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An improved electronic colon cleansing method for detection of colonic polyps by virtual colonoscopy.

Electronic colon cleansing (ECC) aims to segment the colon lumen from a patient abdominal image acquired using an oral contrast agent for colonic material tagging, so that a virtual colon model can be constructed. Virtual colonoscopy (VC) provides fly-through navigation within the colon model, looking for polyps on the inner surface in a manner analogous to that of fiber optic colonoscopy. We have built an ECC pipeline for a commercial VC navigation system. In this paper, we present an improved ECC method. It is based on a partial-volume (PV) image-segmentation framework, which is derived using the well-established statistical expectation-maximization algorithm. The presented ECC method was evaluated by both visual inspection and computer-aided detection of polyps (CADpolyp) within the cleansed colon lumens obtained using 20 patient datasets. Compared to our previous ECC pipeline, which does not sufficiently consider the PV effect, the method presented in this paper demonstrates improved polyp detection by both visual judgment and CADpolyp measure.

Algorithms↗

Primary anastomosis in emergency distal colonic surgery after on-table colonic lavage.

The traditional operative management of emergency distal colon pathology has involved staged procedures, but recently Hartmann's operation has gained popularity. The indications for primary anastomosis without covering colostomy have remained controversial, but the technique of on-table lavage has extended the use of this approach in the acute setting. A series of seven patients having this procedure for diverticular abscess (three), obstructing colonic carcinoma (one), perforating colonic carcinoma (one) and sigmoid volvulus (two) is presented. The saline irrigation is introduced by a Foley catheter inserted via the appendix stump and the effluent is diverted from the proximal colon by anaesthetic scavenger tubing. The lavage is continued until the effluent is clear and anastomosis performed with one-layer interrupted absorbable sutures. There were no deaths in the series; one patient developed a wound infection and average hospitalization was 16 days (range: 6-31 days). Immediate anastomosis in selected cases of emergency distal colonic pathology is thus feasible and safe following on-table colonic lavage.

Acute Disease↗

Colonic chicken skin mucosa: an endoscopic and histological abnormality adjacent to colonic neoplasms.

OBJECTIVES: We recently described an endoscopic finding of pale yellow-speckled mucosa adjacent to colonic neoplasms. This resembled the appearance of chicken skin and was named chicken skin mucosa (CSM). CSM differs from previously reported gastrointestinal xanthelasmas in that this entity always occurs in association with colonic neoplasms. The prevalence, endoscopic characteristics, clinical significance, and possible etiology were investigated. METHODS: Eight hundred fifty-two consecutive colonoscopies were prospectively evaluated for the presence of CSM associated with either cancer or adenomas > or = 1 cm. Electron microscopy and histopathology using hemotoxylin and eosin, mucicarmine, and oil red O stains were performed. Twelve consecutive colon cancer resection specimens were prospectively examined to determine the presence of histologic CSM. RESULTS: CSM was adjacent to eight of 10 distal colorectal cancers, one of four proximal colon cancers, 16 of 42 distal adenomas, and three of 44 proximal adenomas. Four of seven resected distal cancers demonstrated histological evidence of CSM. Biopsies of the CSM revealed that lipid-filled macrophages in the lamina propria were responsible for this endoscopic appearance. Electron microscopy showed that the surface epithelial cells had small intestine-like microvilli. CSM was not seen with other colonic conditions and was not associated with the laxative preparation. In four instances, identification of the CSM alerted the endoscopist to the presence of polyps in locations difficult to visualize. CONCLUSIONS: CSM is an endoscopic entity that occurs as a result of fat accumulation in macrophages in the lamina propria of the mucosa adjacent to colonic neoplasms. Small intestine-like microvilli were present in CSM and the pathophysiological implications remain to be elucidated.

Adenoma↗

Design and clinical use of a modified colon tray for large colon evacuation in the horse.

A modified colon tray to perform large colon evacuations in horses was designed. A funnel-shaped accessory was constructed to create a mechanical separation between the sterile and nonsterile part of the tray. Sterile hooks were used to make a temporary and stabile colostomy. Thirty horses with surgical correction of nonstrangulating large colon obstruction underwent a large colon evacuation with this modified tray. The surgical procedure was uncomplicated and resulted in a positive outcome in 29 horses. This less labour-intensive way to evacuate the large colon results in minor contamination and makes extraluminal lavage becomes superfluous. This modified tray is a very efficacious and practical instrument for emptying the large colon in horses.

Animals↗

Molecular analysis of the microbial diversity present in the colonic wall, colonic lumen, and cecal lumen of a pig.

Random clones of 16S ribosomal DNA gene sequences were isolated after PCR amplification with eubacterial primers from total genomic DNA recovered from samples of the colonic lumen, colonic wall, and cecal lumen from a pig. Sequences were also obtained for cultures isolated anaerobically from the same colonic-wall sample. Phylogenetic analysis showed that many sequences were related to those of Lactobacillus or Streptococcus spp. or fell into clusters IX, XIVa, and XI of gram-positive bacteria. In addition, 59% of randomly cloned sequences showed less than 95% similarity to database entries or sequences from cultivated organisms. Cultivation bias is also suggested by the fact that the majority of isolates (54%) recovered from the colon wall by culturing were related to Lactobacillus and Streptococcus, whereas this group accounted for only one-third of the sequence variation for the same sample from random cloning. The remaining cultured isolates were mainly Selenomonas related. A higher proportion of Lactobacillus reuteri-related sequences than of Lactobacillus acidophilus- and Lactobacillus amylovorus-related sequences were present in the colonic-wall sample. Since the majority of bacterial ribosomal sequences recovered from the colon wall are less than 95% related to known organisms, the roles of many of the predominant wall-associated bacteria remain to be defined.

Anaerobiosis↗

Occlusive colon carcinoma: virtual colonoscopy in the preoperative evaluation of the proximal colon.

PURPOSE: To evaluate the use of preoperative virtual colonoscopy to examine the proximal colon in patients with distal occlusive carcinomas, defined as cancers that cannot be traversed endoscopically. MATERIALS AND METHODS: Twenty-nine patients with occlusive colorectal carcinomas underwent preoperative virtual colonoscopy with use of a standard protocol. Patients with acute bowel obstruction were excluded. Results of virtual colonoscopy were compared with the findings of preoperative colonoscopy, preoperative barium enema examination, intraoperative colon palpation, histopathologic outcome, and postoperative colonoscopy and barium enema examination, where possible. RESULTS: Virtual colonoscopy helped identify all 29 occlusive carcinomas and demonstrated two cancers and 24 polyps in the proximal colon. Both synchronous cancers were confirmed intraoperatively and resected. Postoperative conventional colonoscopy in 12 patients confirmed 16 polyps identified at virtual colonoscopy and demonstrated two subcentimeter polyps missed at virtual colonoscopy. Postoperative barium enema examination was performed in two patients and helped confirm two polyps identified at virtual colonoscopy. Virtual colonoscopy successfully demonstrated the proximal colon in 26 of 29 patients examined compared with preoperative barium enema examination, which failed to adequately demonstrate the proximal colon in any patient examined. CONCLUSION: Virtual colonoscopy is a feasible and useful method for evaluating the entire colon before surgery in patients with occlusive carcinomas.

Aged↗

Characterization of a mouse colonic system B(0+) amino acid transporter related to amino acid absorption in colon.

Previous experiments have shown that an amino acid transport system B(0+) transporter in cultured colonic epithelial cells mediates amino acid absorption. Here we describe the cloning and functional characterization of a system B(0+) transporter selectively expressed in the colon. Using the combination of an expressed sequence tag database search and RT-PCR approaches, we cloned a mouse colonic amino acid transporter, designated mCATB(0+). Northern blot analysis revealed that mCATB(0+) was selectively expressed in the large intestine. In situ hybridization showed the mCATB(0+) mRNA to be localized in absorptive epithelial cells. When expressed in Xenopus oocytes, mCATB(0+) exhibited a Na(+)-dependent stereoselective uptake and a broad specificity for neutral and cationic amino acids, which is characteristic of amino acid transport system B(0+). In vivo [(3)H]glycine uptake assay demonstrated that a system B(0+)-like transporter protein was expressed on the apical surface of the colonic absorptive cells. Our data suggest that a mouse colonic amino acid transporter mCATB(0+) may absorb amino acids from the intestinal contents in the colon.

Amino Acid Sequence↗

Hepatocyte-derived soluble factors regulate proliferation and autocrine growth factor expression in colon cancer cell lines of varying liver-colonizing capability.

We investigated the role of hepatocyte-derived soluble growth factors on cell proliferation and expression of growth factors and their receptors in four colon cancer cell lines of varying liver-colonizing ability. Cocultures of hepatocytes and colon cells and cultures of colon cells with hepatocyte-conditioned medium resulted in growth inhibition of both weakly and strongly metastatic cell lines. Growth inhibition was accompanied by a reduced expression of erb-B2 in the colon cells after 4 days in the presence of hepatocytes. In LS174T and LiM6 cells, there was a dramatic reduction in heregulin-alpha levels in the presence of hepatocytes. Interestingly, after 2 days in culture, hepatocyte-derived soluble factors increased the mRNA levels for the EGF family members amphiregulin and cripto. These studies show an inhibitory effect of hepatocyte-derived soluble factors on the proliferation of colon cell lines, mediated in part by changes in the expression of autocrine growth factors and receptors of the EGF and heregulin family.

Amphiregulin↗

Transplantation of adenomatous polyps, normal colonic mucosa and adenocarcinoma of colon into athymic mice.

Fragments of benign colonic adenomatous polyps of man, adenocarcinoma of the colon of man, and normal colonic mucosa of man and rodent were transplanted under the kidney capsule of athymic mice. Benign human adenomatous cells survived for periods of up to 28 days, normal rodent colonic epithelial cells for 45 days and colonic carcinoma cells for 43 days. This was demonstrated by morphologic criteria, and by the incorporation of tritiated thymidine into DNA of the epithelial cells. The transplantation technique can supplement organ culture methods for the maintenance of adenomatous tissue derived from human colonic mucosa, in order to facilitate studies of growth characteristics and transformation of the cells.

Adenocarcinoma↗

Development of anti-human colonic mucin monoclonal antibodies. Characterization of multiple colonic mucin species.

Structural relationships between colonic mucin species were assessed using a library of monoclonal antibodies (MAbs) directed against purified human colonic mucin (HCM). After immunization of mice with purified mucin from normal human colonic mucosa, 14% of 1,920 fusion products screened were positive for anti-HCM activity in a solid-phase assay. Patterns of selective binding by hybridomas to six discrete HCM species (I-VI) separated by DEAE-cellulose chromatography suggested the presence of both shared and species-specific antigenic determinants among HCM species I-VI. 23 anti-HCMs MAbs (7 IgM, 7 IgG1, and 9 IgG2) demonstrating a range of anti-HCM species specificities, were produced and used to study structural relationships between mucin species. Binding of various mucin species by individual anti-HCM MAbs was shown by competitive solid-phase radioimmunoassay to reflect the presence of identical epitopes on the different species. Adsorption of HCM species on a variety of affinity resins prepared with anti-HCM MAbs demonstrated that binding to multiple mucin species by a single MAb was related to intrinsic structural determinants. Four anti-HCM MAbs recognized protease-sensitive antigenic structures, which suggests that they may be directed to core HCM proteins. 12 of the anti-HCM MAbs were shown by solid-phase assay to recognize either complete (n = 5) or partial (n = 7) isolated colonic mucin oligosaccharide side chains of defined structure. Collectively, these data show the presence of both shared and unique antigenic structural determinants among colonic mucin species. Chromatographic heterogeneity of mucin glycoproteins seems to be related to the existence of biologically significant subclasses in the normal human colon.

Adsorption↗

A noninvasive method for monitoring intestinal ischemia: changes in the pulmonary clearance of helium instilled into the colon as an index of colonic blood flow.

To evaluate the concept that changes in colonic blood flow will predictably alter the absorption of colonic gas, we measured the pulmonary clearance rate of helium (CHe) which was instilled rectally into the colon of rabbits at a dose of 2 ml/kg. CHE reached a plateau after 20 min at 109 nmol/min/kg. Using hypoxemia as a cause for bowel ischemia, at PAO2 = 38 torr, we noted a marked decreased in CHe from 110 nmol/min/kg to 75 nmol/min/kg (p less than 0.025). Because helium absorption from the colon is diffusion limited, a model can be developed relating "subvillus" colonic blood flow to pulmonary helium clearance. From this model we would predict the hypoxemia induced change in CHe to be secondary to colonic hypoperfusion. This type of indirect monitoring could be useful in detecting patients with bowel ischemia.

Animals↗

Spectral analysis of colonic intraluminal pressure in patients who received a colonic replacement following radical esophagectomy.

The aim of this study was to evaluate the motor activity of the interposed colonic segment in patients who had received a colonic replacement following radical esophagectomy using spectral analysis and a 24 hr activity graph. The 24-hr ambulatory pressure waves were recorded in the replaced colon after esophagectomy (n=8) using a solid-state manometric catheter (MicroDigitrapper, Synetics). Motility and spectral analyses of the intraluminal pressure waves were performed by Multigram and Gastrosoft (Synetics). It was revealed that after a meal the 3 cpm (cycles per minute) component of the motility index increased but the 12-15 cpm component decreased. The diurnal rhythm showed that colonic motility was high in the daytime and low during sleep. In contrast, duodenal motility was relatively high even during sleep. The motility index increased as the postoperative period increased. The motility of the replaced colon was higher during the daytime and after meals. The higher motility after meals was characterized by an increase in the 3 cpm component. These motor characteristics may help the function of the replaced colon as a substitute for the esophagus.

Aged↗

Electric activity spreads in the colonic longitudinal but not the circular musculature. Role in colonic motility.

The colon has a circular and longitudinal muscle layers and possesses an electric activity. The current study investigated the spread of this electric activity in the colonic musculature. The tests were performed in 16 patients (mean age 40.6 +/- 10.8 SD years, 10 men, 6 women) during operative correction of their incisional hernias in the anterior abdominal wall. Three electrodes were applied to the longitudinal muscle of the descending colon, and 3 to the circular muscle. The colonic pressure was monitored by a 10-F tube inserted per anus and connected to a pressure transducer. Electric waves in the form of pacesetter potentials (PPs) and action potentials (APs) were recorded from the longitudinal but not the circular muscle coat. The PPs and APs had the same frequency, amplitude and conduction velocity from the 3 electrodes of the same patient. The APs were associated with a rise of the intracolonic pressure. The results were reproducible in the individual subject. Being of the visceral type, the colonic smooth muscle fibers are controlled by non-nervous stimuli. Colonic motility is suggested to be effected by means of 2 mechanisms: the longitudinal muscle fibers activity through the action of the electric waves and the circular muscle fibers through the stretch reflex.

Action Potentials↗

Expression of cripto and amphiregulin in colon mucosa from high risk colon cancer families.

We assessed the expression of the epidermal growth factor (EGF)-related peptides, cripto-I (CR-I) and amphiregulin (AR), in a small panel of human colon adenomas and carcinomas. CR-I immunoreactivity was found in 17/31 (55%) of colon adenomas, and in 33/39 (84%) colon carcinomas. AR immunostaining was observed in 16/26 adenomas (61%) and in 20/26 carcinomas (77%). CR-I and AR staining were also assessed in 29 specimens from 24 individuals that belong to families with high incidence of colorectal carcinoma, and in 5 non-high risk individuals. Expression of CR-I was detected in 18/29 (62%) of high risk colon mucosa specimens, but only in 1/5 (20%) specimens from non-high risk individuals, while AR staining was found in 20/29 (69%) and in 4/5 (80%) of colon mucosa samples from high and low risk individuals, respectively. A majority (21/29; 72%) of the specimens from the high risk individuals had a high proliferative rate, as measured by Ki-67 staining. A statistically significant correlation was found between high proliferative rate, increased expression of CR-I and reduced expression of AR in the mucosa specimens from high risk individuals, suggesting that these might represent early events in colon tumorigenesis.

Adenoma↗

Epitalon and colon carcinogenesis in rats: proliferative activity and apoptosis in colon tumors and mucosa.

The effect of the synthetic pineal peptide Epitalon (Ala-Glu-Asp-Gly) on proliferative activity in colon tumors, and in mucosal epithelial cells adjacent to and located far from tumors was studied in rats. To evaluate the effect of Epitalon on different stages of carcinogenesis, different treatment regimens were used: during the tumor initiation stage, during the tumor-promotion stage, or during the entire process of tumor development. Eighty 2-month-old male LIO rats were exposed weekly to five subcutaneous injections of 1,2-dimethylhydrazine (DMH) at a single dose of 21 mg/kg body weight. Rats were divided into four groups. Control rats (group 1) received saline at a dose of 0.1 ml during the entire experiment. Rats in group 2 were treated with Epitalon at a dose of 1 micro g, five times a week, for 6 months, from the first injection of DMH till the end of the experiment. Rats in group 3 were treated with Epitalon after termination of the carcinogen injections. Rats in group 4 were treated with Epitalon only during the period of DMH exposure (for the first 5 weeks of the experiment). DMH induced proliferation of the secretory epithelium, and this phenomenon was accompanied by a decrease in the size of the stromal area and the area of lymph infiltration in colon tumors and in the colon mucosa adjacent to the tumors (group 1). Epitalon attenuated this effect, especially when the treatment was continued throughout the experiment (group 2). It increased the stromal areas, as well as that of lymphoid infiltration in the colon mucosa adjacent to the tumors. The intensity of lymphoid infiltration was activated in both the colon mucosa adjacent to a tumor and in the tumor. Mitotic activity of tumor cells was significantly inhibited by Epitalon when the treatment was given throughout the experiment (group 2). In parallel, a high level of apoptosis was seen in the same group. Thus, the strongest inhibitory effect of Epitalon on carcinogenesis in the colon mucosa was manifested when the treatment was continued throughout the experiment.

1,2-Dimethylhydrazine↗

Single-parameter DNA flow cytometric analysis of normal-appearing colonic mucosa does not predict the presence of colonic neoplasia.

We wished to determine whether DNA flow cytometric analysis could detect DNA abnormalities in normal-appearing mucosa of patients with colonic neoplasia. Eighty-five patients were studied either at colonoscopy or at surgical resection. Forty-five had macroscopically normal colonoscopy; 13 had adenomatous polyps, and 27 had colorectal carcinoma. Biopsies were obtained from the cancer and from normal-appearing mucosa 5 cm from the lesion. The patients who had normal colonoscopy had rectal biopsies. The samples were prepared for analysis on a Coulter EPICS C flow cytometer. Cells were analyzed for presence of aneuploidy (%AN), percent in DNA synthetic phase (%S), and percent growth fraction (%GF = %S + %G2M). Aneuploidy was present in 12 of 27 carcinomas (44%), but in none of the samples from polyps or normal-appearing colorectal mucosa adjacent to cancers. The %S from cancers was greater than those from polyps (9.6 +/- 6.3 vs. 5.1 +/- 1.8, p less than 0.005). However, %S from specimens arising from normal-appearing mucosa 5 cm distant from cancer could not be differentiated from the rectal mucosa of macroscopically normal colons (5.9 +/- 2.5 vs. 5.2 +/- 2.7). The %GF of cancer specimens was greater than those from adenomas (26.0 +/- 11.0 vs. 10.8 +/- 3.7, p less than 0.005). However, the %GF of normal-appearing mucosa 5 cm distant from the cancer was similar to the findings from mucosa arising from macroscopically normal colons (10.5 +/- 3.3 vs. 11.0 +/- 3.4). In conclusion, DNA flow cytometric analysis of normal-appearing colonic mucosa from patients with colonic carcinoma does not demonstrate abnormalities of DNA content or cell cycle kinetics, and therefore, cannot predict the presence of colonic neoplasia.

Adult↗

Cisapride accelerates colonic transit in constipated patients with colonic inertia.

A double-blind cross-over trial of oral cisapride 10 mg before meals and placebo was performed to determine its effects on colonic transit in patients with severe idiopathic constipation. Nine patients with less than 3 spontaneous bowel movements/wk were studied. After passing a tube to the cecum, 50 muCi of 111In-DTPA were instilled into the cecum and followed for 48 h using colonic transit scintigraphy. In the group as a whole, cisapride had little effect on transit. The patients were then divided into two groups based on transit: functional rectosigmoid obstruction (FRSO) and colonic inertia (CI). In the CI group, cisapride accelerated the half emptying time of the cecum and ascending colon from 2.50 to 1.21 h (p less than 0.05). The progression of the geometric center was also faster after cisapride in CI. In FRSO, the geometric center was unchanged by cisapride except at 48 h. Cisapride thus has a prokinetic effect on colonic transit in patients with severe idiopathic constipation, colonic inertia subtype. It may be a useful agent in the treatment of this group of patients.

Adult↗

Colonic motor responses in the pony: relevance of colonic stimulation by opiate antagonists.

The electrical and mechanical activity of the digestive tract and its response to the administration of opiate agonists and antagonists was assessed from electrodes and strain gauges chronically implanted on the jejunum and the cecocolonic segments in 3 ponies given a diet of hay and concentrates. Before the drugs were given, 10 to 17 migrating myoelectric complexes/day were recorded on the small intestine, and a rhythmic motor activity (base line) was observed on the proximal portion of the colon at the rate of 3.5 to 6.6/hour. Propagated contractions from the proximal to the distal portion of the colon occurred at the rate of 1.5 to 2.3/hour. Each pony was used as its own control and was given morphine (0.5 or 1 mg/kg of body weight, IV) or fentanyl (0.01 or 0.05 mg, IV) at weekly intervals. After an early phase of inhibition of the overall activity that lasted from 0.5 to 3 hours, depending on the dose, the resting muscle tone of the colonic activity was increased for a dose-dependent period. Propagated contractions only reappeared at the end of this 2nd phase. The opiate antagonist naloxone (0.5 mg/kg, IV) elicited a marked propulsive activity on the left replicated colonic segment, characterized by an increase in the number of propagated contractions. The N-methyl-quaternary analog of naloxone (methylnaloxone, which presumably entails selective action at opiate receptors outside the CNS) was also effective, indicating peripheral effects at the dosage level used (0.5 mg/kg, IV). Seemingly, an inhibitory opioid system exists in the control of colonic motor function in ponies and the possible usefulness of opiate antagonists to relieve hypomotility resulting in colonic impaction and constipation.

Animals↗