Evaluation of anorectal function using real-time tissue elastography before and after preoperative chemoradiotherapy.

PURPOSE: This study aimed to clarify the relationship between changes in elasticity and anorectal function before and after chemoradiotherapy. METHODS: This is a single-center prospective cohort study (Department of Surgical Oncology, The University of Tokyo). We established a technique to quantify internal anal sphincter hardness as elasticity using transanal ultrasonography with real-time tissue elastography. Twenty-seven patients with post-chemoradiotherapy rectal cancer during 2019-2022 were included. Real-time tissue elastography with transanal ultrasonography was performed before and after chemoradiotherapy to measure internal anal sphincter hardness as "elasticity" (hardest (0) to softest (255); decreased elasticity indicated sclerotic changes). The relationship between the increase or decrease in elasticity pre- and post-chemoradiotherapy and the maximum resting pressure, maximum squeeze pressure, and Wexner score were the outcome measures. RESULTS: A decrease in elasticity was observed in 16/27 (59.3%) patients after chemoradiotherapy. Patients with and without elasticity decrease after chemoradiotherapy comprised the internal anal sphincter sclerosis and non-sclerosis groups, respectively. The maximum resting pressure post-chemoradiotherapy was significantly high in the internal anal sphincter sclerosis group (63.0 mmHg vs. 47.0 mmHg), and a majority had a worsening Wexner score (60.0% vs. 18.2%) compared with that of the non-sclerosis group. Decreasing elasticity (internal anal sphincter sclerosis) correlated with a higher maximum resting pressure (r = 0.36); no correlation was observed between the degree of elasticity change and maximum squeeze pressure. CONCLUSION: Internal anal sphincter sclerosis due to chemoradiotherapy may correlate to anorectal dysfunction.

An Exploratory Study on the Contractile Effects of Hydroxy-α-Sanshool and Hydroxy-ß-Sanshool, the Active Ingredients of Daikenchuto, on the Internal Anal Sphincter.

Objectives: Daikenchuto (DKT) enhances the contraction of the internal anal sphincter (IAS) in patients with constipation and fecal incontinence; however, the mechanism of its action is unknown. We investigated the effects of the active ingredients of DKT (hydroxy-α-sanshool (HAS) and hydroxy-ß-sanshool (HBS)) on the contractile activity of the canine rectum and IAS. Methods: Three male beagle dogs were prepared for each of the HAS, HBS, and control groups. Force transducers were attached to the rectal and IAS surfaces of the dogs, and the contractile responses were measured by telemetry under conscious conditions. HAS (10 mg/body) and HBS (2.5 mg/body) were administered intrarectally at doses previously identified from an effective dose of DKT extract (1.5 g/body), and contractile responses were recorded up to 6 h after administration. Contractile activity of the rectum and IAS was evaluated by observing the area under the curve (AUC) of the recorded contraction waveform. Plasma concentrations of HAS and HBS were measured before and after administration to confirm IAS exposure to both ingredients. Results: The mean AUC values of the IAS for the control, HAS, and HBS groups at 10 min after administration were 115, 87, and 220 (g-min), respectively, indicating a higher contraction in the HBS group, which was maintained for approximately 3 h. As for the rectum, no contractile response was observed in either the HAS or HBS groups. Plasma concentrations of both ingredients peaked at 20 min after administration. Conclusions: HBS could be involved in the contractile action of DKT on the IAS.

Impact of sex and aging on radiographic and functional parameters of the anal sphincter complex in patients with accidental bowel leakage.

AIMS: Treatment outcomes for accidental bowel leakage (ABL) may be influenced by age-related sarcopenia. We sought to determine if thickness of the anal sphincter complex on endoanal ultrasound correlated with function in women and men with ABL and if women demonstrated age-related anal sphincter thinning. METHODS: Consecutive patients with ABL presenting to our pelvic floor clinic from 2012 to 2017 were included. Clinical data were obtained from medical records. External anal sphincter (EAS), imaged by endoanal ultrasound at proximal, mid and distal locations, and IAS thickness were measured at 12, 3, 6, and 9 o'clock; puborectalis muscle (PRM) was measured at 4, 6, and 8 o'clock; and averaged. Anorectal manometry was conducted when clinically indicated. Data were compared using Mann-Whitney tests and linear regression. Results are reported as mean ± SD or median (IQR). RESULTS: Women (n = 136) were younger than men (n = 26) (61 ± 13 vs. 67 ± 13 years, p = 0.02). More women than men had pelvic surgery and less had colorectal surgery, spinal disorders, or a history of smoking (p < 0.05). Eighty-two percentage of women had an anal sphincter defect versus 31% of men (p < 0.01). All anal sphincter complex components were thinner in women than men with lower squeeze and resting pressures (p < 0.03), even in nulliparous women. Mean resting pressure was lower in older 6.1 (4.6-7.8) versus younger women 8.3 (5.0-12.9) mmHg, p = 0.04. CONCLUSIONS: Women, even nulliparous, with ABL demonstrate thinner and weaker anal sphincters than men, Aging correlated with an increase in anal sphincter thickness, suggesting that age-related changes in the intrinsic components of the anal sphincter complex associated with ABL are complex and are not always well demonstrated on endoanal ultrasound.

Differentiation of Adipose-Derived Stem Cells into Smooth Muscle Cells in an Internal Anal Sphincter-Targeting Anal Incontinence Rat Model.

OBJECTIVE: Studies on development of an anal incontinence (AI) model targeting smooth muscle cells (SMCs) of the internal anal sphincter (IAS) have not been reported. The differentiation of implanted human adipose-derived stem cells (hADScs) into SMCs in an IAS-targeting AI model has also not been demonstrated. We aimed to develop an IAS-targeting AI animal model and to determine the differentiation of hADScs into SMCs in an established model. MATERIALS AND METHODS: The IAS-targeting AI model was developed by inducing cryoinjury at the inner side of the muscular layer via posterior intersphincteric dissection in Sprague-Dawley rats. Dil-stained hADScs were implanted at the IAS injury site. Multiple markers for SMCs were used to confirm molecular changes before and after cell implantation. Analyses were performed using H&E, immunofluorescence, Masson's trichrome staining, and quantitative RT-PCR. RESULTS: Impaired smooth muscle layers accompanying other intact layers were identified in the cryoinjury group. Specific SMC markers, including SM22α, calponin, caldesmon, SMMHC, smoothelin, and SDF-1 were significantly decreased in the cryoinjured group compared with levels in the control group. However, CoL1A1 was increased significantly in the cryoinjured group. In the hADSc-treated group, higher levels of SMMHC, smoothelin, SM22α, and α-SMA were observed at two weeks after implantation than at one week after implantation. Cell tracking revealed that Dil-stained cells were located at the site of augmented SMCs. CONCLUSIONS: This study first demonstrated that implanted hADSc restored impaired SMCs at the injury site, showing stem cell fate corresponding to the established IAS-specific AI model.

Treatment of postoperative intestinal dysfunction of hirschsprung's disease based on the principle of "anorectal balance".

Purpose: Radical surgery is the most effective treatment for Hirschsprung's disease. However, some children still have symptoms of intestinal dysfunction such as constipation, abdominal distension, and recurrent enterocolitis after operation. The purpose of this study was to evaluate treatment outcomes of postoperative intestinal dysfunction in children with Hirschsprung's disease by using the principle of "anorectal balance". Methods: The clinical data of postoperative intestinal dysfunction in children with Hirschsprung's disease in the single treatment group from July 2019 to July 2021 were retrospectively analyzed. All the enrolled children underwent botulinum toxin injection (2.5 U/kg); 3 to 6 months later, the injection was performed again; the children who had received more than two botulinum toxin injections underwent the internal sphincter myectomy. Anorectal manometry was performed routinely after operation, and abdominal distension and defecation were recorded. Results: A total of thirty children with postoperative intestinal dysfunction underwent radical surgery for Hirschsprung's disease were included in this study. Symptoms of constipation, abdominal distension and enterocolitis were improved after botulinum toxin injections in most children compared to before surgery (P < 0.01). After re-injection of botulinum toxin in twelve children, the frequency of defecation increased, the anal resting pressure decreased, and the clinical symptoms were relieved again (P < 0.05). Eleven children underwent internal sphincter myectomy, and the symptoms of constipation, abdominal distension and enterocolitis were significantly improved after the operation (P < 0.01). Conclusion: Botulinum toxin injection and internal sphincter myectomy based on the principle of "anorectal balance" can effectively reduce the resting pressure of the anus and relieve intestinal dysfunction, and have satisfactory clinical effect.

Esfinteroplastia anatómica mediante reconstrucción combinada del esfínter anal interno y externo en el tratamiento quirúrgico de la incontinencia anal / Anatomic sphincteroplasty with combined reconstruction of internal and external anal muscles in the anal incontinence surgical treatment

Los estudios que evalúan la efectividad de la esfinteroplastia clásica muestran una mejoría de alrededor del 75% a corto plazo, constatándose un deterioro en el tiempo con resultados satisfactorios a largo plazo de alrededor del 50%. Tras introducir la realización de la reparación por separado del esfínter anal interno y el externo, se publicaron tasas de éxito del 80%, observando que estos resultados se mantenían a largo plazo. Pensamos que la introducción de modificaciones en la técnica quirúrgica desde una mentalidad anatómica y reconstructiva, que hemos denominado «esfinteroplastia anatómica mediante reconstrucción combinada de esfínter anal interno y externo», puede obtener muy buenos resultados clínicos y manométricos en el seguimiento a corto y medio plazo. Asimismo, el aumento de longitud de la barrera presiva generada por la técnica puede colaborar a que estos resultados se mantengan más estables a lo largo del tiempo que con la técnica clásica (AU)

Several groups studying the results of the classic sphincteroplasty show improvement of 75% of patients treated in a short-term follow-up, with a worsening of this data in the long-term follow-up down to an improvement of 50% of the patients. Some other groups published more optimistic results, showing an 80% success rate without any deterioration of the technique over time after introducing a separate repair of the internal and external muscles. We think that the introduction of some modifications in the classic technique, named “anatomic sphincteroplasty with combined reconstruction of external and internal anal sphincter muscles” may obtain very good clinical and anorectal manometric results both in a short and mid-term follow-up. In addition, increasing the pressive length in the anal canal may contribute to maintain more stable results over time (AU)

Anatomic sphincteroplasty with combined reconstruction of internal and external anal muscles in the anal incontinence surgical treatment.

Several groups studying the results of the classic sphincteroplasty show improvement of 75% of patients treated in a short-term follow-up, with a worsening of this data in the long-term follow-up down to an improvement of 50% of the patients. Some other groups published more optimistic results, showing an 80% success rate without any deterioration of the technique over time after introducing a separate repair of the internal and external muscles. We think that the introduction of some modifications in the classic technique, named "Anatomic sphincteroplasty with combined reconstruction of external and internal anal sphincter muscles" may obtain very good clinical and anorectal manometric results both in a short and mid-term follow-up. In addition, increasing the pressive length in the anal canal may contribute to maintain more stable results over time.

A systematic review of translation and experimental studies on internal anal sphincter for fecal incontinence.

The complexity in the molecular mechanism of the internal anal sphincter (IAS) limits preclinical or clinical outcomes of fecal incontinence (FI) treatment. So far, there are no systematic reviews of IAS translation and experimental studies that have been reported. This systematic review aims to provide a comprehensive understanding of IAS critical role in FI. Previous studies revealed the key pathway for basal tone and relaxation of IAS in different properties as follows; calcium, Rho-associated, coiled-coil containing serine/threonine kinase, aging-associated IAS dysfunction, oxidative stress, renin-angiotensin-aldosterone, cyclooxygenase, and inhibitory neurotransmitters. Previous studies have reported improved functional outcomes of cellular treatment for regeneration of dysfunctional IAS, using various stem cells, but did not demonstrate the interrelationship between those results and basal tone or relaxation-related molecular pathway of IAS. Furthermore, these results have lower specificity for IAS-incontinence due to the included external anal sphincter or nerve injury regardless of the cell type. An acellular approach using bioengineered IAS showed a physiologic response of basal tone and relaxation response similar to human IAS. However, in both cellular and acellular approaches, the lack of human IAS data still hampers clinical application. Therefore, the IAS regeneration presents more challenges and warrants more advances.

Impact of Botulinum Toxin on Hirschsprung-Associated Enterocolitis After Primary Pull-Through.

BACKGROUND: Hirschsprung-associated enterocolitis (HAEC) is a serious potential complication after primary pull-through surgery for Hirschsprung's disease (HSCR). Administration of anal botulinum toxin (BT) injection may improve obstructive symptoms at the internal anal sphincter, leading to improved fecal passage. The timing of administration and effects on delay or prevention of HAEC are unknown. We hypothesized that BT administration increased the postoperative time to HAEC and aimed to investigate whether anal BT administration after primary pull-through surgery for HSCR is associated with increased time to inpatient HAEC admission development. METHODS: We performed a retrospective cohort study examining children with HSCR at US children's hospitals from 2008 to 2018 using the Pediatric Health Information System database with an associated primary pull-through operation performed before 60 d of age. The intervention assessed was the administration of BT concerning the timing of primary pull-through, and two groups were identified: PRO (received BT at or after primary pull-through, before HAEC) and NOT (never received BT, or received BT after HAEC). The primary outcome was time from pull-through to the first HAEC admission. The Cox proportional hazards model was developed to examine the BT administration effect on the primary outcome after controlling for patient-level covariates. RESULTS: We examined a total of 1439 children (67 in the PRO and 1372 in the NOT groups). A total of 308 (21.4%) developed at least one episode of HAEC, including 76 (5.3%) who had two or more episodes. Between 2008 and 2018, the frequency of BT administration has increased from three to 20 hospitals with a frequency of administration between 2.2% and 16.2%. Prophylactic BT (PRO) was not associated with increased time to HAEC event on adjusted analysis. CONCLUSIONS: Among children with HSCR undergoing primary pull-through surgery, prophylactic BT administration did not demonstrate increased time to first HAEC event. A better-powered study with prophylactic BT is required to determine the effect on HAEC occurrence and timing. LEVEL OF EVIDENCE: Level II (retrospective cohort study).

Oscillating calcium signals in smooth muscle cells underlie the persistent basal tone of internal anal sphincter.

A persistent basal tone in the internal anal sphincter (IAS) is essential for keeping the anal canal closed and fecal continence; its inhibition via the rectoanal inhibitory reflex (RAIR) is required for successful defecation. However, cellular signals underlying the IAS basal tone remain enigmatic. Here we report the origin and molecular mechanisms of calcium signals that control the IAS basal tone, using a combination approach including a novel IAS slice preparation that retains cell arrangement and architecture as in vivo, 2-photon imaging, and cell-specific gene-modified mice. We found that IAS smooth muscle cells generate two forms of contractions (i.e., phasic and sustained contraction) and Ca2+ signals (i.e., synchronized Ca2+ oscillations [SCaOs] and asynchronized Ca2+ oscillations [ACaOs]) that last for hours. RyRs, TMEM16A, L-type Ca2+ channels, and gap junctions are required for SCaOs, which account for phasic contraction and 75% of sustained contraction. Nevertheless, only RyRs are required for ACaOs, which contribute 25% of sustained contraction. Nitric oxide, the primary neurotransmitter mediating the RAIR, blocks both types of Ca2+ signals, leading to IAS's full relaxation. Our results show that the oscillating nature of Ca2+ signals generates and maintains the basal tone without causing cytotoxicity to IAS. Our study provides insight into fecal continence and normal defecation.

The not-so-rare absent RAIR: Internal anal sphincter achalasia in a review of 1072 children with constipation undergoing high-resolution anorectal manometry.

BACKGROUND: Our objective is to describe the prevalence of patients with internal anal sphincter achalasia (IASA) without Hirschsprung disease (HD) among children undergoing anorectal manometry (ARM) and their clinical characteristics. METHODS: We performed a retrospective review of high-resolution ARM studies performed at our institution and identified patients with an absent rectoanal inhibitory reflex (RAIR). Clinical presentation, medical history, treatment outcomes, and results of ARM and other diagnostic tests were collected. We compared data between IASA patients, HD patients, and a matched control group of patients with functional constipation (FC). KEY RESULTS: We reviewed 1,072 ARMs and identified 109 patients with an absent RAIR, of whom 28 were diagnosed with IASA. Compared to patients with FC, patients with IASA had an earlier onset of symptoms and were more likely to have abnormal contrast enema studies. Compared to patients with HD, patients with IASA were more likely to have had a normal timing of meconium passage, a later onset of symptoms, and were diagnosed at an older age. At the latest follow-up, the majority of patients diagnosed with IASA (54%) were only using oral laxatives. Over half of patients with IASA had been treated with anal sphincter botulinum toxin injection, and 55% reported a positive response. CONCLUSIONS AND INFERENCES: Patients diagnosed with IASA may represent a more severe patient population compared to patients with FC, but have a later onset of symptoms compared to patients with HD. They may require different treatments for their constipation and deserve further study.

The Japanese Extracted Herbal Medicine Daikenchuto Increases the Contractile Activity of the Internal Anal Sphincter Muscle in Conscious Dogs.

OBJECTIVES: This study aimed to elucidate the effect of the extract of daikenchuto (DKT), a Japanese Kampo medicine, on the contractile activity of the internal anal sphincter in conscious dogs. METHODS: Force transducers were attached to the serosal surface of the rectum and the internal anal sphincter of male beagle dogs. In addition, the contractile activity of the rectum and the internal anal sphincter was continuously measured until 6 h after DKT administration via telemetry in the conscious state. The DKT dose was 1.5 g/body, and the administration route was intrarectal in the expectation of a direct effect on the rectoanal region. DKT was re-administered to the same animal after drug withdrawal, and the plasma concentrations of hydroxy-α-sanshool (HAS) and hydroxy-ß-sanshool (HBS) before and after administration were measured. RESULTS: After DKT administration, the contractile activity of the internal anal sphincter immediately increased, peaked at 10 min, continued for ≥1 h, and had almost disappeared after 4 h. Rectal contraction differed from that of the internal anal sphincter, with no significant contraction observed. HAS and HBS were found in the plasma of animals administered with DKT and persisted up to 2 h after the administration. CONCLUSIONS: This is the first report on in vivo telemetry demonstrating that DKT exhibited contractile effects on the dog's internal anal sphincter. The increased anal pressure and improvement of fecal incontinence symptoms observed in previous clinical studies may have been based on this sphincter contraction.

Low Anterior Resection Syndrome.

PURPOSE OF REVIEW: Low anterior resection syndrome is a highly prevalent condition that can develop after anal sphincter-sparing surgery for rectal cancer and impair quality of life. In this review, we summarize the major features and pathophysiology of this syndrome and discuss treatment approaches. RECENT FINDINGS: Quality of life correlates significantly with severity of low anterior resection syndrome. Prompt assessment and initiation of therapy are essential to rehabilitating damaged mechanical and neural structures. Anorectal manometry demonstrates a global decrease in sphincteric function postoperatively, though in many patients, function does recover. Transanal irrigation, pelvic floor rehabilitation, and biofeedback are the mainstays of the treatment of major LARS. Definitive stoma can be considered in therapy refractory LARS > 2 years. The development of low anterior resection syndrome likely involves an interplay between mechanical and neural pathways. Clinically, patients present at varying levels of severity, and scoring systems are available to help assess patient symptoms and guide therapy. Treatment approaches range from conservative therapies to biofeedback and sacral nerve stimulation. Future randomized controlled trials aimed at risk stratification of patients and development of severity-based treatment algorithms are warranted.

The role of the longitudinal muscle in the anal sphincter complex: Implications for the Intersphincteric Plane in Low Rectal Cancer Surgery?

Intersphincteric resection (ISR) enables radical sphincter-preserving surgery in a subset of low rectal tumors impinging on the anal sphincter complex (ASC). Excellent anatomical knowledge is essential for optimal ISR. This study describes the role of the longitudinal muscle (LM) in the ASC and implications for ISR and other low rectal and anal pathologies. Six human adult en bloc cadaveric specimens (three males, three females) were obtained from the University of Leeds GIFT Research Tissue Programme. Paraffin-embedded mega blocks containing the ASC were produced and serially sectioned at 250 µm intervals. Whole mount microscopic sections were histologically stained and digitally scanned. The intersphincteric plane was shown to be potentially very variable. In some places adipose tissue is located between the external anal sphincter (EAS) and internal anal sphincter (IAS), whereas in others the LM interdigitates to obliterate the plane. Elsewhere the LM is (partly) absent with the intersphincteric plane lying on the IAS. The LM gave rise to the formation of the submucosae and corrugator ani muscles by penetrating the IAS and EAS. In four of six specimens, striated muscle fibers from the EAS curled around the distal IAS reaching the anal submucosa. The ASC formed a complex structure, varying between individuals with an inconstant LM affecting the potential location of the intersphincteric plane as well as a high degree of intermingling striated and smooth muscle fibers potentially further disrupting the plane. The complexity of identifying the correct pathological staging of low rectal cancer is also demonstrated. Clin. Anat. 33:567-577, 2020. © 2019 Wiley Periodicals, Inc.

Internal anal sphincter injury in the immediate postpartum period; Prevalence, risk factors and diagnostic methods in the Swedish perineal laceration registry.

Risk factors for obstetric external anal sphincter injury are well known. Maternal and obstetric risk factors for internal anal sphincter injury are not extensively studied. The rationale of this study was to evaluate the proportion of internal anal sphincter injury in women with external anal sphincter injury, diagnosed immediately after delivery. This study will assess whether there are additional risks for obstetric internal anal sphincter injury. OBJECTIVES: The primary aim was to assess the proportion of internal anal sphincter injury immediately in women with an external sphincter injury and to evaluate maternal and obstetric risk factors for internal anal sphincter injury in women with an external anal sphincter injury only. A secondary aim was to relate the diagnostic methods used for obstetric perineal lacerations to the presence of an internal anal sphincter injury. STUDY DESIGN: A registry study with data from the Swedish Perineal Laceration Registry 2014-2018. From the registry, the maternal and obstetric characteristics of 3,333 primiparous women with isolated external (N = 2,236) versus both external and internal (N = 1,097) anal sphincter injuries were studied, as were the methods used for examining the obstetric anal sphincter injuries. RESULTS: In 32.9 % (1,097/3,333) of primiparous women with an external anal sphincter injury, an internal anal sphincter injury was diagnosed immediately after delivery. A perineal palpatory thickness of less than 10 mm was a diagnostic sign for internal sphincter injury. Well-known risk factors associated with obstetric anal sphincter injuries could not be confirmed as independent risk factors for internal sphincter injury. When the infant is born with an arm beside the head, there is an almost two-fold increased risk for internal sphincter injury. CONCLUSIONS: Our main finding is that 32.9 % of women with external anal sphincter injury also have an internal anal sphincter injury. A palpable perineal thickness of less than 10 mm, a degree 4-laceration and an infant born with a hand by the head increases the risk of internal sphincter injury and should be a clinical warning sign.

Drained mucosal advancement flap versus rerouting Seton around the internal anal sphincter in treatment of high trans-sphincteric anal fistula: A randomized trial.

BACKGROUND: Several sphincter saving techniques have been described for complex anal fistula (CAF) with variable outcomes. The present trial aimed to compare two techniques for CAF; the drained mucosal flap technique and rerouting Seton around the internal anal sphincter (IAS). METHODS: Adult patients with high trans-sphincteric anal fistula were randomly assigned to one of two groups: group I underwent mucosal advancement flap with drainage Seton rerouted around the external anal sphincter, and group II underwent rerouting Seton around the IAS. The two groups were compared in terms of the incidence of postoperative fecal incontinence (FI), healing of fistula, complications, and changes in anal pressures. RESULTS: 97 patients (80 male) of a mean age of 39.5 years were included. One patient developed FI in group I versus 7 in group II (p = 0.03). Failure of healing occurred in 2 patients in group I and 4 in group II (p = 0.43). In group II, the average time for spontaneous fall of Seton was 14 ± 2.8 days whereas in group I the average time for removal of Seton was 40 ± 14.9 days (p < 0.0001). There were no significant differences between the two groups in complication rate. Postoperatively, the decrease in resting anal pressure was significant in Group II but not group I. CONCLUSION: The drained mucosal flap technique was associated with significantly lower incidence of FI, yet longer operative time and longer time to complete healing compared to rerouting Seton around the IAS. The success rates of both techniques was comparable.

Botulinum toxin injections after surgery for Hirschsprung disease: Systematic review and meta-analysis.

BACKGROUND: A large proportion of patients with Hirschsprung disease experience persistent obstructive symptoms after corrective surgery. Persistent obstructive symptoms may result in faecal stasis that can develop into Hirschsprung-associated enterocolitis, a potential life-threatening condition. Important treatment to improve faecal passage is internal anal sphincter relaxation using botulinum toxin injections. AIM: To give an overview of all empirical evidence on the effectiveness of botulinum toxin injections in patients with Hirschsprung disease. METHODS: A systematic review and meta-analysis was done by searching PubMed, EMBASE and the Cochrane Library, using entry terms related to: (1) Hirschsprung disease; and (2) Botulinum toxin injections. 14 studies representing 278 patients met eligibility criteria. Data that were extracted were proportion of patients with improvement of obstructive symptoms or less enterocolitis after injection, proportion of patients with adverse effects and data on type botulinum toxin, mean dose, average age at first injection and patients with associated syndromes. Random-effects meta-analysis was used to aggregate effects and random-effects meta-regression was used to test for possible confounding factors. RESULTS: Botulinum toxin injections are effective in treating obstructive symptoms in on average 66% of patients [event rate (ER) = 0.66, P = 0.004, I 2 = 49.5, n = 278 patients]. Type of botulinum toxin, average dose, average age at first injections and proportion of patients with associated syndromes were not predictive for this effect. Mean 7 duration of improvement after one botulinum toxin injections was 6.4 mo and patients needed on average 2.6 procedures. There was a significant higher response rate within one month after botulinum toxin injections compared to more than one month after Botulinum toxin injections (ER = 0.79, vs ER = 0.46, Q = 19.37, P < 0.001). Botulinum toxin injections were not effective in treating enterocolitis (ER 0.58, P = 0.65, I 2 = 71.0, n = 52 patients). There were adverse effects in on average 17% of patients (ER = 0.17, P < 0.001, I 2 = 52.1, n = 187 patients), varying from temporary incontinence to mild anal pain. CONCLUSION: Findings from this systematic review and meta-analysis indicate that botulinum toxin injections are effective in treating obstructive symptoms and that adverse effects were present, but mild and temporary.

[Morphological characteristic of anal canal in patients with dyssynergic defecation and its correlation with anorectal manometry].

Objective: To evaluate the diagnostic value of three-dimensional endoanal ultrasound (3D-EAUS) for dyssynergic defecation (DD). Methods: A case-control study was performed to retrospectively collectclinical data of 46 DD patients, including 16 males and 30 females with median age of 51 (20 to 70) years, at Nanjing Hospital of Chinese Medicine from February 2012 to April 2015.All the patients met the diagnostic criteria of functional constipation of Rome III. The paradoxical contraction of puborectalis (PR) muscle was found by both rectal examination and anorectal manometry. In the same period,45 healthy volunteers, including 22 males and 23 females with median age of 48 (21 to 72) years, without pelvic operation history, and with normal defecation in recent 6 months, were enrolled as the control group. No significant differences were observed in age and gender between two groups (both P>0.05). Cleveland constipation score of DD group was higher than that of control group [15(8-24) vs. 5(1-9), t=15.720, P<0.001]. 3D-EAUS examination was performed in all the subjects. Thickness and length of internal anal sphincter (IAS) (anterior side and posterior side), thickness of PR muscle, length of external anal sphincter (EAS) plus PR muscle, and puborectalis angle were measured and compared by using student t test between two groups. Correlation between these ultrasound parameters and anorectal manometry was examined by Pearson correlation analysis. Results: Both male and female in the DD group had the greater thickness of IAS, as compared to those in the control group [male: (1.7±0.5) mm vs.(1.5±0.2) mm, t=2.516, P=0.016; female: (1.9±0.4) mm vs.(1.6±0.5) mm, t=2.034,P=0.047]. No significant differences between the two groups were observed with respect to the posterior length of IAS, length of EAS plus PR muscle, and thickness of PR muscle (all P>0.05). Compared to the control group, male in the DD group had smaller puborectalis angle during straining [(87.0±3.6)° vs. (90.5±1.8)°,t=3.502,P=0.002];female in the DD group had smaller puborectalis angle both in resting and straining [resting:(86.5±3.8)° vs. (90.1±2.1)°,t=4.047, P<0.001;straining: (84.1±4.5)° vs. (90.2±2.3)°, t=5.938, P<0.001]. Correlation analysis showed that anterior length of IAS was positively correlated with anal resting pressure (r=0.321, P=0.030); the length of EAS plus PR muscle was positively correlated with anal squeeze pressure (r=0.415, P=0.004). There were no correlations between the thickness and the posterior length of IAS and the anal resting pressure, or between the thickness of PR muscle and the anal squeeze pressure (all P>0.05). Conclusions: The 3D-EAUS can accurately assess the morphological features of anal canal in DD patients. There is a certain positive correlation between 3D-EAUS and anorectal manometry.