ACTA FAC. MED. NAISS. 2003; 20 (4): 223-228
Original article

THE SIGNIFICANCE OF CLINICAL, ENDOSCOPIC AND PATHOHISTOLOGICAL EVALUATION OF ULCERATIVE COLITIS ACTIVITY

Biljana Radovanović-Dinić, Aleksandar Nagorni, Vuka Katić, Goran Bjelaković, Ivanka Stamenković, Dragan Mihajlović
 Clinic of Gastroenterology and Hepatology, Clinical Center Niš 2 Institute of Pathology, Clinical Center Niš 3 Clinic of Surgery, Clinical Center Niš

INTRODUCTION

Ulcerative colitis (UC) is an idiopathic, chronic-relapsing, progressive, inflammatory bowel disease. Inflammatory process is limited to mucosa. The explicitness of intestinal and extraintestinal symptomatology depend on the level of inflammatory process the activity of the disease.
Clinically, it manifests most often through diarrhea, blood and/or mucus in stools, tenesmus, abdominal pain and weight loss (1). The UC diagnosis is established by means of the clinical state analysis, endoscopic and patho-histological findings. The evaluation of UC activity is necessary for the purpose of optimum therapeutic approach and the analysis of the effects. The UC activity should be differentiated from the gravity of the disease which is measured by threatening or developed complications (2,3).
By means of complementary analysis of clinical symptoms and signs, as well as laboratory parameters, it is possible to clinically grade UC activity.
In practice, most often used clinical index of activity is that of Truelove and Witts from 1955 which was modified by Powel and Tuck in 1987 (2). By means of complementary analysis of clinical symptoms and signs (number of stools, blood in stool, body temperature and pulse) and laboratory parameters (sedimentation and hemoglobin), the authors have clinically graded UC activity as mild, moderate and severe (table 1).
With the clinically mildly active UC, present in 60% of the patients, the inflammatory process usually affects the mucous membrane of rectum and sigma rarely the whole colon. The absence of local and system complications is characteristic, as well as of extraintestinal manifestations, except in the case of pancolitis. The prognosis of these patients is good, relapses are rare and there is almost no mortality (4). Clinically moderately active UC is present in 25% of the patients and is characterized by abdominal pains, especially during the night, bloody, slimy, informed stools, loss of appetite and the reduction of body weight. The patients have frequent relapses and the disease tends to become more serious. Clinically severely active UC is present in 15% of the patients. They have to be hospitalized, since they showed severe diarrhea syndrome, anemia, febrility, anorexia, dehydration, hypoalbuminemia and leucocytosis. However, this state rarely responds to therapy, and the outcome is often lethal (4,5).
The adequate endoscopic analysis of the large intestine enables the endoscopic evaluation of UC activity. Most authors suggest the endoscopic classification of UC into inactive (still phase) and active (mild, moderate and severe) (6,7) (table2).
Through the analysis of the biopsy sample of the large intestine, in patients with clinically suspect or evident UC, the pathologist aims to establish or exclude inflammation, differentiate acute from chronic inflammation, exclude the presence of micro-organisms, virus inclusions or parasites and to examine their causal or incidental findings, determine the phase of the disease and, in the active phase, also the level of activity. When we compare the findings, it is necessary to determine the histological progression or the change regression, establish the effect of the therapy and control possible presence of (pre)cancerous lesions (8,9). The patho-histological analysis verifies the active phase, the resolution phase, or the remission phase of UC. The activity of the inflammatory process can be graded as minimal, moderate and severe (table 3).
The activity of the inflammatory process is evaluated according to the presence of cell damage, above all epithelial, and the infiltration of polymorphonuclear leucocytes.
The histochemical analysis of the biopsy samples is important for the determination of UC activity. The hyposecretion of sulfomucin and hypersecretion of sialomucin are important markers of UC activity (1,7,9).
 

THE AIM
The aim of the study is to direct attention to the importance of clinical, endoscopic and patho-histological evaluation of the ulcerative colitis activity.
MATERIALS AND METHODS
A prospective study included 117 patients with chronic ulcerative colitis, examined and treated at the Clinic of Gastroenterology and Hepatology, Clinical Center, Niš. There were 59 male and 58 female patients. The average age of the patients was 41.2 years. The youngest patient was 21 and oldest 70.
All patients underwent colonoscopy, with the use of Olympus colonoscope, type CF 20HI and CF 30HI. Biopsy samples of the large intestine were pathohistologically treated at the Institute of Pathology of The Clinical Center Niš. After the preparation, the samples were colored in classic HE method, histochemical method of PAS and HID-AB (pH2.5) type, and Van Gieson method.
Based on the previously mentioned criteria all the patients received the clinical, endoscopic and patho-histological evaluation of the disease activity.
 

RESULTS
The average duration of UC was 4.44±5.03 years. The extensiveness of the disease analysis verified proctitis in 10 (8.55%) patients, proctosigmoiditis in 36 (30.77%), left-sided colitis in 47 (40.17%), subtotal in 18(15.38%) and total colitis in 6 (5.13%). The analysis of the clinical and laboratory parameters based on the already formed criteria by Truelove and Witts, confirmed inactive UC in 4 (4.27%) patients. The majority of the rest of the patients had a moderately active UC (figure1).
When we correlated the age of the patients, the duration and the extensiveness of UC with the clinical level of activity, we didn't find any statistical significance (p>0.001).The endoscopic examination confirmed the still phase of the disease in 7 (5.98%) patients. The endoscopic examination also confirmed that the greatest number of patients has a severely active UC (Figure 2).
We verified a significant correlation between clinically and endoscopically established UC activity. In 61.24% of the examined patients, there was conformity in clinical and endoscopic levels of activity. When we correlated the age of the patients, the duration and the extensiveness of UC with the histological level of activity, we didn't find any statistical significance (p>0.001).
The patho-histological examinations diagnosed chronic, inactive UC in 7 (5.98%) patients. From the rest of the patients with active colitis, the majority had a moderately active UC (Figure 3).
When we correlated the age of the patients, the duration and the extensiveness of UC with the histological level of activity, we didn't find any statistical significance (p>0.001). The correlation of the clinical and histological levels of activity showed statistical significance. The conformity of the clinical and histological levels of activity was found in 73.59% of the examined. The correlation of the endoscopic and histological levels of activity showed statistical significance. The conformity of the endoscopic and histological levels of activity was found in 65.6% of the examined patients.
We established that the secretion mucin depended neither on the age of the patient nor the duration of the disease. The clinical level of the activity and the extensiveness of UC were in significant negative correlation with the secretion of sulfomucin but not sialomucin.
As opposed to sialomucin, sulfomucins have a significant negative correlation with the patho-histological activity index, which is due to the increase of the UC activity. The presence of dysplasia was verified in 17(17.52%) of the examined patients. The dysplasia of the lone level was found in 12(12.37%) patients whereas the dysplasia of high level was found in 5(5.15%).
Clinical activity and the extensiveness of UC were in statistically significant correlation with the dysplasia level. The correlation of the patho-histological activity index the dysplasia level showed statistical significance. All the patients with the high level dysplasia had a patho-histologically verified, chronic severely active colitis.
 

DISCUSION
The evaluation of the UC activity is significant both from clinical as well as from the scientific aspect.
The activity should be evaluated before and during therapy, as well as immediately before its exclusion. Both clinical doctors and scientists put great effort into objective evaluation of UC activity (11). The aim is to establish relative utility of clinical symptoms and signs, laboratory data, endoscopic and patho-histological findings in defining the activity of the disease, with the purpose of creating a simple activity index for UC patients. In our study we used the activity index by Truell and Witts for the clinical evaluation of UC activity because of its simplicity (2).
By means of correlating the clinical level of activity with the age of the patient, the duration of the disease, the extensiveness and endoscopic activity, we managed to obtain the results which are in accord with those in literature (12-14). The analysis of the endoscopic findings and the evaluation of the UC activity showed that the endoscopically evaluated activity is in significantly positive correlation with the clinical one. The greatest conformity was verified in severely active UC with the evident endoscopic changes.
The results that we obtained are in accord with the results of the studies in the available literature. (11,12,15).
The clinical and endoscopic evaluations of activity give direction to the pathologist in his patho-histological evaluation of UC activity. In order to establish the most correct patho-histological analysis, the pathologist needs to obtain the biopsy sample of adequate size along with complete clinical and endoscopic documentation (16,17).
There is an opinion that a patient should be treated according to the clinical, and not histological evaluation of activity (18,19).We think that the histological evaluation has special importance for the clinical doctor in the initial UC diagnosis when there is scarce symptomatology and in cases when the patient is in clinical remission. The decision about reduction or total cessation of therapy should be made only after the patho-histological confirmation of inactive process.
With the help of the clinical micro-morphological correlation, we established that histologically evaluated activity, as well as the clinical one, do not depend on sex or age of the patient or the duration or extensiveness of the disease. There is a significant statistical correlation between the clinical and the histological indexes of activity. The discrepancy between the clinical and the endoscopic levels of activity in some patients is explained by the fact that more time is needed for the amelioration of the microscopic state of mucous membrane in relation to the clinical state. In cases of evident discrepancy, it is necessary to examine possible complications or superficial diseases, which changed the clinical picture or the patho-histological findings.
In our study, there is a significant correlation between the endoscopic and the histological level of activity, which is in accord with the data in literature (20,21).
In the study of Fung et al. the conformity of the endoscopic and patho-histological index of activity was verified in 72% of the patients, whereas in the study of Niv et al. that conformity was verified in 61% (20,21).
In our study the conformity of the endoscopic and patho-histological indexes of activity was found in 76 (65.6%) patients. The reason for the unconformity of these two indexes of activity might be traced in periodical variations in endoscopic reports of various endoscopists, since certain changes, like ulceration and bleeding, are more often described than some less evident ones (22). In order to reduce subjectivity, Humphrey suggests a special gradation of endoscopic findings (13).
In our study, we verified negative correlation between the clinical, or endoscopic level of activity and the secretion of sulfomucin. As opposed to some authors (23), we did not establish correlation between the secretion of sialomucin and the clinical, or endoscopic activity of the disease, its extensiveness and its duration (24). A significant correlation was verified between the extensiveness of the disease and the level of dysplasia. A significant correlation is also present between the clinical, that is the endoscopic index of activity and the level of dysplasia.
The results that we obtained are in accord with the results of the studies in the available literature (26).
 

CONCLUSION
In order to provide optimal therapeutic treatment for the UC patients and gain control of its effect, we need to perform regular clinical and patho-histological controls, because even if US is seemingly clinically and endoscopically inactive, there may be a certain patho-histological activity which demands therapeutic treatment. For these reasons it is extremely important to take multiple and polytopic biopsy samples even from a seemingly intact mucous membrane during the endoscopic examination.
 

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