Left Colon In Patients Research Articles

Differential mRNA expression in ileal and colonic biopsies in irritable bowel syndrome with diarrhea or constipation.

Altered mucosal functions are documented in jejunal or colorectal mucosa from patients with irritable bowel syndrome (IBS). Our aim was to quantify ileal, ascending, and rectosigmoid colon mucosal expression of genes in IBS-diarrhea (D) and IBS-constipation (C). Forty-four patients with IBS-D, 30 with IBS-C, and 30 healthy volunteers underwent colonoscopic ileal, ascending, and rectosigmoid colon biopsies. Biopsies were stored in RNAlater at -80 °C, purified with on-column DNase, cDNA libraries prepared from 100-200 ng of total RNA, sequenced on Illumina NovaSeq 6000, and analyzed on Illumina's RTA version 3.4.4. Normalized mRNA expression was obtained using MAP-RSeq bioinformatics pipeline. Differential expressions in the groups (Log2-fold change) were measured using the bioinformatics package edgeR 2.6.2, corrected for false discovery rate (PADJ <0.05). There were 30 females with IBS-C and 31 females and 13 males with IBS-D. In IBS-D and IBS-C groups, there were differential expressions of 181 genes in ascending colon and 199 genes in rectosigmoid colon. The majority were gene upregulations in IBS-D with functions reflecting activation of inflammation genes, TRPV1 (visceral hypersensitivity) and neurotransmitters/receptors (specifically purinergic, GABA, and cannabinoid). Although gene differential expressions in the ascending and rectosigmoid colon mucosa of the two groups were different, the diverse upregulated genes involved immune functions, receptors, transmitters, ion channels, and transporters. Conversely, there was reduced expression of PI15 and PI16 genes that inhibit proteases. In patients with IBS-D and IBS-C, differential expressions of genes related to immune, transmitter, nociceptive, protease inhibition, channel, and transporter functions suggest opportunities to reverse the pathobiology and treat patients with IBS.NEW & NOTEWORTHY This study compares gene expression in mucosa of the terminal ileum, right colon, and left colon in patients with diarrhea- or constipation-predominant irritable bowel syndrome (IBS) and contrasts expression between these two disease entities and also between each entity and mucosa from healthy controls. The study shows there is differential expression of genes related to immune, transmitter, nociceptive, ion channel, and transporter functions, as well as reduced serine protease inhibition, in patients with IBS.

The Relationship of Albumin-Bilirubin Grade with Right and Left Colon in Patients with Colon Cancer Treated with Regorafenib

The Relationship of Albumin-Bilirubin Grade with Right and Left Colon in Patients with Colon Cancer Treated with Regorafenib

Chromogranin A cell density as a diagnostic marker for lymphocytic colitis.

BackgroundLymphocytic colitis (LC) can be mistakenly diagnosed as irritable bowel syndrome (IBS). In a previous study on IBS, some patients showed extremely high colonic chromogranin A cell density. Further examination of these patients showed that they suffered from LC.AimsTo investigate whether chromogranin A cell density is increased in LC patients and to examine the possibility of using this increase as a marker for the diagnosis of LC.MethodsFifty-seven patients diagnosed with LC and 54 controls were included in the study. Biopsies from the right and left colon were obtained from both patients and controls, which were immunostained using the Avidin–biotin-complex method for chromogranin A, and cell density was quantified.ResultsIn both the right and left colon of patients with LC, the density of chromogranin A was significantly higher than in controls. This increase in chromogranin A cells occurs whether the number of these cells is expressed as number/mm2 epithelium or as number/field. Chromogranin A cell density for the right and left colon expressed as number of cells/mm2 epithelium or as cell number/field showed a high sensitivity and specificity as a diagnostic marker for LC.ConclusionsChromogranin A is a common marker for endocrine cells, and the present finding suggests that colonic hormones are involved in the pathophysiology of LC. The chromogranin cell density seems to be a good diagnostic marker with high sensitivity and specificity in both the right and left colon, thus sigmoidoscopy can be used in the diagnosis of LC using with this marker.

Clinical Characteristics of Ischemic Colitis According to the Localization

See Article on Page 282-286 Ischemic colitis (IC) occurs as a result of an inadequate blood supply to the colon. The segmental nature of IC can be explained by the vascular anatomy and the blood flow to the colon and the rectum. Colonic blood flow is supplied by three vessels: the superior mesentetic artery, the inferior mesenteric artery, and the superior hemorrhoidal artery. The vascular anatomy, however, is variable and often individually unique. Watershed zones are areas that are frequently susceptible to ischemic insult as a result of their location between two different vascular supplies. These areas include the splenic flexure (Griffiths' point) and the sigmoid colon (Sudeck's point), both of which may have potentially limited collateral blood flow. The significance of these anatomic points in an individual case cannot be determined without angiographic confirmation of vascular anatomy. Overall, the left part of the colon seems to be affected by IC in 75% of the cases. The right part of the colon, including the ileocecal area, can be affected as well, but the incidence is reported to be low. However, Brandt et al. [1] reported an affection of the left colon in only 32.6% of 313 patients and more right-sided and pancolon involvement and less hepatic and splenic flexure involvement than have previous studies. Confirmed again in their study was the predominant association of certain comorbidities, i.e., hypertension, diabetes mellitus, and coronary artery disease, in patients with IC. Chronic kidney disease requiring dialysis was again a more common comorbidity in cases of right colon IC than it was for IC in general. Sepsis was a major cause of IC in patients with pancolon involvement. Chronic obstructive pulmonary disease (COPD), previous stroke, and hyperthyroidism were shown to be the only three statistically significant independent predictors of mortality. Finally, with right colon involvement, surgery was more commonly required, and death was more frequently observed compared with the aggregate of all other patterns of IC. Carlson and Madoff [2] also suggested that the watershed zone was not especially vulnerable. Glauser et al. [3] also suggested that every segment of the colon could be affected by IC. The region of Griffith' point did not show a significant higher incidence of IC than the right colon. The right colon was significantly more often affected than the left colon in patients with non-steroidal anti-inflammatory drug (NSAID) intake. In this study, the author suggests that IC of the right colon is significantly associated with renal failure, requires more surgical treatment and shows higher mortality than IC of the left colon.

Colonic Microflora in Crohnʼs Is Different Than Normals

Purpose: Clinical observations and animal studies point toward a dysbiosis in IBD, however the changes that make up this dysbiosis in Crohn's disease (CD) are largely unknown. Amplicon length heterogeneity is a sophisticated technology that examines 16s ribosomal DNA of bacteria and can be used to define such changes in CD. We therefore hypothesized that ALH is a tool to study the changes in the mucosal microflora in Crohn's disease and can diffrentiate Crohn's disease from normals. Methods: We collected mucosal biopsy samples from the ileum, right colon, and left colon of patients with Crohn's disease (n = 22 for active disease, n = 10 for inactive disease) and healthy controls (n = 10) at the time of colonoscopy. The samples were fingerprinted for bacterial patterns using ALH. The fingerprints were analyzed using principal component analysis with the aid of custom PERL scripts and a multivariate statistical package. ANOSIM was used for statistical analysis. Results: ALH patterns were unique in each subject. There was a visual seperation between normals and Crohn's disease in PCO analysis. ANOSIM statististics revealed a statistically significant difference between active CD, inactive CD and healthy controls. (R = 0.2129, p = 0.001 for comparison of active vs inactive CD// R = 0.1545, p < 0.001 for comparison of active CD vs controls// R = 0.3487, p < 0.001 for comparison of inactive CD vs controls). There was no statistically significant difference between endoscopically involved and noninvolved portions of the colon. Conclusions: Our results show that a dysbiosis exists in the mucosal microflora in CD. ALH is a useful tool in evaluation of dysbiosis in IBD. Further studies are now underway to determine a pattern or set of patterns associated with the presence of CD.

A spectral analysis of the myoelectric activity of the left colon in patients with schistosomiasis mansoni

The objective of the present study was to perform a spectral analysis of the electrical activity of the left colon of patients with hepatosplenic schistosomiasis. Thirty patients were studied, divided into 2 groups: group A was composed of 14 patients (9 males and 5 females) with hepatosplenic schistosomiasis and group B was composed of 16 female patients without schistosomiasis mansoni. Three pairs of electrodes were implanted in the left colon at the moment of the surgical treatment. The signals of the electric activity of the colon were captured after postoperative recovery from the ileus and fed into a computer by means of a DATAQ data collection system which identified and captured frequencies between 0.02 and 10 Hz. Data were recorded, stored and analyzed using the WINDAQ 200 software. For electrical analysis, the average voltage of the electrical wave in the three electrodes of all patients, expressed as millivolts (mV), was considered, together with the maximum and minimum values, the root mean square (RMS), the skewness, and the results of the fast Fourier transforms. The average RMS of the schistosomiasis mansoni patients was 284.007 mV. During a long period of contraction, the RMS increased in a statistically significant manner from 127.455 mV during a resting period to 748.959 mV in patients with schistosomiasis mansoni. We conclude that there were no statistically significant differences in RMS values between patients with schistosomiasis mansoni and patients without the disease during the rest period or during a long period of contraction.

Abnormality of Peptide YY and Pancreatic Polypeptide Immunoreactive Cells in Colonic Mucosa of Patients with Colonic Inertia

The etiopathology of colonic inertia remains unclear. Current studies show that pancreatic polypeptide-fold family members can serve as regulators of colonic motility and transit. Thus, the cells containing these peptides on colonic mucosa could be abnormal in patients with colonic inertia. We aimed to evaluate the immunocytochemical staining of peptide YY (PYY) and pancreatic polypeptide (PP) immunoreactive cells, and detect if alteration of these cells relates to an increase in enterochromaffin cells (EC) demonstrated by chromogranin A (CgA), in the colonic mucosa of patients with colonic inertia. Nineteen consecutive patients (18 female, 1 male; age, 43.7+/-11.5 years) who underwent subtotal colectomy for colonic inertia were assessed. The control group consisted of 15 patients (all female; age, 50.7+/-12.5 years) who underwent colonoscopic biopsies from the right and left colon for indications other than constipation, inflammatory bowel diseases, diarrhea, or neoplasm. Hollande's-fixed, paraffin-embedded tissues of both right and left colons were collected. Immunocytochemical staining of PYY, PP, or CgA was performed on 4-microm tissue sections with the respective primary rabbit antibody, the biotinylated secondary antibody, and enzyme-labeled streptavidin. The average number of positive cells per microscopic field (200x) was calculated. Positive cells were classified as strongly, moderately, and weakly staining. The proportion of the variously stained cells is expressed as the percentage of the entire positive cell population. On both sides of the colon, the percentages of strongly and moderately stained PYY positive cells were higher in the patient group compared to the controls (right side, 10.6 and 27.3 vs. 6.1 and 18.7%, respectively; left side, 9.4 and 23.9 vs. 6.2 and 23.1%, respectively) (P < 0.01). Furthermore, in the patients with colonic inertia, the percentages of strongly and moderately stained PYY-positive cells were higher in the right-side colon than in the left (P < 0.01). There was no difference in the number of PYY-positive cells between the patients and the controls. PP-positive cells were very rare in all specimens and were found in 7 of 19 cases (36.84%) in the right-side colon and 16 of 19 (84.21%) in the left-side colon in the patient group (P < 0.01, left vs. right). In contrast, the number of EC in the left colon of patients (16.8+/-10.2) was significantly higher than that in the right side (9.4+/-6.0) (P < 0.01) or that in the left side in the control group (10.4+/-6.0) (P < 0.05). We conclude that in the colonic mucosa of patients with colonic inertia, PYY-positive cells present with higher immunoreactivity, indicating that they may contain more hormones, especially on the right side of the colon. However, the PPY- and PP-positive cells did not relate to the increased EC. and It is therefore suggested that the altered PYY in the colonic mucosa may partially contribute to the etiopathology of colonic inertia.

Reduced expression of serotonin receptor(s) in the left colon of patients with colonic inertia.

Serotonin regulates colonic motility receptors expressed on neural fibers and smooth muscle. Colonic inertia is characterized by delayed colonic transit. Abnormalities in serotonin receptor protein, as judged by immunoreactivity levels, could contribute to the origin of colonic inertia. The aim of this study was to investigate the expression of serotonin receptor(s) immunoreactivity in the left colon of patients with colonic inertia compared with controls. Sixteen patients who underwent subtotal colectomy for colonic inertia were assessed. Colonic transit time was measured with the radiopaque marker technique and presented as the number of retained markers in the colon on Day 5. The control group consisted of 18 patients who underwent left hemicolectomy for colonic carcinoma; histologically normal tissues from the left colon were used. Immunohistochemical staining for serotonin receptor was performed with a rabbit anti-idiotypic antibody. The average positive area (square pixels) in the mucosa, muscularis mucosa, submucosa, and circular and longitudinal muscles per microscopic field (63x) was calculated based on measurement of the positively stained area in 20 randomly chosen microscopic fields in each related structure. The Scion Image computer analysis system was used. Serotonin receptor(s) immunoreactivity was mainly detected in the muscular mucosa, circular muscles, and longitudinal muscles and rarely in the mucosa and submucosa. In muscularis mucosa and circular muscle, the positive areas were significantly less in the colonic inertia group than in controls (muscularis mucosa: 29.1 +/- 10.8 vs 109.7 +/- 28.2, P < 0.05; circular muscle: 25.6 +/- 6.2 vs 90.2 +/- 19.1, P < 0.01). There were significantly positive correlations in the control group in serotonin receptor(s) immunoreactivity levels between circular muscle and longitudinal muscle (r = 0.54, P < 0.05) and between muscular mucosa and longitudinal muscle (r = 0.57, P < 0.05) but not in colonic inertia patients. In addition, the positive areas in the circular muscle were positively correlated to the colonic transit time (Spearman's rank correlation, 0.83; P < 0.01). In colonic inertia patients, the serotonin receptor(s) immunoreactivity level is lower in muscular mucosa and circular muscle. The absence of a correlation of serotonin receptor(s) immunoreactivity in the muscular mucosa and muscularis propria in the patient group implies that an uncoordinated expression of serotonin receptors may also contribute to colonic inertia. However, the positive correlation between serotonin receptor(s) immunoreactivity levels in the circular muscle and the transit time observed in colonic inertia patients suggests a decrease in stimulatory subtypes and at the same time an increase in inhibitory subtypes of serotonin receptors in this tissue.

Variability in serotonin and enterochromaffin cells in patients with colonic inertia and idiopathic diarrhoea as compared to normal controls.

AIM: To evaluate differences in distribution, density and staining intensity of enterochromaffin cells (EC) and serotonin cells (SC) in the colonic mucosa of patients with colonic inertia (CI), idiopathic diarrhoea (ID) and a control group. METHODS: Three groups were studied: 19 patients' colons after subtotal colectomy for CI, and 17 patients' biopsies for diarrhoea (>3 bowel movements/day) with histological findings of normal mucosa (excluding microscopic, eosinophillic and collagenous colitis). The third group included 15 patients who underwent colonoscopy and biopsy for indications other than constipation, inflammatory bowel disease, diarrhoea or neoplasm (control group). Specimen blocks were obtained in each case from the right and left colon. Immunohistochemical staining for EC and SC were done on 4 micro m sections from Hollandes fixed, paraffin embedded tissues with primary rabbit antibody against chromagranin A or serotonin, and biotynylated secondary antibody and enzyme labelled streptavidin. RESULTS: The number of EC in the mucosa of the left colon in patients with CI (16.8 +/- 10.2) and ID (19.9 +/- 9.7) were significantly higher than they were on the right side (CI: 9.4 +/- 6.0, ID: 12.1 +/- 5.3). However, there were no significant differences between the left and right sides in the control group (L: 10.3 +/- 5.3; R: 13.4 +/- 7.6). Although the quantity of EC in the left colon in both patients with CI (P < 0.05) and ID (P < 0.01) were significantly higher than in the controls, there was no significant difference between CI and ID. In both the right and left colon, the percentage of EC with low positive density was significantly higher (P < 0.01) while those cells with moderate or low staining intensity were significantly lower in patients with CI than in either patients with ID or control group. In patients with CI, the quantity of SC in the mucosa of the left colon (12.1 +/- 6.4) was higher than in the right (CI: 7.9 +/- 3.6; control 4.6 +/- 3.3; ID 4.6 +/- 2.9) (P = 0.0057). In contrast there was no significant difference in SC in either the ID or control groups. The quantity of SC in both sides of the colon was significantly higher both in patients with CI as compared to the control group (P < 0.01) and patients with CI vs. patients with ID (L = P < 0.01; R = P < 0.05). There was a significantly positive correlation between the numbers of EC and SC in patients with CI (L: r = 0.5425, P < 0.05; R: r = 0.745, P < 0.01). CONCLUSION: In patients with CI, EC increases possibly due to an increase in SC. Conversely, in patients with ID, the EC increase results from peptides other than SC. Our results suggest that different aetiological factors contribute to ID and CI.

Altered serotonin immunoreactivities in the left colon of patients with colonic inertia.

BACKGROUND: Serotonin is an important positive regulator of colonic motility and transit. Its quantity and distribution in the left colon could be abnormal in patients with colonic inertia (CI) and contribute to the disease. AIM: To evaluate serotonin positive cells and immuno-reactivities in the mucosa, submucosa and muscularis propria of the left colon from patients with CI was compared to a control group. PATIENTS AND METHODS: Nineteen patients who underwent subtotal colecotomy for CI were assessed. The control group consisted of 15 patients who underwent left hemicolectomy for colonic cancer; histologically normal tissue specimens were used. Immunohistochemical staining for serotonin was performed. In the mucosa, the average number of serotonin positive cells per microscopic field (200 x ) was determined. The positively stained area (square pixels) in the mucosa, submucosa and muscularis propria per microscopic field (200 x ) was calculated utilizing a computer image analysis program. RESULTS: In the mucosa, both the number of serotonin positive cells and positively stained area were significantly higher in the patient group than in controls (P < 0.05). The difference in serotonin positive area in the submucosa in the CI group compared to the control group was not statistically significant. There was a very significant correlation between the serotonin positive area in the submucosa and muscularis propria in controls (r=0.65, p < 0.01), but not in patients with CI. CONCLUSION: The increased serotonin level in patients with CI may contribute to the disease or be an adaptive response to some other pathology. The lack of a positive correlation in serotonin levels between the submucosa and muscularis propria in CI patients suggests that the coordinated distribution of serotonin may be disrupted in CI.

Serum and colon mucosa micronutrient antioxidants: differences between adenomatous polyp patients and controls

OBJECTIVES: Micronutrient antioxidants, by virtue of their free radical scavenging properties, are potential chemopreventive agents against colon cancer. Yet, little is known about the actual concentration of these antioxidants in colonic mucosa. It is also not known whether a relationship exists between serum and mucosal tissue antioxidant levels. Previous studies evaluating the occurrence of polyps after supplementation with vitamin E and β-carotene have yielded mixed results. The aim of this study was to determine the concentrations of seven micronutrient antioxidants (α- and γ-tocopherol, lutein, β-cryptoxanthin, lycopene, and α- and β-carotene) in colonic mucosa and to determine whether serum levels of each antioxidant could predict levels of that antioxidant in the right and left colon of patients with normal mucosa or in those with adenomatous polyps. METHODS: Mucosal tissue concentrations and serum levels of antioxidants were determined in10 patients with adenomatous polyps and 15 control subjects (GI patients with normal colonic mucosa). Mucosal tissue samples were obtained from both the right and left colon in all patients. RESULTS: Patients with polyps similar serum antioxidant status similar to that of control. However, polyp patients had significantly lower concentrations of all seven antioxidants in both the right ( p < 0.0070) and left colon ( p < 0.0026) than did controls. Finally, serum antioxidant levels predict right and left colon antioxidant levels in controls but not in patients with polyps. CONCLUSIONS: Patients with adenomatous polyps have low levels of micronutrient antioxidants in their colon mucosa. Because the serum levels of these antioxidants were similar in controls and polyp patients, our findings suggest an increased level of free radical activity in patients with polyps compared to normal subjects.

Serum and colon mucosa micronutrient antioxidants: differences between adenomatous polyp patients and controls.

Micronutrient antioxidants, by virtue of their free radical scavenging properties, are potential chemopreventive agents against colon cancer. Yet, little is known about the actual concentration of these antioxidants in colonic mucosa. It is also not known whether a relationship exists between serum and mucosal tissue antioxidant levels. Previous studies evaluating the occurrence of polyps after supplementation with vitamin E and beta-carotene have yielded mixed results. The aim of this study was to determine the concentrations of seven micronutrient antioxidants (alpha- and gamma-tocopherol, lutein, beta-cryptoxanthin, lycopene, and alpha- and beta-carotene) in colonic mucosa and to determine whether serum levels of each antioxidant could predict levels of that antioxidant in the right and left colon of patients with normal mucosa or in those with adenomatous polyps. Mucosal tissue concentrations and serum levels of antioxidants were determined in 10 patients with adenomatous polyps and 15 control subjects (GI patients with normal colonic mucosa). Mucosal tissue samples were obtained from both the right and left colon in all patients. Patients with polyps similar serum antioxidant status similar to that of control. However, polyp patients had significantly lower concentrations of all seven antioxidants in both the right (p < 0.0070) and left colon (p < 0.0026) than did controls. Finally, serum antioxidant levels predict right and left colon antioxidant levels in controls but not in patients with polyps. Patients with adenomatous polyps have low levels of micronutrient antioxidants in their colon mucosa. Because the serum levels of these antioxidants were similar in controls and polyp patients, our findings suggest an increased level of free radical activity in patients with polyps compared to normal subjects.

Reduced expression of serotonin receptor (SR) in the left colon of patients with colonic inertia (CI)

Reduced expression of serotonin receptor (SR) in the left colon of patients with colonic inertia (CI)

Reduced expression of serotonin receptor (SR) in the left colon of patients with colonic inertia (CI)

Reduced expression of serotonin receptor (SR) in the left colon of patients with colonic inertia (CI)

Enterochromaffin and serotonin cells are abnormal for patients with colonic inertia.

In recent studies, serotonin and several gut peptides have been shown to serve as regulators of colonic transit. Thus, the distribution, density, and intensity of cells secreting serotonin or certain gut peptides could be abnormal in patients with colonic inertia. The aim of this study was to evaluate the distribution, density, and staining intensity of enterochromaffin and serotonin cells in the colonic mucosa of patients with colonic inertia compared with a control group. Between 1993 and 1998 tissue blocks from the right and left side of the colon were obtained in 19 consecutive patients (18 females; mean age, 43.7 +/- 11.5 years) who underwent subtotal colectomy for colonic inertia. The control group consisted of colonoscopic biopsies from the right and left colon of 15 patients (all females; mean age, 52.7 +/- 16.5 years) for indications other then constipation, inflammatory bowel diseases, or carcinoma. Immunocytochemical staining of enterochromaffin and serotonin cells were performed on 4 microm tissue sections with the primary rabbit antibody against chromogranin A or serotonin, and the biotinylated secondary antibody and enzyme-labeled-streptavidin. The average cell number per microscopic field (x200) was calculated and the proportion of cells with various staining distribution was expressed as the percentage of the entire positive cell population as low, moderate, and high intensity. Student's t-test and chi-squared test were used for statistical analysis, with significance level set at P < 0.05. The quantity of both enterochromaffin cells (16.8 +/- 10.2) and serotonin cells (12.1 +/- 6.4) in the mucosa of the left colon in patients with colonic inertia was significantly higher when compared with the right side of the colon (enterochromaffin cells, 9.4 +/- 6.0; serotonin cells, 7.8 +/- 3.6; P < 0.01). The percentage of both types of cells with low staining intensity was increased, whereas the cells with high and moderate staining intensity were decreased (P < 0.01) in the left colon as compared with the right. The number of enterochromaffin cells in left-sided colonic mucosa was significantly higher in the colonic inertia group than in the control group (16.8 +/- 10.1 vs. 10.4 +/- 6.0; P < 0.05). Moreover, the numbers of serotonin cells in both the right and left colon was also significantly higher in the colonic inertia group than in the control group (right, 7.8 +/- 3.6 vs. 4.1 +/- 2.4; left, 12.1 +/- 6.4 vs. 5.8 +/- 3.7; P < 0.01). In both sides of the colon, the percentage of enterochromaffin and serotonin cells with low staining was significantly higher, whereas percentage of those cells with high or moderate staining was significantly lower in the colonic inertia group than in the control group. In the colonic inertia group there was a significantly positive correlation between numbers of enterochromaffin and serotonin cells (right side, P < 0.01; left side, P < 0.05). In patients with colonic inertia, the number of both enterochromaffin and serotonin cells are significantly increased in the colonic mucosa, especially in the left colon. As indicated by staining distribution, enterochromaffin and serotonin cells contain significantly less hormone than do the same cells in the control group.

Microsatellite instability and p53 mutations in sporadic right and left colon carcinoma

BACKGROUND Left and right colon carcinomas can display different clinical, pathologic, and genetic characteristics. The purpose of this study was to characterize multiple molecular genetic alterations in sporadic colon carcinoma and to correlate them with the location of the tumors and with lymph node metastasis. METHODS One hundred and twenty-five cases of sporadic colon carcinoma (50 in the right colon and 75 in the left colon in patients with no family history of colon carcinoma) were studied. Status of the p53 gene was assessed by polymerase chain reaction (PCR), single strand conformation polymorphism, and sequencing at exons 5-8. Microsatellite instability was analyzed with five microsatellite markers at chromosome 18. The mismatch repair genes hMLH1 and hMSH2 were studied in tumors found to have microsatellite instability by PCR and sequencing. RESULTS In the 125 cases studied, there were 53 tumors with mutations of the p53 gene. p53 mutations correlated with lymph node metastases from right colon carcinoma cases (61%), and all cases with p53 mutations and microsatellite instability were AJCC/UICC Stage III (Dukes Stage C). In the right colon carcinoma cases the rate of microsatellite instability was related to the tumor size (19% in tumors measuring < 4 cm, and 34% in tumors measuring > 4 cm). No correlation between microsatellite instability and p53 mutations was detected. In the left colon carcinoma cases, p53 mutations were detected in 41% of tumors and microsatellite instability in 14%; neither finding was related to the tumor size. Mutations of the hMLH1 and hMSH2 mismatch repair genes were detected in 7 of 24 cases with marked microsatellite instability. CONCLUSIONS Microsatellite instability is prone to occur in sporadic right colon carcinoma during tumor growth and is not associated significantly with mutations in the hMLH1 and hMSH2 mismatch repair genes or in the p53 gene. Concomitant detection of microsatellite instability and p53 mutations in right colon carcinoma is associated with the presence of lymph node metastases. Cancer 1998;83:889-895. © 1998 American Cancer Society.

Microsatellite instability and p53 mutations in sporadic right and left colon carcinoma

Left and right colon carcinomas can display different clinical, pathologic, and genetic characteristics. The purpose of this study was to characterize multiple molecular genetic alterations in sporadic colon carcinoma and to correlate them with the location of the tumors and with lymph node metastasis. One hundred and twenty-five cases of sporadic colon carcinoma (50 in the right colon and 75 in the left colon in patients with no family history of colon carcinoma) were studied. Status of the p53 gene was assessed by polymerase chain reaction (PCR), single strand conformation polymorphism, and sequencing at exons 5-8. Microsatellite instability was analyzed with five microsatellite markers at chromosome 18. The mismatch repair genes hMLH1 and hMSH2 were studied in tumors found to have microsatellite instability by PCR and sequencing. In the 125 cases studied, there were 53 tumors with mutations of the p53 gene. p53 mutations correlated with lymph node metastases from right colon carcinoma cases (61%), and all cases with p53 mutations and microsatellite instability were AJCC/UICC Stage III (Dukes Stage C). In the right colon carcinoma cases the rate of microsatellite instability was related to the tumor size (19% in tumors measuring < 4 cm, and 34% in tumors measuring > 4 cm). No correlation between microsatellite instability and p53 mutations was detected. In the left colon carcinoma cases, p53 mutations were detected in 41% of tumors and microsatellite instability in 14%; neither finding was related to the tumor size. Mutations of the hMLH1 and hMSH2 mismatch repair genes were detected in 7 of 24 cases with marked microsatellite instability. Microsatellite instability is prone to occur in sporadic right colon carcinoma during tumor growth and is not associated significantly with mutations in the hMLH1 and hMSH2 mismatch repair genes or in the p53 gene. Concomitant detection of microsatellite instability and p53 mutations in right colon carcinoma is associated with the presence of lymph node metastases.

Gastrointestinal pH profiles in patients with inflammatory bowel disease.

5-Amino salicylic acid preparations are used in therapy for patients with inflammatory bowel diseases. The bioavailability of these drugs depends on their coating. To determine whether intraluminal pH is decreased by the presence of inflammation, thereby altering the release of 5-amino salicylic acid in the intestinal lumen. Intraluminal gastrointestinal pH was measured by means of a radiotelemetry capsule in 12 healthy controls, in 12 patients with Crohn's disease (five with active disease), and in 11 patients with ulcerative colitis (seven with active disease). The median gastric pH values in the patient groups (Crohn's disease 2.4, range 1.5-4.1; ulcerative colitis 1.95, range 1.55-4.4) were significantly higher than those observed in the controls (1.55, range 0.95-2.6). In the small bowel and colonic segments, all the pH values of Crohn's disease patients were comparable to those of the controls, as were the pH values in the proximal small intestine and in the left colon in patients with ulcerative colitis. However, the latter group had higher pH values in the terminal ileum, the caecum and the right colon. Patients with active disease had comparable median gastrointestinal pH values to patients in remission. The luminal release of 5-amino salicylic acid might not be inhibited by low pH in patients with active inflammatory bowel diseases. This supports a safe disintegration of the slow release mesalazine preparations even in the presence of severe disease.