[Colorectal carcinoma - How can we improve prevention?] / Kolonkarzinom.

Colorectal carcinoma - How can we improve prevention? Abstract. Colorectal cancer (CRC) is the second leading cause of cancer-related death in Europe. Comprehensive screening is useful and cost-effective. However, participation in screening programs in Switzerland is low and falls below 20 %. Immunological stool tests (FIT tests) can - when carried out every two years - detect tumours and advanced adenomas, and thus reduce mortality. These tests have replaced older guaiac faecal tests (e. g. Hämoccult®). The detection and removal of small colon polyps is still only possible through colonoscopy, which is applied for diagnostic and therapeutic purposes and continues to be the gold standard for CRC screening. The decisive factors for screening are risk-adapted prevention with stratification of patients according to risk groups and the general optimization of risk factors. Educating the patient about the advantages and disadvantages of the various screening procedures and making a shared decision are necessary prerequisites for greater participation in screening programs.

Development and validation of a symptom-based activity index for adults with eosinophilic esophagitis.

BACKGROUND & AIMS: Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE) and to provide end points for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patient assessments of disease severity. We also evaluated relationships between patient assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings. METHODS: We collected information from 186 patients with EoE in Switzerland and the United States (69.4% male; median age, 43 y) via surveys (n = 135), focus groups (n = 27), and semistructured interviews (n = 24). Items were generated for the instruments to assess biologic activity based on physician input. Linear regression was used to quantify the extent to which variations in patient-reported disease characteristics could account for variations in patient assessment of EoE severity. The PRO instrument was used prospectively in 153 adult patients with EoE (72.5% male; median age, 38 y), and validated in an independent group of 120 patients with EoE (60.8% male; median age, 40.5 y). RESULTS: Seven PRO factors that are used to assess characteristics of dysphagia, behavioral adaptations to living with dysphagia, and pain while swallowing accounted for 67% of the variation in patient assessment of disease severity. Based on statistical consideration and patient input, a 7-day recall period was selected. Highly active EoE, based on endoscopic and histologic findings, was associated with an increase in patient-assessed disease severity. In the validation study, the mean difference between patient assessment of EoE severity (range, 0-10) and PRO score (range, 0-8.52) was 0.15. CONCLUSIONS: We developed and validated an EoE scoring system based on 7 PRO items that assess symptoms over a 7-day recall period. Clinicaltrials.gov number: NCT00939263.

Cohort Profile Update: The Swiss Eosinophilic Esophagitis Cohort Study (SEECS).

Introduction: The Swiss Eosinophilic Esophagitis Cohort Study (SEECS) is a national cohort that was established in 2015 with the aim of improving quality of care of affected adults with eosinophilic esophagitis (EoE). Between 2020 and 2022, paper questionnaires were gradually replaced by fully electronic data capture using Research Electronic Data Capture (REDCap®) software. We aim to provide an update of the SEECS 8 years after its launch. Methods: The SEECS prospectively includes adults (≥18 years of age) with EoE as well as patients with gastroesophageal reflux disease (GERD) and healthy control subjects (HC). Upon inclusion and follow-up (typically once every 12-18 months), patients and physicians complete REDCap® questionnaires, which are available in German, French, and English. Patient-reported outcomes (PROs) and biologic findings are assessed on the same day using validated instruments (EEsAI PRO for symptoms; EoE-QoL-A for QoL; EREFS for endoscopic activity; modified EoE-HSS for histologic activity). The SEECS biobank includes biosamples from patients with EoE, GERD, and HC. Results: As of July 2023, the SEECS included 778 patients (716 [92%] with EoE, 29 [3.8%] with GERD, and 33 [4.2%] HC; 559/778 [71.9%] were male). Mean age ± SD (years) at enrollment according to diagnosis was as follows: EoE 41.9 ± 12.9, GERD 53.6 ± 16.4, HC 51.7 ± 17.2. Concomitant GERD was found in 200 patients (27.9%) of the EoE cohort. Concomitant allergic disorders (asthma, rhinoconjunctivitis, eczema) were present in 500 EoE patients (74.4%). At inclusion, 686 (95.8%) of EoE patients were on ongoing treatment (orodispersible budesonide tablet [Jorveza®] in 281 patients [41%]; budesonide or fluticasone syrup or swallowed powder in 290 patients [42.3%]; proton-pump inhibitors in 162 patients [23.6%]; elimination diets in 103 patients [15%]; and esophageal dilation at last visit in 166 patients [24.2%]). A total of 8,698 biosamples were collected, of which 1,395 (16%) were used in the framework of translational research projects. Conclusion: SEECS continuously grows and is operational using fully electronic data capture. SEECS offers up-to-date epidemiologic and real-world clinical efficacy data on EoE and promotes clinical and translational research.

Cohort Profile: The Swiss Eosinophilic Esophagitis Cohort Study (SEECS).

BACKGROUND AND AIMS: The prospective, observational Swiss Eosinophilic Esophagitis Cohort Study (SEECS) was set up in 2015 with the following goals in mind: (1) to provide up-to-date epidemiologic data; (2) to assess the appropriateness of care; (3) to evaluate the psychosocial impact; and (4) to foster translational research projects. Data capture relies on validated instruments to assess disease activity and focuses on epidemiologic variables and biosamples (esophageal biopsies and blood specimens). An annual inclusion of 70 new patients with eosinophilic esophagitis (EoE) or proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is intended. We herein describe the SEECS cohort profile. METHODS: The SEECS includes adult patients (age ≥18 years) with EoE or PPI-REE diagnosed according to published criteria. After inclusion, the patients are typically seen once a year for a clinical and endoscopic/histologic follow-up examination. Data are captured using validated questionnaires. Biosamples from patients with gastroesophageal reflux disease (GERD) and controls with a healthy esophagus are collected as well. RESULTS: From January 2016 to July 2017, a total of 111 patients with EoE and 10 patients with PPI-REE were recruited. In addition, esophageal biopsies and blood samples from 11 patients with GERD and 20 controls with a healthy esophagus were collected. The mean age of the patients with EoE and those with PPI-REE was 39.6 ± 12.9 and 44.6 ± 15.6 years, respectively. A male predominance was found among both the patients with EoE (77.5%) and those with PPI-REE (70%). Concomitant allergic disorders were found in 79.3% of the patients with EoE and 90% of the patients with PPI-REE. At inclusion, the EoE patients were treated with the following therapeutic regimens: no therapy (0.9%), PPI (36%), swallowed topical corticosteroids (82.9%), elimination diets (15.3%), and esophageal dilation (19.8%). CONCLUSIONS: The SEECS is the first national cohort study of patients with EoE or PPI-REE. The SEECS will provide up-to-date epidemiologic data and foster translational research projects.

Corticosteroid-dependent eosinophilic oesophagitis: azathioprine and 6-mercaptopurine can induce and maintain long-term remission.

BACKGROUND: Eosinophilic oesophagitis (EO) is a chronic inflammatory disorder of the oesophagus that is rapidly increasing in prevalence. Although systemic and topical corticosteroids are effective in treating EO, some patients develop corticosteroid dependency. Alternative therapeutic approaches that avoid corticosteroids are scarce. AIM: To analyse our experience at inducing and maintaining remission with an immunomodulatory therapy in steroid-dependent EO patients. METHODS: We analysed the clinical and histological response to azathioprine (AZA) and 6-mercaptopurine in three patients with EO (one also with eosinophilic gastroenteritis) and corticosteroid dependency. RESULTS: In all three patients, AZA or 6-mercaptopurine-induced clinical and histological remission that was maintained during the follow-up period (range 3-8 years). Two patients experienced relapses after ceasing AZA therapy. Remission, however, resumed when short-term corticosteroid treatment was followed by AZA. In all the patients, blood eosinophilia disappeared under AZA treatment. Only jumbo biopsies confirmed suspected EO with predominant muscle-layer involvement in one patient. CONCLUSION: In adult patients with corticosteroid-dependent EO, immunomodulatory treatment with purine analogues is a promising therapeutic approach for inducing and maintaining long-term remission without the need for further corticosteroids. Jumbo forcep biopsies might be needed to confirm a diagnosis of muscle-layer predominant EO.

Testing strategies and follow-up for coeliac disease in a general internal medicine outpatient department from 2000 to 2005.

PRINCIPLES: Coeliac disease (gluten sensitive enteropathy) is a genetically determined disorder with an incidence in the general population that is comparable to type 2 diabetes mellitus. Awareness of this fact and of the often atypical and oligosymptomatic manifestations is only now gaining ground in the medical profession. A high index of suspicion is important in order to minimise diagnostic and therapeutic delay. METHODS: Testing patterns and follow-up for coeliac disease in our institution have been analysed retrospectively for the past five years. The current literature was reviewed with respect to recommendations for clinical practice. RESULTS: A total of 271 patients were tested for coeliac disease over a period of five years. Only in 24 patients were positive results found; after further work-up, the final number of cases with certain or presumed coeliac disease was four. Followup was often difficult, many patients being lost after a single visit. CONCLUSIONS: This study showed that the number of tests ordered in our institution, more often for abdominal than atypical symptoms, has started to increase in the past two years. It also showed that screening tests have found their place in general clinical practice, while the final choice of tests needs to be determined in accordance with available guidelines and local resources. Upper endoscopy with small bowel biopsy remains the gold standard for diagnosis, but its place in follow-up is less certain. Coeliac disease is a disorder for which there is a definite treatment (gluten free diet); if it is left untreated diminished quality of life and potentially serious complications may ensue. Further education of the medical profession regarding coeliac disease, its incidence, presentation and treatment, is clearly indicated..

Survival analysis of 19 patients with toxic thyroid carcinoma.

Among patients with differentiated thyroid carcinoma (diffTCa), the rare hyperfunctioning or toxic TCa (ToxTCa) was diagnosed when scintigraphic hot thyroid areas were attributable only to diffTCa (diameter >1 cm by pathological examination) and/or total thyroidectomy failed to induce hypothyroidism. Of 924 cases of all TCa (papillary diffTCa 47.3%, follicular diffTCa 44.2%, others 8.5%), 19 had ToxTCa (2.1%, 15 of 19 follicular, 4 of 19 papillary, P = 0.008). These received a more intensive radioiodine therapy (average cumulated (131)I activities 21.8 vs. 15.2 GBq, P < 0.01). Five-year survival rates for ToxTCa (n = 19, 56%) and diffTCa (n = 545, 94.5%) differed [hazard ratio 4.8, 95% confidence interval (CI) 2.8-8.1, P = 0.001]. However, the differences were attenuated by matching ToxTCa and diffTCa (n = 57, 5-yr survival rate 74%) for age, sex, and histopathologic type (hazard ratio 2.1, 95% CI 1.13-3.9, P = 0.02). Correcting statistically for M(1) against M(0) stage distribution resulted in a further reduction of the hazard ratio (hazard ratio 1.8, 95% CI 0.93-3.48, P = 0.08). An M(1) stage is an important prognostic factor in ToxTCa patients. Thus, ToxTCa, treated with higher activities of (131)I, has a survival prognosis close to that of matched diffTCa cases, both groups consisting mainly (79%) of follicular subtypes.

Evaluation of magnetic resonance colonography at 3.0 Tesla regarding diagnostic accuracy and image quality.

OBJECTIVES: To assess magnetic resonance (MR)-colonography (MRC) for detection of colorectal lesions using two different T1w three-dimensional (3D)-gradient-recalled echo (GRE)-sequences and integrated parallel data acquisition (iPAT) at a 3.0 Tesla MR-unit. MATERIALS AND METHODS: In this prospective study, 34 symptomatic patients underwent dark lumen MRC at a 3.0 Tesla unit before conventional colonoscopy (CC). After colon distension with tap water, 2 high-resolution T1w 3D-GRE [3-dimensional fast low angle shot (3D-FLASH), iPAT factor 2 and 3D-volumetric interpolated breathhold examination (VIBE), iPAT 3] sequences were acquired without and after bolus injection of gadolinium. Prospective evaluation of MRC was performed. Image quality of the different sequences was assessed qualitatively and quantitatively. The findings of the same day CC served as standard of reference. RESULTS: MRC identified all polyps >5 mm (16 of 16) in size and all carcinomas (4 of 4) correctly. Fifty percent of the small polyps 0.6). CONCLUSIONS: MRC using 3D-GRE-sequences and iPAT is feasible at 3.0 T-systems. The high-resolution 3D-FLASH was slightly preferred over the 3D-VIBE because of better image quality, although both used sequences showed no statistical significant difference.

Effect of naloxone-3-glucuronide and N-methylnaloxone on the motility of the isolated rat colon after morphine.

The effect of the opioid antagonists naloxone-3-glucuronide and N-methylnaloxone on rat colon motility after morphine stimulation was measured. The rat model consisted of the isolated, vascularly perfused colon. The antagonists (10(-4) M, intraluminally) and morphine (10(-4) M, intra-arterially) were administered from 20 to 30 and from 10 to 50 min, respectively. Colon motility was determined by the luminal outflow. The antagonist concentrations in the luminal and venous outflow were measured by high-performance liquid chromatography. Naloxone-3-glucuronide and N-methylnaloxone reversed the morphine-induced reduction of the luminal outflow to baseline within 10 and 20 min, respectively. These antagonists were then excreted in the luminal outflow and could not be found in the venous samples. Naloxone, produced by hydrolysis or demethylation, was not detectable. In conclusion, highly polar naloxone derivatives peripherally antagonize the motility-lowering effect of morphine in the perfused isolated rat colon, are stable, and are not able to cross the colon-mucosal blood barrier.

Importance of extracolonic findings at IV contrast medium-enhanced CT colonography versus those at non-enhanced CT colonography.

To compare the clinical importance of extracolonic findings at intravenous (IV) contrast-enhanced CT colonography versus those at non-enhanced CT colonography. IV contrast medium-enhanced (n=72) and non-enhanced (n=30) multidetector CT colonography was performed in 102 symptomatic patients followed by conventional colonoscopy on the same day. The impact of extracolonic findings on further work up and treatment was assessed by a review of patient records. Extracolonic findings were divided into two groups: either leading to further work up respectively having an impact on therapy or not. A total of 303 extracolonic findings were detected. Of those, 71% (215/303) were found on IV contrast-enhanced CT, and 29% (88/303) were found on non-enhanced CT colonography. The extracolonic findings in 25% (26/102) of all patients led to further work up or had an impact on therapy. Twenty-two of these patients underwent CT colonography with IV contrast enhancement, and four without. The percentage of extracolonic findings leading to further work up or having an impact on therapy was higher for IV contrast-enhanced (31%; 22/72) than for non-enhanced (13%; 4/30) CT scans (P=0.12). IV contrast-enhanced CT colonography produced more extracolonic findings than non-enhanced CT colonography. A substantially greater proportion of findings on IV contrast-enhanced CT colonography led to further work up and treatment than did non-enhanced CT colonography.

Virtual colon dissection with CT colonography compared with axial interpretation and conventional colonoscopy: preliminary results.

OBJECTIVE: The aim of this study was to determine whether a new virtual colon dissection 3D visualization technique for CT colonography has a shorter analysis time and better sensitivity for detection of colonic polyps than interpretation of axial CT images. SUBJECTS AND METHODS. CT colonography was performed in 22 patients using 4-MDCT followed by conventional colonoscopy on the same day. The CT colonography data sets were analyzed by virtual colon dissection, which virtually bisects and unfolds the colon along its longitudinal axis to inspect the inner colonic surface for polyps. The same CT data sets were independently evaluated using axial interpretation. All data sets were independently interpreted by two radiologists in a blinded manner. RESULTS: Conventional colonoscopy revealed 31 colonic lesions in 20 patients. Twenty two of the lesions were smaller than 10 mm; nine were 10 mm or larger. Two of the original 22 patients were excluded, one because of residual stool and fluid and the other because of an impassable stenosing rectal wall cancer. For virtual colon dissection, the per-lesion sensitivity was 42% for observer 1 and 68% for observer 2; for axial interpretation, the respective sensitivities were 48% and 61%. For polyps 10 mm or larger, the respective sensitivities were 67% and 89% for virtual colon dissection and 89% and 100% for axial interpretation. The average time for reconstruction and analysis of virtual colon dissection was 36.8 min versus 29.2 min for axial images. Virtual colon dissection was feasible in both the supine and the prone positions in 45.5% of colonic segments, in either the supine or the prone position in 24.5%, and in neither position in 30% of segments. CONCLUSION: Although virtual colon dissection may facilitate detection of colonic polyps in isolated cases, its detection rate is not superior to axial interpretation, which is mainly attributable to failed rendering of insufficiently distended colonic segments or regions with residual feces. Virtual colon dissection is also the more time-consuming of the two procedures. With further improvement of path-finding and image segmentation, however, virtual colon dissection has the potential to be a useful interpretation tool for CT colonography.

Prospective comparison of contrast enhanced CT colonography and conventional colonoscopy for detection of colorectal neoplasms in a single institutional study using second-look colonoscopy with discrepant results.

BACKGROUND: Colorectal cancer is the second leading cause of death from cancer in Western countries. Early detection by colorectal cancer screening can effectively cut its mortality rate. CT colonography represents a promising, minimally invasive alternative to conventional methods of colorectal carcinoma screening. AIMS: The purpose of this prospective single institutional study was to compare the abilities of routine clinical CT colonography and conventional colonoscopy to detect colorectal neoplasms using second-look colonoscopy to clarify discrepant results. PATIENTS AND METHODS: CT colonography was performed in 100 symptomatic patients using contrast enhanced multidetector CT followed by conventional colonoscopy on the same day. If results were discrepant, a second-look colonoscopy was performed after unblinding. CT colonographic findings were compared with those of conventional colonoscopy. RESULTS: Conventional colonoscopy found 122 colorectal neoplasms in 49 patients. The overall sensitivity of CT colonography at detecting patients with at least one polyp 6 mm or larger was 76% and its specificity was 88%. Its by-patient sensitivity for polyps 10 mm or larger was 95% and its specificity was 98%. By-polyp sensitivities were 71% for polyps 10 mm or larger, and 61% for polyps 6 mm or larger. A second-look colonoscopy was performed in 19 patients and two initial false-positive findings of CT colonography were reclassified as true-positive. For conventional colonoscopy, this produced a by-polyp sensitivity of 94% for detection of lesions 6 mm and larger. CONCLUSIONS: CT colonography had both a high by-patient sensitivity and specificity for detection of clinically important colorectal neoplasms 10 mm or larger. This suggests that CT colonography has the potential to become a valuable clinical screening method for colorectal neoplasms.

Subtotal colectomy with primary ileorectostomy is effective for unlocalized, diverticular hemorrhage.

BACKGROUND: A large proportion of patients with acute colonic diverticular bleeding undergo emergency surgery without successful prior localization of the bleeding site. This study sought to determine the surgical techniques of choice for unlocalized, diverticular hemorrhage. METHODS: We reviewed the data on 42 consecutive patients (median age 76 years, range 44-91) with acute colonic diverticular bleeding operated on between November 1993 and December 2000. Mean follow-up was 4.1 years. RESULTS: Preoperative localization of the bleeding site was possible in six patients (14%), by colonoscopy in two and by angiography in four. Ten patients underwent segmental colectomy with primary anastomosis (5 "directed", 5 "blind") and 32 subtotal colectomy with primary ileorectostomy (1 "directed", 31 "blind"). Subtotal colectomy is the more extensive surgical procedure (longer resected bowel, greater blood loss), and although it was performed in older patients, there were no significant differences between segmental and subtotal colectomy with respect to operation time, morbidity, mortality, hospital stay, number of bowel movements, continence scores, rebleeding rate, or patient satisfaction. CONCLUSIONS: Subtotal colectomy with primary ileorectostomy for unlocalized colonic diverticular bleeding is a safe and effective surgical procedure providing complete bleeding control and preserving continence.

Preoperative colonoscopic derotation is beneficial in acute colonic volvulus.

AIMS: Analysis of preoperative and operative management of acute colonic volvulus and development of treatment guidelines in a region of low incidence. METHODS: A study of 42 consecutive patients operated for acute colonic volvulus between 1970 and 2000. RESULTS: There were 20 patients with sigmoid volvulus, 21 with cecal volvulus and 1 with volvulus of the transverse colon. All patients presented as emergencies. The correct preoperative diagnosis was possible for sigmoid volvulus in 95% (19/20) of cases and for cecal volvulus in 67% (14/21). Preoperative colonoscopic volvulus derotation was attempted in 19 patients and successfully completed in 9 patients (47%). The success rates for preoperative colonoscopic derotation were 58 (7/12) and 33% (2/6) for sigmoid and cecal volvulus, respectively. Thirty-four patients (81%) underwent colon resections, 26 times as a single-stage procedure, and 8 patients (19%) underwent non-resectional operative techniques. Overall surgical morbidity was 24%, the reoperation rate 9.5% and mortality 12% (5/42). The subgroup of 9 patients with successful non-operative volvulus derotation, however, underwent semi-elective single-stage colonic resection without surgical morbidity or mortality. There were no recurrences during a median follow-up period of 9.5 years. CONCLUSION: In the absence of clinical, laboratory or radiological signs of bowel necrosis or perforation, colonoscopic volvulus derotation is recommended in all cases of acute colonic volvulus, followed by semi-elective single-stage colonic resection.

Surgical management of large sessile villous and tubulovillous adenomas of the lower rectum.

BACKGROUND: Large sessile adenomas of the rectum are premalignant lesions necessitating complete removal. METHODS: We reviewed the data on 20 consecutive patients with large (>or=2 cm) sessile villous and tubulovillous adenomas of the lower two thirds of the rectum (or=50% or an endosonographic staging of >or=uT2 underwent a low anterior resection of the rectum. The remaining 9 patients underwent a posterior full-thickness local bowel wall resection (modified Mason procedure). The median (range) follow-up period was 3.8 (0.7-8.2) years. RESULTS: Preoperative biopsy examination successfully excluded invasive carcinoma. Overstaging, however, occurred in 9 of 12 patients (75%) undergoing endosonography, resulting in surgical overtreatment of 4 patients. A curative resection (R0) was always achieved. Five patients had complications, but there was no in-hospital mortality and no cases of local recurrence. 4 out of 19 patients complained of minor stool incontinence, and 3 patients reported incomplete rectal emptying or constipation. Fourteen patients described the operative result as excellent (n = 7) or good (n = 7). CONCLUSIONS: Endosonography may lead to overstaging and overtreatment. An individualized approach based on the degree of adenomatous circumferential involvement and endosonographic staging showed no mortality, low morbidity, no local recurrence, and good functional medium-term results.

Interaction of hepatocyte growth factor and non-steroidal anti-inflammatory drugs during gastric epithelial wound healing.

BACKGROUND/AIMS: Expression of the hepatocyte growth factor (HGF) and cyclooxygenase-2 (COX-2) is upregulated at the margins of healing gastric ulcers. We investigated in vitro the interference of HGF, the selective COX-2 inhibitor NS-398 and the nonselective COX inhibitor indomethacin with gastric epithelial wound healing and actin microfilament (actin-MF) formation. METHODS: Standardized gastric epithelial wounds, created in confluent RGM1 rat cell monolayers were treated with: HGF (10 ng/ml), NS-398 (1-100 microM) or indomethacin (0.01- 0.5 mM). The areas of re-epithelialization and cell proliferation were measured 24 h after wounding. Actin-MFs were labeled with fluorescein-conjugated phalloidin and their distribution was examined using a Nikon epifluorescence microscope. RESULTS: HGF caused a significant increase in gastric monolayer wound re-epithelialization and this was not affected by mitomycin C. Both indomethacin and NS-398 inhibited HGF-stimulated re-epithelialization, but the basal wound re-epithelialization rate and cell proliferation was only significantly inhibited by indomethacin. HGF triggered actin stress fiber formation which was inhibited by both indomethacin and NS-398, but only indomethacin interfered with actin-MF formation at the baseline condition. CONCLUSIONS: HGF significantly increased gastric wound re-epithelialization by activating cell migration which may be mediated by the COX-2 pathway.