Search

Background Patients who undergo subtotal colectomy for Ulcerative Colitis (UC) have a persistent risk of colorectal cancer (CRC) in the retained rectum and this increases overtime. There are currently no guidelines for rectal surveillance in this group. We aimed to assess the outcome following colectomy for patients with UC over a ten year period. Methods We conducted a retrospective analysis of patients with UC who underwent colorectal surgery in a tertiary referral centre. The Hospital In-Patient Enquiry system and the St Vincent's Hospital IBD Database were used to identify patients. Patients with colorectal cancer were excluded. Results In a six year period one-hundred and seventy six bowel surgeries were carried out for patients with Inflammatory Bowel Disease. Sixty five of these procedures were performed on patients with UC, eight of which would subsequently be re-diagnosed with Crohn’s Disease. 73.6% (n=42) had a completion proctectomy within ten years, 12% (n=7) were lost to follow up and 5% (n=3) died from non-gastrointestinal disorders. 8.7% (n=5) retained their rectum after ten years. For patients who had a completion proctectomy the median time to surgery was two years. Most of these patients did not have surveillance within the twenty four month time frame. Patients who had a completion proctectomy between three and ten years underwent surveillance endoscopy on average two occasions. All patients in the retained rectum group had surveillance proctoscopy with a median frequency of 2.4 years. The risk of further surgery was a factor for two patients due to obesity and decompensated liver disease. A third patient had an ileorectal anastamosis abroad and continues to have active rectal disease. Dysplasia was found in the rectum of the fourth patient thirteen years post colectomy. The final patient refused surgery but agreed to endoscopic surveillance. A rectal adenocarcinoma was diagnosed ten years post-operation. Conclusion Despite the absence of guidelines for completion proctectomy and/or surveillance of the retained rectal stump, three quarters of our UC patients had undergone completion proctectomy within ten years. A small but significant number of patients have a residual rectal stump after ten years, they require CRC surveillance and clear guidelines on this are needed.

Background Ustekinumab (UST), a monoclonal antibody that blocks interleukins IL-12 and IL-23, is increasingly used in the treatment of Crohn’s disease and Ulcerative Colitis. While therapeutic drug monitoring (TDM) is used with increasing frequency in other biologic agents, there is a paucity of data regarding the clinical utility of TDM for UST. This pilot study aimed to determine whether loss of response (LOR) and treatment failure (TF) can be predicted by post UST-induction serum trough concentrations and antibody levels. Methods A pilot retrospective observational study of patients who received subcutaneous (SC) induction of UST, following LOR to anti-TNF, for treatment of Crohn’s disease in 2016 was performed. We previously demonstrated comparable drug trough levels following SC rather than intravenous UST induction. Patients with available 74 month follow up data were included. Frozen serum samples used for this measurement were retrospectively tested for antibody levels using ELISA. Our IBD database and admissions data were analysed from 2016-2022. We recorded treatment duration, interval shortening, and treatment failure. Treatment failure was defined as switch to another biologic agent and/or surgery. Data were analysed using SPSS software [IBM], with Wilcoxon Rank Sum Test used for hypothesis testing. Results In this pilot study, a total of 10 patients (female=1, mean age 38.5 y) met the inclusion criteria. During the 74 month follow-up period, 3 patients failed treatment (mean age 30 y) while 7 remained on UST (mean age 42 y). All patients required interval shortening (4 weekly dosing). There was no difference in Crohn’s phenotype or smoking status between groups. All TF patients were switched to alternative biologic agents, with 1 patient requiring surgery. The patients who failed treatment were noted to have higher antibody levels (median 6.57 Au/ml vs 5.87 AU/ml, p=0.03) [Fig 1]. Two of these patients were noted to have lower trough levels than those who continued on UST, with one having a higher trough level (median 2.9mcg/ml vs 5.8mcg/ml, p=0.52) [Fig 2]. Conclusion Shortening of dose interval with UST therapy in Crohn’s disease is frequently required. This pilot study suggests an association between treatment failure and higher antidrug antibody levels 8 weeks post induction of UST. There was no significant difference in drug trough levels between groups. The patient with the highest trough level in the cohort failed treatment – This raises the possibility of multiple mechanisms of failure; however, it is impossible to draw conclusions given the sample size. Further studies are required to assess whether measurement of post induction antibody and drug trough levels has clinical utility in guiding treatment decisions.

Background Patients with inflammatory bowel disease (IBD) have attenuated responses to current vaccinations. There is a limited body of evidence suggesting patients with IBD receiving TNF antagonists have an attenuated response to vaccination against COVID-19. We sought to determine the impact of IBD and various medications for the treatment of IBD on antibody responses to vaccination against COVID-19. Methods Patients with IBD (n=270) and healthy controls (HC, n=116) were recruited prospectively and quantitative antibody responses were assessed following 1st and 2nd doses of COVID-19 vaccination. The impact of IBD and medications for treatment of IBD on vaccine response rates was investigated. Results All HC seroconverted post complete vaccination [100%]. A small proportion of patients with IBD failed to seroconvert [2%]. Median IgG spike protein (SP) antibody levels post-complete vaccination in our IBD cohort was significantly lower than HC [2,613 AU/mL versus 6,871 AU/mL, p= Conclusion Patients with IBD who do not seroconvert post-vaccination against COVID-19 are a vulnerable cohort. Patient with IBD have attenuated serological responses to SARS-CoV-2 vaccination. Use of anti-TNF therapy further impacts IgG SP antibody levels. Impaired response to vaccination in our study highlights the importance of booster vaccination programmes for patients with IBD.

Background Novel medications including the introduction of biologic therapies in the last decade have expanded treatment options for patients with ulcerative colitis (UC). Large studies in the USA and Europe have shown colectomy rates in UC patients are reducing over the past two decades. Methods We performed a single-centre retrospective study of our prospectively maintained IBD database. Our aim was to look at changes in colectomy rates in patients with UC over the past three decades and need for biologic therapy. Basic demographics, need for biologic therapy and colectomy rates were collected. Need for colectomy and biologic therapy within, 10 years of diagnosis was determined across three groups dependent on decade of diagnosis. Results 2229 patients with confirmed UC were included in our study. Median age at diagnosis was, 37 years [range, 4.9 -92.6]., 1210 [54.28%] were male., 595 patients were diagnosed between, 1990–2000, 795 between, 2000–2010 and, 790 between, 2010–2020. A total of, 366 (16.4%) patients had a colectomy during follow-up and, 363 (16.3%) were treated with biologic therapies. We found rates of colectomy within, 10 years of diagnosis have significant dropped over the past three decades. From, 1990 -2000, 595 patients were diagnosed with UC and, 131 [22%] patients had colectomies, in, 2000-2010, 794 patients were diagnosed with UC and, 135 [17%] had a colectomy and between, 2010-2020, 784 patients were diagnosed with UC and, 55 [7%] had a colectomy [p = Conclusion Management of UC has changed over the past three decades including the introduction of multiple biologic therapies and the use of therapeutic drug monitoring has allowed a more personalised approach to management of UC. We can see from this study changes in the management of UC over the past decade have resulted in significant reduction in need for colectomy and an increase in the use of biologics.

Background Tofacitinib is an oral small molecule directed against the JAK/STAT pathway. It is the first JAK inhibitor approved for the treatment of ulcerative colitis (UC) and is licenced for use in moderate to severely active disease. This study aims to evaluate tofacitinib effectiveness and safety in real-world clinical practice for moderate-to-severely active UC. Methods Consecutive patients receiving Tofacitinib for UC in four Irish tertiary referral centres were identified. Baseline clinical data and information on therapy outcomes were collected by retrospective review of electronic patient records. Patients included in the study cohort were older than 18 years of age, had a confirmed diagnosis of UC, had received at least one induction dose of tofacitinib, and had available clinical follow-up. The primary study endpoint was 6-month corticosteroid-free remission rate. Secondary endpoints included 3-month clinical response, inflammatory biomarkers responses to tofacitinib therapy, rates of tofacitinib discontinuation, and side effects. Continuous variables are presented as median [range]. P values < 0.05 were considered significant in all analyses. Results Fifty-three UC patients were included; age 40.4 [33.3 – 53.9] years, 66% male, disease duration 5.7 [2.6–10.9] years; follow-up 8.7 [6.4–14.1] months. 43%, 40% and 17% of patients had extensive, left-sided disease and proctitis respectively. At baseline, clinical Mayo subscore was 7 [5–8], CRP 4.0 [1.0–16.7] mg/L and faecal calprotectin 914 [444.0–1000] mcg/g. The 3-month clinical response and 6-month corticosteroid-free remission rates were 69% and 43%, respectively. Following tofacitinib therapy, compared with baseline values, a significant reduction in 3-month clinical Mayo score, 3-month CRP, and post-induction faecal calprotectin was observed, p Conclusion These data are in concordance with prior studies of tofacitinib effectiveness and safety in real world practice. They demonstrate that, in a cohort of UC patients with significant prior therapy exposure, tofacitinib is an effective therapy with an acceptable safety profile.

Appendicectomy may reduce relapses and need for medication in patients with ulcerative colitis, but long-term prospective data are lacking. This study aimed to analyse the effect of appendicectomy in patients with refractory ulcerative colitis.In this prospective multicentre cohort series, all consecutive patients with refractory ulcerative colitis referred for proctocolectomy between November 2012 and June 2015 were counselled to undergo laparoscopic appendicectomy instead. The primary endpoint was clinical response (reduction of at least 3 points in the partial Mayo score) at 12 months and long-term follow-up. Secondary endpoints included endoscopic remission (endoscopic Mayo score of 1 or less), failure (colectomy or start of experimental medication), and changes in Inflammatory Bowel Disease Questionnaire (IBDQ) (range 32-224), EQ-5D™ and EORTC-QLQ-C30-QL scores.A total of 28 patients (13 women; median age 40·5 years) underwent appendicectomy. The mean baseline IBDQ score was 127·0, the EQ-5D™ score was 0·65, and the EORTC-QLQ-C30-QL score was 41·1. At 12 months, 13 patients had a clinical response, five were in endoscopic remission, and nine required a colectomy (6 patients) or started new experimental medical therapy (3). IBDQ, EQ-5D™ and EORTC-QLQ-C30-QL scores improved to 167·1 (P 0·001), 0·80 (P = 0·003) and 61·0 (P 0·001) respectively. After a median of 3·7 (range 2·3-5·2) years, a further four patients required a colectomy (2) or new experimental medical therapy (2). Thirteen patients had a clinical response and seven were in endoscopic remission. The improvement in IBDQ, EQ-5D™ and the EORTC-QLQ-C30-QL scores remained stable over time.Appendicectomy resulted in a clinical response in nearly half of patients with refractory ulcerative colitis and a substantial proportion were in endoscopic remission. Elective appendicectomy should be considered before proctocolectomy in patients with therapy-refractory ulcerative colitis.La apendicectomía puede reducir las recaídas y la necesidad de medicación en pacientes con colitis ulcerosa (ulcerative colitis, UC), sin embargo, faltan datos a largo plazo obtenidos de forma prospectiva. El objetivo de este estudio fue analizar el efecto de la apendicectomía en pacientes con UC refractarios al tratamiento. MÉTODOS: En esta serie prospectiva de cohortes multicéntrica, a todos los pacientes consecutivos con UC refractaria remitidos para proctocolectomía entre noviembre de 2012 y junio de 2015 se les recomendó en su lugar someterse a una apendicectomía laparoscópica. El criterio de valoración principal fue la respuesta clínica (disminución de ≥ 3 puntos del sistema de puntuación parcial de Mayo que varía de 0 a 9) a los 12 meses y en el seguimiento a largo plazo. Los criterios de valoración secundarios incluyeron la remisión endoscópica (puntuación endoscópica de Mayo ≤ 1), fracaso (colectomía o inicio de medicación experimental) y cambios en el IBDQ (rango 32-224), EQ-5D y EORTC-QLQ-C30-QL.En total, 28 pacientes (13 mujeres, mediana de edad 40,5) se sometieron a una apendicectomía. El IBDQ de referencia promedio fue de 127,0; el EQ-5D 0,65 y el EORTC-QLQ-C30-QL 41,1. A los 12 meses, 13 pacientes presentaban una respuesta clínica, cinco estaban en remisión endoscópica y nueve precisaron colectomía (n = 6) o un nuevo tratamiento médico experimental (n = 3). El IBDQ, EQ-5D y EORTC-QLQ-C30-QL mejoraron a 167,1 (P 0,001); 0,80 (P = 0,003) y 61,0 (P 0,001) respectivamente. Después de una mediana de 3,7 años (rango 2,3-5,2), otros cuatro pacientes requirieron una colectomía (n = 2) o un nuevo tratamiento médico experimental (n = 2). Trece pacientes presentaron respuesta clínica y siete se encontraban en remisión endoscópica. La mejora del IBDQ, el EQ-5D y el EORTC-QLQ-C30-QL se mantuvo estable a lo largo del tiempo. CONCLUSIÓN: La apendicectomía consiguió una respuesta clínica en casi la mitad de los pacientes con UC refractaria. La apendicectomía electiva debería ser considerada antes que la proctocolectomía en pacientes con UC refractaria al tratamiento.

Golimumab (GLB) is an antitumour necrosis factor-α (anti-TNF) therapy that has shown efficacy as induction and maintenance therapy for ulcerative colitis (UC). We aimed to describe the outcome of GLB therapy for UC in a real-world clinical practice.Consecutive patients receiving GLB for UC in six Irish Academic Medical Centres were identified. The primary study endpoint was the 6-month corticosteroid-free remission rate. The secondary endpoints included the 3-month clinical response, time free of GLB discontinuation and adverse events.Seventy-two patients were identified [57% men; median (range) age of 41.4 years (20.3-76.8); disease duration 6.6 years (0-29.9); follow-up 8.7 months (0.4-39.2)]. Sixty-four percent of patients were anti-TNF naive. The 3-month clinical response and the 6-month corticosteroid-free remission rates were 55 and 39%, respectively. Forty-four percent of patients discontinued GLB during the follow-up, median (95% confidence interval) time to GLB discontinuation 18.7 months (9.2-28.1). A C-reactive protein more than 5 mg/l at baseline was associated with failure to achieve 6-month corticosteroid-free remission and a shorter time to GLB discontinuation, odds ratio 0.2 (0.1-0.7), P=0.008, and hazard ratio (95% confidence interval) 2.8 (1.3-5.7), P=0.007, respectively. Adverse events occurred in 7% of patients (n=5), all of which were minor and self-limiting.These real-world clinical data suggest that GLB is an effective and safe therapy for a UC cohort with significant previous anti-TNF exposure. An elevated baseline C-reactive protein, likely reflective of increased inflammatory burden, is associated with a reduced likelihood of a successful outcome of GLB therapy.

Background Recent studies report an increased risk of non-melanoma skin cancer (NMSC) in immunosuppressed patients with inflammatory bowel disease (IBD). Concurrently, paediatric IBD incidence is rising, with more patients now exposed to immunomodulators from a younger age. Objectives To investigate NMSC incidence and to examine the risk associated with immunomodulators in the development of NMSC in patients with IBD. Methods This was a retrospective single-centre cohort study. Patients with IBD attending a tertiary adult hospital from 1994 to 2013 were included. Skin cancer incidence was compared with population data from the National Cancer Registry of Ireland (NCRI) to calculate standardized incidence ratio (SIR). Logistic regression was utilized for risk factor analysis. Results Two thousand and fifty-three patients with IBD were studied. The SIR for NMSC in patients with IBD taking immunomodulators overall was 1.8 (95% CI: 1.0–2.7) with age-specific rates significantly elevated across certain age categories. Exposure to thiopurines (OR: 5.26, 95% CI: 2.15–12.93, P < 0.001) and in particular thiopurines and/or tumour necrosis factor alpha (TNF-α) inhibitors (OR: 6.45, 95% CI: 2.69–15.95, P < 0.001) was significantly associated with NMSC. The majority (82%) of those exposed to a TNF-α inhibitor also had thiopurine exposure. Conclusions Compliance with skin cancer preventative measures should be highlighted to all patients with IBD. There should be a low threshold for dermatology referral for immunosuppressed patients, particularly those with a history of exposure to dual immunomodulators from a young age.

Chromosomal abnormalities, including mutations, deletions and allelic losses of different oncogenes and tumour suppressor genes have been discovered in the DNA of cancer cells and the application of molecular biological techniques now permits identification of these alterations in tumours. Although it has been possible to detect potentially important genetic alterations in tumour material for some years, it is now evident that many neoplasms shed tumour cells into sputum, urine, bile, pancreatic juice, faeces and blood of infected patients. Mutated DNA has also been detected free in the plasma of patients with cancer, and the DNA alternations in plasma are identical to those in the DNA of the primary cancer cells. Thus, the identification of DNA mutations in plasma, pancreatic juice and faeces might be a useful approach for the early detection and monitoring of patients with pancreatic cancer. The K-ras gene is mutated in over 90% of pancreatic cancer. These mutations are well defined, reliably detected by DNA application in assays and occur early in the genesis of pancreatic cancer. K-ras mutations can be detected in cancer tissue and pancreatic duct secretions. K-ras mutations have also been detected in stool of patients with pancreatic cancer. Invasive techniques for obtaining pancreatic juice or pancreatic tissue are undesirable and would certainly be inappropriate for cancer screening. Similarly, there is a lack of enthusiasm for developing diagnostic techniques that involve faecal extractions. Isolation of plasma DNA from pancreatic patients and detection of K-ras alterations with a PCR assay and subsequent product sequencing showed K-ras mutations in the plasma of 17 out of 21 patients (81%), and in cases in which both plasma and pancreatic tissue were available, DNA mutations were similar in plasma and tissue. Plasma DNA alterations were found 5-14 months before the clinical diagnosis of pancreatic cancer in 4 patients. K-ras mutations are also demonstrated in micro-dissected tissues taken from patients with pancreatic hyperplasia, with or without chronic pancreatitis. This has lead to the suggestion that pancreatic cell hyperplasia may be a premalignant condition although the demonstration of K-ras alterations in some cases of chronic pancreatitis has raised doubts about the sensitivity and specificity of K-ras testing for pancreatic cancer. However, the detection of K-ras mutations in plasma may still identify patients with or at risk of developing pancreatic cancer as it may only be in these patients that sufficient quantities of mutated DNA enter and can be detected in plasma. Thus, this non-invasive approach to early cancer detection may be applicable both to diagnosis of the symptomatic patient and for screening. A combined approach with other tumour markers such as p53 gene might increase the sensitivity of the test.

The detection of a left-sided polyp on flexible sigmoidoscopy has been suggested as providing a heralding sign for right-sided tumours. We assessed our own experience with right-sided colonic cancers with reference to detection modality, surgical intervention and their association with left-sided polyps. We performed a retrospective review of a prospectively collected colorectal cancer database, with endoscopic and radiological records. Patients were subcategorised on the basis of the presence or absence of left-side polyps. Ninety-one consecutive patients who underwent curative surgery for right-sided colonic cancers were studied. Endoscopy was used to detect right-sided carcinomas in 10 (83%) of the 12 cases with synchronous left-sided polyps and radiological imaging utilised in 2 cases. In patients without evidence of left sided disease endoscopy was used in 40 (51%) of the 79 patients. In our experience most right sided cancers do not have a synchronous polyp evident on the left side 79 (87%).

A 45 year old man with a 5 year history of primary biliary cirrhosis presented with fatigue, weight loss, bone pains, itch and progressive jaundice. Examination revealed jaundice, hyperpigmantadon, cachexin, extensive xanthelasm a and palmar xanthomata, spider naevi, palmar erythema, moderate hepatosplenomegaly, testicnlar atrophy and a proximal myopathy. Investigations revealed a uholestatie liver enzyme profile, hyperbilirubinaemia (73 umoU1), hypoalbuminaemia and profound hypercholesterolaemia (cholesterol 54.5 mmol/l). Antimitochondrial antibodies(M2) were positive at a titre of 1/ 10,240. A liver biopsy revealed grade III primary biliary cirrhosis, for which he was commenced on ursodeoxycbelie acid. Ultrasound of the abdomen revealed several descrete splenic nodules. CT abdomen noted an enlarged lymph node in the porte hepatis. A splenectomy was performed. Pathology revealed an intermediate grade follicular large cell non-Hodgkin's lympbema. Post-operatively, he received six courses of chemotherapy. The serum cholesterol fell sharply to 10 mmol/l after starting ursodeoxycholie acid. This dramatic fall in cholesterol represents an important beneficial effect of ursodeoxycholic acid therapy. It underlines the potential benefits of ursodeoxycholiu acid as a lipid lowering agent in cases of hypercholesterolemia due to impaired live~ cholesterol homeostasis. A review of the literature suggests that non-Hodgkin's lymphoma complicating primary biliary cirrhosis is very rare. It is suggested that lympbema may complicate autoimmune disease as a result of impaired immunoregulation or chronic antigen stimulation. In summary, this case highlights two important findings; firstly, the effect of ursodeoxycholic acid on hepatic cholesterol metabolism, and secondly, the association between primary biliary cirrhosis and non-Hodgkin's lympfioma.

Small amounts of free DNA circulate in both healthy and diseased human plasma/serum, and increased concentrations of DNA are present in the plasma of cancer patients. Characteristics of tumour DNA have been found in genetic material extracted from the plasma of cancer patients. These features include decreased strand stability and the presence of specific oncogene, tumour suppressor gene and microsatellite alterations. Point mutations of the ras genes have been detected in the plasma DNA of patients suffering from haematopoetic malignancies, colorectal and pancreatic cancer, sometimes prior to clinical diagnosis. Rearranged immunoglobulin heavy chain DNA has been found in the plasma of patients with non-Hodgkins lymphoma and acute B cell leukaemia. Microsatellite instability, expressed either as a new allele or a loss of one allele (LOH) occurs in the plasma and serum DNA of patients suffering from head and neck, lung and renal cell cancer. The results obtained in many different cancers have opened a new research area indicating that plasma DNA might eventually be a suitable target for the development of non-invasive diagnostic, prognostic and follow-up tests for cancer.

Introduction As with other chronic diseases, patients with IBD are also at risk for depression, anxiety, low self-esteem and social isolation. The physical symptoms in gastrointestinal disease, including diarrhoea, bleeding per rectum and faecal incontinence are much less socially acceptable than other chronic diseases. Together with the potential for surgery, including stoma formation, this results in a high risk for altered body image and psychosocial distress unique to IBD. Aims/Background In this study we aimed to compare the effects of disease activity on body image and quality of life in these patients and also to assess whether biological treatment offers superior clinical and psychological outcomes or reduction in disability. Method Patients taking biologics attending St. Luke9s IBD service were asked to complete a questionnaire including the Body Image States Scale (BISS), the Stunkard Figure Rating Scales (FRS), the Hospital Anxiety and Depression scale (HADS), the Beck Depression Inventory (BDI), the SF 36 Health Survey, the IBDQ and the sexual satisfaction survey. Clinical markers of disease severity were also examined including recent endoscopic findings, Mayo score and CRP. These were then age and sex matched with IBD patients not taking biologics. Results were statistically analysed p values Results 64 IBD patients were included in this study. 32 patients were taking biologics at time of study (60% M) Median age was 41; IQR (31-54). 55% had UC, 33% had Crohn9s, 13% had indeterminate colitis. These were age, sex and disease matched with 32 respondents not taking biologics. Mayo scores, Hb and CRP were not significantly different between groups. Endoscopic severity was increased in the biologic group though not significantly. There was no significant difference in Beck Depression Inventory scores between treatment groups, however those on biologic treatment who were in remission reported significantly lower disability using the Disability Index (Peyronie et al , 2012) compared to their peers in remission not on biologics (p Conclusion Depression is common in IBD. Clinical and mucosal remission may not only lead to reduced inflammation but also to reduced levels of depression. Treatment with biologics appears to be associated with lower levels of disability in patients with similar pre-treatment clinical severity scores.

clinical load of IBD patients (p value

Unpaired t-test and one-way ANOVA statistical analyses were applied. Results: TNFa and IL-6 were increased in culture supernatants from CD although their intracellular ongoing cytokine production was decreased. LDC from CD had decreased b7 (gut-homing integrin) expression. Following IFX culture, LDC decreased b7 expression (HC only) and reduced CCR9 intensity ratio. There was a trend towards reduction in TLR2 and 4 expression in CD (not statistically significant). IL-12 production by LDC from HC was increased following IFX culture. There was a marked reduction in TNFa in cell supernatant following culture with IFX & a reduction in IL-2. Conclusions: Increased TNFa and IL-6 in culture supernatants from CD patients coupled with a decrease in ongoing production by DC suggests a negative cytokine feedback system. Reduced expression of CCR9 and elevated production of IL-12 in LDC cultured with IFX, shows reduced affinity for gut-homing and increased immunogenicity and may suggest a possible mechanism for IFX-induced paradoxical inflammation. The reduction in TNFa in the supernatant following IFX culture is likely to represent cytokine neutralization.

Anemia of chronic disorders (ACD) and iron deficiency are common features in rheumatoid arthritis (RA), but may be difficult to distinguish without marrow sampling, which is invasive, time consuming, and expensive. We sought simple laboratory measures that identified patients with absent marrow iron stores (iron deficiency).45 anemic patients with RA underwent marrow sampling in addition to a complete blood count and serum ferritin and iron saturation measurements.47% of patients had iron deficiency. These patients had significantly lower mean corpuscular volume (MCV), serum ferritin, and iron saturation. A 3 step algorithm was developed using these laboratory variables to identify iron deficiency. This algorithm correctly classified 94% patients with iron deficiency and 85% with ACD.Our study demonstrates that iron deficiency may be reliably identified by measuring serum ferritin, MCV, and iron saturation in many patients with RA, thereby avoiding the trauma and expense of marrow sampling.

Aims—To determine possible associations between p53 allelic deletion, c-Ki-ras mutational activation, immunohistochemical detection of p53 and ras proteins, various clinicopathological variables, and patient outcome in 168 Dukes' stage B colorectal carcinomas. Methods—Allelic deletion at the p53 tumour suppressor gene locus was detected using polymerase chain reaction (PCR) based loss of heterozygosity (LOH) assays. Overexpressed proteins were detected using the CM1 polyclonal antibody. A PCR based assay was used to detect the presence of activating mutations at codon 12 of c-Ki-ras. Immunostaining was carried out using a monoclonal antibody to p21ras. Results—p53 LOH, CM1 immunostaining, c-Ki-ras mutational activation, and p21ras immunostaining were not predictive of survival by logrank analysis. Multivariate analysis using Cox regression did not predict survival in this group of tumours. Conclusions—Aberrations in ras and p53 are unlikely to play an important role in the subdivision of patients with Dukes' stage B colorectal carcinoma into more accurate prognostic strata. It is possible that later genetic events are more important in conferring a specific phenotype on the resultant Dukes' stage B tumour.