Is chemodenervation with incobotulinumtoxinA an alternative to invasive chronic anal fissure treatments?

BACKGROUND: Botulinum toxin type A is currently strongly recommended for the treatment of anal fissures (AFs). However, there is still no consensus on dosage or injection technique. This study provides further efficacy and safety evidence in a 2-year follow-up. METHOD: Prospective, open-label, single-arm, single-center study carried out in adult patients with AFs non-responsive to previous treatments. Patients were treated with incobotulinumtoxinA (incoBoNT/A) injected in both laterals and posterior intersphincteric groove. Healing rate at 2 years was the primary endpoint. Secondary endpoints included internal anal sphincter pressures, incontinence, and safety. RESULTS: A total of 49 patients were treated with a mean incoBoNT/A dose of 40.5 U (spread across three locations). Healing rate at 2 years was 83.9% with a 24.5% of recurrence throughout the study. Only 7 patients (14.3%) reported adverse events (AEs) that were mild and temporary. Mean reduction in anal resting pressure was -9.1 mmHg at 3 months (p = 0.001). Mean reduction in voluntary squeeze pressure was -27.5 mmHg at 3 months (p < 0.001). Mean pain perception measured with a visual analog scale decreased by -6.5 points at 2 years (p < 0.001). There was an incontinence increase at 1 month of 1.3 points (p = 0.006), but baseline values were restored at 6 months. CONCLUSION: We present results that support the use of incoBoNT/A as a second line for AFs that do not respond to ointment therapy. IncoBoNT/A injection is a less invasive treatment that should be considered before surgery due to its efficacy and its safety which includes no permanent impairment. TRIAL REGISTRATION: ISRCTN90354265; Registered on 16th February 2024. Retrospectively registered.

Botulinum toxin injection in outpatients for chronic anal fissure.

OBJECTIVES: The aim of the study was to evaluate the effect of botulinum toxin (BT) injection on fissure healing in the treatment of chronic anal fissure (CAF) in outpatient conditions without any analgesia and sedation to the internal anal sphincter (IAS). The primary outcome measure was post-procedural pain. The secondary outcome measures were fissure healing and complications. METHODS: Prospectively preserved data of 67 patients who received BT injections for CAF were analyzed prospectively. Demographic data, duration of symptomatic improvement, fissure location and number, parity, post-procedural pain, complications, continence status, response to treatment, and duration of follow-up were examined. Participants received bilateral (50 + 50 units) BT injections into the internal anal sphincter (IAS) in an outpatient setting. RESULTS: Symptomatic improvement was observed in 58% of patients within 1 week. The complete response rate to treatment was 82% at a mean follow-up of 6 months. Patients with partial response to treatment (10%) were successfully treated with topical therapy, and patients with persisting fissures (8%) were successfully treated with partial lateral internal sphincterotomy (LIS). 14 patients (21%) reported some degree of transient incontinence at follow-up. Multiparous women experienced more symptoms of Incontinence (p = 0.00). Pre- and post-procedural Vas Score median values were 4. The 7th-week VAS score median value was 3. CONCLUSION: Dysport injection under sedation-free outpatient conditions is an effective and safe alternative to LIS for the treatment of CAF, with tolerable procedural pain. All patients should be warned of transient incontinence.

Comparison of outcome of botulinum toxin injection with and without glyceryl trinitrate in chronic anal fissure in terms of post operative pain and healing.

Objectives: To compare the outcome of botulinum toxin injection with and without glyceryl trinitrate with respect to postoperative pain and healing in the treatment of anal fissures. METHODS: The prospective, comparative study was conducted at the Department of General Surgery, Mayo Hospital, Lahore, Pakistan, from September 1, 2021, to August 31, 2022, and comprised adult chronic anal fissure patients of either gender. They were randomised using the lottery method into group A which received botulinum toxin injection, and group B which received botulinum toxin injection plus 1g of 0.2% topical glyceryl trinitrate cream. Post-operative pain was measured 24 hours after the procedure using the visual analogue scale. Healing was assessed by examining the wound for the appearance of granulation tissue 4 weeks post-procedure. Data was analysed using SPSS 26. RESULTS: Of the 88 patients, 44(50%) were in group A; 32(72.7%) males and 12(27.3%) females with mean age 33.91±14.8 years. There were 44(50%) patients in group B; 35(79.5%) males and 9(20.5%) females with mean age range 36.33±14.9 years. The mean postoperative pain at 24 hours in group A was 4.67±1.16 and it was 3.06±0.65 in group B (p=0.009). In group A, 23(69.7%) patients showed complete healing at 4 weeks compared to 30(90.9%) in group B (p=0.030). CONCLUSIONS: Botulinum toxin injection with glyceryl trinitrate could be considered as first line of treatment for chronic anal fissure in patients who refuse surgery and with previous sphincter surgery.

L-Arginine is a feasible supplement to heal chronic anal fissure via reducing internal anal sphincter pressure: a randomized clinical trial study.

The hypertonicity of internal anal sphincter resting pressure is one of the main causes of chronic anal fissure. Therefore, the aim of this study was to assess the effect of oral administration of L-arginine on the improvement of the anal fissures by relaxing the internal anal sphincter. Seventy-six chronic anal fissure patients (aged 18-65 years) who were referred to Rasoul-e-Akram Hospital, Tehran, Iran from February 2019 to October 2020 participated in this randomized, double-blind, placebo-controlled trial. Participants were allocated into treatment (L-arginine) and placebo groups. They took a 1000 mg capsule three times a day for 1 month, and then we followed them at the end of the first and third months after the intervention. Clinical symptoms, anal sphincter resting pressure, and quality of life (QoL) were completed at baseline and the end of the study. The analysis of data showed a significant decrease in bleeding, fissure size, and pain for each group; however, in the L-arginine group was more than the control group at the end of the study (P values < 0.001). Following that, a significant increase in QoL was seen just in patients treated with L-arginine (P value = 0.006). In addition, the comparison of anal pressures at baseline and, between groups at the end of the study showed a significant reduction in sphincter pressure in patients treated with L-arginine (P value < 0.001, = 0.049; respectively). The oral administration of 3000 mg L-arginine can heal chronic anal fissures by reducing internal anal sphincter pressure with more negligible side effects. However, we recommend long-term study with more extended follow-up.Clinical trial registry: IRCT20190712044182N1 at Iranian clinical trials, date: 2019-08-27.

Platelet-rich plasma improves acute and chronic anal fissure, a randomized control trial.

Anal fissure is one of the most prevalent diagnosis in patients with anorectal symptoms. Depending on the chronicity, treatment choices vary, from topical and conservative management to operative ones. PRP is a blood-derived product with a three to five-fold platelet count and can be used for restorative purposes. The objective of this study is to assess the therapeutic effect of intralesional PRP in acute and chronic anal fissures and comparing it with the classic topical approach. We included 94 patients with acute and chronic anal fissures and divided them into intervention and control groups. Control patients were treated only with topical compounds, and the intervention group received one dose of intralesional autologous PRP plus the same classic treatment. We assessed patients 2 weeks, 1 month, and 6 months later. The mean pain score in the intervention group was significantly lower than control groups in all visits (p-value <0.001). During the follow-ups, the bleeding rate was significantly lower in the intervention group, so in the sixth month, the bleeding was 4% in the intervention group against 32% of the control (p-value <0.001). The healing rate assessed by examination was 96% in the intervention group against 66% in the control in the sixth month (p-value <0.001). Although there may be no significant difference in healing rate between groups in the acute anal fissure, the PRP group is significantly superior in the chronic setting. We concluded that in anal fissure treatment, PRP plus topical products are significantly superior to alone topical treatment.

Clinical Outcomes of Medical Management Options for Chronic Anal Fissures in a Long-Term Follow-up: Systematic Review and Meta-Analysis.

BACKGROUND: Topical treatments and botulinum toxin injections are valid options for the management of patients with chronic anal fissures (CAF), but little is known about the efficacy of these techniques in long-term follow-up. The aim of this meta-analysis was to evaluate the effectiveness, given to clinical outcomes, of medical treatments with calcium antagonists, nitroglycerin, and botulinum toxin on CAF treatment in adults. METHOD: A systemic review and meta-analysis developed according to PRISMA [PLoS Med. 2009 Jul 21;6(7):e1000100; BMJ. 2010 Mar 23;340:c332] and registered in PROSPERO (Registration number: CRD42020120386). A systematic literature search was conducted through MEDLINE, EMBASE, Web of Science, and Cochrane Library databases. Randomized control trials that compared medical treatment were identified; publications had to have a clinical definition of CAF with at least one of the following signs or symptoms: visible sphincter fibers at the base of the fissure, anal papillae, sentinel piles, and indurated margins. The symptoms had to be chronic for at least 4 weeks. Data were independently extracted for each study, and a meta-analysis was drawn using fixed- and random-effects models. RESULTS: 17 randomized trials met the inclusion criteria. Diltiazem showed a superior effect compared with glycerin (RR = 1.16 [95% CI = 1.05-1.30]; I2 = 18%) and with fewer adverse effects (RR = 0.13 [95% CI = 0.04-0.042]; I2 = 87%). Similar results were evidenced with the use of nifedipine compared with lidocaine (RR = 4.53 [95% CI = 2.99-6.86]; I2 = 28%). Botulinum toxin did not show statistically significant differences compared to glycerin (RR = 0.81 [95% CI = 0.02-29.36]; I2 = 93%) or isosorbide dinitrate (RR = 1.45 [95% CI = 0.32-6.54]; I2 = 85%). Regarding recurrence, nifedipine was superior to lidocaine (RR = 0.18 [95% CI = 0.08-0.44]; I2 = 31%). CONCLUSIONS: Calcium channel blockers performed well regarding the healing of CAF when compared to others in long-term follow-up. The superiority of botulinum toxin was not evidenced compared to topical treatments. More studies are needed to better assess recurrence rates.

Pelvic floor physical therapy in patients with chronic anal fissure: long-term follow-up of a randomized controlled trial.

BACKGROUND: Chronic anal fissure is a common benign anorectal disease with a high recurrence rate. Pelvic floor physical therapy has been proven effective in the short-term management in patients with chronic anal fissure and pelvic floor dysfunction (PAF-trial). The aim of this study was to determine the outcomes of the PAF-trial and fissure recurrence in patients who completed the 2 months of pelvic floor physical therapy at 1-year follow-up. METHODS: Electromyographic registration of the pelvic floor, digital rectal examination, visual analog scales, patient-related outcome measurements, and quality of life were assessed at baseline and at 1-year after inclusion. The primary outcome was muscle tone at rest during electromyographic registration of the pelvic floor at baseline and at 1-year follow-up. Secondary outcomes contained fissure recurrence, pain ratings, pelvic floor dysfunction, complaint reduction measured with a proctology specific patient-reported outcome measurement, and quality of life. RESULTS: The treatment protocol was followed by 137 patients. Ninety-seven patients (71%) completed the 1-year follow-up, 48 women (49.5%) and 49 men (50.5%) with a mean age of 44.4 ± 11.6 years (range 19-68). In the total group of patients, mean resting electromyographic values of the pelvic floor significantly improved from baseline to follow-up at 1 year (mean estimated difference 2.20 µV; 95% CI, 1.79 to 2.61; p < 0.001). After 1 year, the fissure recurred in 15 patients (15.5%). VAS-pain significantly decreased from baseline to follow-up (mean estimated difference 4.16; 95% CI, 3.75 to 4.58; p < 0.001). Dyssynergia was found in 72.9% at baseline and decreased to 14.4% at 1-year follow-up (p < 0.001). Complaint reduction measured with the Proctoprom significantly improved from baseline to 1-year follow-up (p < 0.001). Quality of life (RAND-36) significantly improved in eight of nine domains at 1-year follow-up. No significant improvement was found in the domain vitality. CONCLUSIONS: In the PAF-trial, we demonstrated that pelvic floor physical therapy yields a significant and clinical benefit in the time course and therefore should be advocated as adjuvant conservative treatment in patients with chronic anal fissure. TRIAL REGISTRATION: The trial is registered at the Dutch Trial registry (NTR7581)  https://trialsearch.who.int.

Efficacy and safety of Propionibacterium extract gel versus glyceryl trinitrate ointment in the treatment of chronic anal fissure: a randomized controlled trial.

AIM: Chronic anal fissure (CAF) is an extremely frequent finding in clinical practice. Several topical agents have been proposed for its treatment with the common goal of increasing anodermal blood flow to promote healing. The aim of this study was to compare the efficacy and safety of a Propionibacterium extract gel (PeG) and 0.4% glyceryl trinitrate ointment (GTN) in patients with CAF. METHOD: Patients were randomly allocated to a PeG or GTN group and medication was administered every 12 h for 40 days. The primary outcome was the success rate, as measured by a decrease in the REALISE scoring system for anal fissure at 10, 20 and 40 days after initiating either treatment. The secondary outcomes recorded at the same time points were healing rate, visual analogue scales for itching and burning, rate of complications and adverse events, patient quality of life and satisfaction, and cost analysis. RESULTS: A total of 120 patients were enrolled, and 96 patients (PeG, n = 53; GTN, n = 43) completed the primary outcomes. A significant decrease over time in the REALISE score was observed in both groups. Adverse events occurred more frequently in the GTN group than in the PeG group, peaking at visit 1 [37 (63.8%) vs. 2 (3.4%), respectively], with headache being the most prevalent. The between-treatment cumulative average costs per patient were significantly higher for GTN than that for PeG at each follow-up visit. There were no other significant differences between the two groups for any of the other outcomes. CONCLUSION: While there was no difference in healing rates between the two treatments, PeG was more cost-effective and associated with fewer adverse events.

Mucosal vs. cutaneous advancement flaps for the treatment of chronic anal fissures: a randomized clinical trial.

PURPOSE: The aim of this study was to compare two surgical treatment methods for chronic anal fissures (CAF), mucosal advancement flap anoplasty (MAFA) and cutaneous advancement flap anoplasty (CAFA). METHODS: A randomized, blinded clinical trial was conducted on patients with CAF refractory to medical treatment referred to a tertiary-level hospital between January 2021 and December 2022. The patients were assigned to two groups by block randomization and were compared in terms of outcome, pain reduction, and complications. RESULTS: There were 30 patients (male to female ratio 2:3, median age 42 years [range 25-59 years]). Both techniques reduced anal pain significantly (p = 0.001); however, there were no significant differences between MAFA and CAFA groups in recurrence, duration of healing, postoperative pain, and postoperative bleeding. No patient suffered from fecal incontinence (Wexner score = 0) or flap necrosis postoperatively. Only two patients in the MAFA group (1 and 3 months after surgery) and one patient in the CAFA group (2 months after surgery) had recurrence (total recurrence rate = 10%, healing rate = 90%). All of the patients were satisfied with their surgical results. CONCLUSION: Mucosal and cutaneous anal advancement flap techniques are effective and comparable surgical procedures for the treatment of chronic anal fissures with minimal complications, fast healing process, and minimal postoperative pain and complications. CLINICAL TRIAL ID: IRCT20120129008861N4 ( www.irct.ir ).

Botulinum toxin injection is an effective alternative for the treatment of chronic anal fissure.

OBJECTIVES: There are few published data on the optimized use of botulinum toxin A (BTA) for the treatment of chronic anal fissure (CAF). The aim of this study was to investigate the effect of injection of 100 IU BTA into the internal anal sphincter (IAS) at the side opposite of the fissure, using an anal retractor, sedation, and perianal transcutaneous pudendal nerve block. METHODS: The prospectively maintained data of 132 patients who underwent BTA injection for CAF were retrospectively analyzed. Demographic data, symptom duration, fissure location, post-procedure pain, complications, continence status, response to treatment, and follow-up period were investigated. Postoperative analgesic requirements of patients who did and did not receive pudendal nerve block were compared. RESULTS: Eighty-two patients were male and the median age was 40 (18-74) years. Sixty-six patients required no, 46 required oral, and 20 required parenteral analgesics. No complications were observed. Complete response was observed in 105 patients (79.5%). Symptomatic improvement was observed in 67.4% of patients within 3-7 d. Median follow-up was 24 (18-42) months. The median Wexner's incontinence score was 0 (0-8) at 1 month. In all, 104 patients had no, 22 patients had minor, and 6 patients had non-minor incontinence. All patients with incontinence recovered fully within 4 (2-13) weeks. CONCLUSIONS: BTA injection using an anal retractor under sedation and perianal transcutaneous pudendal nerve block is an effective and safe alternative to partial lateral internal sphincterotomy (LIS) for the treatment of CAF.

A systematic review and meta-analysis of the efficacy of topical sphincterotomy treatments for anal fissure.

BACKGROUND: Anal fissure is a common condition that can be treated medically or surgically. Chemical sphincterotomy is often used before surgical intervention. This study aims to evaluate the effectiveness of topical agents for chemical sphincterotomy on healing of anal fissures and side-effects. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) compliant systematic review was performed using MEDLINE, EMBASE, Scopus, and CENTRAL databases. Eligible studies included randomized controlled trials which compared topical sphincterotomy agents with topical placebo agents or each other. Studies that included surgical treatments were excluded. Overall evidence was synthesized according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. RESULTS: Thirty-seven studies met the study selection criteria. Seventeen studies show that glyceryl trinitrate (GTN) was significantly more likely to heal anal fissure than placebo (relative risk (RR) = 1.96, 95% confidence interval (95%CI) = 1.35-2.84, I2 = 80%). Eleven studies showed a marginally significant difference between healing rates for diltiazem vs GTN, RR = 1.16, (1.01-1.33) I2 = 48%. There was no significant difference in healing between diltiazem and placebo, RR = 1.65, (0.64-4.23), I2 = 92%. GTN significantly reduced pain on the visual analog scale compared to the placebo group, MD-0.97 (-1.64 to -0.29) I2 = 92%. There was high certainty of evidence that GTN was significantly more likely to cause headache than placebo (RR = 2.73 (1.82-4.10) I2 = 58%) and diltiazem RR = 6.88 (2.19-21.63) I2 = 17%. CONCLUSION: There is low certainty evidence topical nitrates are an effective treatment for anal fissure healing and pain reduction compared to placebo. Despite widespread use of topical diltiazem, more evidence is required to establish the effectiveness of calcium channel blockers compared to placebo.

Botulinum toxin injection for the treatment of chronic anal fissure: uni- and multivariate analysis of the factors that promote healing.

PURPOSE: Anal fissure is caused by a pathological contraction of the internal anal sphincter. Lateral internal sphincterotomy remains the gold standard for the treatment of fissure. Botulinum toxin injections have been proposed to treat this condition without any risk of permanent injury of the internal sphincter. We investigate clinical and pathological variables and the effects of different dosage regimens of botulinum toxin to induce healing in patients with idiopathic anal fissure. METHODS: This is a retrospective study at a single center. The patients underwent a pre-treatment evaluation that included clinical inspection of the fissure and anorectal manometry. We collected and analyzed demographic data, pathological variables, associated pathological conditions, and treatment variables. Success was defined as healing of the fissure, and improvement of symptoms was defined as asymptomatic persistent fissure. RESULTS: The findings of 1003 patients treated with botulinum toxin injections were reported. At 2 months evaluation, complete healing was evident in 780 patients (77.7%). Resting anal tone (77.1 ± 18.9 mmHg) was significantly lower from baseline (P < 0.0001) and from 1-month value (P = 0.0008). Thirty-nine not healed patients underwent lateral internal sphincterotomy, and 184 were re-treated with 50 UI of botulinum toxin. In these patients, the healing rate was 93.9% (171 patients). Dose and injection site of toxin correlates with healing rate. There were no relapses during an average of about 71 months. CONCLUSION: Our data show that injection of botulinum toxin into the internal anal sphincter is a safe and effective alternative to surgery in patients with chronic anal fissure.

Injection of botulinum toxin significantly increases efficiency of fissurectomy in the treatment of chronic anal fissures.

PURPOSE: While acute anal fissures can be treated with topical therapy to reduce sphincter hypertonia (e.g., isosorbide dinitrate, glyceryl trinitrate, diltiazem), chronic fissures may require more invasive instrumental therapy. Currently, the golden standard remains lateral internal sphincterotomy; however, this carries the long-term risk of faecal incontinence. Fissurectomy can be a valuable alternative, but is less efficient because of absence of correction of underlying hypertonia. In this study, we aim to evaluate the additional effect of injection of botulinum toxin during fissurectomy in the treatment of chronic anal fissures. METHODS: A single-centre retrospective analysis of 293 isolated superficial fissurectomies with or without injection of botulinum toxin was performed, with pain relief as primary endpoint. RESULTS: The majority of patients undergoing fissurectomy were women (65%, mean age 45.0 years vs. 35% men, mean age 48.3 years), often because of ventral fissures (30% in women vs. 8% in men). Fissurectomy resulted in resolution of complaints in 81.1%, while additional injection of botulinum toxin resulted in resolution in 90.1% (p < 0.05). Complication rate was identical between the two groups, mainly (flatus) incontinence (4.5% vs 4.9% with botulinum toxin) and post-operative bleeding (1.8% vs 2.5% with botulinum toxin). CONCLUSION: Injection of botulinum toxin significantly increases the efficiency of fissurectomy in the treatment of chronic anal fissures without additional complications.

Botulinum Toxin Injection Plus Topical Diltiazem for Chronic Anal Fissure: A Randomized Double-Blind Clinical Trial and Long-term Outcome.

BACKGROUND: Chemical sphincterotomy avoids the risk of permanent incontinence in the treatment of chronic anal fissure, but it does not reach the efficacy of surgery and recurrence is high. Drug combination has been proposed to overcome these drawbacks. OBJECTIVE: This study aimed to compare the clinical, morphological, and functional effects of combined therapy with botulinum toxin injection and topical diltiazem in chronic anal fissure and to assess the long-term outcome after healing. DESIGN: This is a randomized, controlled, double-blind, 2-arm, parallel-group trial with a long-term follow-up. SETTINGS: This study was conducted at a tertiary care center. PATIENTS: A total of 70 consecutive patients were referred to the gastroenterology department of a hospital in Valencia, Spain. INTERVENTION: After botulinum toxin injection (20 IU), patients were randomly assigned to local diltiazem (diltiazem group) or placebo gel (placebo group) for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome was fissure healing (evaluated by video register by 3 independent physicians). Secondary outcomes included symptomatic relief (30-day diary), effect on anal sphincters (manometry), safety, and long-term recurrence (24 months and 10 years). RESULTS: Healing was achieved per protocol in 13 of 25 (52%) patients of the diltiazem group and 11 of 30 (36.7%) patients of the placebo group (p = 0.25); on an intention-to-treat basis in 37.1% and 31.4% (p = 0.61). Both groups displayed significant reduction of anal pressures. Thirty percent reported minor and transitory incontinence, without differences between groups. Nine (69.2%) of the diltiazem group and 6 (54.5%) of the placebo group experienced a relapse at 24 months (p = 0.67). The overall recurrence rate at 10 years was 83.3% (20/24 patients). LIMITATIONS: This study was limited by the loss of patients during the trial. The low healing rate led to a small cohort to assess recurrence. CONCLUSIONS: Combined botulinum toxin injection and topical diltiazem is not superior to botulinum toxin injection in the treatment of chronic anal fissure. Both options offer suboptimal healing rates. Long-term recurrence is high (>80% at 10 years) and might appear at any time after healing. See Video Abstract at http://links.lww.com/DCR/B527. INYECCIN DE TOXINA BOTULNICA MS DILTIAZEM TPICO EN FISURA ANAL CRNICA UN ENSAYO CLNICO ALEATORIZADO DOBLE CIEGO Y RESULTADOS A LARGO PLAZO: ANTECEDENTES:La esfinterotomía química evita el riesgo de incontinencia permanente en el tratamiento de la fisura anal crónica, pero no alcanza la eficacia de la cirugía y la recurrencia es alta. Se ha propuesto la combinación de fármacos para superar estos inconvenientes.OBJETIVO:Comparar los efectos clínicos, morfológicos y funcionales de la terapia combinada con inyección de toxina botulínica y diltiazem tópico en fisura anal crónica y evaluar el resultado a largo plazo después de la cicatrización.DISEÑO:Ensayo aleatorizado, controlado, doble ciego, de dos brazos, de grupos paralelos con un seguimiento a largo plazo.ESCENARIO:Estudio realizado en un centro de atención terciaria.PACIENTES:Un total de 70 pacientes consecutivos referidos al servicio de gastroenterología de un hospital de Valencia, España.INTERVENCIÓN:Después de la inyección de toxina botulínica (20UI), los pacientes fueron asignados al azar a diltiazem local (grupo de diltiazem) o gel de placebo (grupo de placebo) durante 12 semanas.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la cicatrización de la fisura (evaluado por registro de video por tres médicos independientes). Los resultados secundarios incluyeron alivio sintomático (diario de 30 días), efecto sobre los esfínteres anales (manometría), seguridad y recurrencia a largo plazo (24 meses y 10 años).RESULTADOS:La curación se logró por protocolo en 13/25 (52%) en el grupo de Diltiazem y 11/30 (36,7%) en el grupo de Placebo (p = 0.25); por intención de tratar en el 37.1% y el 31.4%, respectivamente (p = 0.61). Ambos grupos mostraron una reducción significativa de las presiones anales. El 30% refirió incontinencia leve y transitoria, sin diferencias entre grupos. 9 (69.2%) del grupo de Diltiazem y 6 (54.5%) del grupo de placebo recurrieron a los 24 meses (p = 0.67). La tasa global de recurrencia a los 10 años fue del 83.3% (20/24 pacientes).LIMITACIONES:La pérdida de pacientes a lo largo del ensayo. La baja tasa de curación llevó a una pequeña cohorte para evaluar la recurrencia.CONCLUSIONES:La inyección combinada de toxina botulínica y diltiazem tópico no es superior a la inyección de TB en el tratamiento de la fisura anal crónica. Ambas opciones ofrecen tasas de curación subóptimas. La recurrencia a largo plazo es alta (> 80% a los 10 años) y puede aparecer en cualquier momento después de la curación. Consulte Video Resumen en http://links.lww.com/DCR/B527.

Chronic Migraine With Apparent Loss of Response to Onabotulinum Toxin Type A Due to Local Nitroglycerin Treatment for an Anal Fissure: A Case Report.

Many patients with chronic migraine are difficult to treat. We present a patient with chronic migraine with good response to onabotulinum toxin type A whose headaches worsened in clear temporal relationship to local treatment with glyceryl trinitrate for an anal fissure. Our case shows that the use, even at distance, of nitric oxide donors can be a precipitating factor for migraineurs and should be always inquired in chronic migraine patients. In addition, the presence of frequent headaches should always be ruled out before prescribing such medications.

Management options for chronic anal fissure: a systematic review of randomised controlled trials.

INTRODUCTION: Anal fissure is the most common cause of severe anorectal pain in adults, contributing significantly to coloproctology workloads. There are a wide variety of management options available, including topical nitrites, calcium channel blockers, botulinum toxin injection and sphincterotomy. The aim of this study was to review current options for the treatment of chronic anal fissure. METHODS: A comprehensive search identifying randomized controlled trials comparing treatment options for anal fissure published between January 2000 and February 2020 was performed. The primary outcome assessed was healing at 8 weeks post commencing treatment. Secondary outcomes included recurrence, intolerance of treatment and complications. RESULTS: A total of 2822 studies were identified. After removal of duplicates and non-relevant studies, we identified nine randomized controlled trials which met pre-defined criteria. There was a total of 775 patients. At 8 weeks, healing rates were 95.13% in those treated with sphincterotomy, 66.7% in the botulinum toxin group, 63.8% in the nitrate group, 52.3% for topical diltiazem and 50% for topical minoxidil. Recurrence was highest amongst those treated with botulinum toxin injection (41.7%) and lowest for sphincterotomy (6.9%). Although the absolute number is low, there was a risk of permanent incontinence with sphincterotomy. CONCLUSION: This review of the randomized control data demonstrates that healing was significantly higher amongst those treated with sphincterotomy versus more conservative modalities. Topical nitrites had similar outcomes to botulinum toxin injection but were poorly tolerated in comparison to other treatments. The benefit of sphincterotomy was at a cost of increased complications, notably permanent incontinence.

Treatment of chronic anal fissure: a feasibility study on Levorag® Emulgel versus Diltiazem gel 2.

PURPOSE: To compare the standard treatment, diltiazem gel 2%, with Levorag® Emulgel for chronic anal fissures. METHODS: This was a single-blinded, randomised, controlled, clinical trial with a non-inferiority design. Patients with a chronic anal fissure were randomised to treatment with diltiazem or Levorag® Emulgel twice daily for 8 weeks. Primary endpoint was complete healing of the anal fissure after 12 weeks. Secondary endpoints included incidence of adverse events and efficacy on pain relief. RESULTS: In total, 55 patients were included. Inclusion was terminated prematurely due to a slow inclusion rate. Complete fissure healing at 12 weeks follow-up was overall achieved in 31 of 55 (56%) patients, 18 of 29 (62%) in the diltiazem group compared with 13 of 26 (50%) in the Levorag® Emulgel group (P = 0.424). Pain relief was significantly better at day seven in patients treated with diltiazem (P = 0.040) compared with Levorag® Emulgel, whereas there were no differences in early (3 days) or late (12 weeks) pain relief. Three patients (10.3%) developed severe perianal exanthema during diltiazem treatment, whereas no side effects were observed in the Levorag® Emulgel group. CONCLUSION: The study demonstrated statistical non-inferiority of Levorag® Emulgel compared with diltiazem in the treatment of chronic anal fissure. Diltiazem resulted in a more prompt pain relief and also in a substantial number of local allergic reactions. Levorag® Emulgel may therefore be an alternative in these patients. TRIAL REGISTRATION: Clinicaltrials.gov no. NCT02158013.

Analgesic injection of botulinum toxin in anal fissures is efficient and can be performed safely in patients actively receiving chemotherapy.

PURPOSE: Injection of botulinum toxin into the internal anal sphincter is a well-documented intervention to reduce anal hypertonia in the treatment of anal fissures. In patients receiving chemotherapy, painful anal conditions are frequent, secondary to change in bowel habits and reduced immunity. However, injection of botulinum toxin is often not offered due to fear of complications. METHODS: In this retrospective longitudinal observational study, performed in a tertiary hospital setting, we analysed patient characteristics, outcome and complication rates of botulinum toxin injection in patients actively receiving chemotherapy. RESULTS: Twenty-six patients were treated with 20-50 IU botulinum toxin while actively receiving chemotherapy because of intractable pain and hypertonia. The fissure was located dorsally in 69% (n = 18) and ventrally in 19% (n = 5), while in 3 patients (12%), no fissure was documented. The majority of the patients (88%, n = 23) had complete (54%, n = 14) or partial (35%, n = 9) relief of pain. In three patients, additional anal pathology developed in the weeks following botulinum toxin injection: thrombosis of grade IV haemorrhoids, perianal haematoma and an intersphincteric abscess. CONCLUSIONS: Injection of botulinum toxin in the anal sphincters is a safe and effective analgesic option in patients with anal fissure while actively receiving chemotherapy.

[A case of "early" syphilis]. / Une syphilis « précoce ¼.

INTRODUCTION: Syphilis mainly affects men who have sex with men (MSM) between the ages of 20 and 49. Herein we report a case in a teenager illustrating extension of the epidemic to other populations. PATIENTS AND METHODS: A 15-year-old boy consulted in May 2018 for an anal fissure and painful oral erosions. He reported having had unprotected anal sex with another male teenager of the same age three months earlier. Syphilis serology was positive, with a positive treponemal test (TT) and non-treponemal test (VDRL) at 1/128. A treponemal bacterial DNA PCR assay was also positive for swabs obtained from the oral erosions and anal fissure. Due to a history of allergy to penicillin the patient was treated with doxycycline 200mg daily for 14 days. One month later, the mucosal lesions had subsided, and 3 months later the VDRL titer had decreased by 2 dilutions. CONCLUSION: This case of "early" syphilis illustrates a change in the French epidemiology of sexually transmitted diseases (STIs). STIs currently affect very young and previously unexposed metropolitan French populations. These infections are increasing in teenagers due to an increase in high-risk sexual behavior associated with a lack of knowledge of STIs. This case is a reminder of the current decline in the level of knowledge about STIs among teenagers as compared to young people of the same age in the 1990s.

Surgical Sphincter Saving Approach and Topical Nifedipine for Chronic Anal Fissure with Hypertonic Internal Anal Sphincter.

PURPOSE: The role of augmented internal anal sphincter (IAS) tone in the genesis of posterior chronic anal fissure (CAPF) is still unknown. Lateral internal sphincterotomy is the most employed surgical procedure, nevertheless it is burdened by high risk post-operative anal incontinence. The aim of our study is to evaluate results of sphincter saving procedure with post-operative pharmacological sphincterotomy for patients affected by CAPF with IAS hypertonia. Methods: We enrolled 30 patients, undergone fissurectomy and anoplasty with V-Y cutaneous flap advancement; all patients received topical administration of nifedipine 0.3% and lidocaine 1.5% ointment-based therapy before and for 15 days after surgery. The primary goal was patient's complete healing and the evaluation of incontinence and recurrence rate; the secondary goal included the evaluation of manometry parameters, symptom relief and complications related to nifedipine and lidocaine administration. Results: All wounds healed within 40 days after surgery. We didn't observe any de novo postoperative anal incontinence case. We reported 2 cases of recurrences, healed after conservative therapy. We didn't report any local complications related to the administration of the ointment therapy; with whom all patients reported a good compliance. Conclusions: Fissurectomy and anoplasty with V-Y cutaneous advancement flap and topical administration of nifedipine and lidocaine, is an effective treatment for CAPF with IAS hypertonia.