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PubMed1998

Subtotal colectomy vs. intraoperative colonic irrigation in the management of obstructed left colon carcinoma.

PURPOSE: Whether primary anastomosis should be performed after segmental resection with intraoperative colonic irrigation or subtotal colectomy is not yet established in the surgical treatment of obstructive left colon carcinoma. In this prospective, nonrandomized study, we present the results of 66 patients undergoing one-stage surgery for obstructed left colon carcinoma. PATIENTS AND METHODS: We compared two techniques, subtotal colectomy (35 patients) and intraoperative colonic irrigation with segmental resection and immediate anastomosis (31 patients). RESULTS: The mortality rate was similar in both groups, 8.5 percent in the subtotal colectomy group and 3.2 percent in the intraoperative colonic irrigation group. The surgical complication rate was significantly higher in the intraoperative colonic irrigation group (41.9 percent) than in the subtotal colectomy group (14.2 percent; P < 0.05). Mean operating time was significantly lower in the subtotal colectomy group than in the intraoperative colonic irrigation group (P < 0.05). Both groups had a similar mean duration of hospital stay. Ten patients who underwent subtotal colectomy (31.2 percent) presented with diarrhea in the immediate postoperative period, which disappeared spontaneously or with antidiarrheal medication; a disabling diarrhea persisted in two patients only (6.2 percent). CONCLUSION: We believe that subtotal colectomy is the treatment of choice for obstructed left-sided colonic carcinoma. Segmental resection with intraoperative colonic irrigation is more appropriate than subtotal colectomy only in patients with carcinomas of the rectosigmoid junction or with previous anal incontinence to avoid the appearance of postoperative diarrhea.

Adult↗
PubMed2002

Patchy field defects of apoptosis resistance and dedifferentiation in flat mucosa of colon resections from colon cancer patients.

BACKGROUND: Abnormal areas in normal-appearing flat colonic mucosa (field defects) may predispose individuals to colon cancer. Markers of field defects would indicate cancer risk. METHODS: We evaluated apoptosis capability, dedifferentiation, frequency of simple aberrant crypts, aberrant crypt foci, microadenomas, and total nicotinamide adenine dinucleotide levels at locations within normal-appearing flat mucosa obtained from colon resections. RESULTS: Among goblet cells from colonic mucosa samples of individuals without colonic neoplasia, there was a high mean deoxycholate-induced apoptotic index (AI) of 59.1% and high Dolichos biflorus agglutinin (DBA) lectin reactivity (differentiation) in 85.0% of samples. In contrast, flat mucosa samples from colon cancer patients had a significantly (P <.01) lower average AI of 37.4%, and a significantly (P =.03) lower percentage (40.5%) had high DBA reactivity. For colon cancer patients, AI and DBA reactivity values were patchy within a resection. Nicotinamide adenine dinucleotide levels were highly variable among individuals without neoplasia, and aberrant crypt foci and microadenomas were rare. CONCLUSIONS: AI and aberrant DBA reactivity are promising indicators of colon cancer risk. Our results attest to the importance of obtaining multiple samples to assess colon cancer risk because of the patchy nature of field defects.

Adenocarcinoma↗
PubMed1979

Cell population kinetics of 1,2-dimethylhydrazine-induced colonic neoplasms and their adjacent colonic mucosa in the mouse.

The parameters of cell population kinetics of symmetrical 1,2-dimethylhydrazine-induced colonic neoplasms and their adjacent colonic mucosa in the mouse were analyzed using the fraction labeled-mitoses curve method and compared with those of three groups of epithelial cells in the crypt of the descending colon of normal mouse. The analysis of three groups of epithelial cells in the crypt of normal mouse indicates that differentiation of epithelial cells was associated not only with a smaller proliferative pool of cells but also with a shortening of the duration of G2 phase and a prolongation of mitotic time. Other parameters of cell cycle did not change significantly. The mean cell cycle time of neoplastic cells in chemically induced colonic neoplasms was similar to that of epithelial cells in normal colon, but the variance was much greater in neoplastic cells. In neoplastic cells, the proliferative pool was greater, the G1 phase prlonged, and the S phase and the mitotic time became shorter as compared to epithelial cells in normal colon. The duration of G2 phase of neoplastic cells fell between the values of presumptive stem cells and differentiating cells in normal colon, compatible with the hypothesis that neoplastic cells are transformed stem cells defective in cellular differentiation. In the colonic mucosa immediately adjacent to neoplasms, the fraction-labeled-mitoses curve showed a flat second wave, indicating that the group of cells initially labeled by the pulse became a mixture of cells, some continuing the proliferative cycle normally, some going out of cycle, some slowing down in their passage from S through G2 to M, and some being arrested in mitotic phase. Such heterogeneous behavior of cells may be closely related to expansion of neoplasms. With some assumptions, however, cell cycle parameters of those normally cycling cells were estimated: the cell cycle time and the duration of G1 phase and mitotic phase were prolonged as compared to neoplastic cells and epithelial cells of normal colon.

Adenocarcinoma↗
PubMed1997

A colonic tissue architecture assay applied to human colon carcinoma cells.

A two-component tissue architecture assay system has been devised that tests the ability of human colon carcinoma cells to conform to the specific three-dimensional cell-cell and cell-substratum interactions characteristic of normal colonic tissues. Dissociated fetal rat colonic cells (FRCC) were allowed to reaggregate in suspension with or without the addition of different proportions (0.1%, 1%, and 10% of the total cells) of the human colon carcinoma cell lines, SW-1222 and LS-174T. Cellular aggregates obtained after 36 hours, incubation exhibited cell sorting by the formation of recognizable epithelial colonic crypt-like structures with glandular lumens in a mesenchyme-like background. Carcinoembryonic antigen (CEA)-positive SW-1222 cells in 10% mixed aggregates were organized into numerous well-formed glandular structures with a polarized apical distribution of CEA. LS-174T cells, on the other hand, were self-sorted but structurally disorganized with a continuous cell surface CEA distribution. Pure FRCC and mixed aggregates were implanted under the kidney capsules of Swiss nu/nu (nude) or CD-1 nu/nu mice and allowed to grow for a period of 7-10 days. Whereas the normal FRCC readily formed colonic tissue, the SW-1222 cells exhibited a capacity for differentiation into colonic crypts which became progressively less normal and more tumor-like as the proportion of carcinoma cells in the aggregates was increased. The LS-174T cells demonstrated poor differentiation at all concentrations. Cell surface levels of CEA and the CEA family member nonspecific crossreacting antigen (NCA), both overexpressed in colon cancer, were higher in LS-174T than in SW-1222 cells, whereas family member biliary glycoprotein (BGP), downregulated in colon carcinoma was higher in the SW-1222 cells. These results thus support the suggestion that deregulated expression of CEA family members can be involved in the ability of colonocytes to differentiate and conform to normal tissue architecture as assessed by the assay. The assay is therefore amenable to genetic analysis of normal and perturbed architectural phenotypes.

Animals↗
PubMed1993

Immortalization and neoplastic transformation of normal rat colon epithelium: an in vitro model of colonic neoplastic progression.

BACKGROUND: Because of the refractory nature of colon epithelium to growth and maintenance in vitro, the cell lines currently available for study are derived from tumors. Unlike most epithelial model systems, there exist no preneoplastic, nontumorigenic colon cell lines for manipulation and study. METHODS: Intact fetal rat colon was cultured in the presence of a feeder layer of cells producing a retrovirus that harbors the SV40 LT gene resulting in the establishment of immortalized colon cell lines. RESULTS: The epithelial and intestinal origin of cell lines was established from the constitutive expression of keratin and villin, respectively. All cell lines displayed an absence of anchorage independent growth and failed to produce tumors in vivo. Neoplastic transformation of immortalized rat colon epithelial cell lines was achieved following introduction of individual oncogenic ras gene members or the v-src oncogene. Probing of cell lysates with phosphotyrosine antibodies revealed altered phosphotyrosyl protein profiles associated with different stages of colonic neoplastic progression. CONCLUSIONS: The establishment of immortalized nontumorigenic colon epithelial cell lines facilitates the biochemical analysis of events associated with different stages of colonic neoplastic progression. In addition, this simple culture technique lends itself to studies involving alternative genetic elements implicated in the genesis of colon tumors.

Animals↗
PubMed1995

Psychosensory modulation of colonic sensation in the human transverse and sigmoid colon.

BACKGROUND & AIMS: Psychosensory stimulation increases the perception of stimuli in different regions of the human colon. The aim of this study was to determine the perception of pain and gas during distention of two colonic regions in healthy volunteers during stress and relaxation. METHODS: In 22 healthy subjects, phasic distentions of transverse and sigmoid colon were performed using infinitely compliant balloons, and symptoms were measured before and during one of three randomized treatments: sham or active relaxation or mental stress. Anxiety ratings and somatic cold-pain sensitivity were included in a multivariate regression model. RESULTS: Mental stress increased levels of anxiety (P < 0.05) and the sensation of gas (P < 0.01), but not pain (P = NS), during transverse colon distentions and the sensations of gas and pain during sigmoid distentions (P < 0.05). Active relaxation reduced only sensation of gas in the sigmoid colon. Somatic pain sensitivity and pretreatment colonic sensory scores were significantly associated with the sensory scores during treatments. CONCLUSIONS: Psychosensory stimulation increases colonic sensation during short-term distention in two regions of the human colon; relaxation alone exerts a smaller influence on sensations arising in the sigmoid colon.

Adult↗
PubMed2004

Age-related loss of EGF-receptor related protein (ERRP) in the aging colon is a potential risk factor for colon cancer.

Although in Fischer-344 rats, aging is associated with increased activation of EGF-receptor (EGFR) in mucosa of much of the gastrointestinal tract, including the colon, regulation of this process is poorly understood. We hypothesize that loss of suppressor of EGFR may partly be responsible for this process. To test this hypothesis, we examined the expression of EGFR related protein (ERRP), a recently identified negative regulator of EGFR, in the colonic mucosa during aging and following administration of the colonic carcinogen dimethylhydrazine (DMH) that resulted in the formation of aberrant crypt foci (ACF), which are considered to be precursor of adenoma and carcinoma. In Fischer-344 rats, aging is associated with increased activation of EGFR in the colonic mucosa, as evidenced by 30-35% increase in the levels of tyrosine phosphorylated EGFR in the proximal and distal colon of aged (20-22 months old) than in young (4-6 months old) rats. In contrast, the levels of ERRP in both regions of the colon of aged rats were decreased by 50-60%, compared to their younger counterparts. Administration of DMH, which induced a greater number of ACF in the colon of aged rats than in young animals, resulted in a corresponding reduction in ERRP in the colon. These results suggest that loss of ERRP expression is a common event during aging and early stages of chemically induced colon cancer. We also suggest that loss of ERRP could be a risk factor for developing colorectal cancer in the older population.

1,2-Dimethylhydrazine↗
PubMed2005

Differentiating colonic diverticulitis from colon cancer: the value of computed tomography in the emergency setting.

BACKGROUND: The purpose of this study was to establish practical diagnostic criteria to differentiate colonic diverticulitis from colon cancer by computed tomography (CT) in the emergency department (ER). METHODS: Helical CT scans of 40 patients admitted to the ER with the clinical diagnosis of diverticulitis and 14 patients diagnosed with colon cancer were retrospectively reviewed. In total, 18 imaging parameters were analyzed and were compared between the 2 groups of patients. RESULTS: Thirteen parameters were found to be statistically significant for the diagnosis of colonic diverticulitis in excluding colon cancer: pericolic infiltration (p < 0.001); presence of lymph nodes (p < 0.001); inflamed diverticula (p = 0.001); non-inflamed diverticula (p = 0.001); degree of enhancement (p = 0.001); intestinal obstruction (p = 0.001); involved wall thickness (p = 0.005); lymph node size (p = 0.007); fascial thickening (p = 0.009); pattern of enhancement (p = 0.012); involved length (p = 0.014); free air (p = 0.035); and abscess formation (p = 0.042). Among these parameters, the most valuable imaging findings for diverticulitis were the presence of non-inflamed diverticulum, inflamed diverticulum, mild degree of enhancement, and small lymph node size. Three were found to have high specificity but low sensitivity: target enhancement pattern; abscess formation; and free air. When colonic obstruction is present, colon cancer is more likely than diverticulitis. CONCLUSION: Specific CT criteria help to differentiate colonic diverticulitis from colon cancer. CT scan with intravenous contrast administration would be the best noninvasive imaging modality in the ER for the accurate diagnosis and appropriate management of such disease.

Adult↗
PubMed1992

Diet-induced increase of colonic bile acids stimulates lytic activity of fecal water and proliferation of colonic cells.

The proposed intermediate steps in the relationship between a diet-dependent increase in colonic bile acids and proliferation of colonic cells were studied in rats. Male Wistar rats were fed diets supplemented with increasing amounts of steroids to increase the bile acid concentration of the colon. After 2 weeks, in vivo colonic proliferation was measured using tritiated thymidine incorporation into DNA. Luminal lytic activity was measured as lysis of erythrocytes by fecal water. To quantify hemolysis in the presence of fecal water, a method was developed which measures Fe-release using atomic absorption spectrophotometry. This method proved to be superior to the cell-counter method published earlier. Our results showed that steroid supplementation increased, in a dose-dependent manner, the total fecal and the soluble bile acid concentration as well as lytic activity of fecal water and colonic proliferation. A highly significant correlation between lytic activity of fecal water and colonic proliferation (r = 0.85, n = 24, P less than 0.001) was observed. These results indicate that the increase in colonic proliferation is mediated by diet-dependent increases in soluble colonic bile acid concentration and luminal lytic activity. This sequence of effects illustrates how diet could influence the risk for colon cancer.

Animals↗
PubMed2004

Colonic regular contractile frequency patterns in irritable bowel syndrome: the 'spastic colon' revisited.

BACKGROUND: Irritable bowel syndrome is a frequent gastrointestinal disorder of which the pathophysiological basis is still not completely understood. Among the various proposed mechanisms, colonic motility may play a role, at least in a subset of patients. AIMS: To investigate the regular colonic contractile patterns in patients with irritable bowel syndrome. Our working hypothesis was that an increase of these patterns in such condition might represent a motility equivalent of the so-called 'spastic colon'. PATIENTS AND METHODS: Twelve patients of both genders were investigated by means of 24 h colonic manometry, and the results were compared to those from 20 healthy controls. Regular contractile patterns (with frequencies ranging from 2 to 8 per min) were calculated for the entire recording period and in single colonic segments. RESULTS: Overall, colonic frequency patterns were significantly more frequent in patients than controls (12.6% vs 6.4% of the total contractile activity, P < 0.001); in both groups, the 3 cycles/min frequency was predominant, especially in the sigmoid colon. More than 40% patients displayed a correlation between abdominal pain and occurrence of regular contractile frequencies. CONCLUSIONS: Abnormal colonic motility may play some role in the pathogenesis of symptoms related to irritable bowel syndrome, with an excess of regular contractile activity related to the so-called 'spastic colon'.

Adult↗
PubMed2006

Low colonic glutathione detoxification capacity in patients at risk for colon cancer.

BACKGROUND: Colon carcinogenesis is a multifactorial process influenced by hereditary as well as environmental factors. The glutathione/glutathione S-transferase detoxification system in the colon is important for protection against carcinogens. We investigated the levels of glutathione/glutathione S-transferase in normal colon mucosa of patients with colorectal cancer and in patients at high risk for colorectal cancer compared with those in healthy controls. MATERIALS AND METHODS: Glutathione content was analyzed by high-performance liquid chromatography, and glutathione S-transferase enzyme activity by spectrophotometric determination with 1-chloro 2,4-dinitrobenzene. Normal colon tissue of patients with colon adenoma (n = 64), colorectal cancer (n = 37), familial adenomatous polyposis (FAP; n = 19), hereditary non-polyposis colorectal cancer families with (HNPCC+Ad; n = 34) or without (HNPCC-Ad; n = 33) adenoma was investigated. RESULTS: Glutathione levels were significantly lower in the normal colon mucosa of patients with cancer, FAP, HNPCC-Ad or HNPCC+Ad compared with adenoma patients or healthy controls. Glutathione S-transferase enzyme activity in the distal colon was significantly lower in patients with cancer or FAP compared with the adenoma patients or healthy controls, whereas values in carcinoma patients were significantly lower compared with both the HNPCC-Ad and HNPCC+Ad groups. CONCLUSIONS: An association of low colonic glutathione/glutathione S-transferase activity levels and high clinical risk for the development of colorectal cancer was observed. This low glutathione detoxification capacity might contribute to the colon cancer risk.

Adenoma↗
PubMedDate not supplied

Colonic luminal pressure in horses with strangulating and nonstrangulating obstruction of the large colon.

Colonic luminal pressure (median, range) measured during ventral midline celiotomy in 69 horses with strangulating obstruction (SO) of the large colon (SO; > or = 270 degrees large colon volvulus; 27 cm H2O: 2 to 80 cm H2O) was greater (P = .0023) than that measured in 37 horses with nonstrangulating obstruction (NSO) of the large colon (NSO; < or = 180 degrees volvulus or a nonstrangulating displacement; 18 cm H2O; 6 to 46 cm H2O). Sixty-five percent (45 of 69) of horses with SO and all horses with NSO survived. Survival analysis was restricted to 59 horses with large-colon SO that survived to hospital discharge or met the criteria specified for classification as nonsurvivors. Colonic luminal pressure in nonsurvivors (48.5 cm H2O; 34 to 80 cm H2O) was higher (P =.0001) than that measured in survivors (18 cm H2O; 2 to 50 cm H2O) of SO. From response operating characteristic curves, a luminal pressure of 38 cm H2O optimized the distribution of horses with SO into survivor and nonsurvivor groups. Sensitivity, specificity, and positive and negative predictive values for a colonic luminal pressure greater than 38 cm H2O in predicting nonsurvival were 0.89, 0.91, 0.72 and 0.97, respectively. Measurement of colonic luminal pressure may be useful for predicting survival in horses with colonic volvulus.

Animals↗
PubMed1985

Mechanical properties of the colon: comparison of the features of the African and European colon in vitro.

The tensile properties of the colon have been examined using methods which gave repeatable results. They showed little change after storage in salt for up to five weeks. The burst strength remained unchanged along the length of the colon. The tensile strength fell distally, as the thickness of the colonic wall increased. The width at burst decreased distally as did the internal diameter. The visco-elastic property of stress relaxation was constant in all regions. The tensile property of the colon was well developed at birth, but fell with age as did the width at burst and the internal diameter. Stress relaxation was unaffected. Because there may be a mechanical abnormality of the colonic wall in diverticular disease and as Europeans are prone to this condition while Africans are not commonly affected, European and African colons were compared. The tensile strength in a Kampala group was greater than in an Edinburgh one, but fell significantly in both groups with age. The width at burst was greater in the Kampala group, but also declined with age. Stress-relaxation was similar in both groups. In view of the similar properties in childhood of colons from Edinburgh and Kampala, the strength of the adult African compared with European colons may derive later from environmental factors such as diet. There were, however, no differences between the colons with and without diverticular disease in European subjects over the age of 50 years.

Adolescent↗
PubMedDate not supplied

Aberrant crypt foci in the colonic mucosa of rats treated with a genotoxic and nongenotoxic colon carcinogen.

Aberrant crypt foci (ACFs) are putative preneoplastic lesions in the colonic mucosa identified by examining methylene blue-stained whole mounts of colon. ACFs have been previously described in rats treated with genotoxic colon carcinogens. This study determined whether or not a nongenotoxic colon carcinogen could induce ACFs and compared the morphology of these ACFs with those induced by a genotoxic colon carcinogen. Six-wk-old Fischer-344 rats were administered dextran sulfate (DSS, nongenotoxin) in the drinking water or azoxymethane (AOM, genotoxin) by single subcutaneous injection. Rats were sacrificed at 9 and 14 wk after study initiation. Colons were fixed and stained with methylene blue, and the mucosal surface of transilluminated whole mounts was examined with a microscope. The number of ACFs and number of crypts per focus (multiplicity) were recorded. Representative ACFs were processed into glycol methacrylate for hexosaminidase enzyme histochemistry and sections of the remaining colon containing ACFs were embedded in paraffin for morphologic evaluation. In whole mounts, ACFs from AOM- and DSS-treated rats had elongated slit-to-oval-shaped lumens surrounded by a thickened and intensely stained epithelium. DSS-induced aberrant crypts differed from those induced by AOM in that they were frequently larger, tended not to form discrete foci circumscribed by normal crypts, and were located adjacent to ulcers. Total ACFs and large foci (4 or more crypts/focus) were significantly more numerous in AOM-treated rats at both time points. Histologically, DSS-induced ACFs had segmental to diffuse loss of hexosaminidase activity, mucin depletion to increased prominence of goblet cells, and marked distortion of crypt architecture. AOM-induced ACFs had diffuse loss of hexosaminidase activity, variable depletion of mucin, and less distortion of crypt architecture. Variable degrees of epithelial dysplasia were seen in ACFs with both carcinogens, but dysplasia was more severe in DSS-induced ACFs. Colonic mucosal neoplasms were induced by both carcinogens. In subchronic studies, the ACF assay may be a useful method to improve the identification and characterization of xenobiotic-induced changes in colonic mucosal crypts.

Animals↗
PubMed2005

Expression of serum amyloid A, in normal, dysplastic, and neoplastic human colonic mucosa: implication for a role in colonic tumorigenesis.

Serum amyloid A (SAA) is an acute phase reactant, whose level in the blood is elevated in response to trauma, infection, inflammation, and neoplasia. Elevated levels of SAA in the serum of cancer patients were suggested to be of liver origin rather than a tumor cell product. The role of SAA in human malignancies has not been elucidated. We investigated the expression of SAA at various stages of human colon carcinoma progression. Nonradioactive in situ hybridization applied on paraffin tissue sections from 26 colon cancer patients revealed barely detected SAA mRNA expression in normal looking colonic epithelium. Expression was increased gradually as epithelial cells progressed through dysplasia to neoplasia. Deeply invading colon carcinoma cells showed the highest levels of SAA. Expression was also found in colon carcinoma metastases. Cells of lymphoid follicles of the intestinal wall, inflammatory cells, ganglion cells, and endothelial cells, also expressed SAA mRNA. Immunohistochemical staining revealed SAA protein expression that colocalized with SAA mRNA expression. RT-PCR analysis confirmed the expression of the SAA1 and SAA4 genes in colon carcinomas, expression that was barely detectable in normal colon tissues. These findings indicate local and differential expression of SAA in human colon cancer tissues and suggest its role in colonic tumorigenesis.

Adenocarcinoma↗
PubMed1999

Inhibitory effects of ursodeoxycholic acid on N-methylnitrosourea-induced colon carcinogenesis and colonic mucosal telomerase activity in F344 rats.

Bile acids are known to promote colon carcinogenesis. However, one study showed that ursodeoxychlic acid (UDCA) prevented azoxymethane-induced rat colon tumorigenesis. The aim of the present study with 3 sets of experiments was to explore the inhibitory effect of UDCA supplemented in the diet on colon carcinogenesis induced by the intrarectal administration of N-methylnitrosourea (MNU) in F344 rats. In experiment I, 5 rats per group were fed a diet supplemented with 0% (control), 0.4%, 0.08% or 0.016% UDCA or chenodeoxycholic acid (CDCA) for 5 weeks after receiving 3 intrarectal doses of 4 mg MNU in week 1. The formation of colonic aberrant crypt foci (ACFs, preneoplastic lesions) at week 6 showed a 24% and 23% reduction in the 0.4% and 0.08% UDCA groups, respectively, as compared to the control group, while it increased for the 0.4% and 0.08% CDCA groups, and was unaffected in the 0.016% UDCA and CDCA groups. In experiment II based on the results of experiment I, all rats received an intrarectal dose of 2 mg MNU 3 times a week for 3 weeks, and then were administered with 0%, 0.4% or 0.08% UDCA for 27 weeks. At week 30, the incidence of colon tumors in the UDCA groups was significantly lower than that in the control group: 20/50 (40%) and 9/25 (36%) vs. 17/25 (68%). The number of large-sized ACFs with 4 or more ACs showed a 47% and 59% reduction in the normal-appearing mucosa in the UDCA groups as compared to the control group, while the number of small-sized ACFs with 1-3 ACs was similar in all groups. The normal-appearing mucosa showed a noticeable level of telomerase activity (semiquantitative PCR-based TRAP assay) in the control group, and significantly reduced levels in the UDCA groups compared to the control group: 19.8 and 32.7 vs. 71.0 TPG unit in mean value. The colon tumors showed a high level of enzyme activity in both the control and UDCA groups. In experiment III, 6 rats per group were fed a diet supplemented with 0%, or 0.4% UDCA or CDCA for 5 weeks after receiving 3 intrarectal doses of 4 mg MNU in week 1. Two control groups did not receive any treatment with MNU and bile acids. The MNU-treated groups showed significantly elevated levels of colonic mucosal telomerase activity at week 6 as compared to the control group (6.5 TPG unit in mean value). It was noted that both UDCA and CDCA administration reduced the enzyme activity as compared to the group with MNU treatment alone: 24.7 and 25.2 vs. 40.1 TPG unit in mean value. Thus, the present study suggested that orally administered UDCA inhibited the growth of ACFs and the development of carcinomas in the colon of rats treated with MNU. Also, UDCA may suppress MNU-induced telomerase activation in normal-appearing but ACF-containing colon mucosa, and its mechanism appears to be different from that responsible for the anti-tumor promoting action of UDCA.

Animals↗
PubMed1989

[A clinicopathological study on colonic carcinomas arising from right side colon].

This paper discusses the clinicopathological characteristics of colonic carcinomas arising from right side colon. Out of 214 cases of resected colonic carcinomas during the past 13 years, 36 cases of a right side colon carcinoma (in the cecum, in the ascending colon, or in the hepatic flexure) were encountered. Several characteristics have been associated with this type of cancer. They are as follows: 1) in half of these cases an abdominal pain but no anal bleeding, as has been noted in carcinomas of the sigmoid or rectum; 2) in histological type, poorly differentiated adenocarcinomas or mucinous carcinomas in 30.5% of these 36 cases, and associated with a far distant nodal involvement (n3, n4) in advanced carcinomas; and 3) although there was no difference in the 5-year survival rate between a right side colon carcinoma or a colon carcinoma at another site, the prognosis for those given a curative resection for a right side colon carcinoma was poor--only 22% due to hepatic metastases, indicating that colonic carcinomas of the right side has a poor prognosis due to the subsequent risk of highly potential malignancies.

Abdominal Pain↗
PubMed1993

Chemoprevention of colon carcinogenesis by the natural product of a simple phenolic compound protocatechuic acid: suppressing effects on tumor development and biomarkers expression of colon tumorigenesis.

Our previous study has shown that dietary administration of protocatechuic acid (PCA) acts as potential chemopreventive agent in inhibiting diethylnitrosamine-induced liver carcinogenesis in male F344 rats. The present study was designed to determine the modifying effect of PCA on azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats and the effect on intermediate biomarkers, i.e., colonic mucosal ornithine decarboxylase activity and colonic epithelial proliferation, which can be used as effective predictors of colon cancer. Staring at 6 weeks of age, groups of animals were fed the basal diet and experimental diet containing PCA at dose levels of 250, 500, and 1000 ppm. At 7 weeks of age, all animals except the PCA alone group (1000 ppm) and untreated controls were given s.c. injections of AOM at a dose level of 15 mg/kg body weight/week for 3 weeks. PCA at 3 doses was fed during the initiation phase (before 1 week, during, and after 1 week of AOM exposure) or postinitiation phase (for 28 weeks starting 1 week after the last injection of AOM). All animals were then killed at 32 weeks after the start and colonic tumor incidence and multiplicity were determined. Animals intended for cell proliferation study were given injections of bromodeoxyuridine/5-fluoro-2'-deoxyuridine (1 ml/100 g body weight) 1 h prior to be killing. The rate of colonic cell proliferation in the distal portion was assessed by immunohistochemistry using antibromodeoxyuridine and by counting silver-stained nucleolar organizer regions protein. The colonic mucosal ornithine decarboxylase activity was also measured at the termination. The results indicate that dietary PCA administration at 500 and 1000 ppm during the initiation or postinitiation phase significantly inhibited intestinal carcinogenesis induced by AOM as revealed by the reduction of tumor incidence and multiplicity. The data also demonstrate that PCA at 500 ppm and 1000 ppm significantly inhibited bromodeoxyuridine labeling index and also silver-stained nucleolar organizer regions protein number at three doses when animals were fed PCA at the initiation or postinitiation stage. Also, feeding of PCA at 1000 ppm during the initiation and postinitiation phase exerted a pronounced inhibitory effect on the colonic ornithine decarboxylase levels. PCA feeding did not cause any toxicity. These results demonstrate that PCA is a possible new chemopreventive agent for colon carcinogenesis through the suppression of manifestation of intermediate biomarkers induced by AOM, although the precise mechanisms of PCA-induced inhibition during the initiation and postinitiation phases remain to be elucidated.

Adenocarcinoma↗