Споредба на успехот од терапијата со botulinum toxin a, локален nifedipine во комбинација со lidocaine, и анална дилатација во третман на примарните хронични анални фисури

Abstract

Introduction: Basically, the occurrence of primary chronic anal fissures (CAF) is the result of development of an increased tone of internal anal sphincter (IAS) and hypoperfusion of the anal canal, in particular at it’s posterior midline. Surgical treatment modalities are effective, but can be cause of permanent side effects, such as minor and major anal incontinence (AI). Manual anal dilatation (MAD) is one of the surgical methods. The mane goal in treating CAF is to reduce the IAS tone and improve local perfusion that can be achieved pharmacologically too, with local administration of calcium channel blockers and by injection therapy with botulinum toxin A (ITBT). The primary aim of this study is to compare the success of ITBT versus therapy with MAD and local nifedipine in combination with lidocaine (LNCL) in the treatment of primary CAF. Secondary goals are to compare the occurrence of side effects, in particular prevalence of AI among patients with CAF treated by ITBT, LNCL and the technique of MAD, as well as to assess the clinical and demographic characteristics of patients at the time of diagnosis, which might have a predictive value as risk factors for the success of therapy and final prognosis, for all three types of treatment. Methods: Patients with CAF included in this study were treated with ITBT, anal dilatation or LNCL in ambulatory setting or by hospitalization. After treatment with any of the three methods, patients were followed-up and clinically monitored at intervals of 4 and 12 weeks after the intervention. Few outcome measures were followed. Healing of the fissure confirmed by an external anal examination and anoscopy as a measure of success, persistence or recurrence of CAF and referral to surgical treatment as measures of treatment failure, presence or disappearance of pain and bleeding, AI and local complications, the time required to return to normal activities after the intervention and days of sick leave and absence from work. Results: A total of 94 patients with CAF divided into three groups were included in the study. Thirty-one patients were treated with ITBT, in 33 patients a MAD was done and the third group of 30 patients was treated with LNCL. The average age of the respondents (53.2% males and 46.8% females), was 46.6 ± 13.9 years. The tested differences for sex and age distribution among the three groups were insignificant (p = 0.79 and p = 0.99 respectively), thus showing that groups were homogeneous. The repair of the CAF was confirmed in 71% of patients from the ITBT group, 78.8% of patients from the MAD group and 53.3% of LNCL group, after 12 weeks, at second visit. Significant difference was confirmed between the MAD and the LNCL group (p = 0.032). The distribution difference of patients sent to surgical treatment among the same groups was at the boundary of statistical significance (p = 0.059). At first control after 4 weeks, only 2 patients from the ITBT group, 48.5% of the MAD group and 20% of patients treated with LNCL rated the pain as strong one, measured by visual analogous scale (VAS). The difference between ITBT and MAD group, for p = 0.0000001 and between the MAD and LNCL group, for p = 0.02 was significant. According to the VAS measurements after 12 weeks, 71% of patients in the ITBT group, rated the anal pain as weakest (score 1). The majority of patients (33.3%) in the MAD group, estimated the pain with score 2 and 3, while in the LNCL group 30% of patients and 26.7% with a score of 1 and 2, respectively. After 12 weeks of intervention, patients of the three groups significantly differently perceived anal pain (p = 0.002). This overall significance is due to the significant difference between ITBT and MAD group (p = 0.00024) and between the ITBT and LNCL group (p = 0.018) in favour of ITBT. The duration of pain before initiating of treatment had a significant impact on the need for surgical intervention and treatment failure. In the group treated by ITBT, the mean duration of pain was significantly longer in patients who were referred for surgical treatment (p = 0.003) and it was 45.37 ± 27.9 days versus 16.30 ± 9.1 days in patients with healing achieved. The mean duration of pain in the MAD group was significantly longer in patients referred for surgical treatment (p = 0.015) and it lasted 39.71 ± 25.7 days versus 19.11 ± 17.4 days in those who achieved complete recovery. The type of conservative therapy for CAF had a significant influence on the presence of bleeding during defaecation (p = 0.00012), after 4 weeks. In this period, 64.5% of patients treated by ITBT, 81.8% with MAD and 30% with LNKL bled. Patients from the three groups had significantly different duration of bleeding, between the 4th and 12th week (p <0.0001). The time to disappearance was on average 4.7 ± 2.5 weeks in patients in the ITBT group, 8.7 ± 2.05 weeks in the MAD group (longest) and 4.2 ± 1.5 weeks in the LNCL group (the shortest time). Patients treated with MAD had a significantly longer duration of bleeding during defaecation compared to patients treated with ITBT (p = 0.00012) and LNCL (p = 0.0001). Significant difference was confirmed in the distribution of patients with and without anal incontinence, depending on the mode of treatment (p < 0.0001), after 12 weeks of intervention. Anal incontinence was confirmed in 9.68% of patients in the ITBT group, 54.55% in the MAD and in none of the patients in the LNCL group, which was significant for p = 0.00013 and p = 0.0000017, respectively. All 3 patients treated with ITBT who developed anal incontinence had flatus and mucus with occasional occurrence less than once a week, and Pescatori score 2. In the 18 patients treated with MAD, 77.8% had incontinence for flutus and mucus with occasional occurrence less than once a week and Pescatori score 2, while the remaining 22.2% had incontinence of flutus and mucus once a week and Pescatori score 3. The average duration of incontinence in the group of 18 patients treated with MAD was 66.11 ± 20.8 days. The difference in duration of incontinence between the group treated with ITBT and MAD is at the boundary of statistical significance (p = 0.053). Conclusions: Injection therapy with botulinum toxin A is a more effective method of treating CAF compared to MAD and LNCL. ITBT does not cause significantly more frequent incontinence than LNCL. Therapy with LNCL, significantly more often and faster than ITBT and MAD, reduces and removes bleeding in patients with CAF. The duration of pain before initiation of therapy in patients treated with ITBT and MAD significantly affects the outcome of the treatment and has a predictive value with respect to the prognosis. Manual anal dilatation is characterized by a significantly higher rate of anal incontinence compared to the other two forms of therapy. Although MAD persists for a long time and gives results in terms of CAF recovery, it is not safe, it exhibits significantly higher rates of morbidity and complications and should be avoided whenever possible.