Michela Costantino

Randomized controlled trial of botulinum toxin versus laparoscopic heller myotomy for esophageal achalasia

Objective:To compare laparoscopic cardia myotomy and fundoplication with botulinum toxin (BoTx) injection in patients with esophageal achalasia. Summary Background Data:Although myotomy is thought to offer better results, recent studies have reported 80% success rates after 2 BoTx injections a month apart. No randomized controlled trials comparing the 2 treatments have been published so far. Materials and Methods:Newly diagnosed achalasia patients were randomly assigned to BoTx injection or laparoscopic myotomy. Symptoms were scored; lower esophageal sphincter resting and nadir pressures were measured by manometry; barium swallow was used to assess esophageal diameter pre- and post-treatment. Eight to one hundred units of BoTx were injected twice, a month apart, at the esophagogastric junction. Myotomy included anterior partial (Dor) or Nissen fundoplication. Results:Eighty patients were involved in the study: 40 received BoTx and 40 underwent myotomy. Mortality was nil. One surgical patient bled from the trocar site. Median hospital stay was 6 days for surgery; BoTox patients were treated as day-hospital admissions. All patients completed the follow-up. After 6 months, the results in the 2 groups were comparable, although symptom scores improved more in surgical patients (82% confidence interval [CI] 76–89 vs. 66% CI 57–75, P < 0.05). The drop in lower esophageal sphincter pressure was similar in the 2 groups; the reduction in esophageal diameter was greater after surgery (19% CI 13–26 vs. 5% CI 2–11, P < 0.05). Later on, symptoms recurred in 65% of the BoTx-treated patients and the probability of being symptom-free at 2 years was 87.5% after surgery and 34% after BoTx (P < 0.05). Conclusion:Laparoscopic myotomy is as safe as BoTx treatment and is a 1-shot treatment that cures achalasia in most patients. BoTx should be reserved for patients who are unfit for surgery or as a bridge to more effective therapies, such as surgery or endoscopic dilation.

Etiology, Diagnosis, and Treatment of Failures After Laparoscopic Heller Myotomy for Achalasia

ObjectiveTo assess the causes of failure of laparoscopic Heller myotomy and to verify whether endoscopic pneumatic dilation is a feasible treatment.Summary Background DataLaparoscopic Heller myotomy has proved an effective treatment for esophageal achalasia, with good or excellent results in 90% of

The role of botulinum toxin injection and upper esophageal sphincter myotomy in treating oropharyngeal dysphagia.

The aims of this study were to assess the efficacy and safety of botulinum toxin (BoTox) injection in the cricopharyngeus muscle (CP) and CP myotomy in patients with oropharyngeal dysphagia (OPD) and to identify factors predicting the outcome of these treatments. The study involved patients with persistent OPD despite 2–6 months of rehabilitation, who all underwent clinical evaluation, esophageal manometry, upper gastrointestinal endoscopy, and videofluoroscopy (VFS). Patients received 5–10 BoTox units injections in the CP, identified by electromyography. Surgical myotomy of the upper esophageal sphincter was performed when dysphagia persisted after two BoTox injections. After treatment, patients were reevaluated with clinical interviews and VFS. The study population included 21 patients (15 mean and 6 women; median age, 68 years), classified into three groups, based on the etiology of their OPD: eight (38%) had central nervous system abnormalities, five (24%) had peripheral nerve disease, and eight (38%) were classified as idiopathic. The median time since the onset of dysphagia was 18 months. Thirteen of 21 patients (62%) needed supplemental/total gastrostomy feeding, and 5 of 21 (24%) had tracheostomy. One patient died, on posttreatment day 7, due to massive aspiration. No other BoTox-related complications were observed. After BoTox injection, dysphagia improved in 9 of 21 (43%) patients. Severely altered VFS findings and CP incoordination or low activity predicted BoTox failure at multivariate analysis. Dysphagia improved in 8 of 11 (72.7%) patients who failed to respond to BoTox and underwent myotomy. A mild impairment of VFS findings and a higher pressure of pharyngeal contractions best predicted response to BoTox with or without myotomy. BoTox injection can be used as the first therapeutic option in patients with OPD: it is safe and simple and relieves dysphagia in 43% of cases. If BoTox fails, CP myotomy can be offered to patients with preserved oral and tongue activity at VFS and an intact bolus propulsion ability on manometry.

Tailored approach to Zenker's diverticula.

Background: Zenkers diverticula (ZD) can be treated by diverticulostomy or open surgery (upper esophageal sphincter myotomy and diverticulectomy or diverticulopexy). The aim of this study was to compare the outcome of the two alternative treatments. Methods: Fifty eight patients were scored for symptoms and upper esophageal sphincter (UES) pressure; relaxations and intrabolus pressures were recorded by manometry. Treatment depended on operative risk and ZD size. Twenty four patients with high surgical risk and/or a <3-CM OR >5-cm pouch underwent diverticulostomy; the other 34 had open surgery. Results: Mortality was nil. Five patients had postoperative complications after open surgery (plt;0.05). Hospital stay was shorter after diverticulostomy (p<0.001). Follow-up (41 months; range, 1–101) was obtained in 53 patients. Postoperative manometry showed a UES pressure reduction, improved UES relaxation, and lower intrabolus pressure in both groups (p<0.05). In the diverticulostomy group, three patients complained of severe dysphagia. vs none in the open surgery group (p<0.05). Conclusion: Diverticulostomy is safe, quick, and effective for most patients with medium-sized ZD, but open surgery offers better long-term results and should be recommended for younger, healthy patients with small or very large diverticula.

Esophageal achalasia: Is the herpes simplex virus really innocent?☆

This study was designed to test the hypothesis that mononuclear cells in the myenteric plexus of patients with achalasia may be activated by herpes simplex virus type 1 (HSV-1). Strips of esophageal muscle were obtained from patients with achalasia and multiorgan transplant donors who served as control subjects. After muscle digestion, mononuclear cells were purified through a Percoll gradient and cultured in medium, either alone or containing ultraviolet-inactivated HSV-1 or poliovirus (multiplicity of infection 1:1.5). As an indicator of HSV-1-induced lymphocyte activation, we determined T-cell proliferation by means of 3H-thymidine incorporation and interferon gamma release. DNA was extracted from esophageal muscle of achalasia patients and control subjects, and used as a template for PCR analysis using primer pairs specific for HSV-1. Circulating anti-HSV-1 and HSV-2 antibodies were detected by enzymelinked immunosorbent assay on serum samples. Fifteen patients with naive achalasia and eight control subjects were studied. The prevalence of circulating anti-HSV-1 and HSV-2 antibodies proved similar in the two groups, and no HSV-1 DNA was detected by polyermase chain reaction in the esophageal muscle samples. The proliferative index in mononuclear cells from achalasia patients stimulated with HSV-1 showed a 3.4-fold increase in comparison with control subjects (P < 0.01). In addition, a 1.4-fold increase in interferon gamma release after incubation with HSV-1 was observed in cells from achalasia patients but not control subjects. The results of this study indicate that HSV-1-reactive immune cells are present in lower esophageal sphincter muscles of patients with achalasia. We hypothesize that the HSV-1-reactive lymphocytes in lower esophageal sphincter muscles of achalasia patients may contribute to damage of the neurons in the myenteric plexus and lead to the motor dysfunction.

Minimally invasive surgery for esophageal achalasia.

BACKGROUND Esophageal achalasia is characterized by loss of peristaltic activity and failure of relaxation of the lower esophageal sphincter (LES). The characteristic dysphagia may be alleviated by surgery, dilations, or botulinum toxin injections. Video-endoscopic surgery is used increasingly. PATIENTS AND METHODS This paper reports our experience with 142 consecutive achalasia patients treated by laparoscopic Heller myotomy and Dor antireflux fundoplication and followed for a median 26 months. RESULTS Overall, the actuarial lifetable analysis showed a 90% probability of a patients being symptom free over a 5-year period. Radiologic assessment showed a significant reduction in esophageal diameter and manometry a significant reduction in the resting tone and residual pressure of the LES. Twenty-four-hour pH monitoring showed postoperative reflux in 6.7% of patients. Persistent dysphagia or chest pain (i.e., failure of treatment) were reported by 15 patients (10.6%): 14 of them were subsequently treated with multiple pneumatic dilations, which were successful in 12 cases. CONCLUSION Laparoscopic Heller myotomy with Dor fundoplication is a feasible and effective treatment for achalasia, with an actuarial success rate of 90% at 5 years. With additional dilation, a 98% success rate can be achieved.

Botulinum toxin injection versus laparoscopic myotomy for the treatment of esophageal achalasia: Economic analysis of a randomized trial

Background: The treatment of esophageal achalasia is still controversial: current therapies are palliative and aim to relieve dysphagia by disrupting or relaxing the lower esophageal sphincter muscle fibers with botulinum toxin. The aim of this study was to compare the clinical and economic results of two such treatments: laparoscopic myotomy and botulinum toxin injection. Methods: A total of 37 patients with esophageal achalasia were randomly assigned to receive laparoscopic myotomy (20) or two Botox injections 1 month apart (17). All patients were treated at the same hospital and were part of a larger multicenter study. Symptom score, lower esophageal sphincter pressure, and esophageal diameter at barium swallow were compared. The economic analysis was performed considering only the direct costs (cost per treatment and cost effectiveness, i.e., cost per patient healed). Results: Mortality and morbidity were nil in both groups. The actuarial probability of being asymptomatic at 2 years was 90% for surgery and 34% for Botox (p < 0.05). The initial cost was lower for Botox (€1,245) than for surgery (€3,555), but when cost effectiveness at 2 years was considered, this difference nearly disappeared: Botox €3,364, surgery €3,950. Conclusion: Botox is still the least costly treatment, but the minimal difference in the longer term does not justify its use, given that surgery is a risk-free, definitive treatment.

Role of acid and bile reflux in development of specialised intestinal metaplasia in distal oesophagus

BACKGROUND Barretts oesophagus is defined as specialised intestinal metaplasia in the distal oesophagus, regardless of extension. AIM To study distal oesophagus function, and acid and bile exposure in patients with Long Segment (>3 cm), Short Segment (1 to 2 cm) and Ultra-short Segment (<1 cm) Barretts Oesophagus, and in patients with gastro-oesophageal reflux disease without intestinal metaplasia. PATIENTS Study population comprised 17 patients with Long, 8 with Short, 9 with Ultra-Short Segment Barretts oesophagus, 32 with reflux disease and 12 healthy volunteers. METHODS Patients were evaluated by manometry and by 24-hour pH and bile monitoring. RESULTS Patients with intestinal metaplasia had greater acid exposure of the distal oesophagus than healthy volunteers. Patients with Long Segment Barretts oesophagus had a longer history of symptoms, worse lower oesophageal sphincter pressures and longer bile and acid exposure than the other patients. Long Segment Barretts oesophagus was predicted by low oesophageal pressure and increased bile exposure, age and male sex. CONCLUSION Acid exposure in the distal oesophagus is probably the aetiological factor behind intestinal metaplasia, but a severely damaged antireflux barrier and bile in the refluxate are necessary for Long Segment Barretts Oesophagus to develop.

Esophageal achalasia: Is the herpes simplex virus really innocent?

This study was designed to test the hypothesis that mononuclear cells in the myenteric plexus of patients with achalasia may be activated by herpes simplex virus type 1 (HSV-1). Strips of esophageal muscle were obtained from patients with achalasia and multiorgan transplant donors who served as control subjects. After muscle digestion, mononuclear cells were purified through a Percoll gradient and cultured in medium, either alone or containing ultraviolet-inactivated HSV-1 or poliovirus (multiplicity of infection 1:1.5). As an indicator of HSV-1-induced lymphocyte activation, we determined T-cell proliferation by means of 3H-thymidine incorporation and interferon gamma release. DNA was extracted from esophageal muscle of achalasia patients and control subjects, and used as a template for PCR analysis using primer pairs specific for HSV-1. Circulating anti-HSV-1 and HSV-2 antibodies were detected by enzymelinked immunosorbent assay on serum samples. Fifteen patients with naive achalasia and eight control subjects were studied. The prevalence of circulating anti-HSV-1 and HSV-2 antibodies proved similar in the two groups, and no HSV-1 DNA was detected by polyermase chain reaction in the esophageal muscle samples. The proliferative index in mononuclear cells from achalasia patients stimulated with HSV-1 showed a 3.4-fold increase in comparison with control subjects (P < 0.01). In addition, a 1.4-fold increase in interferon gamma release after incubation with HSV-1 was observed in cells from achalasia patients but not control subjects. The results of this study indicate that HSV-1-reactive immune cells are present in lower esophageal sphincter muscles of patients with achalasia. We hypothesize that the HSV-1-reactive lymphocytes in lower esophageal sphincter muscles of achalasia patients may contribute to damage of the neurons in the myenteric plexus and lead to the motor dysfunction.

Minimally Invasive Surgery for the Treatment of Function Diseases of the Gastroesophageal Junction

The Gastroesophageal junction (GEJ) constitutes a complex anatomical and functional entity the importance of which derives from its situation at the confines of the thorax and abdomen. The critical element in the function of the GEJ is the lower oesophageal sphincter (LES), that performs two main roles: (1) to relax during swallowing, allowing passage of food and liquid into the stomach, and (2) to maintain a resting tone that prevents free reflux of gastric contents into the lower oesophagus. Malfunction or anatomical changes in the LES lead to a variety of characteristic symptoms (heartburn, chest pain, regurgitation and dysphagia) and to different diseases. From a very schematic view, failure to relax properly at swallowing leads to oesophageal achalasia, and in other ways to epiphrenic diverticula. On the other hand, the inability to act properly as a barrier to reflux of gastric contents leads to gastroesophageal reflux disease and its complications. All these pathologies can be effectively treated by means of surgery.