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Evaluation of preoperative radiation therapy in operable colorectal cancer.

MATERIALS AND METHODS: Patients with operable colorectal cancer in the ascending colon, descending colon, and rectum were randomized to 500 cGy before definitive surgery. Patients with stage A and B1 lesions received no further treatment. All patients with stage B2, B3, C1, C2, and C3 received a minimum of 4500 cGy postoperatively. RESULTS: Three hundred fifty-three patients were registered for the study. Three hundred one patients were available for analyses. Follow-up was a minimum of 5 years on all study patients. The majority of patients had rectal cancer. Complications of treatment were acceptable. Two hundred thirty-one patients had stage B2, B3, C1, C2, or C3 tumors. Estimated 5-year rates for no preoperative therapy versus preoperative therapy were as follows: local recurrence 29% versus 26%; metastasis 41% versus 43%; and survival 54% versus 54%. No statistical benefit was observed for preoperative treatment. CONCLUSIONS: In a prospective randomized trial designed to test the value of low-dose preoperative irradiation followed by surgery and postoperative irradiation, the authors were unable to observe any benefit to low-dose preoperative therapy in patients with unfavorable stages.

Adult↗

Clinical value of technetium-99m-HMPAO-labeled leukocyte scintigraphy and spiral computed tomography in active Crohn's disease.

OBJECTIVES: The diagnostic accuracy of technetium-99m-HMPAO-labeled leukocyte scintigraphy (LS) and spiral CT for the detection of inflammatory activity was assessed; the extent of the inflammation and the complications were compared with the clinical and laboratory parameters and with the endoscopic and radiological findings in patients with clinically active Crohn's disease (CD). METHODS: Twenty-eight patients (13 men, 15 women, average age 32.5 yr, range: 18-59 yr) with an acute exacerbation of CD were enrolled in the study. The disease behavior type and the maximum extent of inflammation were established by means of endoscopy (jejunoscopy and colonoscopy) and enteroclysis. Nine patients with severe complications (abscess and stenosis) underwent operation. The GI tract was divided into five segments (small bowel, ascending colon, transverse colon, descending colon, and rectosigmoid), the LS, CT, endoscopic, and radiological pictures of all segments were graded (range: 0-3) and the scores were summed and compared. RESULTS: The investigations indicated that LS and CT had sensitivities of 76.1% and 71.8%, specificities of 91.0% and 83.5%, and accuracies of 82.6% and 77.5%, respectively, for detection of segmental inflammatory activity. With regard to the disease behavior type, the sensitivities of LS and CT were, respectively, 77% and 100% in the penetrating-fistulizing, 80% and 73% in the stricturing, and 68% and 64% in the inflammatory form of CD. CT detected all abdominal abscesses, whereas the diagnostic value of LS for the detection of the complications of CD was lower. The inflammatory activity scores measured by LS displayed a closer correlation than that of CT with the Best index (r = 0.71, p < 0.0005 vs r = 0.63, p < 0.001), the van Hees index (r = 0.61, p < 0.005 vs r = 0.59, p < 0.005), the serum fibrinogen level (r = 0.67, p < 0.005 vs r = 0.59, p < 0.005), or the C-reactive protein level (r = 0.64, p < 0.005 vs r = 0.51, p < 0.01). CONCLUSIONS: Both LS and CT are valuable noninvasive diagnostic methods in cases involving severe, active CD. LS seemed better for the detection of segmental inflammatory activity, whereas CT displayed excellent suitability for the recognition of complications: abdominal abscesses were diagnosed with 100% efficiency.

Abdominal Abscess↗

Position-specific expression of Hox genes along the gastrointestinal tract.

Hox genes play a critical role in morphogenesis of the early embryo along the anteroposterior axis. In mammals, 39 Hox genes with extensive homology are organized into 13 paralogous groups, forming four clusters on four separate chromosomes. The genes within each cluster are arranged in a 3' to 5' direction and expressed in a temporally and spatially coordinated manner along the anteroposterior axis in the vertebrae, limbs and viscera, including the gastrointestinal tract, but little is known about their spatial expression in the adult gastrointestinal tract. We used the quantitative polymerase chain reaction (PCR) intercalater method with SYBR Green to quantify human Hox gene expression in the adult gastrointestinal tract tissue: esophagus, stomach, duodenum, jejunum, ileum, ileocecum, cecum, ascending colon, transverse colon, descending colon and rectum. Hox gene expression was normalized to glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) gene expression. The spatial expression pattern was analyzed by the multivariate method. The expression level of all 39 Hox genes could be measured in a reproducible manner. Genes with higher expression in the foregut-derived segments tended to have lower expression in hindgut-derived segments, whereas those with low expression in the former tended to have higher in the latter. Principal components analysis and permax analysis revealed a position-specific expression pattern of Hox genes along the anteroposterior axis of the adult gastrointestinal tract. The pattern recapitulates the expression pattern in the embryonic gastrointestinal tract. We suggest that Hox genes may play a pivotal role in the position-specific regenerative process of intestinal epithelial cells.

Chromatography, High Pressure Liquid↗

Gastrointestinal tract location of Escherichia coli O157:H7 in ruminants.

Experimentally inoculated sheep and cattle were used as models of natural ruminant infection to investigate the pattern of Escherichia coli O157:H7 shedding and gastrointestinal tract (GIT) location. Eighteen forage-fed cattle were orally inoculated with E. coli O157:H7, and fecal samples were cultured for the bacteria. Three distinct patterns of shedding were observed: 1 month, 1 week, and 2 months or more. Similar patterns were confirmed among 29 forage-fed sheep and four cannulated steers. To identify the GIT location of E. coli O157:H7, sheep were sacrificed at weekly intervals postinoculation and tissue and digesta cultures were taken from the rumen, abomasum, duodenum, lower ileum, cecum, ascending colon, descending colon, and rectum. E. coli O157:H7 was most prevalent in the lower GIT digesta, specifically the cecum, colon, and feces. The bacteria were only inconsistently cultured from tissue samples and only during the first week postinoculation. These results were supported in studies of four Angus steers with cannulae inserted into both the rumen and duodenum. After the steers were inoculated, ruminal, duodenal, and fecal samples were cultured periodically over the course of the infection. The predominant location of E. coli O157:H7 persistence was the lower GIT. E. coli O157:H7 was rarely cultured from the rumen or duodenum after the first week postinoculation, and this did not predict if animals went on to shed the bacteria for 1 week or 1 month. These findings suggest the colon as the site for E. coli O157:H7 persistence and proliferation in mature ruminant animals.

Animals↗

MR colonography in patients with incomplete conventional colonoscopy.

PURPOSE: To assess dark-lumen magnetic resonance (MR) colonography for the evaluation of colonic segments in patients in whom conventional colonoscopy could not be completed. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. Within 24 hours of incomplete conventional colonoscopy, 37 patients (22 women, 15 men; age range, 25-63 years) underwent MR colonography. Contrast material-enhanced T1-weighted three-dimensional images were collected after rectal administration of water for colonic distention. Data from MR colonography were evaluated by two radiologists. With a three-point scale, image quality was characterized in terms of colonic distention (1 = good; 2 = moderate, diagnostic; and 3 = poor, nondiagnostic) and presence of artifacts (1 = none; 2 = moderate, diagnostic; and 3 = extensive, nondiagnostic). Depiction of colorectal disease was assessed according to the following colonic segments: cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. RESULTS: Four patients had history of colorectal cancer, and each had undergone partial colonic resection of two segments. Hence, 214 segments were evaluated. Conventional colonoscopy failed in assessment of 127 of 214 potentially visible colonic segments in the 37 patients. MR image quality was rated diagnostic in 35 patients and permitted assessment of 206 of 214 potentially visible segments. Nondiagnostic image quality in two patients was attributed to inadequate distention of prestenotic colonic segments owing to high-grade tumor stenosis. All inflammation- and tumor-induced stenoses and all five polyps identified at conventional colonoscopy in poststenotic segments were correctly detected at MR colonography. However, MR-based assessment of prestenotic segments revealed two lesions suspected of being carcinoma, five polyps, and four segments affected by colitis. CONCLUSION: MR colonography proved reliable in evaluating the majority of colonic segments inaccessible with conventional colonoscopy. The identification of additional disease at MR colonography underscores the need for a second diagnostic step in the setting of incomplete conventional colonoscopy.

Adult↗

Tobacco smoking and colorectal hyperplastic and adenomatous polyps.

Colorectal adenomas and possibly some hyperplastic polyps are precursors of colorectal cancer. Tobacco use is associated in epidemiologic studies with these polyps, although links between smoking and colorectal cancer are less consistent. To characterize the role of tobacco in early colorectal carcinogenesis, we compared tobacco use among 4,383 subjects with histologically verified benign (hyperplastic or adenomatous) polyps of the distal colon (descending colon, sigmoid, and rectum) with tobacco use among 33,667 subjects who were endoscopy negative for distal colon tumors, in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Trial, a randomized trial of flexible sigmoidoscopy. Risks, estimated by the odds ratio (OR), associated with current cigarette use were OR = 4.4 [95% confidence interval (95% CI), 3.7-5.2] for hyperplastic polyps only, OR = 1.8 (95% CI, 1.5-2.1) for adenomas only, and OR = 6.2 (95% CI, 4.7-8.3) for subjects with both hyperplastic and adenomatous polyps concurrently. Effects were weaker among ex smokers; the smoking-associated ORs remained consistently higher for hyperplastic polyps. This pattern was also seen in relation to cigarettes smoked per day, smoking duration, and pack-years. Tobacco-associated risks for multiple polyps were also stronger when hyperplastic disease was involved. In conclusion, tobacco use, particularly recent use, increases risk for both adenomatous and hyperplastic polyps, but the risks are substantially greater for hyperplastic lesions.

Adenomatous Polyposis Coli↗

Prevalence and biodiversity of helminth parasites in donkeys from South Africa.

Seven donkeys (Equus asinus) from North-West and Mpumalanga Provinces in South Africa were examined at necropsy. Quantitative samples were collected from the gastrointestinal tract for recovery of helminth parasites from the stomach, small intestine, cecum, ventral colon, dorsal colon, descending colon, and cranial mesenteric artery. Fifteen genera and 29 species of helminths were identified comprising 27 species of nematodes in the Ascarididae, Atractidae, Habronematidae, Onchocercidae, Oxyuridae, and Strongylidae; 1 species of cestode in the Anoplocephalidae; and 1 species of trematode in the Paramphistomatidae. In addition, 2 species of oestrid fly larvae in the Gastrophiliidae were identified. The most abundant group in number of species was the cyathostomes (small strongyles) and, of these, Cyathostomum montgomeryi, Cylicocyclus sp. (a), and Cylicostephanus minutus were the most numerous. The most prevalent cyathostomes were C. montgomeryi and Cylicocyclus sp. n. (a). Strongylus vulgaris was the most abundant and prevalent large strongyle species. The occurrence of small strongyle species and their prevalences in this study are compared with 3 other studies on donkeys in Africa.

Animals↗

Segmental differences in drug permeability, esterase activity and ketone reductase activity in the albino rabbit intestine.

Possible segmental differences in drug permeability as well as esterase and ketone reductase activities in the albino rabbit intestine were investigated. Beta adrenergic antagonists and timolol prodrugs spanning four orders of magnitude in distribution coefficient were used as model drugs. Drug penetration was evaluated in Ussing chambers using isolated segments of the duodenum, jejunum, ileum, ascending colon, descending colon, and rectum. Esterase and ketone reductase activities were determined in homogenates of the above segments using timolol ester prodrugs and levobunolol as substrates, respectively. The results indicate that the hydrophilic beta adrenergic antagonists atenolol and sotalol and moderately lipophilic metoprolol penetrated all intestinal segments equally well, whereas moderately lipophilic timolol and lipophilic propranolol, levobunolol and betaxolol were better absorbed from the large than from the small intestinal segments. Changes in lipophilicity exerted a more pronounced effect on the penetration of beta adrenergic antagonists in the large than the small intestinal segments. A similar pattern existed for timolol prodrugs. In addition to segmental differences in drug permeability, segmental differences in esterase and ketone reductase activities also existed. The level of esterase and ketone reductase activities in the small intestinal segments was, on average, 12 times and 5 times higher, respectively, than in the large intestinal segments. The implication of the above findings is that segmental differences in drug permeability and metabolism must be considered in the design of oral drug delivery systems.

Adrenergic beta-Antagonists↗

The role of mucosal biopsy in the diagnosis of chronic diarrhea: value of multiple biopsies when colonoscopic finding is normal or nonspecific.

OBJECTIVES: There are controversies about taking routine mucosal biopsy when the gross colonoscopic finding is normal. This study was conducted to determine the frequency of clinically important histological abnormalities, prospectively, in chronic diarrhea patients with grossly normal or nonspecific colonoscopic findings. METHODS: One hundred and eighteen patients suffering from nonbloody diarrhea with average frequency of more than two times a day for more than 4 weeks were included. Multiple biopsies (cecum, ascending colon, mid-transverse colon, descending colon, sigmoid colon and rectum) were taken during colonoscopic examinations and each biopsy specimen was reviewed by one pathologist after H&E and Masson-trichrome staining. RESULTS: Clinically significant abnormalities (2 collagenous colitis, 1 lymphocytic colitis, 1 eosinophilic enterocolitis, 1 ulcerative colitis and 4 melanosis coli) were observed in 9 patients (7.6%). Sixteen cases (13.6%) of borderline histological abnormalities were observed (8 cases of possible collagenous colitis and 8 cases showing some features of lymphocytic colitis). Ninety two cases (78.8%) showed nonspecific inflammation only. CONCLUSION: Clinically important histological lesions can exist in significant percentage in spite of normal or nonspecific colonoscopic findings, which can justify routine mucosal biopsy in the evaluation of chronic diarrhea patients. The clinical significance of borderline histological abnormalities needs to be determined by careful follow-up studies.

Adolescent↗

Relations between Leu(5)-enkephalin- (LENK) and VIP-immunoreactive nerve fibres during human drug-resistant colitis. A case study.

The double immunofluorescence technique was used to examine the distribution and interrelationship between LENK- and VIP-immunoreactive nerve fibres within the muscle layer and myenteric plexus of the large intestine in a young female patient (aged 17 years) suffering from colitis ulcerosa activa (CUA). As the CUA was found to be totally drug-resistant, a pancolotomy was performed by means of the Soave technique. Varicose nerve fibres, immunoreactive either to LENK or VIP, but not to both substances simultaneously, were found in all fragments of the bowel studied. A striking feature was their distribution pattern within the studied layers. In all cases LENK-IR fibres were closely accompanied by VIP-IR terminals. The density of the examined fibres depended on the bowel fragment studied, and was the greatest in the sigmoid colon, descending colon and rectum, while the lowest number was found in the caecum. The results of the present study may thus be indicative for the involvement of LENK- and VIPIR nerve fibres in the control of bowel functions during CUA, possibly on the basis of a "cross-talk" between terminals running in close vicinity to each other.

Adolescent↗

What types of colorectal cancer overexpress the MAGE protein?

BACKGROUND/AIMS: Tumor-specific antigens such as Melanoma-associated antigens could be attractive targets for immunotherapy. It will be a great help for cancer immunotherapy to distinguish what types of tumor expresses tumor-specific antigen. METHODOLOGY: We investigated the expression pattern of MAGE-A1 by immunohistochemical typing methods in human colorectal cancers obtained from consecutive patients undergoing surgical treatment at the hospital of the University of Tokyo. RESULTS: In 35 of 89 cases (39%), MAGE-A1 positive immunoreactivity was detected in the malignant glands. MAGE-A1 positive immunoreactivity was significantly higher among the patients under the age of 70 than among those 70 years of age and older (p=0.04). Among the patients under the age of 70, the tumors located in the distal colon (descending colon, sigmoid colon and rectum) showed significantly more positive MAGE-A1 immunoreactivity than those in the proximal colon (cecum, ascending colon and transverse colon) (p=0.04). The expression pattern of MAGE-A1 was not associated with gender, size, depth, histological type, vessel invasion, lymphatic invasion, lymph nodal invasion or stage of disease. CONCLUSIONS: Relatively better results can be expected with MAGE-A1 immunotherapy among patients with distal colon cancer under the age of 70.

Age Factors↗

K-ras mutation in Greek patients with poorly and moderately differenciated tumours of the lower intestinal tract.

The K-ras protooncogene is activated via mutations in approximately 40% of primary colorectal adenocarcinoma. This finding suggests that these genetic alterations are important events in the genesis of colon cancer and should be correlated with other parameters in order to infer some conclusions relevant to the etiology and the pathogenesis of this type of cancer. In our study we examined whether the incidence of K-ras mutations detected in 23 samples with colorectal adenocarcinomas, was related to different anatomical sites within the lower intestinal tract (transverse colon, descending colon and rectosigmoid region) and also the correlation between K-ras mutations and depth of invasion, level of tumour cell differentiation and metastasis to the regional lymph nodes. For this study the critical regions for the activation of the K-ras protooncogene were amplified by the PCR technique and the particular sequences analysed, after their membrane transfer, by differential hybridization with selected synthetic oligonucleotides. Our results demonstrated that 39% of the adenocarcinomas examined contained point mutations, and 66.6% of these were located in the second position of K-ras codon 12, whereas the other 33.3% were located in the second position of codon 13. 77.8% of the mutations were located at the rectosigmoid region and the relevance of the mutations was higher in poorly differenciated tumours. The depth of invasion was associated with the presence of a mutation whereas no correlation was found between the presence of a mutation anb the regional lymph node metastasis.

Adult↗

The clinical significance of colonoscopy in hemorrhagic colitis due to enterohemorrhagic Escherichia coli O157:H7 infection.

BACKGROUND AND STUDY AIMS: Although hemorrhagic colitis due to enterohemorrhagic Escherichia coli O157:H7 (O157) infection has recently attracted increasing attention as an important enteric infection, the colonoscopic findings associated with this disease have not been sufficiently characterized. The aim of this study is to characterize the colonoscopic features of hemorrhagic colitis due to O157 infection. PATIENTS AND METHODS: The colonoscopic findings in ten patients with hemorrhagic colitis due to O157 infection were retrospectively reviewed. To assess the severity of inflammation in each part of the large intestine, colonoscopic findings were categorized into four grades: grade 1, intact mucosa; grade 2, sporadic erythema and erosion; grade 3, mostly diffuse inflammation; and grade 4, diffuse, severe inflammation. RESULTS: Eight out of ten patients had grade 4 findings in the cecum and ascending colon, grade 3 in the transverse colon and descending colon, and grade 2 in the sigmoid colon. Two of these eight patients also had grade 4 inflammation in the proximal transverse colon. Five of these eight patients revealed longitudinal ulcer-like lesions in the transverse colon and/or descending colon. The remaining two patients had grade 3 findings in the cecum to the descending colon and grade 2 findings in the sigmoid colon. All patients exhibited grade 1 finding in the terminal ileum and the rectum. Based on these colonoscopic findings, the ten patients were divided into the typical group (eight patients) and the mild-type group (two patients). CONCLUSIONS: The characteristic colonoscopic findings in most patients with hemorrhagic colitis due to O157 infection were as follows: 1) severe inflammation, including primarily marked edema and facile hemorrhage, and 2) inflammation predominating at the right-side colon; and 3) frequent appearance of longitudinal ulcer-like lesions.

Adolescent↗

Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man.

Suspensions of isolated epithelial cells (colonocytes) from the human colon were used to assess utilisation of respiratory fuels which are normally available to the colonic mucosa in vivo. Cells were prepared from operative specimens of the ascending colon (seven) and descending colon (seven). The fuels that were used were the short chain fatty acid n-butyrate, produced only by anaerobic bacteria in the colonic lumen, together with glucose and glutamine, normally present in the circulation. The percentage oxygen consumption attributable to n-butyrate, when this was the only substrate, was 73% in the ascending colon and 75% in the descending colon. In the presence of 10 mM glucose these proportions changed to 59% and 72%. Aerobic glycolysis was observed in both the ascending and descending colon. Glucose oxidation accounted for 85% of the oxygen consumption in the ascending colon and 30% in the descending colon. In the presence of 10 mM n-butyrate these proportions decreased to 41% in the ascending colon and 16% in the descending colon. Based on the assumption that events in the isolated colonocytes reflect utilization of fuels in vivo, the hypothesis is put forward that fatty acids of anaerobic bacteria are a major source of energy for the colonic mucosa, particularly of the distal colon.

Anaerobiosis↗

Comparison of transport mechanisms in isolated ascending and descending rat colon.

The mechanisms of water and ion transport in ascending and descending rat colon were compared using an everted open mucosal sac preparation. Net water flux, measured gravimetrically, was similar in both segments (15.3 plus or minus 1.2 and 13.7 plus or minus 1.3mul h(-1) mg(-1), NS). Net catonic flux J(Na+K),net anionic flux J(Cl-HCO3), and net solute flux Josm were also similar; but the constituents of these flux , namely JNA, JK, and JHCO3, were significantly different. The descending colon absorbed significantly less Na and secreted significantly more HCO3. Only the descending colon absorbed K, whereas net JK across the ascending colon was zero. The PD across either segment ranged from 3 to 7 mV, mucosal side negative. Consideration of net flux and electrochemical gradient indicated that in both segments Na was absorbed actively. The nature of Cl transport could not be ascertained. Assuming transmural movement, HCO3 was secreted (or H ion absorbed) actively. Only the descending colon absorbed K actively. Across the ascending colon K was distributed close to electrochemical equilibrium. The compostion of the absorbates was calculated from Ji/Jv after correction of Jv for filtered water. Both absorbates were equally hypertonic (448.5 plus orminus 9.3 and 421.7 plus or minus 13.2; NS.)The ascending colon absorbate contained a significantly higher Na concentration and no K. The descending colon absorbate contained 15 mM K, about 3 times the K concentration in the bathing solution. It was concluded that the ascending colon and descending colon displayed quantitative differences in Na absorption and HCO3 secretion and a qualitative difference in K transport.

Animals↗

Effects of age, sex, and post mortem interval on intestinal lengths of horses during development.

Lengths of small intestine, caecum, ascending colon and descending colon were measured in intestinal tracts from 103 foetuses, foals and adult horses. Intestinal tracts from 21 of the horses were measured at varying intervals after death. Total intestinal length increased markedly from mid-gestation to one year of age, then showed little increment up to 35 years. Small intestinal length increased most rapidly in the first month of life. Caecal length increased most rapidly from one to six months and length of ascending colon increased most rapidly between one week and one year. Descending colon length increased gradually after birth. Periods of rapid increase in length of various intestinal segments and alterations in the percentage of total intestinal length were associated with periods of rapid body growth and changes in dietary composition. Sex and post mortem interval did not affect intestinal length significantly.

Animals↗

Mucosal surface area and fermentation activity in the hind gut of hydrated and chronically dehydrated working donkeys.

The effects of mild chronic dehydration on fermentation rate and mucosal surface area in the cecum, dorsa and ventral colon, and descending colon of the hindgut were investigated in South African donkeys (n = 11) in agricultural work. Dehydration representing a 6% drop in BW (n = 6) was associated with increased fermentation activity in the cecum (252 +/- 22.9 vs. 161 +/- 13.5 micromol/g of DM.h(-1), P < 0.01) and enhanced fluid retention in the ventral colon (0.81 +/- 0.026 vs. 0.73 +/- 0.034 mL/g gut, P < 0.05). Fermentation activity in the next segment of the hindgut, the ventral colon, of dehydrated donkeys was also greater numerically (92.5 +/- 22.60 vs. 77.9 +/- 10.40 micromol/g of DM.h(-1)), but this difference was not significant. Total mucosal and crypt surface area per unit volume of gut (Sv, microm2/microm3) was greater in dehydrated donkeys for the cecum (253 +/- 23.0 vs. 161 +/- 13.5, P < 0.01), the ventral colon (286 +/- 6.2 vs. 171 +/- 9.8, P < 0.01), the dorsal colon (276 +/- 18.2 vs. 256 +/- 11.0, P < 0.05), and the descending colon (260 +/- 20.3 vs. 191 +/- 15.2, P < 0.05). Enhanced fermentation activity and enhanced mucosal absorptive or secretory capacity within the hindgut during chronic dehydration was associated with an observed maintenance of appetite. These adaptations in the hindgut are valuable physiological attributes for working donkeys in semi-arid regions where they are frequently exposed to chronic dehydration.

Animals↗