Short-term Results of Platelet-Rich Plasma in the Treatment of Chronic Anal Fissure: Randomized Controlled Clinical Study.

BACKGROUND: Anal fissure is one of the most common benign anal disorders, and medical treatments play an important role in its management. OBJECTIVE: The purpose of this study was to investigate the short-term effects and success of platelet-rich plasma in the treatment of chronic anal fissure. DESIGN: The study is a 2 parallel group, randomized, controlled clinical trial. SETTINGS: The study was performed in 2 tertiary university hospitals. PATIENTS: Forty-four patients with chronic anal fissure were randomly assigned to platelet-rich plasma treatment or control group. Presenting symptoms and pain scores were recorded on enrollment. The control patient self-administered topical glyceryl trinitrate. Platelet-rich plasma was injected locally in the intervention group followed by self-administered glyceryl trinitrate. MAIN OUTCOME MEASURES: The primary outcome measure is a reduction in pain scores. RESULTS: On day 10 and 1 month after treatment, the mean pain score was significantly lower in the patients treated with platelet-rich plasma than in the controls (p = 0.005 and p < 0.005). By 1 month after treatment, the mean pain score declined by 5.7 points in the platelet-rich plasma-treated group compared with a 4.1 mean pain score decline in the control group (mean difference:1.6 points (95% CI, 0.3-2.9)). According to the repeated-measures analyses, pain scores decreased in both groups, but the decrease in the treatment group was statistically higher than in the control group (p < 0.001). Complete epithelialization and recovery rates were significantly higher in the platelet-rich plasma group than in controls at all follow-up times, with p values ranging from 0.034 to <0.001. The observed difference in complete epithelialization after 2 months of treatment between the platelet-rich plasma group and the control group was 56.2% with a 95% CI of 14.03% to 98.4%. LIMITATIONS: This study was limited by its small sample size, and long-term follow-up of the patients was not presented. CONCLUSIONS: Platelet-rich plasma reduced concerns and accelerated epithelialization and healing in patients with chronic anal fissures. See Video Abstract at http://links.lww.com/DCR/B461.RESULTADOS A CORTO PLAZO DEL PLASMA RICO EN PLAQUETAS EN EL TRATAMIENTO DE LA FISURA ANAL CRÓNICA: ESTUDIO CLÍNICO CONTROLADO ALEATORIZADO. ANTECEDENTES: La fisura anal es uno de los trastornos anales benignos más comunes y los tratamientos médicos juegan un papel importante en su manejo. OBJETIVO: El propósito de este estudio fue investigar los efectos a corto plazo y el éxito del plasma rico en plaquetas en el tratamiento de la fisura an33al crónica. DISEO: El estudio es un ensayo clínico controlado, aleatorizado y de dos grupos paralelos. ESCENARIO: El estudio se llevó a cabo en dos hospitales universitarios terciarios. PACIENTES: Cuarenta y cuatro pacientes con fisura anal crónica fueron asignados aleatoriamente al grupo de tratamiento con plasma rico en plaquetas o al grupo control. Los síntomas de presentación y las puntuaciones de dolor se registraron en la inscripción. Los pacientes de control se autoadministraron trinitrato de glicerilo tópico. El plasma rico en plaquetas se inyectó localmente en el grupo de intervención seguido de trinitrato de glicerilo autoadministrado. PRINCIPALES MEDIDAS DE RESULTADO: La principal medida de resultado es una reducción en las puntuaciones de dolor. RESULTADOS: El día 10 y un mes después del tratamiento, la puntuación media de dolor fue significativamente menor en los pacientes con plasma rico en plaquetas que en los controles (p = 0.005 y p <0.005, respectivamente). Un mes después del tratamiento, la puntuación media de dolor disminuyó 5.7 puntos en el grupo tratado con plasma rico en plaquetas en comparación con una disminución de la puntuación media de dolor de 4.1 en el grupo de control (diferencia media: 1.6 puntos [intervalo de confianza del 95%; 0.3-2.9] Según los análisis de medidas repetidas, las puntuaciones de dolor disminuyeron en ambos grupos, pero la disminución en el grupo de tratamiento fue estadísticamente mayor que en el grupo de control (p <0.001). Las tasas de epitelización completa y recuperación fueron significativamente más altas en los pacientes con plasma rico en plaquetas que en los controles en todos los tiempos de seguimiento, con valores de p que van desde 0.034 a <0.001. La diferencia observada en la epitelización completa después de dos meses de tratamiento entre el grupo de plasma rico en plaquetas y el grupo de control fue del 56.2% con un intervalo de confianza del 95% del 14.03% al 98.4%. LIMITACIONES: Este estudio estuvo limitado por el pequeño tamaño de la muestra y porque no se proporcionó un seguimiento a largo plazo de los pacientes. CONCLUSIONES: El plasma rico en plaquetas redujo las molestias y aceleró la epitelización y la curación en pacientes con fisuras anales crónicas. Consulte Video Resumen en http://links.lww.com/DCR/B461. (Traducción-Dr. Jorge Silva Velazco).

Rs531564 polymorphism in microRNA-214 regulates interleukin-6R expression in anal fissure patients to affect the risk of anal abscess formation.

BACKGROUND: Anal abscess is an important complication of anal fissure (AF), whereas interleukin-6R (IL-6R) has been implicated in the development of abscess. In this study, we aimed to explore the possible molecular mechanisms underlying the regulatory effects of miRNAs on IL-6R and other inflammatory factors related to the induction of anal abscess in AF. METHODS: Bioinformatics analysis, luciferase assay, real-time polymerase chain reaction, and Western blot analysis were performed to identify the possible regulatory relationships between IL-6R and miR-124/miR-125a by comparing the differentiated expression of miR-125a, miR-124, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and IL-4 among different groups of AF patients. RESULTS: IL-6R messenger RNA (mRNA) was identified as a target gene of miR-124 because the luciferase activity in cells cotransfected with wild-type IL-6R and miR-124 mimics was significantly reduced. In addition, the expression of IL-6R mRNA and protein was significantly inhibited in the presence of miR-124 or an IL-6R inhibitor, confirming the presence of a negative regulatory relationship between miR-124 and IL-6R. Moreover, miR-124 and inflammatory factors were differentially expressed in AF patients carrying different genotypes of rs531564 polymorphism. CONCLUSIONS: miR-124 and inflammatory factors TNF-α, IFN-γ, and IL-4 may be used as indicators of anal abscess development in AF patients. In addition, miR-124 polymorphism rs531564 is involved with the pathogenesis of anal abscess in AF patients, and the presence of rs531564 may increase the incidence of anal abscess via upregulating the expression of IL-6R, TNF-α, IFN-γ, and IL-4.

[EXPEDIENCY OF THE INTRATISSUE ELECTROPHORESIS APPLICATION IN PREOPERATIVE PREPARATION OF PATIENTS, SUFFERING CHRONIC ANAL FISSURE].

The experience of preoperative application of the intratissue electrophoresis with the dioxysol solution was analyzed for the patients, suffering chronic anal fissure. In the patients, beginning from the first day, there was proved the reduction of the pain syndrome severity, hemodynamic disorders, an acute inflammatory reactions in the anal fissure tissue, the young granulations growth in the edge of the wound and resection. Application of the method proposed have promoted the inflammatory process severity reduction, the reparative processes in anal fissure stimulation, the operation wound epithelization acceleration, the anal sphincter muscle spasmelimination, which constitutes the main pathogenetic mechanism of the disease.

Fistula tract curettage and the use of biological dermal plugs improve high transsphincteric fistula healing in an animal model.

PURPOSE: The treatment of high transsphincteric fistula is a complex procedure, which may be associated with the risk of recurrence and fecal incontinence. In this study, we used an animal model to compare different types of sphincter-preserving treatments for transsphincteric fistula. METHODS: Sixteen female New Zealand rabbits, weighing 2.8-4.8 kg underwent a surgical creation of high transsphincteric fistula. After 6 weeks, magnetic resonance imaging (MRI) was performed in order to confirm fistula formation and measure the fistula diameter. The rabbits were divided into three groups. Group 1 received no plug treatment (control). Autologous dermal graft and acellular dermal matrix were used as a plug in groups 2 and 3, respectively. Five weeks after treatment, fistula tract healing was determined by measuring the largest fistula diameter with MRI. All rabbits were euthanized and the anorectum excised en bloc for histopathological examination. RESULTS: According to the MRI findings, all groups showed significant healing after the treatment (p < 0.05). The healing rate of fistula diameters after treatment was 40, 66, and 29% in the control, dermal graft, and acellular dermal matrix groups, respectively. In terms of negative healing parameters such as neutrophil, eosinophil, lymphocyte, and plasmocyte accumulation, dermal graft and acellular dermal matrix groups showed significantly lower results than those in the control group (p < 0.05). CONCLUSION: According to MRI and histopathological results, fistula tract curettage and fistula orifice closure improved transsphincteric anal fistula healing. Additionally, in this study, plug treatment favoring autologous dermal graft resulted in better healing.

Crohn's disease: is there any link between anal and luminal phenotypes?

PURPOSE: Perianal Crohn's disease (CD) encompasses a variety of lesion similar to luminal disease, which are usually not distinctly assessed. Links between luminal and perianal CD phenotype remains therefore underreported, and we aimed to describe both luminal and perianal phenotype and their relationships. METHODS: From January 2007, clinical data of all consecutive patients with CD seen in a referral center were prospectively recorded. Data recorded until October 2011 were extracted and reviewed for study proposal. RESULTS: A total of 282 patients (M/F, 108/174; aged 37.8 ± 16.2 years) were assessed that included 154 cases (54.6%) with anal ulceration, 118 cases (41.8%) with fistula, 49 cases (17.4%) with stricture, and 94 cases without anal lesion (33.3%). Anal ulcerations were associated with fistulas (N = 87/154) in more than half of patients (56.5%) and were isolated in 55 patients (35.7%). Most of strictures (94%) were associated with other lesions (N = 46/49). Harvey-Bradshaw score was significantly higher in patients with ulcerations (p < 0.001) as compared to those with perianal fistulas (p = 0.15) or with anal strictures (p = 0.16). Proportions of complicated behavior (fistulizing or stricturing) of luminal CD were similar according to anal lesions: anal fistulas were not significantly associated to penetrating Montreal phenotype (N = 4/31 p = 0.13) as well as anal stricture and stricturing Montreal phenotype (N = 3/49, p = 0.53). CONCLUSIONS: The phenotype of luminal disease does not link with the occurrence and the phenotype of perianal Crohn's disease. Anal ulcerations denote a more severe disease on both luminal and perianal locations and should consequently be taking into account in physician decision-making.

Cutaneous presentation of disseminated histoplasmosis as a solitary peri-anal ulcer. Case report and discussion.

Disseminated histoplasmosis has a diverse and non-specific range of clinical signs and symptoms. In a significant minority of patients, cutaneous lesions are apparent at the time of initial presentation, affording an opportunity to establish the diagnosis from a skin biopsy. The most frequently reported clinical scenario in immunocompromised patients with cutaneous involvement is that of multiple papulo-nodular lesions on the face, trunk or extremities. The following report features an immunocompetent patient who presented with a solitary ulcerated plaque on the buttocks close to the anal verge. This case presentation underscores the broad spectrum of clinical presentations as well as the potential for diagnostic confusion with protozoa such as Leishmania or Trypanosoma species during histopathologic examination if special stains for fungal organisms are not performed.

Anal fissure in children: a 10-year clinical experience with nifedipine gel with lidocaine.

BACKGROUND: We aimed to evaluate efficacy and safety of the use of nifedipine gel with lidocaine in the treatment of acute anal fissures in children by reviewing the cases of 106 children with acute anal fissure treated conservatively by nifedipine gel with lidocaine between the years 2003-2012. METHODS: The patients included in this study were 48 males and 58 females. Their clinical presentation consisted of constipation, rectal bleeding, anal pain, perianal itching, abdominal pain, irritability and rectal prolapse. Posterior, anterior, both anterior and posterior, multiple, both posterior and lateral locations were the main physical findings in 65, 23, 10, 7, and 1 cases. RESULTS: Ninety-nine patients completed the 4-week treatment course of nifedipine gel with lidocaine successfully (93.40%), with complete healing of the fissure. The recurrence rate observed was very low (6.60%). CONCLUSIONS: Topical 0.2% nifedipine with lidocaine appears an efficient mode of treatment for anal fissures in children, with a significant healing rate and no side effects.

[CHANGES OF HISTOSTRUCTURE OF CHRONIC ANAL FISSURE, DEPENDING ON DURATION OF THE DISEASE].

The results of histological investigation of the chronic anal fissure (AF) edges in 95 patients with the disease duration from 6 mo to 4.5 yrs were analyzed. Basing on estimation of severity of an acute inflammation signs and the granulation and cicatricial tissue presence there was established, that duration of an acute inflammation in the AF may constitute up to 6 - 7 mo; subacute--from 8 to 11 mo, chronic cicatricial process was observed in terms from 12 mo and more.

Prospective Single-Center Observational Study of Routine Histopathologic Evaluation of Macroscopically Normal Hemorrhoidectomy and Fissurectomy Specimens in Search of Anal Intraepithelial Neoplasia.

BACKGROUND: The necessity for routine histopathologic evaluation of hemorrhoidectomy specimens considered free of suspicious areas after careful visual and manual inspection remains controversial. OBJECTIVE: The purpose of this work was to prospectively study the prevalence of anal intraepithelial neoplasia in macroscopically normal operative specimens. DESIGN AND PATIENTS: From October 2005 to September 2010, all hemorrhoidectomy and fissurectomy specimens were sent for routine histopathologic analysis. SETTING: This study was conducted at a tertiary referral center. MAIN OUTCOME MEASURES: The primary outcome measured was the histopathologic examination of surgical samples. RESULTS: Among the specimens from 2997 procedures, routine histopathologic evaluation found anal intraepithelial neoplasia in 97 patients (3.2%), despite the fact that visual and manual inspection had determined that the specimens were free of any suspected anal intraepithelial neoplasia or human papillomavirus-related lesion. The pathological diagnoses for these macroscopically normal specimens were AIN1 in 22 (23%) patients, AIN2 in 48 (49%) patients and AIN3 in 27 (28%) patients, making the prevalence of high-grade and low-grade disease 2.5% (anal intraepithelial neoplasia 2/3) and 0.7% (anal intraepithelial neoplasia 1). LIMITATIONS: This study was limited by being a single-center study. CONCLUSION: This prospective single-center study demonstrated that the prevalence of infraclinical anal intraepithelial neoplasia in macroscopically normal hemorrhoidectomy and fissurectomy specimens is not negligible (3.2% with 2.5% high-grade disease).

A rare case of myeloid sarcoma presenting as anal fissure.

Myeloid sarcoma is a tumor composed of myeloblasts occurring at an extramedullary site. It may develop in patients with acute myeloid leukemia, myeloproliferative or myelodysplastic syndrome, sometimes preceding onset of the systemic disease. Frequent sites of myeloid sarcoma are bones or various soft tissues. Gastrointestinal involvement is very rare. We report a unique case of myeloid sarcoma presenting as a painful anal fissure, in a patient with a history of acute myeloid leukemia. The diagnosis was achieved by a surgical excisional biopsy and immunoistochemical staining.

[MORPHOGENESIS OF THE ANODERM STRUCTURAL CHANGES IN PATIENTS WITH CHRONIC ANAL FISSURES].

The objective of the study is to find peculiarities of the anoderm structural changes of morphogenesis in patients with chronic anal fissures (CAF) for further substantiation of therapeutic methods. The material of the study was the tissues of dissected anal complex (bottom and margins of ulcer, hypertrophic anal papilla, sentinel pile) from 33 patients. Histological examination found the defect of the stratified squamous epithelium. The epidermis of the marginal area of the wound, hypertrophic with signs of parakeratosis and acanthosis, hanged over the bottom. The surface of the bottom and margins of the wound in 31 cases (94%) was with thickening of rough fibrous masses. The bottom of ulcer in 29 (88%) cases is presented by sclerosed connective tissue. An increased amount of collagen fibers was found forming fuchsinophil is bundles. In 24 (73%) cases the scar on the fuchsine bottom of fissure was 3,4 mm (0,3±0,02) in deep. There are separate complexes of newly formed blood vessels with prevailing localization in the lateral walls of the wound. The blood vessels were with main by fibrosis in deep areas of the wound. Moderate interstitial edema and focal interstitial inflammatory infiltration mostly of lymphocytes and fibroblasts were detected; the amount of macrophages was not substantial. Considering cicatrical rebuilding of the anoderm of ulcer bottom caused, first of all, by hypoxia leading to activation of collagen-producing function of fibroblastes and absence of the signs of epithelization, patients with CAF should be treated surgically dissecting the bottom and margins of fissure in the complex with hypertrophic anal papilla and sentinel pile.

[SURGICAL TREATMENT OF POSTOPERATIVE STRICTURE OF ANAL CHANNELL].

The results of treatment of 50 patients, suffering postoperative stricture of anal channell (SACH), who were treated in Proctology Department of Ivano-Frankivskiy Rural Clinical Hospital in 2006-2014 yrs, were analyzed. After conduction of hemorrhoidectomy in accordance to Milligan-Morgan method for chronic hemorrhoids grades III-IV a SACH have occurred in 46 (92%) patients, excision of a chronic anal fissura was performed in 3 (6%) and excision of perianal pointed condylomas--in 1 patient. In 2006-2007 yrs 11 (22%) patients were operated in accordance to approaches, which were conventional at that time (comparison group). In 2008 - 2014 yrs 39 (78%) patients were admitted to hospital (main group), in whom new approaches for diagnosis, conservative and surgical treatment were applied, 30 (76.9%) of them were operated. The proposed method on isolated roentgen contrast investigation of anal channell have permitted to determine objectively a form, diameter and grade of the anal channel stricture, and it may be applied as a screening procedure, as additional objective criterion while choosing a surgical tactic. Application of the improved operative technique for SACH have permitted to lower its occurrence rate from 45.4 to 6.7%.

Anal signs of child sexual abuse: a case-control study.

BACKGROUND: There is uncertainty about the nature and specificity of physical signs following anal child sexual abuse. The study investigates the extent to which physical findings discriminate between children with and without a history of anal abuse. METHODS: Retrospective case note review in a paediatric forensic unit. CASES: all eligible cases from 1990 to 2007 alleging anal abuse. CONTROLS: all children examined anally from 1998 to 2007 with possible physical abuse or neglect with no identified concern regarding sexual abuse. Fisher's exact test (two-tailed) was performed to ascertain the significance of differences for individual signs between cases and controls. To explore the potential role of confounding, logistic regression was used to produce odds ratios adjusted for age and gender. RESULTS: A total of 184 cases (105 boys, 79 girls), average age 98.5 months (range 26 to 179) were compared with 179 controls (94 boys, 85 girls) average age 83.7 months (range 35-193). Of the cases 136 (74%) had one or more signs described in anal abuse, compared to 29 (16%) controls. 79 (43%) cases and 2 (1.1%) controls had >1 sign. Reflex anal dilatation (RAD) and venous congestion were seen in 22% and 36% of cases but <1% of controls (likelihood ratios (LR) 40, 60 respectively), anal fissure in 14% cases and 1.1% controls (LR 13), anal laxity in 27% cases and 3% controls (LR 10).Novel signs seen significantly more commonly in cases were anal fold changes, swelling and twitching. Erythema, swelling and fold changes were seen most commonly within 7 days of last reported contact; RAD, laxity, venous congestion, fissure and twitching were observed up to 6 months after the alleged assault. CONCLUSIONS: Anal findings are more common in children alleging anal abuse than in those presenting with physical abuse or neglect with no concern about sexual abuse. Multiple signs are rare in controls and support disclosed anal abuse.

Anal fissures in infants may be a pathognomonic sign of infants with cow's milk allergy.

OBJECTIVE: To study the association between analfissures and cow's milk allergy (CMA) in infants. METHODS AND METHOD: In a prospective study, 72 confirmed cases of CMA in infants were examined for anal fissure by pediatricians with five years' experience. A positive finding was defined as when an anal fissure was detected by at least two out of three examiners. RESULTS: Of infants with CMA with and without gastrointestinal GI symptoms, 79% and 83% had anal fissures, respectively The prevalence of anal fissure in these infants is significantly higher than in normal infants. CONCLUSION: Anal fissure may be a pathognomonic sign of cow's milk allergy in infants.

[Significance of nontraumatic anal sphincter relaxation for the success of plastic and miniinvasive interventions in coloproctology].

The investigation objective was to estimate the role of nontraumatic anal sphincter (AS) stretching, as a leading factor of success in minimally invasive and/or plastic proctological interventions. One-centre randomized investigation was performed in 83 patients: In 22 of them the AS fissura was revealed (in 16), suprasphincteric fistula (in 3) and coexistent rectocele 2-3 Ap (according to POP-Q classification) with thinning of the AS anterior segment, the degree III hemorrhoids and anterior AS fissure presence. Ninety units of botulotoxin preparation (Disport) were injected between internal and external AS portions 5-15 days preoperatively. The treatment results without botulotoxin injection were compared retrospectively. After botulotoxin injection performance the AS spasm elimination was noted, leading to the pain subsiding promotion before and postoperatively in all the patients observed. The spasm elimination have permitted to escape the anal high fistula recurrence as a result of the mucosal flap shift after intraluminal closure of the fistula or because of the fistula intermuscular electrowelding "suture" rupture, also have guaranteed the plastic sutures on AS, even while the stage II-III rectocele presence, not depending of performance of its simultant surgica correction.

Hiding intersphincteric and transphincteric sepsis in a novel pathological approach to chronic anal fissure.

AIM: The purpose of this study was to investigate whether endoanal ultrasonographic findings could better characterize chronic anal fissures, mostly in those patients with persistent and recurrent disease after medical treatment. METHODS: Between January 2004 and April 2010, patients referred to our departments suspected for anal fissure were considered in a database. Physical examination and anoscopy confirmed the diagnosis of anal fissure in 543 patients. Chronicity was defined on the basis of morphological features of the fissure and mainly on its persistence or recurrence after medical therapy. Moreover, 172 out of 543 patients were selected with respect to the inclusion criteria and submitted to endoanal ultrasonography. RESULTS: Seventeen out of 172 were anterior fissures (9.8%) and 155 posterior (90.2%). In 112 (65.1%) out of 172 patients submitted to endoanal ultrasonography, an associated chronic abscess was demonstrated, with expression of 91 intersphincteric and 21 low transphincteric fistulas, respectively. According to clinical data as well as comorbidities and previous surgery, there were no significant differences between patients with associated abscess and those with only chronic anal fissure. CONCLUSION: The authors assume that chronic fissures may persist because of hiding sepsis in the anal canal and that chronic anal fissure might be the clinical and pathological expression of a coexisting intersphincteric or low transphincteric fistula, and the ultrasonographic findings strongly support this theory.

Sacral nerve stimulation: a novel treatment of chronic anal fissure.

OBJECTIVE: The purpose of this pilot study of 5 patients was to test the feasibility of a new treatment approach for chronic anal fissure utilizing minimally invasive sacral nerve stimulation before designing and conducting a larger prospective controlled study. MEASUREMENTS: The patients underwent uneventful placement of one temporary 8-electrode Octad lead for sacral nerve root stimulation. Stimulation was conducted for 20 minutes 3 times per day. The lead was removed after 3 weeks of stimulation. RESULTS: The patients experienced an immediate improvement in perineal pain after the initiation of sacral nerve stimulation. The pain relief effect lasted 10 to 12 hours, so stimulation was conducted for short episodes to ensure patient comfort and to extend the battery life of the external neurostimulator. For all patients, the chronic anal fissure healed by the end of the third week of temporary sacral nerve stimulation. There was no recurrence of anal fissure 1 year after treatment in all of the study participants. CONCLUSION: Sacral nerve stimulation offers an effective alternative treatment option for chronic anal fissure in patients who chose not to pursue more invasive surgical interventions.