The role of topical diltiazem in the treatment of chronic anal fissures that have failed glyceryl trinitrate therapy

Objective The treatment of anal fissures has evolved over the last 5 years with the development of topical treatments aimed at reducing sphincter hypertonia. This is thought to improve anal mucosal blood flow and promote healing of the fissure. This study reports the use of topical diltiazem in patients with chronic anal fissures that have failed previous treatment with topical 0.2% glyceryl trinitrate (GTN). Patients and methods Forty‐seven patients with chronic anal fissure who had previously failed at least one course of topical GTN were recruited prospectively from a single centre. Patients were instructed to apply 2 cm (approximately 0.7 g) of 2% diltiazem cream to the anal verge twice daily for eight weeks. Symptoms of pain, bleeding and itching were recorded on a linear analogue score prior to starting the cream and then repeated at 2 weekly intervals. Patients were asked to report side‐effects throughout the study period. Healing of the fissure was assessed after 8 weeks of treatment. Results Forty‐six patients completed treatment; of these, 22 had healed fissures (48%). Ten of the 24 patients with persistent fissures were symptomatically improved and wished no further treatment. Of the 14 patients who remained symptomatic, one was given a repeat course of 0.2% glyceryl trinitrate with subsequent healing of the fissure, 10 were recruited into an ongoing study involving injections of botulinum toxin into the internal anal sphincter and three were referred for surgery. Conclusion This study shows that topical 2% diltiazem is an effective and safe treatment for chronic anal fissure in patients who have failed topical 0.2% GTN. The need for sphincterotomy can be avoided in up to 70% of cases.     

Randomized controlled trial of oral vs intravenous therapy for the clinically diagnosed acute uncomplicated diverticulitis

Objective  Despite the high prevalence of hospitalization for left iliac fossa tenderness, there is a striking lack of randomized data available to guide therapy. The authors hypothesize that an oral antibiotic and fluids are not inferior to intravenous (IV) antibiotics and 'bowel rest' in clinically diagnosed acute uncomplicated diverticulitis.
Method  A randomized controlled trial was constructed in two District General Hospitals. All clinically diagnosed patients presenting with acute uncomplicated diverticulitis were eligible for the study. Oral and IV regimens utilizing ciprofloxacin and metronidazole were compared. The primary outcomes studied were surrogates for resolution of symptoms (including tenderness on day 3 and length of stay) and failure of oral therapy. Secondary endpoints studied were serial constitutional and biomarker trends.
Results  There were 41 patients in the oral arm and 38 in the IV arm ( n  = 79). No patient had to be converted to IV antibiotics from the oral group. There was a complete resolution of symptoms in both groups. Tenderness was equivalent in both groups on day 3. Among secondary endpoints, a serial decrease in C reactive protein was the best serological predictor of resolution for both groups.
Conclusion  Oral antibiotics are not inferior to intravenous antibiotics in achieving resolution of clinically diagnosed diverticulitis.     

硝苯地平、肝素钠在组织移植中的应用

目的分析硝苯地平、肝素钠在组织移植病例中的抗凝作用，为临床合理使用抗凝药物提供依据。方法对２０例行游离组织移植的患者，术后除常规使用低分子右旋醣酐、丹参外，随机给予硝苯地平（硝苯地平组１０例）和硝苯地平加肝素钠（肝素钠组１０例）药物。两组均于手术前、手术中、手术后２４、７２、１２０小时抽血，进行血液生物化学测定，观察药物的凝血作用。结果术后２４、７２小时肝素钠组的白陶土部分凝血活酶时间（ｋＰＴＴ）均较术前明显延长；术后７２小时和术前相比，两者差异有显著性意义（Ｐ＜０．０１）。两组各时间段的凝血酶原时间、抗凝血酶－Ⅲ、纤溶酶原、Ｄ－二聚体等，与术前相比均无显著性差异。结论肝素钠的抗凝血作用较强，可减少血栓的形成与扩展；但其作用时间长，故仅宜小剂量使用，作游离皮瓣移植时要慎用。硝苯地平有减轻术后机体高凝状态的作用，无不良反应，宜推广使用     

Randomized controlled trial of topical phenylephrine in the treatment of faecal incontinence

BACKGROUND: Anal incontinence due to internal sphincter dysfunction is not amenable to simple surgical repair. The alpha-adrenergic agonist phenylephrine produces contraction of the internal sphincter and raises resting pressure when applied topically in healthy volunteers. The effect of topical phenylephrine in the treatment of faecal incontinence due to internal sphincter dysfunction was investigated. METHODS: Thirty-six patients (22 women) aged 28-81 (mean 58) years with faecal incontinence and ultrasonographically structurally normal anal sphincter muscles were treated with topical 10 per cent phenylephrine and placebo gels, allocated in random order in a double-blind crossover study. Maximum resting anal sphincter pressure and anodermal blood flow were measured. A symptom questionnaire was completed and incontinence score determined using a validated scale. RESULTS: There were no significant differences in incontinence score, resting anal pressure and anodermal blood flow between the active and placebo treatments. Six patients on active treatment and two on placebo experienced more than 75 per cent subjective improvement. Three patients developed allergic dermatitis to phenylephrine. CONCLUSION: This is the first study of the use of a topical pharmacological agent to treat faecal incontinence. This concentration of topical phenylephrine did not produce a significant improvement in symptoms or function. A subgroup of patients may respond. Further studies are required with increased concentrations.     

Botulinum toxin injection vs topical nitrates for chronic anal fissure: an updated systematic review and meta‐analysis of randomized controlled trials

Aim

Chronic anal fissures (CAFs) are frequently encountered in coloproctology clinics. Chemical sphincterotomy with pharmacological agents is recommended as first‐line therapy. Topical nitrates (TN) heal CAF effectively but recurrences are common. An alternative treatment modality is injection of botulinum toxin (BT) into the anal sphincter. We aimed to perform an updated systematic review and meta‐analysis to compare the effectiveness of BT and TN in the management of CAF.

Method

PubMed, EMBASE and Cochrane databases were searched for relevant articles from inception until March 2017. All randomized controlled trials (RCTs) that reported direct comparisons of BT and TN were included. Two independent reviewers performed methodological assessment and data extraction. Random effects models were used to calculate pooled effect size estimates.

Results

Six RCTs describing 393 patients (194 BT, 199 TN) were included. There was significant heterogeneity among the trials. On random effects analysis there were no significant differences in incomplete fissure healing (OR = 0.47, 95% CI 0.13–1.68, P = 0.24) or recurrence (OR = 0.70, 95% CI 0.39–1.25, P = 0.22) between BT and TN, respectively. BT was associated with a higher rate of transient anal incontinence (OR = 2.53, 95% CI 0.98–6.57, P = 0.06) but significantly fewer total side effects (OR = 0.12, 95% CI 0.02–0.63, P = 0.01) and headache (OR = 0.10, 95% CI 0.02–0.60, P = 0.01) compared with TN.

Conclusion

BT is associated with fewer side effects than TN but there is no difference in fissure healing or recurrence. Patients need to be warned regarding the risk of transient anal incontinence associated with BT.     

Quality of life in patients with chronic anal fissure after topical treatment with diltiazem

AIM: To assess the physical and mental health of fissure patients before and after topical treatment with diltiazem.METHODS: Consecutive patients were enrolled prospectively into the study. Quality of life was measured with the short-forum 36 health survey (SF-36) before and after 6-wk treatment with diltiazem. Patients scored symptoms of pain, bleeding, and irritation using numeral rating scales at the initial and follow-up visits. Fissure healing was assessed and side effects were noted.RESULTS: Fissures healed in 21 of 30 (70%) patients. There were significant reductions in the scores of pain, bleeding, and irritation after 1 wk of treatment, respectively. Four patients experienced perianal itching and one patient reported headache. When measured at baseline, pain and irritation showed a negative impact on two of the eight subscales on the SF-36, respectively (bodily pain and social functioning for pain; vitality and mental health for irritation). Repeating the SF-36 showed an improvement in bodily pain (P = 0.001). Patients whose fissures healed reported an improvement in bodily pain, health-perception, vitality, and mental health (P < 0.05).CONCLUSION: Successful treatment of chronic anal fissure with topical diltiazem leads to improvement in health-related quality of life.     

A prospective randomized trial of diltiazem and glyceryltrinitrate ointment in the treatment of chronic anal fissure

Objective The aim of this study was to compare prospectively diltiazem with GTN ointment in the treatment of anal fissure. Patients and methods Of 43 outpatients with chronic anal fissure, 22 patients were randomized to topical diltiazem (2%) ointment and 21 patients to glyceryltrinitrate (GTN) (0.5%) ointment twice daily for 8 weeks. During the course of treatment each patient was seen three times. Side‐effects and healing were recorded. Results Healing occurred in 19 of 22 patients treated with diltiazem and 18 of 21 patients were cured with GTN (P = 0.95). Those who were treated with nitroglycerin ointment developed headache and dizzness developed after GTN in 33.3% of cases while no patient had any side‐effects after diltiazem. Conclusions Diltiazem and glyceryltrinitrate (GTN) were equally effective in healing anal fissure but the former resulted in fewer side‐effects.     

2％硝苯地平生肌玉红膏治疗肛裂临床观察

为观察2％硝苯地平生肌玉红膏局部外用治疗肛裂的疗效,将62例肛裂患者随机分为治疗组和对照组各31例,分别采用2％硝苯地平生肌玉红膏和马应龙麝香痔疮膏涂抹于肛裂裂口处,每日2次,急性肛裂治疗1周,慢性肛裂治疗6周,进行疗效对比。结果显示,总有效率治疗组（96．8％）明显优于对照组（80．6％）,总治愈率治疗组（64．5％）亦优于对照组（45．1％）。结果表明,2％硝苯地平生肌玉红膏局部外用治疗肛裂有良好的疗效。     

Randomized prospective controlled trial of lateral internal sphincterotomy versus injection of botulinum toxin for the treatment of idiopathic fissure in ano

BACKGROUND: Chronic anal fissure is a significant cause of morbidity. Internal sphincterotomy has long been the operative treatment of choice. Concerns remain, however, on its effects on continence. Botulinum toxin has been used as an agent for chemical sphincterotomy, causing temporary alleviation of sphincter spasm and allowing the fissure to heal. The aim of the present study was to compare the results of sphincterotomy to botulinum toxin. METHODS: The study was designed as a randomized controlled trial. All adult patients over the age of 18 with chronic idiopathic fissure in ano who had failed conservative treatment were included in the trial. Patients were randomized to receive either Botox or sphincterotomy. Pain, healing of fissure and continence scores were the outcomes assessed. RESULTS: A total of 38 patients were studied. Seventeen patients were randomized to receive Botox and 21, sphincterotomy. Patients in the Botox group were found to have significantly higher 2-week pain scores and reoperation rates, and poor healing. Continence scores were not significantly different in the two groups. CONCLUSION: Sphincterotomy gives better results than Botox in the treatment of fissure. Botox, however, is safe with no complications and no detriment to continence and could be used in certain situations.     

A prospective, randomized, controlled trial of primary wound closure after lateral internal sphincterotomy

BACKGROUND: Much of the lateral internal sphincterotomy (LIS) complications is related to LIS incision. In this study, incisions sutured primarily or left to secondary healing after open LIS procedure are compared regarding the wound healing and complications associated with wounds. METHODS: Planning a prospective, randomized clinical study, 39 patients were separated into two groups. Open LIS was performed on both of the groups. While the incisions of the patients in group 1 (n = 22) were closed with two interrupted sutures using 3-0 chromic catgut, the incisions of the patients in group 2 (n = 17) were left open. The patients were followed up for 90 days postoperatively. RESULTS: Hematoma in 1 (4.5%), ecchymosis in 7 (31.8%), and wound infection in 1 (4.5%) developed in patients of group 1. In this group no significant external bleeding was seen. Wound healing duration was 15.05 +/- 5.60 days. In group 2 no hematoma developed (P = 0.98), but 2 (11.7%) ecchymoses (P = 0.25), 4 (23.5%), wound infections (P = 0.14), and 3 (17.6%) postoperative significant external bleedings (P = 0.07) were seen. Wound healing duration was 33.94 +/- 6.67 days (P <0.001). CONCLUSIONS: To achieve early wound healing, primary closure of open LIS incision is useful, but this technique has no significant effect on wound-related complications in comparison with secondary healing.     

Randomized clinical trial comparing oral nifedipine with lateral anal sphincterotomy and tailored sphincterotomy in the treatment of chronic anal fissure

BACKGROUND: The conventional treatment of chronic anal fissure is lateral sphincterotomy (LAS). The alternative options of tailored sphincterotomy (TS) and 'chemical sphincterotomy' using medication such as nifedipine have recently become available. METHODS: A prospective randomized trial was conducted to compare LAS with TS and oral nifedipine. The main endpoints were fissure healing, symptom relief, recurrence and continence. RESULTS: One hundred and thirty-two patients were treated and followed up for 4 months. LAS was significantly more effective than TS in providing pain relief (P = 0.004) and better patient satisfaction (P = 0.020) at 4 weeks. Surgery (LAS and TS) was associated with significantly better fissure healing rates (both P < 0.001 at 16 weeks) and less recurrence (both P = 0.003) than nifedipine. There were substantial problems with compliance in the nifedipine group (17 of 41 patients), related to side-effects and slow healing. There were no differences in continence between the three treatment groups. CONCLUSION: LAS was most effective in providing pain relief and allowing rapid fissure healing, with minimal recurrence and no increased risk of incontinence, in patients with good anal sphincter function.     

Randomized controlled trial of the application of topical b-FGF-impregnated gelatin microspheres to improve tissue survival in subzone II fingertip amputations

We undertook a randomized controlled trial of subzone II fingertip amputations, comparing standard treatment with topical application of gelatin microspheres prepared with basic fibroblast growth factor (b-FGF) to provide a slow, sustained release of b-FGF with microsphere degradation. Forty-eight digits from 42 patients were randomized into the two study arms. The microspheres were applied as a paste on exposed tissue surfaces, whereas standard treatment was without any topical treatment. Patients were treated either with microsurgical revascularization or by simple composite graft, based on the surgeon's clinical decision. Tissue survival of the replanted fingertips was measured by a blinded evaluator 3 weeks postoperatively. A modest improvement in survival was seen with b-FGF-microsphere application for both revascularized and composite grafted fingertips, though this did not achieve statistical significance. Whether the slow release of b-FGF through a bioresorbable carrier gives any improvement in outcome in patients with subzone II fingertip amputations is unproven.     

Randomized controlled trial of vacuum therapy for intermittent claudication

ObjectiveThe “gold standard” treatment of intermittent claudication (IC) is supervised exercise therapy (SET). Intermittent vacuum therapy (IVT) has recently been promoted as an additional treatment of IC. During IVT, negative pressure and atmospheric pressure are alternatingly applied to the lower extremities, possibly resulting in improved circulation. The aim of this study was to determine a potential additional effect of IVT in IC patients undergoing a standardized SET program.MethodsIC patients were recruited from three Dutch general hospitals between December 2015 and July 2017. They received a standardized SET program but were also randomly assigned to an intervention group receiving an IVT treatment (−50 mBar negative pressure) or a control group receiving a sham treatment (−5 mBar negative pressure). IVT was provided in a dedicated clinic during 12 sessions of 30 minutes during a 6-week period. The primary outcome measure was a change in maximal treadmill walking distance. Secondary outcome measures were a change in functional treadmill walking distance, 6-minute walk test, ambulatory ability, and quality of life.ResultsA total of 78 patients were randomized, of whom 70 were available for intention-to-treat analysis (control, n = 34; intervention, n = 36). At 6 and 12 weeks, increases in walking distance were of equal magnitude. Median (interquartile range) change in maximal treadmill walking distance during 12 weeks was +335 (205-756) meters in control patients and +250 (77-466) meters in intervention patients (P = .109), whereas functional treadmill walking distance increased +230 (135-480) meters and +188 (83-389) meters (P = .233), respectively. Mean ± standard deviation change in the 6-minute walk test was +36 ± 48 meters and +55 ± 63 meters (P = .823), respectively. Ambulatory ability and quality of life improved equally in both groups.ConclusionsIVT does not confer any additional beneficial effects in IC patients undergoing a standardized SET program.     

Transcutaneous needle-free injection of botulinum toxin: a novel treatment of childhood constipation and anal fissure

Purpose

Constipation is a common problem in children, and when it becomes chronic fecal impaction, overflow soiling and megarectum may develop. Children with chronic idiopathic constipation (IC) may not respond to conventional treatments of laxatives, enemas, and toilet training. The aims of the study were to evaluate the long-term outcome of transcutaneous needle-free injection of botulinum toxin (TNFBT) into the external anal sphincter (EAS) and to assess the extent of the toxin penetration into the sphincter.

Method

Children were recruited if symptomatic with chronic constipation, soiling, painful defecation, and withholding behavior requiring disimpaction of stool and rectal biopsy under general anesthesia. A total dose of 200 U of botulinum toxin (BT) (Dysport; Ipsen Limited, Slough, United Kingdom) was injected transcutaneously into the EAS at 3 and 9-o'clock positions using J-tip needle-free syringes (National Medical Products Inc, Irvine, Calif). The depth and width of toxin penetration was assessed by endosonography. Outcome was measured by a validated symptom severity (SS) score questionnaire. The total SS score ranged between 0 (best) and 65 (worst). The outcome was compared with 31 children in a comparable historical control group at 3 and 12-month follow-up.

Results

Sixteen children were recruited with median age of 6.11 (range, 3-14.85) years and median duration of symptoms of 3.9 years (1.6-11.5). On endosonography, the median depth and width of BT penetration was 8 (7-10) mm and 8 (6-10) mm, respectively. At 3-month follow-up, the median SS score improved in all children after TNFBT from 32.50 (5-57) to 7.50 (0-26) (Wilcoxon's P < .0001).There were significant improvements in symptoms of constipation, soiling, painful defecation, general health and behavior, and fecal impaction of rectum (P < .05). Anal fissures healed in all 4 children. The SS score in the control group improved from 33 (12-49) to 15 (0-40) (P < .0001). At 12-month follow-up, the improvement of SS score in TNFBT group was significantly more than the control group as follows: 4 (0-25) vs 15 (0-51), respectively (Mann-Whitney U P < .002). Three patients had a second TNFBT injection for relapsed symptoms. There were no complications. The transcutaneous needle-free injection of botulinum toxin eliminates the risk of intravascular injection or needlestick injury. The transcutaneous needle-free injection of botulinum toxin also has other therapeutic applications including an alternative therapy to biofeedback training for dyssynergia of the EAS, treatment of muscle limb spasticity in cerebral palsy, and cosmetic treatment of overactive facial muscles and wrinkles and hyperhydrosis.

Conclusion

Transcutaneous needle-free injection of botulinum toxin into the external anal sphincter is a novel and safe new treatment of chronic idiopathic constipation and anal fissure in children. A second injection may be required in 20% of patients.     

Randomized controlled trial of bipolar diathermy vs ultrasonic scalpel for closed hemorrhoidectomy

AIM:To compare hemorrhoidectomy with a bipolar electrothermal device or hemorrhoidectomy using an ultrasonically activated scalpel.METHODS:Sixty patients with grade Ⅲ or Ⅳ hemorrhoids were prospectively randomized to undergo closed hemorrhoidectomy assisted by bipolar diathermy(group 1) or hemorrhoidectomy with the ultrasonic scalpel(group 2).Operative data were recorded,and patients were followed at 1,3,and 6 wk to evaluate complications.Independent assessors were assigned to obtain postoperative pain scores,oral analgesic requirement and satisfaction scores.RESULTS:Reduced intraoperative blood loss median 0.9 mL(95% CI:0.8-3.7) vs 4.6 mL(95% CI:3.8-7.0),P = 0.001 and a short operating time median 16(95% CI:14.6-18.2) min vs 31(95% CI:28.1-35.3) min,P < 0.0001 was observed in group 1 compared with group 2.There was a trend towards lower postoperative pain scores on day 1 group 1 median 2(95% CI:1.8-3.5) vs group 2 median 3(95% CI:2.6-4.2),P = 0.135.Reduced oral analgesic requirement during postoperative 24 h after operation median 1(95% CI:0.4-0.9) tablet vs 1(95% CI:0.9-1.3) tablet,P = 0.006 was observed in group 1 compared with group 2.There was no difference between the two groups in the degree of patient satisfaction or number of postoperative complications.CONCLUSION:Bipolar diathermy hemorrhoidectomy is quick and bloodless and,although as painful as closed hemorrhoidectomy with the ultrasonic scalpel,is associated with a reduced analgesic requirement immediately after operation.