Combined treatment of achalasia – botulinum toxin injection followed by pneumatic dilatation: long‐term results

Injection of botulinum toxin (BT) and pneumatic dilatation are available methods in nonsurgical treatment of achalasia. Authors anticipate beneficial effect of prior BT injection on the success of pneumatic dilatation and duration of its effect. There are no long‐term data available to assess efficacy of combined treatment. From 1998 to 2007, 51 consecutive patients (20 men and 31 women, age 24–83) with achalasia were included and prospectively followed up. Each patient received injection of 200 IU of BT into the lower esophageal sphincter (LES) during endoscopy and 8 days later pneumatic dilatation (PD) under X‐ray control was performed. The follow‐up was established every 3 months first year and then annually. The efficacy was evaluated by a questionnaire concerning patient's symptoms and manometry. Results were compared with 40 historical controls (16 men and 24 women, age 26–80) treated by PD alone using the same method and follow‐up. Fifty‐one patients underwent combined treatment. Four patients failed in follow‐up and were not included for analysis. The mean duration of follow‐up was 48 months with range 12–96 months. Thirty‐four of forty‐seven (72%) patients were satisfied with results with none or very rare and mild troubles at the time of the last visit. Forty‐one patients were followed up more than 2 years. Effect of therapy lasted in 75% (31/41) of them. In 17 patients, more than 5 years after treatment, effect lasted in 12 (70%). Mean tonus of LES before therapy was 29 mm Hg (10–80), 3 months after therapy decreased to 14 mmHg (5–26). The cumulative 5 years remission rate (±95% CI) in combined treated patients 69% ± 8% was higher than in controls 50% ± 9%; however it, was not statistically significant (P= 0.07). In control group 1, case of perforation (2.5%) occurred. Eight patients (17%) with relapse of dysphagia were referred to laparoscopic Heller myotomy with no surgical complication. The main adverse effect was heartburn that appeared in 17 patients (36%). Initial injection of BT followed by PD seems to be effective for long‐term results with fewer complications. But the combined therapy is not significantly superior to PD alone.     

Endoscopic botulinum toxin injection into the minor papilla for treatment of idiopathic recurrent pancreatitis in patients with pancreas divisum.

BACKGROUND: In some patients with pancreas divisum, obstruction to the flow of pancreatic juice into the duodenum is the presumptive cause of acute recurrent pancreatitis. However, identification of those patients who may benefit from minor papilla sphincterotomy or stent placement is difficult. METHODS: Five patients with acute recurrent pancreatitis and pancreas divisum were therefore treated by endoscopic injection of 50 units of botulinum toxin into the minor papilla in an outpatient setting. RESULTS: Botulinum toxin injection was successfully performed on six occasions in 5 patients and no adverse effects were noted. Two patients relapsed after 9 and 10 months, respectively, but had definite relief of symptoms after needle-knife sphincterotomy. One patient relapsed 7 months after botulinum toxin injection but became symptom free again after a second botulinum toxin injection. Another patient is still in clinical remission 4 months after botulinum toxin administration, and 1 patient did not respond to either botulinum toxin administration or to sphincterotomy and stent placement. CONCLUSIONS: Endoscopic injection of botulinum toxin into the minor papilla in patients with pancreas divisum and acute recurrent pancreatitis is a safe procedure that is easy to perform and provides short-term relief in some patients. Response to botulinum toxin injection may predict whether patients with pancreas divisum and acute recurrent pancreatitis will benefit from other forms of endoscopic therapy.     

Long-term follow-up of achalasia patients treated with botulinum toxin

AIMS: To evaluate long-term efficacy of intrasphincteric injection of botulinum toxin in untreated achalasia patients; to analyse whether age can be a predictor of response; and to verify whether any objective measurements correlate with symptom relief MATERIALS AND METHODS: A total of 37 patients (mean age 61.4+/-17.5 years) were enrolled, all of whom injected endoscopically with 100 U of botulinum toxin. Symptom score, oesophageal manometry and oesophageal radionuclide emptying were assessed prior to treatment and 4 weeks, 3 months and 1 year after botulinum toxin. In the case of failure or relapse (symptom score >2), treatment was repeated. RESULTS: All but 6 patients (83.7%) were in clinical remission one month after botulinum toxin. At 12 months, mean symptom score was 0.9+/-0.5 (p<0.05 vs basal); mean lower oesophageal sphincter pressure was 22.0+/-6.3 (p<0.05 vs basal), and 10-min radionuclide retention was 14.0%+/-7.2 (p<0.05 vs basal). Of the 35 patients followed, 12 (34.3%) had a relapse and were re-treated; 4 out of 12 did not respond after re-treatment. Efficacy of first injection of botulinum toxin lasted for a mean period of 15.6 months (range 2-30). Up to day 31 (83.7%) patients were still in remission. We observed a trend towards a better response to botulinum toxin treatment in patients over 50 years (p=0.053). Moreover no correlation was found between any objective achalasia measurements and symptom relief (r coefficient between 0.1 and 0.5) CONCLUSIONS: Results show that: 1) one or two intrasphincteric injections of botulinum toxin result in clinical and objective improvement in about 84% of achalasia patients and are not associated with serious side-effects; 2) patients over 50 years showed better benefit than younger patients; 3) no correlation was found between any objective measurements and symptom relief.     

Long-term follow-up (42 months) of chronic anal fissure after healing with botulinum toxin

BACKGROUND & AIMS: Botulinum toxin is an effective treatment in idiopathic chronic anal fissure, but the long-term outcome after healing is not well documented. We analyzed the long-term outcome of patients in whom an anal fissure had healed after botulinum toxin injection and the factors contributing to recurrence. METHODS: Fifty-seven patients who had completely healed 6 months after injection of botulinum toxin were reassessed every 6 months. The follow-up was 42 months in all patients. Clinical and manometric differences between the permanently healed and the relapsed group were statistically analyzed. RESULTS: Four patients were lost to follow-up. A fissure recurrence was shown in 22 patients (41.5%). Statistical differences between the permanently healed and the relapsed group were detected when analyzing the anterior location of the fissure (6% vs. 45%), a longer duration of the disease (38% vs. 68%), the need for reinjection (26% vs. 59%), a higher total dose injected to achieve definitive healing (13% vs. 45%), and the percentage decrease of maximum squeeze pressure after injection (-28% vs. -13%; P < 0.05). CONCLUSIONS: The late recurrence rate of chronic anal fissure is high when the effect of botulinum toxin disappears. The highest risk of recurrence is associated with anterior location of the anal fissure, prolonged illness, the need for reinjection and for high doses to achieve healing, and a lower decrease of maximum squeeze pressure after treatment.     

内镜下注射肉毒毒素治疗贲门失弛缓症的研究

将48例贲门失弛缓症患者随机分为两组，A组注射肉毒毒素治疗，B组用小气囊扩张治疗。分别于治疗后1周、3个月和1年比较两组患者的临床症状积分、下食管插约肌的压力（LESP）、松弛率（LESRR）。结果：治疗后1周、3个月和1年的有效率及治疗前后LESP、LESRR的差值，注射肉毒毒素组均高于小气囊扩张组；两组均无并发症发生。认为内镜下食管下括约肌内注射肉毒毒素治疗贲门失弛缓症的近期疗效高，且患者痛苦小。     

Long-term efficacy of Botulinum toxin in classical achalasia: a prospective study

OBJECTIVE: We sought to examine the long-term efficacy of intrasphincteric Botulinum toxin A injection in a prospective cohort study of 30 patients with achalasia. METHODS: Thirty patients with classical achalasia were treated with intrasphincteric Botulinum toxin A injection. Follow-up consisted of clinical assessment, symptom scoring, and postinjection manometry. RESULTS: Symptomatic improvement for >3 months was seen in 23 of 30 patients (77%). Of the 23 initial responders, seven (30%) experienced a sustained symptomatic response after a single Botulinum toxin injection (mean follow-up, 21 months). The remaining 16 initial responders (70%) eventually relapsed (mean initial response, 11 months). Nine received a 2nd Botulinum toxin injection, and seven experienced an ongoing response (mean duration, 9 months); two patients eventually required a 3rd injection with good effect (mean duration, 22 months). The remaining seven patients who relapsed after Botulinum toxin opted for pneumatic dilation or surgical myotomy. Five of the seven patients who had no initial response received a 2nd injection but again did not respond. A residual lower esophageal sphincter pressure <18 mm Hg after the first Botulinum toxin injection predicted a good response to Botulinum therapy (single or multiple injections, p < 0.002, positive predictive value = 0.71, negative predictive value = 1.0). Neither initial nor sustained response to Botulinum toxin could be predicted based on gender, age, duration of illness, previous pneumatic dilation, or esophageal motility before treatment. CONCLUSIONS: We found that 77% of patients with classical achalasia experienced a good symptomatic response after Botulinum toxin and 30% of initial responders achieve sustained symptomatic relief after a single treatment with Botulinum toxin. The initial responders who relapsed did well with subsequent Botulinum toxin A. Lack of an initial symptomatic response and residual lower esophageal sphincter pressure > or =18 mm Hg after Botulinum toxin are associated with a poor response.     

气囊扩张与肉毒毒素注射联合治疗贲门失弛缓症的临床研究

目的：比较单纯小气囊扩张、单纯肉毒毒素(BT)注射和两者联合治疗贲门失弛缓症的疗效与副作用。方法：48例患者随机被分为3组：扩张组只用小气囊扩张治疗；注射组只注射BT治疗；联合组两种方法联合应用。分别于术前，治疗后1周、3个月和1年时比较3组患者的临床症状积分(有效率)、下食管括约肌的压力(LESP)、松弛率(LESRR)。结果：在治疗后1周、3个月和1年时，有效率及治疗前后LESP和LESRR的差值，联合组和注射组该3项指标均高于扩张组；在治疗后l周和3个月时，联合组与注射组相比无明显差异；但1年时，联合组高于注射组。3组均无并发症发生。结论：小气囊扩张术与下食管括约肌内注射BT联合治疗贲门失弛缓症，具有疗效高、持续时间长、患者痛苦小等优点。值得临床上推广应用。     

Endoscopic approach to achalasia

Achalasia is a primary esophageal motor disorder. The etiology is still unknown and therefore all treatment options are strictly palliative with the intention to weaken the lower esophageal sphincter (LES). Current established endoscopic therapeutic options include pneumatic dilation (PD) or botulinum toxin injection. Both treatment approaches have an excellent symptomatic short term effect, and lead to a reduction of LES pressure. However, the long term success of botulinum toxin (BT) injection is poor with symptom recurrence in more than 50% of the patients after 12 mo and in nearly 100% of the patients after 24 mo, which commonly requires repeat injections. In contrast, after a single PD 40%-60% of the patients remain asymptomatic for ≥ 10 years. Repeated on demand PD might become necessary and long term remission can be achieved with this approach in up to 90% of these patients. The main positive predictors for a symptomatic response to PD are an age > 40 years, a LES-pressure reduction to < 15 mmHg and/ or an improved radiological esophageal clearance post-PD. However PD has a significant risk for esophageal perforation, which occurs in about 2%-3% of cases. In randomized, controlled studies BT injection was inferior to PD and surgical cardiomyotomy, whereas the efficacy of PD, in patients > 40 years, was nearlyequivalent to surgery. A new promising technique might be peroral endoscopic myotomy, although long term results are needed and practicability as well as safety issues must be considered. Treatment with a temporary self expanding stent has been reported with favorable outcomes, but the data are all from one study group and must be confirmed by others before definite recommendations can be made. In addition to its use as a therapeutic tool, endoscopy also plays an important role in the diagnosis and surveillance of patients with achalasia.     

Controlled trial of botulinum toxin injection versus placebo and pneumatic dilation in achalasia

BACKGROUND & AIMS: Intrasphincteric injection of botulinum toxin has been suggested as an alternative treatment modality in esophageal achalasia. A controlled trial comparing botulinum toxin, placebo, and pneumatic dilation is reported. METHODS: Sixteen patients received random intrasphincteric injections of either botulinum toxin or saline. The efficacy of treatment was assessed by symptom score, esophageal manometry, and scintigraphy. In case of failure, pneumatic dilation was performed. RESULTS: One month after injection, symptoms had improved in all patients treated with botulinum toxin (symptom score, 0.9 +/- 0.6 vs. 5.5 +/- 1.4; P < 0.02). In the placebo group, symptoms were unchanged in all patients, who were all dilated. Lower esophageal sphincter pressure decreased by 49% after treatment with botulinum toxin (P < 0.03) and by 72% after dilation (P < 0.01). Similarly, esophageal retention decreased by 47% after treatment with botulinum toxin (P < 0.02) and by 59% after dilation (P < 0.02). No significant difference in symptom score and esophageal function test results was found between patients treated with botulinum toxin injections and those undergoing dilation. However, 7 of the 8 patients in the botulinum toxin group required a second injection because of recurrent dysphagia. CONCLUSIONS: Treatment of achalasia with botulinum toxin was as effective as pneumatic dilation in relieving symptoms and improving esophageal function. The effect of the first injection was temporary, but the effect of the second injection lasted longer. (Gastroenterology 1996 Dec;111(6):1418-24)     

Botulinum toxin versus pneumatic dilatation in the treatment of achalasia: a randomised trial

Background—Intrasphinctericinjection of botulinum toxin is a new treatment option for achalasia.
Aims—To compare the immediate andlong term efficacy of botulinum toxin with that of pneumatic dilatation.
Methods—Symptomatic patients withachalasia were randomised to botulinum toxin (22 patients, median age57 years) or pneumatic dilatation (20 patients, median age 56 years).Symptom scores were assessed initially, and at one, three, six, nine,and 12months after treatment. Objective assessment includedoesophageal manometry initially and at one month, and bariumoesophagram initially and at one, six, and 12 months post-treatment.
Results—Pneumatic dilatationresulted in a significantly (p=0.02) higher cumulative remission rate.At 12 months, 14/20 (70%) pneumatic dilatation and 7/22 (32%)botulinum toxin treated patients were in symptomatic remission(p=0.017). Failure rates were similar initially, but failure over timewas significantly (p=0.01) higher after botulinum toxin (50%) thanpneumatic dilatation (7%). Pneumatic dilatation resulted insignificant (p<0.001) reduction in symptom scores, and loweroesophageal sphincter pressure, oesophageal barium column height, andoesophageal diameter. Botulinum toxin produced significant reduction insymptom scores (p<0.001), but no reduction in objective parameters.
Conclusions—At one year pneumaticdilatation is more effective than botulinum toxin. Symptom improvementparallels objective oesophageal measurements after pneumatic dilatationbut not after botulinum toxin treatment for achalasia.

Keywords:achalasia; pneumatic dilatation; botulinum toxin; barium oesophagram

     

Achalasia: outcome of patients treated with intrasphincteric injection of botulinum toxin.

BACKGROUND: To evaluate the safety and clinical efficacy of botulinum toxin (BT) in patients with achalasia followed up for six months. METHODS: Fifty five symptomatic patients with manometrically proven achalasia were included in a multicentre prospective trial. Before and two weeks and two months after intrasphincteric injection of BT, symptoms of dysphagia, regurgitation, and chest pain were scored on a 0-3 scale, and lower oesophageal sphincter pressure (LOSP) was assessed. The symptom score was determined again at six months, clinical improvement being defined by < or = 3, relapse by > 3, and failure as a relapse after two injections or loss to follow up. RESULTS: Except for transient chest or epigastric pain (22%), no side effects were observed. There was a significant decrease in LOSP after treatment. Symptom scores were significantly improved at two weeks (2.0 (SD 1.6)), two months (1.7 (1.8)), and six months (1.9 (2.0)) compared with pretreatment values (5.1 (1.8), p < 0.001). At six months, 33 patients had clinical improvement (27 after one injection), 17 were considered failures, and five had just relapsed. Although there was a trend for age (older patients being more responsive), age, sex, prior duration of symptoms, initial symptom score, weight loss, LOSP, magnitude of oesophageal contractions, vigorous or non-vigorous achalasia, previous dilatations, and radiological features were not predictive of results. CONCLUSIONS: This multicentre series confirms that intrasphincteric injection of BT is a safe procedure, resulting in clinical improvement in 60% of patients with achalasia at six months. The therapeutic role of BT in achalasia needs further evaluation with regard to other alternatives.     

Treatment of chest pain in patients with noncardiac,nonreflux, nonachalasia spastic esophageal motor disorders using botulinum toxin injection into the gastroesophageal junction

OBJECTIVE: The aim of this study was to determine if botulinum toxin injection in the gastroesophageal junction improves symptoms in patients with noncardiac chest pain with a spastic esophageal motility disorder. METHODS: Twenty-nine noncardiac chest pain patients with nonachalasia, nonreflux-related spastic esophageal motility disorders were enrolled in this open label trial of botulinum toxin injection at the gastroesophageal junction. Chest pain was the major complaint in all patients. Symptoms of chest pain, dysphagia, regurgitation, and heartburn were scored before and 1 month after botulinum toxin injection. A response to botulinum toxin was defined as at least a 50% reduction in the symptom score with a possible total chest pain score of 4. The duration of response was defined as the time period, between the time of injection and the point in time, at which the severity of the symptoms returned to the preinjection score. RESULTS: Seventy-two percent of the patients responded with at least 50% reduction in chest pain. In these responders, there was a 79% reduction in the mean chest pain score from a preinjection score of 3.7 to a postinjection score of 0.78 (p < 0.0001). The mean duration of the response for chest pain in these patients was 7.3+/-4.1 months (range 1-18 months). There was also a significant reduction in the mean regurgitation score, dysphagia score, and total symptom score (p < 0.0001). CONCLUSIONS: Botulinum toxin injection at the gastroesophageal junction leads to significant symptomatic improvement in patients with spastic esophageal motility disorders whose major complaint is chest pain.     

Therapeutic effects of different doses of botulinum toxin in chronic anal fissure

PURPOSE: The aim of this study was to evaluate the clinical and manometric results of three different doses of botulinum toxin and two methods of injection for the treatment of chronic idiopathic anal fissure. METHODS: Sixty-nine patients with chronic anal fissure were included in a non-randomized, prospective trial of intrasphincteric injection of botulinum toxin. All patients reported postdefecatory anal pain lasting more than two months. Scoring systems were developed for anal pain, bleeding, and defecatory difficulty. Maximum resting and squeeze anal pressures were determined before and one month after treatment. Twenty-three patients undergoing a 5-U injection of diluted botulinum toxin A (BOTOX) on each side of the anal sphincter (total dose, 10 U) constituted the first group. In a second group 27 patients were injected as previously described, with an additional 5-U injection below the fissure (total dose, 15 U). The 19 patients constituting the third group received a 7-U injection on each side of the anus and below the fissure (total dose, 21 U). All patients were followed up for at least six months. RESULTS: Pain relief one month after treatment was more evident in the second and the third group (48 percent of patients in the first group, 74 percent in the second group, and 100 percent in the third group). A significant reduction of the mean resting pressure was demonstrated only in Groups II and III (P < 0.05), whereas the mean squeeze pressure significantly decreased in the three groups (P < 0.01 in Group I and P < 0.001 in Groups II and III). Fifty-two percent of the patients in the first group, 30 percent in the second group, and 37 percent in the third group were reinjected during the follow-up period, because of persistence of symptomatology or early relapse. The need for surgery was similar in the first and the second group (17 and 19 percent, respectively) and clearly lower in the last group (5 percent). No serious complications or incontinence attributable to this therapeutic modality developed in any patient. CONCLUSIONS: Intrasphincteric injection of botulinum toxin is a reliable new option in the treatment of uncomplicated chronic anal fissure. The healing rate is related to the dose and probably to the number of puncture sites. No permanent damage to the continence mechanism was detected in these patients.     

Treatment of patients with achalasia with botulinum toxin: a multicenter prospective cohort study

Botulinum toxin (BT) injection is an alternative treatment of achalasia. The aim of the study was to examine outcomes of patients treated with BT in the Czech Republic. Since 1997, 49 patients with achalasia have been treated with BT. We prospectively evaluated the effect of BT injection on 41 patients during a median follow-up of 24 months (range 9-62). Esophageal manometry was performed before and at 3-5 months after the injection. In 16 patients, BT was injected from the antegrade angle only (subgroup A), in 15 patients, BT was injected from both retrograde and antegrade angles (subgroup B) and, in 10 patients, BT injection was combined with subsequent balloon dilatation (subgroup C). Immediate clinical response was achieved in 93% of patients. Clinical remission was sustained beyond 3 months in 83% of patients (responders). Fourteen responders (41%) did not experience a relapse during the median of 22 months. Twenty responders (59%) experienced symptomatic relapse approximately 8 months after the injection. Ten relapsers underwent BT reinjection, five (50%) of them were asymptomatic for another 14 months. The remaining five (50%) patients reported a second relapse approximately 6 months after the reinjection. Median duration of the symptom-free period was 11.5 months after the first BT injection, and 10.5 months after the second (P = 0.21). We did not find any significant predictor of a favorable outcome; responders tended to be older and to have a lower basal lower-esophageal-sphincter pressure. Patients in subgroup C were more likely to be in remission at 1 and 2 years as compared with patients in subgroup A. BT injection is an effective treatment of achalasia in the short term. However, almost 70% of patients experience a relapse within 2 years. BT injection should therefore be reserved for patients at risk for more invasive procedures or for patients who prefer this treatment.     

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 representing278 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 associatedsyndromes. 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, I2 = 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 was6.4 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, I2 = 71.0, n = 52 patients). There were adverse effects in on average 17% of patients(ER = 0.17, P 0.001, I2 = 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.     

Pneumatic dilation versus intrasphincteric botulinum toxin injection in the treatment of achalasia cardia in India: an economic analysis.

BACKGROUND: Pneumatic dilation (PD) is an established therapeutic option for achalasia cardia. Recently, intrasphincteric botulinum toxin (BT) has been used to treat achalasia cardia in view of its simplicity and safety. However, it is likely to be a costly treatment as repeated injections are often needed due to its short-lasting effect. No economic analysis of PD and BT strategies has been done in India. METHODS: A decision tree was constructed using decision analysis software (DATA 4.0; TreeAge Software, Williamstown, MA, USA). Probability estimates for BT injection and PD (and, in case of failure, surgery) were obtained from published literature, preferably from India. Direct "out-of-pocket" costs (in Indian rupees; currently US$ 1 = 49 rupees approximately) for baseline analysis were obtained from our hospital and from some private hospitals. Sensitivity analysis was done using a wide range of probability and cost estimates. RESULTS: Intrasphincteric BT injection strategy was more costly at 18,520 rupees per patient than PD strategy (4,568 rupees), yielding an incremental cost of 13,952 rupees per patient successfully treated. Sensitivity analysis supported the conclusions of the baseline analysis. CONCLUSION: Primary intrasphincteric BT injection strategy was costlier than primary PD strategy in the treatment of achalasia cardia in India, and therefore cannot be justified despite its efficacy, relative ease of administration and safety.     

Role of rectal biopsy in predicting response to intrasphincteric botulinum toxin injection for obstructive symptoms after a pullthrough operation

Objective: Our aim was to correlate the pathological results and clinical response in patients who underwent botulinum toxin (BT) injection for obstructive symptoms (OS) after a pullthrough operation for Hirschsprung's disease (HD). Methods: Between August 2002 and February 2006, 16 of 107 HD patients (15%) were referred with persistent OS after pull-through (PT) operation in this center. They underwent rectal biopsy and BT injection in the internal sphincter. Their responses to BT injection were evaluated by the constipation score before, and at 1, 3 and 8 months after the injection, and anorectal manometry (ARM) before and at 2 weeks, and 1 and 8 months after the injection. The association between response to BT and acetylcholinesterase (AChE) staining of rectal biopsy was also assessed. Results: Fourteen of 16 patients (87%) had improvement in bowel function after 2 weeks, and two patients did not respond at all. Six of the 14 patients with early response had recurrence of symptoms after 2-3 months. Eight patients with normal ganglia and negative AChE had good response with no recurrence on follow-up. However, 4 of 6 recurrences were neurogenic dysfunctions and 2 were intestinal neuronal dysplasia (2-4+AChE). Two patients with no response had an aganglionic segment (4+AChE). Four of 6 patients with recurrence showed improvement with BT re-injection and only 2 did not improve. Conclusion: A higher degree of AChE staining is associated with lack of response to BT injection. This is also a test for predicting the severity of neurogenic dysfunction in the intestinal wall.     

Comparison of Botulinum Toxin Injection and Lateral Internal Sphincterotomy for the Treatment of Chronic Anal Fissure

PURPOSE: Botulinum toxin injection into the internal anal sphincter has been shown to be an effective treatment for chronic anal fissure. A randomized, prospective trial was conducted to compare botulinum toxin with lateral internal anal sphincterotomy as definitive management for chronic anal fissure. METHODS: Patients diagnosed as having chronic anal fissure were randomly assigned to one of the two treatment arms. In the botulinum toxin group (n = 61), 20 to 30 U (approximately 0.3 U/kg) of type A botulinum toxin (Botox®) was injected into the internal anal sphincter. The injection was repeated two months later if complete healing was not accomplished. Patients in the sphincterotomy group (n = 50) underwent lateral internal anal sphincterotomy. The same investigators evaluated the patients on postoperative/postinjection days 7 and 28, and then in a blinded manner at 2, 6, and 12 months. RESULTS: In the botulinum group, single injection resulted in complete healing in 45 of the 61 patients (73.8 percent) at the second month. Of the 16 failures, 6 patients refused further treatment, and 10 were treated with a second injection, which resulted in an overall healing rate of 86.9 percent (53/61) at 6 months. In the sphincterotomy group, the success rate was 82 percent (41/50) at day 28 and 98 percent (49/50) at the second month (P = 0.023 and P < 0.0001, respectively, compared with the botulinum group—single injection). At 6 months, 2 patients in the LIS group developed recurrences, and the healing rate was similar to that of the botulinum group (86.9 vs. 96.4 percent; P = 0.212). At 12 months, the success rate of the Botox® group fell to 75.4 percent (46/61) with 7 recurrences, whereas it remained stable in the sphincterotomy group (94 percent, P = 0.008). Sphincterotomy was associated with a significantly higher complication rate (8 cases of anal incontinence vs. none in the botulinum toxin group; P < 0.001). Full return to daily activities took significantly less time in the botulinum group (1 vs. 14.8 ± 5.7 days; P < 0.0001). CONCLUSION: Although the healing rate of chronic anal fissure is considerably high with botulinum toxin injection with earlier recovery and less complications compared with sphincterotomy, it occasionally requires a repeat injection, and the healing is slower. The early (two months) and late (one year) healing rates are significantly higher in the sphincterotomy group, the two groups reaching similar healing rates only at six months.     

Antithyroid drugs and Graves' disease: a prospective randomized evaluation of the efficacy of treatment duration.

A prospective randomized study was performed in patients with hyperthyroid Graves' disease (GD) in order to compare long (18 months) and short term (6 months) antithyroid drug treatment on the remission rate. A therapeutic protocol was offered to all GD patients who had not been treated for this disease previously. All patients studied who followed the protocol were rechecked 2 yr after treatment was withdrawn, or earlier in the case of relapse. Of the patients having undergone long term treatment, 61.8% still were in remission 2 yr after treatment withdrawal, whereas only 41.7% of the patients treated for 6 months were in remission (P less than 0.05). Such findings clearly establish that treatment duration has a direct beneficial incidence on the remission rate. These results were confirmed by the fact that treatment for 18 months resulted in remission in 7 of 15 patients who had previously relapsed after a 6-month course of therapy. This improvement in relation to treatment duration might be due to the immunosuppressive action of carbimazole. No significant difference was observed between relapse and remission groups, regardless of treatment duration, for HLA ABDr, serum T3 and T4, and T3/T4 ratio determined before treatment. Only the thyroid-stimulating antibody levels determined at the time of diagnosis and at the end of treatment were higher in the relapse group, a difference that was relevant only globally, due to value scattering. Furthermore, thyroid-stimulating antibody levels at the end of treatment may indicate remission or, conversely, continuance of the pathological process.(ABSTRACT TRUNCATED AT 250 WORDS)     

Achalasia treatment in the elderly: is botulinum toxin injection the best option?

BACKGROUND : Achalasia treatment in elderly patients is a matter of controversy. Botulinum toxin injection has been proposed as the best option in this group of patients as it is a safe procedure. However, concern persists regarding its short-term effect. AIMS : To analyse the clinical and economic effectiveness of botulinum toxin injection in the treatment of achalasia patients who are elderly. METHODS : Seventeen consecutive achalasia patients older than 65 years were treated with 80 units of botulinum toxin. Clinical follow-up at 1, 6 and 12 months was performed. Control manometry when symptoms recurred was carried out. Results were compared with those of an historical control group of 16 achalasia patients also older than 65 years and who had been treated with endoscopic dilation. The costs of both procedures were compared. RESULTS : Twenty-nine botulinum toxin injections were performed in the 17 patients of the botulinum toxin group (follow-up, 12-36 months). In the dilation group only two patients had to be retreated (follow-up, 12-108 months). No major complications were observed in either group. The average duration of symptom alleviation was 48 +/- 33 months for endoscopic dilation and 13.8 +/- 9.5 months for botulinum toxin injection. Maintaining a patient free of symptoms cost E348.31 per year for botulinum toxin injection, whilst if endoscopic dilation was chosen the cost was only E117.47 per year. CONCLUSIONS : The effect of botulinum toxin injections wanes with time in elderly patients, necessitating repeated injections to keep the patients symptom-free. Due to the required repeated injections this procedure is more expensive than endoscopic dilation.