Integrating the Patient Perspective to Validate a Measure of Disease Severity in Inflammatory Bowel Disease: Online Survey of Patients and Their Physicians.

BACKGROUND: The patient perspective is essential for assessing disease severity, but it is not always adequately considered. We describe how a comprehensive clinical disease severity index (DSI) for inflammatory bowel disease (IBD) correlates with patient global self-assessment (PGSA). METHODS: In an individually linked parallel online survey, physicians provided the DSI, and patients provided self-assessed severity using a global question and visual analog scale (0-100) (PGSA). Mean DSI values by PGSA were calculated with 95% confidence intervals. Pearson correlation (r) and the intraclass correlation coefficient were calculated for PGSA vs DSI. Positive predictive values for identifying severe disease with PGSA categories as a reference were based on a threshold >22 points. RESULTS: The primary analysis included 89 pairs (46 Crohn's disease [CD], 43 ulcerative colitis [UC]) with strict criteria and 147 pairs when less stringent. Common reasons for exclusion were missing values for albumin or colonoscopy. Mean DSI values showed no clear trend with increasing PGSA in CD but good discrimination between moderate, severe, and very severe PGSA in UC. For PGSA on the visual analog scale, r was 0.54 for CD and 0.59 for UC (difference in means: CD 27.7, UC 13.8; intraclass correlation coefficient: CD 0.48, UC 0.58). A high DSI predicted severe disease in 76.2% of CD and 65.2% of UC. CONCLUSIONS: The DSI showed good discrimination for patient-reported disease severity in UC but performed unsatisfactorily in CD. Correlations were moderate. Further refinement of the DSI is suggested to better reflect the patient perspective.

The performance of an inflammatory bowel disease severity score was compared with self-perceived severity based on an individually linked online survey of patients and their physicians. Agreement and prediction of severe disease were moderate and should be improved by integrating the patients' perspective.

Transabdominal ultrasound in inflammatory bowel disease. Conventional and recently developed techniques--update.

Transabdominal ultrasound is clinically useful in detecting Crohn's disease (initial diagnosis) by evaluating bowel wall thickness and surrounding structures including periintestinal inflammatory reaction, extent and localization of involved bowel segments and detection of extraluminal complications such as fistula, abscesses, carcinoma and ileus. Transabdominal ultrasound presently is accepted as a clinically important first line tool in assessing patients with Crohn's disease irrespective of their clinical symptoms and/or disease activity. It helps to better characterize the disease course in individual patients and can guide therapeutic decisions. In this review the current literature will be analysed.

Effectiveness of education for gastric cancer patients: a controlled prospective trial comparing interactive vs. lecture-based programs.

OBJECTIVE: Although patient education may enhance knowledge, coping with illness, and quality of life among cancer patients, it is uncertain which didactic method is most effective. We compared the impact of an interactive, patient-oriented group program to a lecture-based, information-only program in gastric cancer patients. METHODS: In this prospective, controlled trial, 121 gastric cancer patients attending inpatient rehabilitation after surgical treatment received either the interactive intervention or lectures providing information. The outcomes were patients' disease-related knowledge, active coping with illness, and quality of life (QoL) at the end of their stay and 6 and 12 months thereafter. RESULTS: Both groups improved their knowledge and QoL during rehabilitation; however, knowledge was significantly higher in the interactive group compared to the lecture group. This difference was maintained at the 6- and 12-months follow-ups. In addition, the interactive group proved superior to the lecture group regarding active coping with illness and QoL at the end of rehabilitation, but not during follow-up. CONCLUSIONS: A structured, interactive patient education program proved superior to lecture-based provision of information in regards to short-term and long-term knowledge as well as short-term coping and QoL. PRACTICE IMPLICATIONS: In gastric cancer patients, interactive patient education seems preferable over lectures.

[Celiac sprue and malignancies: analysis of risks and prevention strategies]. / Einheimische Sprue und Malignomrisiko.

Although the absolute risk of enteropathy-associated malignancies in celiac disease is generally very small due to low prevalence/incidence rates, the relative risk may be considerable so that prevention strategies based on appropriate data seem clinically desirable. The great majority of the case-control and cohort studies which have been published in the last years point to a significantly elevated risk for tumors in the gastrointestinal (GI) tract in terms of hazard/odds ratios, observed/expected ratios, and/or standardized incidence/morbidity ratios in the magnitude>5.0, whereas the risk for tumor outside the GI tract seems to be much lower (PubMed December 2007). Chronic inflammation with persistent symptoms/complaints and especially chronic refractory disease type II are considered to be particular individual risk factors. In addition, genetic factors and/or certain gene combinations may unfavorably influence the course of the disease. In the absence of controlled and prospective trials and corresponding evidence-based guidelines as they have been published for colon cancer, the strategies of prevention in patients with celiac disease differ from center to center according to their own experience/ expertise. Besides regular clinical, serologic/immunologic and endoscopic/histologic assessment a careful history taking with special regard to the disease course and a detailed ultrasound examination of the entire abdomen in patients at risk may play an important role in the long-term follow-up.

Short-term moderate exercise programs reduce oxidative DNA damage as determined by high-performance liquid chromatography-electrospray ionization-mass spectrometry in patients with colorectal carcinoma following primary treatment.

OBJECTIVE: Oxidative DNA damage is believed to be involved in tumor formation and may be an important biomarker for malignant transition or relapse. A decrease of such damage has been observed in human and animal studies following dietary intervention and/or changes in lifestyle such as physical exercise at different levels of intensity. The purpose of this study was to carry out a clinical trial comparing the effects of a short-term (2 weeks) exercise program of moderate intensity (0.3-0.4 x maximal exercise capacity) (MI) versus high intensity (0.5-0.6 x maximal exercise capacity) (HI) on individual urinary excretion of 8-oxo-dG before and after completion of the exercise programs. MATERIAL AND METHODS: In this short-term, prospective and randomized trial, 19 patients with colorectal cancer were allocated to the MI group following primary therapy and 29 to the HI group. Urinary 8-oxo-dG excretion concentration was determined by a highly sensitive detection method using high-performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC-ESI-MS). Concentrations were determined immediately before and after completion of the exercise programs. RESULTS: Using HPLC-ESI-MS, it was shown that MI exercise significantly reduced urinary 8-oxo-dG excretion levels from 8.47 +/- 1.99 to 5.81 +/- 1.45 (ng/mg creatinine, mean +/- SE, p = 0.02), whereas HI exercise resulted in a non-significant increase from 5.00 +/- 1.31 to 7.11 +/- 1.63 (ng/mg creatinine, p = 0.18). Clinical characteristics (gender, age, body mass index (BMI), diet, chemotherapy/irradiation) were not associated/correlated with urinary 8-oxo-dG levels. CONCLUSIONS: By using HPLC-ESI-MS it was shown that short-term MI exercise after primary therapy in patients with colorectal cancer was associated with lower levels of urinary 8-oxo-dG, suggesting decreased oxidative DNA damage. In contrast, HI exercise tended to increase DNA damage. A prospective trial is now warranted to prove that reduced oxidative DNA damage lowers the risk of relapse of colorectal cancer in treated patients.

[Crohn's disease and cancer risk. Incidence/prevalence, clinical characteristics, and potential prevention strategies]. / Morbus Crohn und Malignomrisiko: Häufigkeit, klinische Charakteristika und mögliche Präventionsstrategien.

Epidemiologic data concerning the risk for colorectal cancer in ulcerative colitis are based on a variety of large and well-conducted cohort studies. Guidelines for tumor prevention have been published by the German Gastroenterology Society (DGVS) in 2004. By contrast, the risk constellations in Crohn's disease are less clear and guidelines are lacking. Based on a recent literature search (PubMed March 2007), the published data predominantly expressed as relative risk and/or standardized incidence/mortality ratio are critically reviewed with recommendations for tumor prevention strategies based on individual risk constellations.

Colonic ornithine decarboxylase in inflammatory bowel disease: ileorectal activity gradient, guanosine triphosphate stimulation, and association with epithelial regeneration but not the degree of inflammation and clinical features.

The role of colonic mucosal ornithine decarboxylase (ODC) in inflammatory bowel disease (IBD) remains controversial. This study assessed mucosal ODC activity in IBD patients segment by segment with regard to patient characteristics, disease activity/duration, medication, degree of mucosal inflammation, and presence/absence of epithelial regeneration and guanosine triphosphate (GTP) stimulation. Mucosal ODC activity was determined in biopsy specimens from the terminal ileum, cecum/ascending, transverse, and descending colon, and the sigmoid/rectum of 35 patients with IBD (18 with Crohn's disease, 17 with ulcerative colitis) and 29 controls, using the amount of 14CO2 liberated from (carboxyl-14C)ornithine hydrochloride. GTP-stimulatable activity was expressed as the ratio of ODC activity in the presence and absence of GTP (70 micromol/L). Mucosal inflammation was assessed endoscopically/microscopically with previously described criteria. Presence/absence of mucosal regeneration also was determined by predefined criteria. Mucosal ODC-activity did not significantly differ in IBD patients and controls. There was a 4.4-fold activity gradient from the ileum to the rectum. Mucosal ODC activity was significantly higher in areas with epithelial regeneration compared to those without regeneration, and was stimulated by GTP by a factor of 1.42 in Crohn's disease and 1.19 in ulcerative colitis patients compared to controls (p < 0.004). On the other hand, there was no significant association/relationship of mucosal ODC activity with disease activity/duration and the endoscopic/histologic degree of mucosal inflammation. The observation of unchanged mucosal ODC activity in patients with IBD and the absence of a significant relationship with clinical and endoscopic/histologic disease characteristics speaks against a major role of ODC in IBD as a major disease marker. The role of the ileorectal gradient, the enhanced activity in areas with epithelial regeneration, and the GTP-stimulatable form, however, need further investigation with regard to a possible involvement in carcinogenesis in IBD.

Prospective comparison of short- and long-term effects of pelvic floor exercise/biofeedback training in patients with fecal incontinence after surgery plus irradiation versus surgery alone for colorectal cancer: clinical, functional and endoscopic/endosonographic findings.

OBJECTIVE: The influence of irradiation on the clinical severity of incontinence, sphincter function, morphologic features and short/long-term treatment effects of sphincter training therapy is still insufficiently understood in irradiated patients with fecal incontinence after surgery for colorectal cancer. These parameters were compared in irradiated and non-irradiated patients and followed prospectively with regard to short- and long-term training effects. MATERIAL AND METHODS: Forty-one patients having been irradiated after surgery (50.0+/-5.0 Gy) and 54 non-irradiated patients with fecal incontinence participated in this prospective, non-randomized trial. Baseline evaluation included a semiquantitative severity assessment score of fecal incontinence (modified Cleveland Incontinence Score (MCIS)), rectal manometry and endoscopy. After 3 weeks (short term) of intensive in-hospital pelvic floor exercise combined with biofeedback training, a second evaluation was made. In addition, anal endosonography (EUS) was performed in cases of treatment failure. After one year (long term) a third evaluation was made clinically (MCIS score). RESULTS: Irradiated patients presented with a significantly higher degree of fecal incontinence (lower MCIS) compared to non-irradiated patients: 7.4+/-2.2 versus 8.7+/-2.7 points (p<0.001). Rectosigmoidal inflammation was more frequent in irradiated than non-irradiated patients (26.9% versus 9.3%) (p<0.03). Sphincter pressure, sensation/pain threshold and the rectoanal inhibitory reflex were similar in both groups. A significant short-term training effect was observed in both groups following sphincter training therapy in terms of an increase in MCIS from 7.4+/-2.2 to 9.4+/-2.7 points in the irradiated group and from 8.7+/-2.7 to 11.4+/-2.5 points in the non-irradiated group (p<0.0001). After one year the scores were 8.2+/-3.8 and 10.7+/-4.4 points, respectively (p<0.0001). There was a significant correlation (p<0.001) between baseline MCIS and the short- and long-term MCIS. In patients with short-term treatment failure (16.6%) anal EUS revealed structural defects of the external sphincter in four patients. There was no association of sphincter diameter with sphincter pressure, sensation/pain threshold and short/long-term MCIS. CONCLUSIONS: The main result of this study is that irradiated patients show short- and long-term training effects comparable with those of non-irradiated patients despite the higher degree of incontinence at baseline. The correlation between the initial MCIS and short- and long-term treatment effects may be regarded as an important clinical predictor for treatment outcome. Functional and morphologic features are less suitable for this purpose.

Decreased interleukin-1 receptor antagonist response following moderate exercise in patients with colorectal carcinoma after primary treatment.

Clinical and experimental studies have shown that a moderately increased physical activity level may have beneficial effects in terms of exercise conditioning, resistance to infection and decreased relative risk of cancer. Modulation of the innate and adaptive components of the immune system with a shift of cytokines and their antagonists to a more pro- and less anti-inflammatory response was found to be a prominent feature in non-tumor patients and healthy volunteers. As quantitative data concerning the cytokine/antagonist response following exercise are not available for tumor patients, we compared the effects of a post-operative rehabilitation program with moderate exercise (ME) intensity (0.55-0.65 x maximal aerobic power) with a program with low exercise (LE) intensity (0.30-0.40 x maximal aerobic power) in patients with curatively treated colorectal carcinoma (UICC II and III) measuring pro- (IL-1beta, IL-6, tumour necrosis factor (TNF)) and anti-inflammatory cytokines (IL-1 receptor antagonist, sTNF receptors I and II). Twenty-three patients participated in this prospective trial, N = 13 in the ME group, N = 10 in the LE group. Exercise was performed daily 30-40 min for 2 weeks. Basal (circulating) and LPS-stimulated (phasic) cytokine and antagonist response was determined before exercise and after 1 and 2 weeks using appropriate ELISA tests. The LPS-stimulated interleukin-1 receptor antagonist (IL-1ra) response in the ME group gradually decreased from 31,532.6 (160.0-70,028.0) to 18,033.0 pg/ml (5040.0-52,570.0) after one and to 22,892.0 pg/ml (6376.0-34,726.0) after 2 weeks (P < 0.05) with a concomitant decrease of the corresponding IL-1ra/IL-6 and IL-1ra/IL-1beta ratio: 2.51-1.41 and 4.1-3.1, respectively. In contrast, in the LE group LPS-stimulated cytokines and antagonists did not significantly change during exercise. Circulating cytokines and antagonists remained unchanged in both groups. In providing quantitative data in patients with curatively-treated colorectal cancer, we demonstrated that a short-term rehabilitation program with moderate exercise leads to a decreased LPS-induced antagonist response with a shift to a more pro-inflammatory state (decreased antagonist/cytokine ratio). Whether this change of the phasic immune response to moderate exercise may be clinically beneficial (decreased rates of infection, relapses and/or second tumours) is possible, but has to be investigated in long-term studies.

Effects of bile acids on base hydroxylation in a model of human colonic mucosal DNA.

BACKGROUND AND AIMS: Increased intestinal bile acids as a possible consequence of a high fat/meat, low fiber diet are believed to play an important role in the formation of colon cancer. Interactions of bile salts particularly secondary bile acids with different cell components including DNA may contribute to carcinogenesis. To further investigate DNA damage by bile salts, we assessed the effects of a bile salt mixture containing deoxycholate and chenodeoxycholate on base hydroxylation in Chelex-treated DNA from calf thymus as a model of human colonic mucosal DNA in the presence and absence of reactive oxygen metabolites (ROM). METHODS: Chelex-treated DNA from calf thymus (to remove residual iron impurities) was incubated with different bile salt concentrations (4 microM, 4.0 mM) (20.0% deoxycholate, 21.0% chenodeoxycholate) in the presence and absence of an OH generating system (25 microM FeCl3, 50 microM H2O2, 100 microM nitrilotriacetic acid) for 18 h (37 degrees C). After hydrolyzation, lyophilization and derivatization hydroxylated DNA bases were characterised and quantitated with gas chromatography-mass spectrometry (GS-MS) and SIM analysis. Two concentration ranges of bile salts were used, micromolar concentrations being present in plasma, millimolar in the gut lumen. RESULTS: In the absence of ROM Chelex-treated DNA preparations contain only small amounts of hydroxylated base products. Bile salts at 4.0 mM significantly increased the amounts of 5-OH uracil and cis-thymine glycol. In the presence of ROM bile salts at 4.0 microM increased the production of 8-OH adenine and 8-OH guanine whereas bile salts at 4.0 mM inhibited ROM-induced base hydroxylation. DISCUSSION: In the absence of ROM millimolar concentrations of a bile salt mixture with deoxycholate and chenodeoxycholate increase basal (spontaneous) DNA hydroxylation, whereas, they are without effects at micromolar concentrations. In the presence of ROM micromolar concentrations enhance oxidative DNA damage and millimolar concentrations were inhibitory. These results support the view that bile acids may cause oxidative DNA damage depending on their concentrations and the surrounding conditions both directly (enhancement of basal hydroxylation) and indirectly (enhancement of ROM-induced hydroxylation).