Case 296: Phlebosclerotic Colitis.

History A 55-year-old woman without systemic underlying disease, such as diabetes mellitus, inflammatory bowel disease, autoimmune disease, or chronic kidney disease, presented with generalized dull abdominal pain of 1-week duration. She had ingested herbal medicine for physical conditioning for several years. Laboratory findings, including biochemistry, electrolyte levels, and complete blood count, were all within normal limits, except for elevated serum C-reactive protein level (7.719 mg/dL; normal range, <1 mg/dL). The patient underwent initial evaluation with conventional abdominal radiography. She underwent subsequent evaluation with noncontrast CT of the abdomen and colonoscopy.

Prognostic and Diagnostic Values of miR-506 and SPON 1 in Colorectal Cancer with Clinicopathological Considerations.

PURPOSE: One of the most common cancers in the world is colorectal cancer, which has increased significantly in recent decades. In the carcinogenicity process in the colon, there are genes involved in various cellular processes, such as cell cycle, apoptosis, and cell migration. According to studies carried out, both miR-506 and SPON 1 genes are involved in the process which initiates and promotes cancer. In this study, alterations in the expression of target genes from the viewpoint of carcinogenicity were studied and evaluated. METHODS: Fifty tumor tissues and normal marginal tissue were collected from patients who were undergoing colorectal cancer surgery. After the extraction of RNA, the real-time PCR method was performed to evaluate the gene expression. Also, alterations of gene expression in response to defined amounts of chemotherapeutic drugs (IC50) were evaluated. P < 0.05 was considered statistically significant. RESULTS: The relative expression level of miR-506 in tumor tissues was significantly decreased in comparison with healthy marginal tissues (P = 0.044). On the other hand, the SPON1 gene expression level was decreased too in tumor tissues in comparison with healthy marginal tissues (P = 0.019). There was also a significant relationship between the expression of target genes and clinicopathological involvement. However, there was no significant alteration in these genes along with the chemotherapeutic drug. CONCLUSION: These findings suggest that the relative expression of miR-506 and SPON 1 gene can be considered as a diagnostic or predictive biomarker for colorectal cancer. However, further studies on protein levels should be conducted.

Role of Ulcerative Colitis Endoscopic Index of Severity (UCEIS) versus Mayo Endoscopic Subscore (MES) in Predicting Patients' Response to Biological Therapy and the Need for Colectomy.

BACKGROUND: The main goal in the treatment of ulcerative colitis (UC) is to achieve mucosal healing. Despite being unvalidated, the most widely used scoring system is the Mayo endoscopic subscore (MES). However, the recently established and validated Ulcerative Colitis Endoscopic Index of Severity (UCEIS) represents an interesting alternative method in assessing endoscopic disease activity. OBJECTIVE: Due to a lack of reliable prognostic factors, the aim of this study was to investigate the diagnostic accuracy of the UCEIS and the MES, in predicting response to biological therapy and the need for colectomy. METHODS: We conducted a retrospective, uncontrolled, single-center study on UC patients with endoscopically active disease even with concomitant conventional and/or biological therapy, who had already started or had been changed a biological treatment. RESULTS: Sixty-one UC patients were enrolled. At baseline, 71% were naive to biological therapies and 41% had an extensive colitis. At control time (median time of 11.5 months), MES and UCEIS scores significantly decreased from those at baseline (from 2.6 to 1.8 and 5 to 3.2, respectively, p < 0.001). UCEIS, but not MES, was found to be significantly associated with unresponsiveness to therapy (p = 0.040). Moreover, when UCEIS was ≥7, all patients underwent colectomy after a median time of 5 months (p < 0.001). CONCLUSION: UCEIS may be superior to MES because of its accuracy and predictive role. Therefore, UCEIS should be considered for use in daily clinical practice.

Theranostic Gastrointestinal Endoscopy: Bringing Healing Light to the Lumen.

Current conventional endoscopes have restricted the accuracy of treatment delivery and monitoring. Over the past decade, there have been major developments in nanotechnology and light triggered therapy, potentially allowing a better detection of challenging lesions and targeted treatment of malignancies in the gastrointestinal tract. Theranostics is a developing form of personalized medicine because it combines diagnosis and targeted treatment delivered in one step using advances in nanotechnology. This review describes the light-triggered therapies (including photodynamic, photothermal, and photoimmunotherapies), nanotechnological advances with nanopowder, nanostent, nanogels, and nanoparticles, enhancements brought to endoscopic ultrasound, in addition to experimental endoscopic techniques, combining both enhanced diagnoses and therapies, including a developed prototype of a "smart" multifunctional endoscope for localized colorectal cancer, near-infrared laser endoscope targeting the gastrointestinal stromal tumors, the concept of endocapsule for obscure gastrointestinal bleed, and a proof-of-concept therapeutic capsule using ultrasound-mediated targeted drug delivery. Hence, the following term has been proposed encompassing these technologies: "Theranostic gastrointestinal endoscopy." Future efforts for integration of these technologies into clinical practice would be directed toward translational and clinical trials translating into a more personalized and interdisciplinary diagnosis and treatment, shorter procedural time, higher precision, higher cost-effectiveness, and less need for repetitive procedures.

Dysplastic Aberrant Crypt Foci: Biomarkers of Early Colorectal Neoplasia and Response to Preventive Intervention.

The discovery of aberrant crypt foci (ACF) more than three decades ago not only enhanced our understanding of how colorectal tumors form, but provided new opportunities to detect lesions prior to adenoma development and intervene in the colorectal carcinogenesis process even earlier. Because not all ACF progress to neoplasia, it is important to stratify these lesions based on the presence of dysplasia and establish early detection methods and interventions that specifically target dysplastic ACF (microadenomas). Significant progress has been made in characterizing the morphology and genetics of dysplastic ACF in both preclinical models and humans. Image-based methods have been established and new techniques that utilize bioactivatable probes and capture histologic abnormalities in vivo are emerging for lesion detection. Successful identification of agents that target dysplastic ACF holds great promise for intervening even earlier in the carcinogenesis process to maximize tumor inhibition. Future preclinical and clinical prevention studies should give significant attention to assessing the utility of dysplastic ACF as the earliest identifiable biomarker of colorectal neoplasia and response to therapy.See all articles in this Special Collection Honoring Paul F. Engstrom, MD, Champion of Cancer Prevention.

Effect of interval between preoperative radiotherapy and surgery on clinical outcome and radiation proctitis in rectal cancer from FOWARC trial.

OBJECTIVE: The aim of this study was to evaluate the effect of the interval between CRT and surgery on radiation proctitis, the pathologic response, and postoperative morbidity. METHODS: This was a cohort study from a phase III, randomized controlled trial (FOWARC study, NCT01211210). Data were retrieved from the leading center of the trial. Patients were divided into the short-interval (≤7 weeks) group and the long-interval (>7 weeks) group. The rate of radiation proctitis, pathologic complete regression (pCR) and morbidities were calculated for each group. Multivariate analysis was used to verify the impact of interval on radiation proctitis. RESULTS: Surgery was performed in 60 patients after an interval of ≤7 weeks and in 97 patients after an interval of >7 weeks. The two groups according to interval were comparable in terms of baseline demographic and clinicotherapeutic characteristics. Radiation proctitis was identified by imaging in 9 (15.0%) patients in short-interval group and in 31 (32.0%) patients in long-interval group (P = .018). Multivariate analysis confirmed the correlation between long interval and radiation proctitis (P = .018). The long interval was significantly associated with longer median operation time compared to the short interval (P = .022). The rates of pCR and postoperative complications were not different between two groups. CONCLUSIONS: A longer interval after CRT may be associated with higher rate of radiation proctitis and longer operation time. Moreover it did not increase the rate of pCR.

Colitis with wall thickening and edematous changes during oral administration of the powdered form of Qing-dai in patients with ulcerative colitis: a report of two cases.

Orally administered Qing-dai, called indigo naturalis in Latin, is reportedly useful for the treatment of ulcerative colitis. We herein describe two patients with ulcerative colitis who developed colitis with wall thickening and edematous changes during oral administration of the powdered form of Qing-dai. In Case 1, a 35-year-old man developed colitis similar to ischemic colitis with bloody stool that recurred each time he ingested Qing-dai. He had no signs of recurrence upon withdrawal of Qing-dai. In Case 2, a 43-year-old woman underwent ileocecal resection for treatment of an intussusception 2 months after beginning oral administration of Qing-dai. Edema and congestion but no ulceration were present in the mucosa of the resected specimen. Both patients exhibited abdominal pain with bloody diarrhea, and abdominal computed tomography showed marked wall edema affecting an extensive portion of the large bowel.

Twice-daily Budesonide 2-mg Foam Induces Complete Mucosal Healing in Patients with Distal Ulcerative Colitis.

BACKGROUND AND AIMS: Mucosal healing is an important therapeutic goal for ulcerative colitis. Once-daily administration of budesonide 2-mg foam is widely used for inducing clinical remission. No study has assessed the usefulness of twice-daily budesonide 2mg foam on mucosal healing in ulcerative colitis patients. We explored the efficacy for mucosal healing of once- or twice-daily budesonide foam in distal ulcerative colitis patients. METHODS: This study was a multicentre, randomised, double-blind, placebo-controlled trial. In all, 165 patients with active, mild to moderate distal ulcerative colitis were randomised to three groups: once- or twice-daily budesonide 2mg/25ml foam, or placebo foam, for 6 weeks. Complete mucosal healing [endoscopic subscore = 0] and the safety profile were assessed at Week 6. Prespecified and post hoc analyses were used. RESULTS: The percentages of complete mucosal healing in the twice-daily budesonide foam group were 46.4% compared with 23.6% in the once-daily group [p = 0.0097], or 5.6% in the placebo group [p < 0.0001]. The percentages of clinical remission and the percentages of endoscopic subscore ≤ 1 in the twice-daily budesonide foam group were 48.2% and 76.8%, compared with 50.9% and 69.1% in the once-daily group [no difference], or 20.4% and 46.3% in the placebo group [p = 0.0029 and p = 0.0007], respectively. In the subgroup of patients with previous use of a 5-aminosalicylic acid suppository or enema, there was a greater percentage of complete mucosal healing in the twice-daily budesonide foam group [32.0%] compared with that in the once-daily [8.7%, p = 0.0774] or placebo groups [4.8%, p = 0.0763], though there was no significant difference. No serious adverse event occurred. CONCLUSIONS: A significantly greater percentage of patients receiving twice-daily administration of budesonide foam compared with once-daily administration/placebo achieved complete mucosal healing. This is the first study to evaluate the endoscopic efficacy of twice-daily administration of 6-week budesonide foam treatment for ulcerative colitis.

Effects of corn oil administered orally on conspicuity of ultrasonographic small intestinal lesions in dogs with lymphangiectasia.

Lymphangiectasia is one of the causes of protein-losing enteropathy in dogs and characteristic ultrasonographic small intestinal lesions have been previously described. The purpose of this study was to determine whether corn oil administered orally (COAO) would result in increased conspicuity of these characteristic small intestinal ultrasonographic lesions in dogs with lymphangiectasia. Affected dogs were included if they underwent corn oil administered orally and had a surgical full-thickness intestinal biopsy diagnosis of lymphangiectasia. Control dogs had normal clinical examination and standard laboratory test findings. Ultrasound images of duodenum, jejunum, and ileum were obtained prior to and 30, 60, 90, and 120 min after corn oil administered orally for all dogs. Parameters recorded for each ultrasound study were intestinal wall thickness, mucosal echogenicity, and presence or absence of hyperechoic mucosal striations (HMS) and a parallel hyperechoic mucosal line (PHML). Nine affected and five controls dogs were included in the study. Seven of the nine dogs with lymphangiectasia had hyperechoic mucosal striations prior to corn oil administered orally. Jejunal hyperechoic mucosal striations were significantly associated with lymphangiectasia at multiple time points (P < 0.05) and were best identified in dogs with lymphangiectasia 60 or 90 min after corn oil administered orally. Increased mucosal echogenicity was observed in all dogs at multiple time points after corn oil administered orally. A parallel hyperechoic mucosal line was present in the jejunum in 4/5 healthy and 6/9 dogs with lymphangiectasia at one or more time points after corn oil administered orally. Findings indicated that corn oil administered orally improves conspicuity of characteristic ultrasonographic lesions in dogs with lymphangiectasia, however some of these lesions may also be present in healthy dogs that recently received a fatty meal.

[Polygonal mosaic-like pattern of the colonic mucosa in cecal volvulus: CT findings]. / Patrón en mosaico de la pared del colon en un caso con vólvulo de ciego: hallazgos en TC.

A polygonal mosaic-like pattern of colonic mucosa is a rare radiological finding that was first described in studies using barium enema. We describe the CT findings of this pattern in a case of cecal volvulus.

Early invasive colorectal carcinomas with submucosal invasion: radiographic characteristics with barium double contrast images.

BACKGROUND: We assessed the radiographic characteristics of early colorectal carcinomas with submucosal invasion (CCSI) with the use of double-contrast images. METHODS: From 1989 to 1997, 193 patients with 196 CCSI lesions underwent double-contrast barium enema examinations. Three gastrointestinal radiologists retrospectively reviewed the radiographic characteristics of the lesions and classified them as protruding and depressed types by consensus. Further, subclassifying the protruding into lobular and smooth types was accomplished on the basis of surface structure. Each type was compared with pathologic findings of resected specimens. RESULTS: The incidence of the protruding type was 98.0%, and that of the depressed type was only 2.0%. The proportion of smooth lesions was 49.0% for the protruding type; these had a mean diameter of 17.9 mm, which was significantly smaller than the 23.1 mm mean observed for lobular lesions (p < 0.01). Of the smooth lesions, 44.7% demonstrated massive invasion, whereas 91.8% of lobular lesions exhibited only slight or moderate invasion into the submucosa (p < 0.01). The extent of invasion of the smooth lesions was greater than that for their lobular counterparts in terms of venous and lymph node involvement. CONCLUSION: Almost all CCSIs could be identified radiologically as protruding lesions; these had a smooth rather than a lobulated surface and demonstrated greater malignancy, despite the smaller size. It is clinically important to discriminate these from other polypoid lesions in establishing patient treatment. Double-contrast imaging is useful for evaluation of the surface characteristics of CCSIs in barium enema studies.

[Importance of coloncontrast enema]. / Stellenwert des Kolondoppelkontrasteinlaufs.

Screening for colorectal cancer starts with digital exploration of the rectum and was extended in 1977 using the haemoccult test. It was referred to detect 24% of malignancies, but with a high number of false positive findings. Combination of regular follow up examinations and coloscopy reached a sensitivity of 80%. International studies demonstrated the need of a complete colon examination, so that the coloscopy is actually an important screening method in Germany. The coloncontrast examination is a safe, cost-effective method with a low complication rate. It is suitable especially for patients, in which the colonoscopic evaluation of the colon was not complete and provides additional morphological informations in many cases.

Mesenteric phlebosclerosis: a new disease entity causing ischemic colitis.

PURPOSE: Nonthrombotic stenosis or occlusion of the mesenteric veins is a rare cause of intestinal ischemia. The aim of this study was to describe a new disease entity causing chronic ischemic colitis. METHODS: Seven patients were diagnosed as having mesenteric phlebosclerosis. All seven patients had calcifications in the small mesenteric veins and their intramural branches. No evidence of vasculitis or portal hypertension was recognized. None of the patients had a history of gastrointestinal disease or of prolonged drug use. We report clinical, laboratory, radiographic, endoscopic, and histopathologic findings. RESULTS: Clinical findings included abdominal pain and diarrhea of a gradual onset and chronic course. A positive fecal occult blood test and mild anemia were often found. The patients had linear calcifications and stenosis in the right colon, which were discovered by plain abdominal radiography and barium enema, respectively. Endoscopic findings included edematous, dark colored mucosa and ulcerations. Four patients underwent a subtotal colectomy because of persistent abdominal pain or ileus. The histopathologic findings were macroscopically characterized by a dark purple or dark brown colored colonic surface, the swelling and disappearance of plicae semilunares coli, and marked thickening of the colonic wall, while they were microscopically characterized by marked fibrous thickening of the venous walls with calcifications, marked submucosal fibrosis, deposition of collagen in the mucosa, and foamy macrophages within the vessel walls. CONCLUSIONS: These peculiar lesions have not previously been fully described. The cause and pathogenesis still remain unknown. We conclude that such lesions represent a new clinicopathologic disease entity and propose the term "idiopathic mesenteric phlebosclerosis."

Feasibility of iodine-125 labeled anti-human hemoglobin antibody in the detection of bleeding sites from the large bowel-A preliminary study.

A monoclonal anti-human hemoglobin antibody that cross-reacts with mouse hemoglobin was labeled with Iodine-125 through the Chloramine-T method. The labeled antibody was used in an attempt to recognize bleeding sites from the large bowel in a mouse model, through a non-invasive enema-like study. In vitro experiments after double column chromatography of the labeled antibody and 10% trichloroacetic acid conjugation revealed that about 80% of the radioactivity was incorporated into protein. Inhibition assay containing cold (non-radiolabeled) antibody showed that Iodine-125 radiolabeled antibody preserved its immunoreactivity. Autoradiographs exquisitely demonstrated accumulation of isotope in the corresponding intestinal bleeding areas. These findings suggest that this method can be useful for scintigraphic localization of bleeding sites in the large bowel.

Magnesium ions and barium coating of colonic mucosa: is it a simple question of viscosity?

The aim of the present study was to verify whether magnesium-induced increase of barium coating of the colonic mucosa is specifically due to the increase of barium suspension viscosity. One hundred sixty-one patients scheduled for double-contrast barium enema (DCBE) were randomised in one group of 23 patients (control group, CG), and three groups of 23 pairs (G1, G2 and G3), i.e. 138 patients. The DCBE was performed with standard technique using a barium suspension with dynamic viscosity of 280 cPs (CG), or with viscosity increased to 320 cPs (G1), 2500 cPs (G2) or 3200 cPs (G3), by extemporaneous addition of MgSO4 1, 2 or 3 g in one member of the pair, Na2SO4 1, 4.2 or 8 g in the other one. Three radiologists evaluated on an ordinal scale mucosal coating and free fluid. In all magnesium subgroups barium coating was better than in CG (p < 0.008), the highest value being obtained in G2. No difference was observed as regards free fluid. Inside paired groups, mucosal coating was more effective in magnesium than in sodium members (p < 0.0002). Viscosity of barium suspension being equal inside each group, this effect must be attributed to magnesium-specific interactions with additives of the barium suspension inducing events other than viscosity changes.

Do magnesium ions influence barium mucosal coating of the large bowel?

The aim of the present study was to verify whether the presence of magnesium in the colon lumen at the time of the double-contrast barium enema (DCBE) examination changes the quality of barium mucosal coating. The two members of 38 pairs of patients undergoing DCBE with a standardised technique were randomly subjected to bowel preparation with sennosides and magnesium sulphate, or sennosides and sodium sulphate. Mucosal coating, residual fluid and colon cleansing were assessed independently by three radiologists. The null hypothesis was tested by means of Wilcoxon's signed-rank test. Barium mucosal coating was judged to be better in the members to whom magnesium sulphate was administered (p = 0.0007). There was no difference in the amount of residual fluids (p = 0.3198). Colon cleansing was judged to be better in the members to whom sodium sulphate was administered (p = 0.0166). These results demonstrate, in a simple way, that magnesium ions increase barium coating of the colon mucosa in vivo. The underlying mechanisms (increase in viscosity of barium suspension through water subtraction owing to the hydrophilism of magnesium ions, or interactions with the polysaccharide additives) need further investigation. A first clinical application could be the integration of magnesium ions in a newly designed isotonic electrolyte solution containing polyethylene glycol for the oral colon wash-out.

Bowel preparation for the double-contrast barium enema: how to maintain coating with cleansing?

AIM: Poor mucosal coating, due to excess of fluid in the colon lumen, is a problem when the oral lavage method (4 litres of an iso-osmotic saline solution containing polyethylene glycol) is used as a preparation for double-contrast barium enema. Our aim was to assess the value of prior administration of sennosides to obtain a clean colon with a reduced volume of polyethylene glycol (PEG)-saline solution, but maintaining good mucosal coating. MATERIALS AND METHODS: After a 2-day low-residue diet, three different oral preparations were compared: (i) 4 litres of a PEG-saline solution (SELG) and 15 mg of bisacodyl (116 patients, SELG-4 group); (ii) 156 mg of sennosides, 15 g of magnesium sulphate, and 2 litres of water (116 patients, SennMg group); (iii) 156mg of sennosides and 2 litres of SELG (116 patients, SennSELG group). Compliance, complaints, cleansing, mucosal coating, and fluid retention were evaluated. RESULTS: Compliance was > 94% in every group. A higher percentage of mild nausea was observed in SELG-4 group, of mild abdominal cramping in SennMg group, of substantial abdominal cramping in SennSELG group (P < 0.02). Cleansing was better in SennSELG than in both the SELG-4 (P = 0.0003) and SennMg (P = 0.0353) group. Mucosal coating was better in SennMg than both SELG-4 (P = 0.0034) and SennSELG (P < 0.0001) group. There was more residual fluid in the SennSELG group than both in SELG-4 (P = 0.0029) and SennMg (P = 0.0059) group. CONCLUSION: For colon cleansing, the combination of sennosides and PEG-saline solution was better than either the 4 litre PEG protocol or the combination of sennosides and magnesium sulphate. For mucosal coating, the protocol combining sennosides and magnesium sulphate was more effective than either protocols using the PEG-saline solution. This may be due to the interaction of residual magnesium ions in the colon lumen with the barium suspension.

Detrimental effects on villus form during conventional oral rehydration therapy for diarrhoea in calves; alleviation by a nutrient oral rehydration solution containing glutamine.

This paper examines the possibility that treatment of diarrhoea with conventional oral rehydration solutions (ORSs) may be detrimental to villus structure by imposing nutrient deprivation and that such detrimental effects may be reduced or avoided by using a nutrient ORS. A conventional WHO-type ORS (W) was compared with two nutrient solutions (N and G) both containing high glucose concentrations and the latter containing glutamine; their effects on enteric structure were assessed by morphometric analysis of samples obtained from diarrhoeic calves after 96 h treatment. Comparisons were also made with samples from controls and diarrhoeic calves at the stage where oral rehydration would have begun in the treated groups. As in our previous ORS studies, diarrhoea was induced with enterotoxigenic Escherichia coli (09:K30:K99). We measured villus length and width, crypt depth and width and calculated villus surface area in proximal, mid and distal small intestine (PSI, MSI, DSI), using standard morphometric techniques. Proximal and distal spiral colon samples (PC, DC) were examined for crypt depth and width; mitoses per crypt were counted in samples from all regions. Non-diarrhoeic calves showed the expected gradient of villus length through PSI, MSI and DSI, hence data for each region are normalized as a percentage of the control value for that region. PSI showed the greatest loss of villus length and surface area (50%) with diarrhoea. In MSI and DSI the villus loss was greater with solution W and N or G, as were increased mitoses and crypt depth. Crypt depth and mitoses also increased in the colon with solution W. Colonic crypt width increased with diarrhoea and conventional oral rehydration but less so with G; there is reason to believe that such changes have functional significance. Crypt changes in colon, MSI and DSI were least with solution G. The changes developing in diarrhoeic calves prior to treatment were thus less apparent in those treated with a nutritional ORS, particularly if it contained glutamine.

[Endorectal echotomography in assessing the spread of rectal cancer]. / Endorektal'naia ékhotomografiia v otsenke rasprostranennosti raka priamoi kishki.

Endorectal echotomography is one of modern methods to diagnose rectal carcinoma spreading. On the basis of examination of 56 patients with the above pathology the authors have studied the ultrasonic semiotics of tumourous lesion of rectum and its regional lymphatic apparatus during different stages of the illness. The article contains an outline of the methods of investigation. The findings from ultrasonic diagnosis were compared with the results of clinical, endoscopic investigations and histological analysis of the operative material. A high diagnostic value was shown of the method in the assessment of local spread of the tumor: sensitivity--94.6%, specificity--83.3%, general precision--91.8%. Endorectal ultrasonic tomography permits the enlarged pararectal lymphatic nodes to be visualized but the method's demerit is lack of ultrasonic criteria in the differential diagnosis between the metastatic lesion of the lymphatic node and inflammatory type changes.