The combination of imatinib and hormone or S-1 chemotherapy could be maintained without serious adverse events after the relapse of the primary cancer.

[A Case of Recurrent Premenopausal Hormone Receptor Positive Breast Cancer with Liver, Lung and Bone Metastasis Successfully Treated with Endocrine Therapy].

Here we report a 48-year-old female with recurrent breast cancer. She had received chest muscle-conserving mastectomy and lymph node dissection at another hospital, diagnosed as pStage ⅡB, T2N1M0 premenopausal left endocrine positive/ HER2 negative breast cancer at the age of 45. Although postoperative adjuvant therapy was started with LH-RH agonist plus tamoxifen, and chest radiation, tamoxifen therapy was intolerantly discontinued due to severe adverse events of hot flash after 1 year later. Three years later, she presented with back pain and was referred to our hospital. As PET-CT revealed recurrence of multiple bone and lung metastases and solitary liver metastasis which did not seem to be life-threatening, palliative radiation therapy and endocrine therapy with leuprorelin and anastrozole(LA)were started. Eighteen months later, PET-CT showed complete disappearance of liver and lung metastases and remarkable regression of bone metastases except for the right sciatic bone. LA therapy could be maintained for a total of 30 months until metastatic recurrence on liver and bone emerged. LA endocrine therapy may be effective for patients with premenopausal hormone-positive breast cancer even if the difficult situation such as tamoxifen intolerance.

Real-time surgical needle detection using region-based convolutional neural networks.

OBJECTIVE: Conventional surgical assistance and skill analysis for suturing mostly focus on the motions of the tools. As the quality of the suturing is determined by needle motions relative to the tissues, having knowledge of the needle motion would be useful for surgical assistance and skill analysis. As the first step toward demonstrating the usefulness of the knowledge of the needle motion, we developed a needle detection algorithm. METHODS: Owing to the small needle size, attaching sensors to it is difficult. Therefore, we developed a real-time video-based needle detection algorithm using a region-based convolutional neural network. RESULTS: Our method successfully detected the needle with an average precision of 89.2%. The needle was robustly detected even when the needle was heavily occluded by the tools and/or the blood vessels during microvascular anastomosis. However, there were some incorrect detections, including partial detection. CONCLUSION: To the best of our knowledge, this is the first time deep neural networks have been applied to real-time needle detection. In the future, we will develop a needle pose estimation algorithm using the predicted needle location toward computer-aided surgical assistance and surgical skill analysis.

Development of a Skill Evaluation System for the Camera Assistant Using an Infant-Sized Laparoscopic Box Trainer.

AIMS: Our aims were to develop a training system for camera assistants (CA), and evaluate participants' performance as CA. METHODS: A questionnaire on essential requirements to be a good CA was administered to experts in pediatric endoscopic surgery. An infant-sized box trainer with several markers and lines inside was developed. Participants performed marker capturing and line-tracing tasks using a 5-mm 30° scope. A postexperimental questionnaire on the developed system was administered. The task completion time was measured. RESULTS: The 5-point evaluation scale was used for each item in the questionnaire survey of experts. The abilities to maintain a horizontal line (mean score: 4.5) and to center the target in a specified rectangle on the monitor (4.5) as well as having a full understanding of the operative procedure (4.3) were ranked as highly important. Fifty-two participants, including 5 surgical residents, were enrolled in the evaluation experiment. The completion time of capturing the markers was significantly longer in the resident group than in the nonresident group (244 versus 124 seconds, P = .04), but that of tracing the lines was not significantly different between the groups. The postexperimental questionnaire showed that the participants felt that the line-tracing tasks (3.7) were more difficult than marker-capturing tasks (2.9). CONCLUSIONS: Being proficient in manipulating a camera and having adequate knowledge of operative procedures are essential requirements to be a good CA. The ability was different between the resident and nonresident groups even in a simple task such as marker capturing.

Intelligent control of neurosurgical robot MM-3 using dynamic motion scaling.

OBJECTIVE Advanced and intelligent robotic control is necessary for neurosurgical robots, which require great accuracy and precision. In this article, the authors propose methods for dynamically and automatically controlling the motion-scaling ratio of a master-slave neurosurgical robotic system to reduce the task completion time. METHODS Three dynamic motion-scaling modes were proposed and compared with the conventional fixed motion-scaling mode. These 3 modes were defined as follows: 1) the distance between a target point and the tip of the slave manipulator, 2) the distance between the tips of the slave manipulators, and 3) the velocity of the master manipulator. Five test subjects, 2 of whom were neurosurgeons, sutured 0.3-mm artificial blood vessels using the MM-3 neurosurgical robot in each mode. RESULTS The task time, total path length, and helpfulness score were evaluated. Although no statistically significant differences were observed, the mode using the distance between the tips of the slave manipulators improves the suturing performance. CONCLUSIONS Dynamic motion scaling has great potential for the intelligent and accurate control of neurosurgical robots.

Long-Term Clinical Course after Conservative and Endoscopic Treatment of Colonic Diverticular Bleeding.

BACKGROUND/AIM: What naturally happens to patients after they undergo conservative and endoscopic treatment of colonic diverticular bleeding (CDB) is largely unknown. We retrospectively track the long-term outcome of the recurrence of CDB between patients with endoscopic and conservative treatment. METHODS: The group was divided into 2 groups: patients treated with injection and/or clipping (endoscopic group) and patients in whom such treatment could not be performed (conservative group). CDB recurrence was assessed via a questionnaire, and recurrence rates were investigated between groups using the Kaplan-Meier's method. The Cox proportional hazards model was performed to identify potential risk factors for recurrence. RESULTS: Eighty-eight patients answered the questionnaires. The median (interquartile range) follow-up period was 42.7 (61.8) months. Twenty-four (38.7%) of 62 conservatively treated patients and 16 (61.5%) of 26 endoscopically treated patients experienced recurrence of CDB during the follow-up period. Kaplan-Meier's analysis showed that the rate of recurrence was significantly higher (p < 0.05) in cases with endoscopic treatment than in those with conservative treatment (mean time to recurrence = 55.3 months (95% CI 30.8-79.9) vs. 99.9 months (95%CI 80.7-119.1)). The Cox proportional hazards model did not identify any significant variables. CONCLUSION: We should carefully follow-up patients to check for the recurrence of CDB, even when it could be successfully treated endoscopically. Can endoscopic treatment of CDB prevent CDB recurrence? Also, what happens to the patient's well-being after they undergo conservative and endoscopic treatment (cases diagnosed by Jensen's criteria) is largely unknown. We examined a population of patients undergoing conservative or endoscopic treatment to clarify the clinical course, particularly with regard to CDB recurrence.

Periappendicitis during adalimumab treatment for ileocecal Crohn's disease in a 29-year-old male.

A 29-year-old male was diagnosed with ileocolic Crohn's disease (CD) approximately 2 years ago. Adalimumab was prescribed as CD remission induction therapy. Three months after beginning adalimumab, watery diarrhea and lower abdominal pain developed. He was admitted under a diagnosis of CD exacerbation. Despite fasting and antibiotic treatment, symptoms of acute panperitonitis appeared. He was diagnosed as acute appendicitis and we performed emergency surgery for peritoneal drainage and ileocecal resection on the fifth hospital day. We diagnosed periappendicitis based on the operative findings. This is the first report of periappendicitis with CD during adalimumab treatment.

[Timely colonoscopy leads to faster identification of bleeding diverticulum].

We conducted a retrospective study of the efficacy of a polyethylene glycol purge before colonoscopic examination in 110 patients with colonic diverticular bleeding. The patients' data were assessed for the timing of colonoscopy and the methods used to stop bleeding. The rate at which bleeding diverticula were identified was markedly higher when a purge was used than when it was not (28.2% vs. 12.0%, p=0.11). In addition, the identification rate was significantly higher when colonoscopic examination was performed within 18 hours of the final hematochezia than when it was performed after 18 hours (40.5% vs. 10.5%, p<0.01). These findings suggest that patients with diverticular bleeding should undergo colonoscopy following an orally administered colonic purge, providing their condition permits. Furthermore, colonoscopy should be performed within 18 hours of the final hematochezia in order to improve identification of the bleeding diverticulum.

Anti-high mobility group box 1 and box 2 non-histone chromosomal proteins (HMGB1/HMGB2) antibodies and anti-Saccharomyces cerevisiae antibodies (ASCA): accuracy in differentially diagnosing UC and CD and correlation with inflammatory bowel disease phenotype.

BACKGROUND: The development of a supportive diagnostic method has long been required to differentially diagnose ulcerative colitis (UC) and Crohn's disease (CD). Several antibodies circulate in the sera of patients with inflammatory bowel disease. We previously identified the high mobility group box 1 and box 2 non-histone chromosomal proteins (HMGB1 and HMGB2) as novel antigens of perinuclear type anti-neutrophil cytoplasmic antibodies (pANCA) and discovered anti-HMGB1/HMGB2 antibodies in sera from patients with UC. Here, we evaluated the ability of anti-HMGB1/HMGB2 antibodies combined with anti-Saccharomyces cerevisiae antibodies (ASCA) to differentially diagnose UC and CD. METHODS: We measured titers of anti-HMGB1/HMGB2 antibodies and ASCA in the sera of 213 patients with UC and 93 with CD, using enzyme-linked immunosorbent assays. RESULTS: Among the patients with UC, 26.8% were positive for anti-HMGB1/HMGB2 antibodies, with 85.0% specificity towards CD and a positive predictive value of 80.3%. Corticosteroids significantly suppressed the titer of anti-HMGB1/HMGB2 antibodies. Among the patients with CD, 24.7% were positive for ASCA, with 96.2% specificity towards UC and a positive predictive value of 74.2%. Interestingly, the positivity rate of anti-HMGB/HMGB2 antibodies was higher (35.7%) in patients with the ileitis type of CD than in patients with CD in the colon (6.2%; significant difference, P < 0.01). The specificity of anti-HMGB1/HMGB2 antibodies in UC for CD in the colon was 93.8%. CONCLUSIONS: CD in the colon and UC can be differentially diagnosed using anti-HMGB/HMGB2 antibodies combined with ASCA.

[Advanced gallbladder cancer that showed complete response to gemcitabine plus S-1 chemotherapy].

A 57-year-old man with advanced gallbladder cancer and accompanying hepatic, colonic and duodenal invasion and para-aortic lymph node metastasis was referred to our hospital. Gemcitabine plus S-1 administration was chosen. Gemcitabine was administered intravenously at a dose of 1000 mg/m(2) on days 1 and 15, and repeated every 4 weeks. S-1 was administered orally at a dose of 40 mg/m(2) b.i.d. on days 1-14. Chemotherapy was effective for the primary gallbladder tumor and lymph node metastasis. The primary tumor and metastatic lymph nodes were shown to have disappeared by a FDG-PET CT study after 10 courses of chemotherapy. Informed consent was obtained prior to performing surgery of the primary lesion. Pathological examination showed fibrosis and a small focus of residual cancer in the resected gallbladder. Complete resection was achieved as all the margins were negative. The findings suggest that gemcitabine plus S-1 treatment may be effective against advanced gallbladder cancer.

Ectopic expression of blood type antigens in inflamed mucosa with higher incidence of FUT2 secretor status in colonic Crohn's disease.

BACKGROUND: Host-intestinal microbial interaction plays an important role in the pathogenesis of inflammatory bowel diseases (IBDs). The surface molecules of the intestinal epithelium act as receptors for bacterial adhesion and regulate the intestinal bacteria. Some known receptors are the mucosal blood type antigens, which are regulated by the fucosyltransferase2 (FUT2) gene, and individuals who express these antigens in the gastrointestinal tract are called secretors. Recent research has revealed that the FUT2 gene is associated with Crohn's disease (CD) in western populations. METHODS: To clarify the contribution of mucosal blood type antigens in IBD, we determined the incidence of five previously reported single-nucleotide polymorphisms of the FUT2 gene in Japanese patients. We also used immunohistochemistry to investigate the antigen expression in mucosal specimens from IBD patients and animal models. RESULTS: Genetic analysis revealed that all of the patients with colonic CD were secretors, whereas the incidence of secretors was 80, 80, 67, and 80%, respectively, for the control, ileocolonic CD, ileal CD, and ulcerative colitis groups (P = 0.036). Abnormal expression of blood type antigens was observed only in colonic CD. Interleukin-10⁻/⁻ mice, but not dextran sulfate sodium colitis mice, had enhanced colonic expression of blood type antigens, and the expression of these antigens preceded the development of colitis in the interleukin-10⁻/⁻ mice. CONCLUSIONS: FUT2 secretor status was associated with colonic-type CD. This finding, taken together with the immunohistochemistry data, suggests that the abnormal expression of blood type antigens in the colon may be a unique and essential factor for colonic CD.

POEMS syndrome with idiopathic portal hypertension: autopsy case and review of the literature.

Polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome is a rare multi-system disease. Reported herein is an autopsy case of POEMS syndrome in a subject who developed idiopathic portal hypertension (IPH). The patient was a 38-year-old woman who was initially admitted to the Saiseikai Central Hospital because of polyneuropathy and edema. Diagnosis of POEMS syndrome was established on additional symptoms (splenomegaly and papilloedema) and serum M-protein. Corticosteroid was given for 10 years. The patient was admitted again at the age of 48 years because of gastrointestinal bleeding due to portal hypertension. The patient died of hepatoencephalopathy at 58 years of age. The liver at autopsy demonstrated dense portal fibrosis and obliteration of small portal vein branches, which are characteristic histological findings of IPH. Portal hypertension is a rare symptom in POEMS syndrome. Only three cases of IPH associated with POEMS syndrome (including the present one) have been reported so far. In the previous two reports, liver biopsy failed to determine the cause of portal hypertension. This is the first report on the occurrence of histological findings compatible with IPH in the liver. Although it is not confirmed whether IPH is related to POEMS syndrome, elevated serum cytokines such as vascular endothelial growth factor and coagulation abnormality could have contributed to the development of IPH in the present case.

CD4+NKG2D+ T cells in Crohn's disease mediate inflammatory and cytotoxic responses through MICA interactions.

BACKGROUND & AIMS: Crohn's disease (CD) is an inflammatory bowel disease characterized by uncontrolled immune responses to bacterial flora, with excessive activation of T lymphocytes. MICA is a stress-induced major histocompatibility complex-related molecule expressed on normal intestinal epithelial cells (IECs) and recognized by the NKG2D-activating receptor on CD8(+) T cells, gammadelta T cells, and natural killer cells. We examined the role of MICA-NKG2D interactions in the activation of T lymphocytes in CD. METHODS: MICA expression was analyzed by flow cytometry on IECs isolated from patients with active inflammatory bowel disease and controls. NKG2D expression and function were analyzed on lamina propria and peripheral blood lymphocytes. RESULTS: MICA expression was significantly increased on IECs in CD, with higher expression in macroscopically involved areas. A subset of CD4(+) T cells expressing NKG2D was increased in the lamina propria from patients with CD compared with controls and patients with ulcerative colitis. CD4(+)NKG2D(+) T cells with a Th1 cytokine profile and expressing perforin were increased in the periphery and in the mucosa in CD. CD4(+)NKG2D(+) T-cell clones were functionally active through MICA-NKG2D interactions, producing interferon-gamma and killing targets expressing MICA. IECs from patients with CD had the ability to expand this subset in vitro. CD4(+)NKG2D(+) lamina propria lymphocytes from patients with CD highly expressed interleukin-15R alpha, and interleukin-15 increased NKG2D and DAP10 expression in CD4(+)NKG2D(+) T-cell clones. CONCLUSIONS: These findings highlight the role of MICA-NKG2D in the activation of a unique subset of CD4(+) T cells with inflammatory and cytotoxic properties in CD.

Intestinal epithelial cells from inflammatory bowel disease patients preferentially stimulate CD4+ T cells to proliferate and secrete interferon-gamma.

Previous studies have suggested that intestinal epithelial cells (IECs) have the capacity to function as nonprofessional antigen presenting cells that in the normal state preferentially activate CD8+ T cells. However, under pathological conditions, such as those found in inflammatory bowel disease (IBD), persistent activation of CD4+ T cells is seen. The aim of this study was to determine whether the IBD IECs contribute to CD4+ T cell activation. Freshly isolated human IECs were obtained from surgical specimens of patients with or without IBD and cocultured with autologous or allogeneic peripheral blood T lymphocytes. Cocultures of normal T cells and IECs derived from IBD patients resulted in the preferential activation of CD4+ T cell proliferation that was associated with significant IFN-gamma, but not IL-2, secretion. Cytokine secretion and CD4+ T cell proliferation was inhibited by pretreatment of the IBD IECs with the anti-DR MAb L243. In contrast, normal IECs stimulated the proliferation and cytokine secretion by CD4+ T cells to a significantly lesser degree than IBD IECs. Furthermore, blockade of human leukocyte antigen-DR had a lesser effect in the normal IEC-CD4+ T cell cocultures. We conclude that IECs can contribute to the ongoing CD4+ T cell activation seen in IBD. We suggest that the apparent differences between the secreted levels of IFN-gamma indicate that it may play a dual role in intestinal homeostasis, in which low levels contribute to physiological inflammation whereas higher levels are associated with an uncontrolled inflammatory state.