Does clinical validation and the implementation of new models of outpatient service delivery have the potential to reduce waiting lists? A pilot study in Letterkenny University Hospital.

INTRODUCTION: The traditional outpatient paradigm of seeing patients prior to diagnostic tests and treatment is unsustainable without additional funding. New models of service delivery such as "one-stop clinics", direct access to diagnostics and advanced nurse practitioner (ANP)-led clinics have the potential to improve the efficiency of existing services. METHODS: To determine the most effective changes to improve service provision, the reasons for encounter (RFE) to a urology clinic were assessed using the International Classification Primary Care. To test these changes, a clinical validation process was performed on existing waiting patients waiting ≥ 15 months. Direct access to diagnostics and an ANP-led clinic were introduced. The impact of this validation process was measured prospectively using independently-collated National Treatment Purchase Fund waiting list data. RESULTS: From January to December 2017, 1114 new patients were referred. The 3 most frequent RFEs were haematuria, urinary frequency/urgency and cystitis and accounted for 48% of referrals overall. A new outpatient pathway, combining direct access to diagnostics and an ANP-led clinic, was implemented on 508 existing patients waiting ≥ 15 months. The validation process resulted in referral directly to a consultant-led clinic in 36%, to an ANP-led clinic in 12%, direct access to diagnostics in 38% and removal in 13%. This change was implemented in July 2017 and there was a 76% reduction in the number of patients waiting ≥ 12 months by December 2017. CONCLUSION: New models of outpatient service delivery have the potential to reduce existing waiting lists and could be implemented in other Irish hospital groups.

Victimisation in urban primary schools of high-poverty areas: associations with health-related quality of life, depression and social support.

BACKGROUND: Although a widespread issue, research on victimisation among primary school children in high-poverty regions is limited. The aim of this research was to explore victimisation incidence and associated mental health correlates from first-wave data of the 'Healthy Schools' programme in a high-poverty urban region. METHOD: The study explored victimisation incidences among 458 Irish primary school children and associations with depression, health-related quality of life (HRQoL) and social support. RESULTS: Victimisation (33.8%) was consistent with recent literature. On the stand-alone victimisation question, victims scored lower on all HRQoL subscales compared with nonvictims. Further categorisation revealed that frequent victims scored lower on four of these subscales, compared with nonvictims. Furthermore, over half of children felt that their school was not doing enough to combat school aggression. CONCLUSIONS: Although from a high-poverty area, rates were consistent with data from more affluent areas. Results stress an importance on specific school aggression behaviours when measuring victimisation rates, along with corresponding health consequences. Future research should continue to adopt the behaviour-based assessment of victimisation to provide an overall picture of the problem.

Enrichment of Inflammatory IL-17 and TNF-α Secreting CD4(+) T Cells within Colorectal Tumors despite the Presence of Elevated CD39(+) T Regulatory Cells and Increased Expression of the Immune Checkpoint Molecule, PD-1.

T cell infiltration into colorectal tumors has been shown to correlate with improved patient outcomes. However, more detailed information on the makeup and relationships between the infiltrating T cell subsets is lacking. We therefore correlated the extent of immune infiltration into colorectal tumors with the frequencies of various T cell subsets. We prospectively recruited 22 patients at the time of surgical resection for colorectal cancer. The Klintrup-Mäkinen (KM) score was used to estimate the extent of immune infiltration into colorectal tumors. The frequencies of CD4 and CD8 T cells that produced cytokines or expressed the inhibitory molecule programed cell death 1 (PD-1) were determined by flow cytometry in colorectal tumor and matched uninvolved colonic tissue. In addition, the frequency of CD4 regulatory T cell (Treg) subsets was determined. An increased frequency of CD4 T cells producing IL-17 (Th17 cells) was observed in colorectal tumor tissue compared with adjacent uninvolved tissue. These Th17 cells mostly coproduced TNF-α, but not IFN-γ. IL-17 expression correlated positively with TNF-α and IL-10. Increased expression of the immune checkpoint molecule PD-1 was found in colorectal tumors compared with adjacent uninvolved tissue. There was a negative correlation between expression of PD-1 and IFN-γ, but not IL-17, for both CD4(+) and CD8(+) T cells. CD4(+)CD25(+)CD127(lo) and CD4(+)CD25(+)CD127(lo)FoxP3(+)CD39(+) Treg cells were enriched in colorectal tumors. A positive correlation between KM score and percentage CD4(+)CD25(+)CD127(lo) Treg cells was observed in tumors, suggesting that increased immune infiltration is associated with an increased proportion of Treg cells. In addition, there was a negative correlation between the frequency of CD4(+)CD25(+)CD127(lo) Treg cells and the expression of IFN-γ and IL-2, but not IL-17, in tumors. Taken together, these data suggest that both PD-1 expressing T cells and Treg cells within the tumor may have a suppressive effect on T cells secreting IFN-γ, IL-2, or TNF-α, but not Th17 cells.

Prognostic significance of tumor budding in rectal cancer biopsies before neoadjuvant therapy.

Tumor budding is an increasingly important prognostic feature for pathologists to recognize. The aim of this study was to correlate intra-tumoral budding in pre-treatment rectal cancer biopsies with pathological response to neoadjuvant chemoradiotherapy and with long-term outcome. Data from a prospectively maintained database were acquired from patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy. Pre-treatment rectal biopsies were retrospectively reviewed for evidence of intra-tumoral budding. Multivariate logistic regression was used to identify factors contributing to cancer-specific death, expressed as hazard ratios with 95% confidence intervals. Of the 185 patients with locally advanced rectal cancer, 89 patients met the eligibility criteria, of whom 18 (20%) exhibited budding in a pre-treatment tumor biopsy. Intra-tumoral budding predicted a poor pathological response to neoadjuvant chemoradiotherapy (higher ypT stage, P=0.032; lymph node involvement, P=0.018; lymphovascular invasion, P=0.004; and residual poorly differentiated tumors, P=0.005). No patient with intra-tumoral budding exhibited a tumor regression grade 1 or complete pathological response, providing a 100% specificity and positive predictive value for non-response to neoadjuvant chemoradiotherapy. Intra-tumoral budding was associated with a lower disease-free 5-year survival rate (33 vs 78%, P<0.001), cancer-specific 5-year survival rate (61 vs 87%, P=0.021) and predicted cancer-specific death (hazard ratio 3.51, 95% confidence interval 1.03-11.93, P=0.040). Intra-tumoral budding at diagnosis of rectal cancer identifies those who will poorly respond to neoadjuvant chemoradiotherapy and those with a poor prognosis.

Depth-dependent differences in community structure of the human colonic microbiota in health.

OBJECTIVE: The aims of this study were to develop techniques for spatial microbial assessment in humans and to establish colonic luminal and mucosal spatial ecology, encompassing longitudinal and cross-sectional axes. DESIGN: A microbiological protected specimen brush was used in conjunction with a biopsy forceps to sample the colon in nine healthy volunteers undergoing colonoscopy. Terminal Restriction Fragment Length Polymorphism analysis was used to determine the major variables in the spatial organization of the colonic microbiota. RESULTS: Protected Specimen Brush sampling retrieved region-specific, uncontaminated samples that were enriched for bacterial DNA and depleted in human DNA when compared to biopsy samples. Terminal Restriction Fragment Length Polymorphism analysis revealed a segmentation of bacterial communities between the luminal brush and biopsy-associated ecological niches with little variability across the longitudinal axis of the colon and reduced diversity in brush samples. CONCLUSION: These results support the concept of a microbiota with little longitudinal variability but with some degree of segregation between luminal and mucosal communities.

A comparative study of short- and medium-term outcomes comparing emergent surgery and stenting as a bridge to surgery in patients with acute malignant colonic obstruction.

BACKGROUND: The use of self-expanding metal stents as a bridge to surgery in the setting of malignant colorectal obstruction has been advocated as an acceptable alternative to emergency surgery. However, concerns about the safety of stenting have been raised following recent randomized studies. OBJECTIVES: The aim of the current study was to compare outcomes. DESIGN: This was an observational, comparative study. SETTINGS: This study was conducted at a tertiary referral center and university teaching hospital. PATIENTS AND INTERVENTIONS: Patients with malignant colonic obstruction (n = 49) treated by either emergency surgery (n = 26) or with stent placement (n = 23) as a bridge to surgery were identified and followed. MAIN OUTCOME MEASURES: Short-term outcomes including stoma rates and postoperative morbidity and medium-term oncological outcomes were compared based on an "intention-to-treat" analysis. RESULTS: Patients in both groups were well matched on clinicopathological parameters. Technical and clinical successful stent deployment was achieved in 91% and 83%. This did not adversely impact cancer-specific and overall survival (log rank = nonsignificant). No difference was observed in stoma rates, primary anastomosis rates, perioperative mortality rates, or reoperation rates between the 2 groups. Significantly fewer patients underwent total colectomy in the stent group in comparison with the emergency surgery group (1/23 vs 6/26: p = 0.027). There was no difference in postoperative morbidity (59% vs 66%: p = 0.09). There was a significant reduction in readmission rates in the stent group (5/26 vs 0/23: p = 0.038). LIMITATIONS: The small sample size of this study could lead to type II error. In addition, the study was nonrandomized and demonstrated a limited length of follow-up. CONCLUSION: Despite a high rate of technical and clinical success in selected patients with colonic obstruction, stenting has no impact on stoma rates. Despite concerns about the rate of stent-associated perforation, stenting does not adversely impact disease progression or survival. Future comparative trials are essential to better define the role of stenting in this setting and to ensure that we are not using costly technology to create an elective operative situation without concomitant patient benefits.

Inhibition of dendritic cell maturation by the tumor microenvironment correlates with the survival of colorectal cancer patients following bevacizumab treatment.

Development of bevacizumab has improved survival in colorectal cancer, however, currently there are no biomarkers that predict response to bevacizumab and it is unknown how it influences the immune system in colorectal cancer patients. Dendritic cells are important for the induction of an antitumor immune response; however tumors are capable of disabling dendritic cells and escaping immune surveillance. The aim of this study was to assess the numbers of CD11c+ cells infiltrating tumor tissue and to examine the effects of tumor conditioned media (TCM) and bevacizumab conditioned media (BCM) on dendritic cell maturation and correlate our findings with patient survival. colorectal cancer explant tissues were cultured with or without bevacizumab, to generate BCM and TCM, which were used to treat dendritic cells. CD80, CD86, CD83, CD54, HLA-DR, and CD1d expression was measured by flow cytometry. Interleukin (IL)-10 and IL-12p70 were measured by ELISA. The Cox proportional hazards model was used to associate survival with dendritic cell inhibition. TCM and BCM inhibited lipopolysaccharide (LPS)-induced dendritic cell maturation and IL-12p70 secretion (P < 0.0001), while increasing IL-10 secretion (P = 0.0033 and 0.0220, respectively). Inhibition of LPS-induced CD1d (P = 0.021, HR = 1.096) and CD83 (P = 0.017, HR = 1.083) by TCM and inhibition of CD1d (P = 0.017, HR = 1.067), CD83 (P = 0.032, HR = 1.035), and IL-12p70 (P = 0.037, HR = 1.036) by BCM was associated with poor survival in colorectal cancer patients. CD11c expression was elevated in tumor tissue compared with normal tissue (P < 0.001), but this did not correlate with survival. In conclusion, TCM and BCM inhibit dendritic cells, and this inhibition correlates with survival of colorectal cancer patients receiving bevacizumab.

Stage II colonic adenocarcinoma: a detailed study of pT4N0 with emphasis on peritoneal involvement and the role of tumour budding.

AIMS: Evaluation of peritoneal involvement in colonic cancer (CC) can be difficult. We studied pT4N0 cancers and their association with pathological prognostic markers, including tumour budding. METHOD AND RESULTS: Tumours were classified as (i) at the peritoneal surface or free in the peritoneal cavity (pT4a subgroup n = 44); (ii) directly invading adjacent organ (pT4b subgroup n = 8); or (iii) showing inflammatory involvement of the peritoneum (pT4I subgroup n = 25). A published pT3N0 cohort was used to compare Stage II subgroups. Standard pathological markers including tumour budding were assessed. Elastin staining was performed in the pT4I subgroup. Seventy-seven Stage II CCs met inclusion criteria. There was no significant difference in survival across subgroups. pT4b tumours were larger than pT4a tumours (P < 0.001). Over-represented features in pT4a versus pT4b tumours were tumour budding (P = 0.02) and infiltrative margin (P = 0.02). Tumour budding did not predict survival. Using multivariate analysis, neural invasion was the only parameter predictive of survival (hazard ratio = 2.8; 95% CI 1.2-6.4; P = 0.02). CONCLUSION: Stage II pT4I CCs have a similar outcome to T4a/b tumours. Elastin staining is useful in defining this group. Tumour budding may facilitate peritoneal invasion in pT4a tumours, but does not predict outcome in pT4N0 disease. Only neural invasion independently predicted poor outcome.

A prospective analysis of patient outcome following treatment of T3 rectal cancer with neo-adjuvant chemoradiotherapy and transanal excision.

BACKGROUND: Local excision is an alternative to anterior or abdomino-perineal resection in patients with early rectal cancer. In more advanced disease, neo-adjuvant therapy (CRXT) can result in significant disease regression such that local excision may be considered. The primary aim was to assess oncological outcome in patients with T3 rectal cancer treated with CRXT and local excision due to unsuitability for or aversion to anterior resection and stoma. The secondary aim was to examine oncological outcomes in patients treated in a similar way in the published literature. METHODS: Between July 2006 and July 2009, patients with rectal cancer staged T3, N0/N1, M0 who were deemed unfit for or who refused anterior resection were offered long-course CRXT. Patients were restaged 8 weeks following completion. If there was a good response (regression grade 2 or 3 clinically and radiologically), full thickness transanal excision was performed. All patients were followed regularly (monthly CT abdomen/pelvis and annual endoscopy) to assess for recurrence of disease. A literature search of PubMed was performed to identify all prospective data available of T3 rectal cancers managed with CRXT and local excision. RESULTS: Ten patients were treated over 3 years. Six patients had complete pathological response, while four patients had a partial response. The resection margins following local excision were clear in all. There was no local recurrence (median follow-up 24 months, range 9-42 months). CONCLUSION: Neo-adjuvant chemoradiotherapy and local excision is an option in patients unfit for or averse to major surgical resection if there is a good response to CRXT.

The use of minimally invasive surgery in the management of idiopathic omental torsion: The diagnostic and therapeutic role of laparoscopy.

Omental torsion is an unusual and infrequently encountered cause of acute abdominal pain in adults. Computed tomography (CT) is a useful adjunct to clinical history and examination in establishing the diagnosis; however, definitive diagnosis is frequently established at the time of exploratory surgery. Treatment may be conservative or operative, with laparoscopic resection the surgical approach of choice. We report the case of a 60-year-old man who presented with a 3-day history of severe right-sided abdominal pain. Abdominal CT scan revealed a right upper quadrant mass with a whirl-like appearance, suspicious for omental infarction. Diagnostic laparoscopy was undertaken, the diagnosis confirmed and the diseased omentum resected. The patient was discharged the following day and made an uncomplicated recovery.

Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.

Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that directly influence dendritic cell maturation and function are not well characterised. Our aim was to identify tumour-associated inflammatory mediators which influence the function of dendritic cells. Tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. Pre-treatment of monocyte derived dendritic cells with this tumour conditioned media inhibited the up-regulation of CD86, CD83, CD54 and HLA-DR in response to LPS, enhancing IL-10 while reducing IL-12p70 secretion. We examined if specific individual components of the tumour conditioned media (CCL2, CXCL1, CXCL5) could modulate dendritic cell maturation or cytokine secretion in response to LPS. VEGF was also assessed as it has a suppressive effect on dendritic cell maturation. Pre-treatment of immature dendritic cells with VEGF inhibited LPS induced upregulation of CD80 and CD54, while CXCL1 inhibited HLA-DR. Interestingly, treatment of dendritic cells with CCL2, CXCL1, CXCL5 or VEGF significantly suppressed their ability to secrete IL-12p70 in response to LPS. In addition, dendritic cells treated with a combination of CXCL1 and VEGF secreted less IL-12p70 in response to LPS compared to pre-treatment with either cytokine alone. In conclusion, tumour conditioned media strongly influences dendritic cell maturation and function.

Treatment and outcomes of anorectal melanoma.

INTRODUCTION: anorectal melanoma is an uncommon disease constituting less than 3% of all melanomas. Due to its rarity, there are a lack of randomized control trials regarding appropriate management and current evidence is based mainly on retrospective studies. METHODS: in view of the controversial surgical treatment of anorectal melanoma, we review the most published literature in an attempt to elucidate its typical clinical features along with current thinking with respect to management approaches to this aggressive disease. Using the keywords "anorectal" and "malignant melanoma", a medline search of all articles in English was performed and the relevant articles procured. Additional references were retrieved by cross reference from key articles. RESULTS: anorectal melanoma affects the elderly with a slight preponderance for females. It commonly presents disguised as benign disease with local bleeding or suspicion for haemorrhoidal disease. There is no convincing evidence to indicate that radical resection of primary anorectal melanoma is associated with improvement in local control or survival, and local excision is an acceptable treatment option. CONCLUSION: optimum management depends on several factors and the therapeutic goals should be to lengthen survival and preserve quality-of-life. Given that wide local excision is a more limited intervention with comparable survival it should be considered as the initial treatment choice. Unfortunately prognosis for patients with this disease remains poor despite choice of treatment strategy with overall five year disease-free survival less than twenty percent in most studies.

Increased topoisomerase IIalpha expression in colorectal cancer is associated with advanced disease and chemotherapeutic resistance via inhibition of apoptosis.

Topoisomerase IIalpha is a nuclear enzyme that regulates the tertiary structure of DNA. The influence of topoisomerase IIalpha gene (TOP2A) or protein alterations on disease progression and treatment response in colorectal cancer (CRC) is unknown. The study investigated the clinical relevance of topoisomerase IIalpha in CRC using in vivo and in vitro models. Differentially expressed genes in early and late-stage CRC were identified by array comparative genomic hybridization (CGH). Cellular location of gene amplifications was determined by fluorescence in situ hybridization (FISH). Topoisomerase IIalpha levels, proliferation index, and HER2 expression were examined in 228 colorectal tumors by immunohistochemistry. Overexpression of topoisomerase IIalpha in vitro was achieved by liposome-based transfection. Cell growth inhibition and apoptosis were quantified using the crystal violet assay and flow cytometry, respectively, in response to drug treatment. Amplification of TOP2A was identified in 3 (7.7%) tumors using array CGH and confirmed using FISH. At the protein level, topoisomerase IIalpha staining was observed in 157 (69%) tumors, and both staining and intensity levels were associated with an aggressive tumor phenotype (p values 0.04 and 0.005, respectively). Using logistic regression analysis, topoisomerase IIalpha remained significantly associated with advanced tumor stage when corrected for tumor proliferation (p=0.007) and differentiation (p=0.001). No association was identified between topoisomerase IIalpha and HER2. In vitro, overexpression of topoisomerase IIalpha was associated with resistance to irinotecan (p=0.001) and etoposide chemotherapy (p=0.03), an effect mediated by inhibition of apoptosis. Topoisomerase IIalpha overexpression is significantly associated with alterations in tumor behavior and response to drug treatment in CRC. Our results suggest that gene amplification may represent an important mechanism underlying these changes.

Ureterocolic fistula in the presence of a solitary kidney.

Among the entero-urinary fistulae, those between the ureter and colon are rare. Most spontaneous ureterocolic fistulae are caused by urinary calculi. We report a case of a spontaneous ureterocolic fistula which occurred as a consequence of diverticular disease. This rare presentation was further complicated as it occurred in the presence of a solitary kidney. The patient underwent a laparoscopic defunctioning loop ileostomy and after 6 weeks underwent definitive surgical treatment of the ureterocolic fistula. We describe the presentation and management of this fistula and review the current literature.

Long-term clinical results of ileocecal resection for Crohn's disease.

BACKGROUND: The efficacy of biologic agents in Crohn's disease (CD) has led to proposals that they be introduced early in the disease (top-down treatment) with the aim of reducing corticosteroid dependency and surgical resection. However, the long-term use of biologic agents in limited CD may be difficult to justify. The aims were to assess outcomes for ileocecal resection in CD and evaluate its role in the current era. METHODS: The study included 139 CD patients who underwent ileocecal resection between 1980 and 2000. Data were retrieved from a prospectively maintained database. Disease recurrence was defined as symptoms in addition to endoscopic or radiological evidence of disease activity. Severe disease recurrence was defined as a need for repeat resection surgery. RESULTS: Seventy-two (52%) patients developed disease recurrence. Median (interquartile range) time to recurrence was 7.1 (5-10.6) years. Forty-nine (35%) patients required repeat resection surgery. Median (IQ range) time to repeat surgery was 7.2 (4.9-10.8) years. The presence of granulomas was associated with disease recurrence (P = 0.03) and repeat resection surgery (P = 0.01). CONCLUSIONS: Long-term outcomes for ileocecal resection in CD are excellent with 48% of patients remaining symptom-free and only 35% requiring repeat resection surgery at 10 years. This should be borne in mind when considering biologic therapy.

Mutually exclusive promoter hypermethylation patterns of hMLH1 and O6-methylguanine DNA methyltransferase in colorectal cancer.

Hypermethylation of CpG islands in gene promoter regions is an important mechanism of gene inactivation in cancer. Many cellular pathways, including DNA repair, are inactivated by this type of epigenetic lesion, resulting in proposed mutator phenotypes. Promoter hypermethylation of hMLH1 has been implicated in a subset of colorectal cancers that show microsatellite instability (MSI). Transcriptional silencing of O6-methylguanine DNA methyltransferase (MGMT) has also been described in a variety of neoplasms and has been associated with a consequent mutational spectrum. We investigated the relationship between hMLH1 promoter hypermethylation and MGMT promoter hypermethylation in 110 colorectal cancers using methylation-specific polymerase chain reaction. Expression of hMLH1 and MGMT was assessed by immunohistochemistry. MSI testing was performed using the National Cancer Institute consensus panel of five microsatellite markers. Promoter hypermethylation of hMLH1 was detected in 12% of tumors. This was significantly associated with the MSI-high phenotype (P < 0.01) and loss of hMLH1 expression (P < 0.01). Methylation of the MGMT promoter was detected in 43% of tumors, which were mostly microsatellite stable or MSI-low (P = 0.041) and showed loss of MGMT expression (P < 0.01). We demonstrated an inverse relationship between hMLH1 promoter hypermethylation and MGMT promoter hypermethylation (P = 0.041), suggesting that a number of distinct hypermethylation-associated pathways may exist in colorectal cancer.

Diverse populations of T cells with NK cell receptors accumulate in the human intestine in health and in colorectal cancer.

T cells expressing NK cell receptors (NKR) display rapid MHC-unrestricted cytotoxicity and potent cytokine secretion and are thought to play roles in immunity against tumors. We have quantified and characterized NKR+ T cells freshly isolated from epithelial and lamina propria layers of duodenum and colon from 16 individuals with no evidence of gastrointestinal disease and from tumor and uninvolved tissue from 19 patients with colorectal cancer. NKR+ T cell subpopulations were differentially distributed in different intestinal compartments, and CD161+ T cells accounted for over one half of T cells at all locations tested. Most intestinal CD161+ T cells expressed alpha beta TCR and either CD4 or CD8. Significant proportions expressed HLA-DR,CD69 and Fas ligand. Upon stimulation in vitro, CD161+ T cells produced IFN-gamma and TNF-alpha but not IL-4. NKT cells expressing the Valpha24Vbeta11 TCR, which recognizes CD1d,were virtually absent from the intestine, but colonic cells produced IFN-gamma in response to the NKT cell agonist ligand alpha-galactosylceramide. NKR+ T cells were not expanded in colonic tumors compared to adjacent uninvolved tissue. The predominance, heterogeneity and differential distribution of NKR+ T cells at different intestinal locations suggests that they are central to intestinal immunity.

Cyclosporin therapy in severe ulcerative colitis: is it worth the effort?

PURPOSE: Cyclosporin is advocated in the treatment of acute severe ulcerative colitis that has failed to respond to high-dose corticosteroid therapy. This approach is controversial, with critics highlighting the temporary nature of remissions and the potential for adverse effects. There have been few reports of the long-term outcome of those patients who do respond. The purpose of this study was to investigate the clinical outcome of all patients treated with cyclosporin at our institution over the past five years. METHODS: We conducted a retrospective study of 46 patients who presented to a tertiary referral center. Initial responders were those who avoided colectomy; a sustained response was defined as a remission that lasted while the patient was taking oral cyclosporin and for three months after this therapy was discontinued. RESULTS: Thirty-two (69 percent) of 46 patients had an initial response to therapy, and 50 percent met criteria for a sustained response. Eleven of 23 sustained responders subsequently relapsed. At a mean of 22 months' follow-up, 26 percent of patients remain well and have never relapsed. Serious infective complications occurred in two patients, possibly attributable to therapy. No factors predictive of a likely response were identifiable on retrospective analysis. CONCLUSIONS: This study confirms the efficacy of cyclosporin in the management of severe ulcerative colitis. Although many initial responders subsequently relapse, such patients may benefit from having even a short time to adjust to the need for surgery. A substantial minority (26 percent) of all patients treated remain in long-term remission.