New treatments for achalasia: novel ideas, but are they ready for prime time?

Achalasia is a rare disorder (1/100,000 people per year)without any age or gender predilection [1]. Patients typi-cally present with dysphagia for solids and liquids, regur-gitation of undigested food, nocturnal coughing, chest pain,and weight loss. These symptoms result from impaired,usually absent, peristalsis and incomplete relaxation of thelower esophageal sphincter (LES) leading to stasis of foodin the esophagus and esophageal dilation. Why the entericesophageal neurons gradually disappear in patients withachalasia remains unknown. Evidence is accumulating thatan autoimmune response targeted against these neurons,triggered by an infectious agent, possibly HSV-1, may beinvolved [2]. The diagnosis is made by a combination oftests including barium esophagram, esophageal manome-try, and upper endoscopy.No treatment for achalasia can restore muscular activityto the denervated esophagus; as a consequence, esophagealaperistalsis is rarely reversed. All treatments are thusdirected at reducing the gradient across the LES with threegoals [3]:1. Relieving patients symptoms, especially dysphagia andbland regurgitation2. Improving esophageal emptying3. Preventing the long term development of megaesoph-agus.In the modern era of achalasia treatment, LES disruptionis best accomplished by pneumatic dilation using Rigiﬂexballoons or laparoscopic myotomy, and, less effectively, bypharmacological agents, such as intrasphincteric botulinumtoxin injection (Botox) or systemic calcium channelblockers. Symptoms of dysphagia and regurgitation are theeasiest to treat; chest pain relief is more unpredictable [4].Overall, using single or multiple treatment modalities, over90 % of achalasia patients will do well [5]. Nevertheless,achalasia is never ‘‘cured’’ by our current treatments.Therefore, recurrences will occur requiring ‘‘touch up’’treatments with higher recurrence rates with longer periodsof follow-up. This editorial will review the currentlyavailable treatments and potential new endoscopic treat-ments for achalasia.Nitrates and calcium channel blockers decrease restingLES pressure in a dose-dependent manner, with a maximumeffect of 50 %, thereby temporarily relieving dysphagia.These drugs are taken 15–30 min before meals, butimprovement is incomplete and short-lived, efﬁcacydecreases with time and adverse effects (headaches, dizzi-ness, pedal edema) are common [6]. Primary pharmacologictherapy for achalasia now is endoscopic intrasphinctericBotox injection. As a potent inhibitor of acetylcholinerelease from nerve endings, Botox counteracts the unop-posed LES contraction mediated by cholinergic neuronsobserved in achalasia, helping to reduce LES resting pres-sure. Botox injections, usually 100–200 U, decrease LESpressure by 50 %, markedly improving symptoms inapproximately 75 % of achalasia patients. Nonetheless,50 % or more relapse within 6 months, probably due toregeneration of the presynaptic membranes at the neuro-muscular junctions. Best responses, sometimes up to1.5–2 years after a single Botox injection, are more likely inolder patients ([60 years) and those with vigorous achalasia[7]. This treatment may have a cost advantage for elderlypatients with a predicted life expectancy of\2 years [1].