Botulinum toxin (BoNT) has traditionally been utilized to relieve tension in muscular and connective tissue diseases (CTD). However, its usage has rapidly expanded and now encompasses usage for neurological, gastrointestinal, psychological, cardiovascular, ophthalmology, orthopedics, and more. More recently, its usage has been utilized for sequelae of CTDs such as Raynaud's disease and reduced oral aperture secondary to scleroderma/systemic sclerosis. Beyond its current applications, BoNT holds promise in various medical fields but is not FDA-approved in these conditions. Thus, the design and conduction of well-designed randomized controlled trials are essential in establishing the efficacy and safety of BoNT treatment which can help accelerate regulatory approval for new indications. The versatility of BoNT suggests that its therapeutic applications continue to expand, offering novel therapies for a wide range of conditions. This review aims to comprehensively evaluate the literature on BoNT's current FDA-approved indications and potential non-FDA uses in other medical conditions. Additionally, this review offers potential insights and future possibilities for BoNT treatment.

Correcting a gut sphincter malfunction is a difficult problem. Because each sphincter has two opposite functions, that of closure and opening, repairing one there is a risk of damaging the other. Indeed, widening a narrow sphincter, such as lower esophageal sphincter (LES) and anal sphincter, may cause gastroesophageal reflux and fecal incontinence, respectively, whereas narrowing a wide sphincter, may cause a difficult transit. All the corrective treatments for difficult or retrograde transit concerning LES and anal sphincter with their unwanted consequences have been analyzed and discussed. To overcome the drawbacks of sphincter surgical repairs, researchers have devised devices capable of closing and opening the gut lumen, named artificial sphincters (ASs). Their function is based on various mechanisms, e.g., hydraulic, magnetic, mechanical etc, operating through many complicated components, such as plastic cuffs, balloons, micropumps, micromotors, connecting tubes and wires, electromechanical clamps, rechargeable batteries, magnetic devices, elastic bands, etc. Unfortunately, these structures may facilitate the onset of infections and induce a local fibrotic reaction, which may cause device malfunctioning, whereas the compression of the gut wall to occlude the lumen may give rise to ischemia with erosions and other lesions. Some ASs are already being used in clinical practice, despite their considerable limits, while others are still at the research stage. In view of the adverse events of the ASs mentioned above, we considered applying bioengineering methods to analyze and resolve biomechanical and biological interaction problems with the aim to conceive and build efficient and safe biomimetic ASs.

Gastroesophageal reflux (GER) is known to be associated with chronic lung diseases. The driving force of GER is the transdiaphragmatic pressure (Pdi) generated mainly by costal and crural diaphragm contraction. The latter also enhances the esophagogastric junction (EGJ) pressure to guard against GER.

The relationship between Pdi and EGJ pressure was determined using high resolution esophageal manometry in patients with interstitial lung disease (ILD, n = 26), obstructive lung disease (OLD, n- = 24), and healthy subjects (n = 20).

The patient groups did not differ with respect to age, gender, BMI, and pulmonary rehabilitation history. Patients with ILD had significantly higher Pdi but lower EGJ pressures as compared to controls and OLD patients (p < 0.001). In control subjects, the increase in EGJ pressure at all-time points during inspiration was greater than Pdi. In contrast, the EGJ pressure during inspiration was less than Pdi in 14 patients with ILD and 7 patients with OLD. The drop in EGJ pressure was usually seen after the peak Pdi in ILD group (p < 0.0001) and before the peak Pdi in OLD group, (p = 0.08). Nine patients in the ILD group had sliding hiatus hernia, compared to none in control subjects (p = 0.003) and two patients in the OLD, (p = 0.04).

A higher Pdi and low EGJ pressure, and dissociation between Pdi and EGJ pressure temporal relationship suggests selective dysfunction of the crural diaphragm in patients with chronic lung diseases and may explain the higher prevalence of GERD in ILD as seen in previous studies.

Achalasia is a rare esophageal motility disorder characterized by abnormal esophageal peristalsis and the inability of the lower esophageal sphincter to relax, resulting in poor esophageal emptying. This can be relieved by endoscopic and surgical treatments; each comes with certain advantages and disadvantages.

This review aims to guide the clinician in clinical decision making on the different treatment options for achalasia regarding the efficacy, safety, and important predictors.

Botulinum toxin injection is only recommended for a selective group of achalasia patients because of the short term effect. Pneumatic dilation improves achalasia symptoms, but this effect diminishes over time and requiring repeated dilations to maintain clinical effect. Heller myotomy combined with fundoplication and peroral endoscopic myotomy are highly effective on the long term but are more invasive than dilations. Gastro-esophageal reflux complaints are more often encountered after peroral endoscopic myotomy. Patient factors such as age, comorbidities, and type of achalasia must be taken into account when choosing a treatment. The preference of the patient is also of great importance and therefore shared decision making has to play a fundamental role in deciding about treatment.

Achalasia is a primary esophageal dysmotility disorder. Despite the high volume of studies addressing the conventional treatments for achalasia, few are debated regarding the non-conventional treatments, such as cardiectomy, cardioplasty, endoluminal substances injection (ethanolamine oleate, polidocanol, botulinum toxin), stents, and certain drugs (beta-agonists, anticholinergic, nitrates, calcium channel blockers, and phosphodiesterase inhibitors).

A critical review was performed.

Endoscopic, surgical, and pharmacological treatments were included. A qualitative synthesis was presented.

Non-conventional therapeutic options for treating achalasia encompass medical, endoscopic, and surgical procedures. Clinicians and patients need to know all the tools for the management of achalasia. However, several currently available studies of non-conventional treatments lack high-quality evidence, and future randomized trials are still needed.

Laryngopharyngeal reflux disease (LPRD) might be associated with reflux symptoms, and its severity is correlated with the Reflux Symptoms Index. Diagnosis is often challenging because of a lack of accurate diagnostic tools. Although an association between LPRD and gastroesophageal reflux disease (GERD) exists, the extent to which esophageal pressure changes in patients with LPRD with GERD has been unknown. Therefore, this study surveys the clinical assessments and extent of esophageal pressure changes in LRPD patients with various GERD severities, and compares esophageal sphincter pressures between ages, genders, and body mass index (BMI). This observational study assessed patients with LPRD and GERD. High-resolution esophageal manometry was used to gather data pertaining to the area pressure on the upper esophageal sphincter (UES) and lower esophageal sphincter (LES), and the correlation between such pressure and symptom severity was determined. We compared the esophageal pressure of different UES and LES levels in the following categories: gender, age, BMI, and GERD severity. We analyzed correlations between esophageal pressure and clinical assessments among 90 patients with throat globus with laryngitis with LPRD. LPRD was measured using laryngoscopy, and GERD was measured using esophagoscopy and 24 h PH monitoring. There were no significant differences in the clinical assessments among the four grades of GERD. The LPRD patients with serious GERD had a lower UES and LES pressure. The lowest pressure and longer duration of LES and UES were also observed among patients with LPRD of grade D GERD. No significant differences in UES and LES pressures among ages, genders, or BMIs were noted.

The esophagogastric junction (EGJ) is a complex barrier between the thoracic and abdominal luminal gut compartments, comprised primarily of the lower esophageal sphincter (LES) and crural diaphragm. Although closed at rest, the EGJ relaxes to allow antegrade bolus transit and retrograde venting of air. Abnormal relaxation is the hallmark of achalasia spectrum disorders, while increased frequency of transient lower esophageal sphincter relaxations and/or EGJ disruption are seen in gastroesophageal reflux disease. High resolution manometry (HRM) is the modern day gold standard for assessment of EGJ morphology and function, with better performance characteristics compared with endoscopy and barium esophagography. Conventional LES metrics defining EGJ function include resting LES pressure as well as postswallow residual pressures. Newer HRM-based metrics include EGJ contractile integral, which measures static barrier function at rest, and EGJ morphology, which characterizes the relationship between LES and crural diaphragm. Provocative maneuvers assess dynamic EGJ function during physiological or pharmacologic stress. The most useful of these maneuvers, the rapid drink challenge, assesses for latent obstruction, while multiple rapid swallows evaluate adequacy of deglutitive inhibition. Amyl nitrate and cholecystokinin administration can segregate motor from structural obstruction. Newer provocative tests (straight leg raise maneuver, abdominal compression) and novel diagnostic tools (functional lumen imaging probe) complement HRM evaluation of the EGJ. Although current HRM metrics and maneuvers show promise in identifying clinically relevant EGJ abnormalities, future investigations evaluating management outcomes will improve segregation of normal from abnormal EGJ morphology and function.

Smooth muscles of the lower esophageal sphincter (LES) and skeletal muscle of the crural diaphragm (esophagus hiatus) provide the sphincter mechanisms at the esophagogastric junction (EGJ). We investigated differences in the 3-dimensional (3D) pressure profile of the LES and hiatal contraction between healthy subjects and patients with achalasia esophagus.

We performed a prospective study of 10 healthy subjects (controls; 7 male; mean age, 60 ± 15 years; mean body mass index, 25 ± 2) and 12 patients with a diagnosis of achalasia (7 male; mean age, 63 ± 13 years; mean body mass index, 26 ± 1), enrolled at a gastroenterology clinic. Participants underwent 3D high-resolution manometry (3DHRM) with a catheter equipped with 96 transducers (for the EGJ pressure recording). A 0.5-mm metal ball was taped close to the transducer number 1 of the 3DHRM catheter. EGJ pressure was recorded at end-expiration (LES pressure) and at the peak of forced inspiration (hiatal contraction). Computed tomography (CT) scans were performed to localize the circumferential location of the metal ball on the catheter. Esophagus, LES, stomach, right and left crus of the diaphragm, and spine were segmented in each CT scan slice images to construct the 3D morphology of the region.

The metal ball was located at the 7 o'clock position in all controls. The circumferential orientation of metal ball was displaced 45 to 90 degrees in patients with achalasia compared with controls. The 3D-pressure profile of the EGJ at end-expiration and forced inspiration revealed marked differences between the groups. The LES turns to the left as it entered from the chest into the abdomen, forming an angle between the spine and LES. The spine-LES angle was smaller in patients with achalasia (104°) compared with controls (124°). Five of the 10 subjects with achalasia had physical breaks in the left crus of the diaphragm CONCLUSIONS: Besides LES, the 3D pressure profile of the EGJ can indicate anatomic and functional abnormalities of the crural diaphragm muscle in patients with achalasia esophagus. Further studies are needed to define the nature of hiatal and crural diaphragm dysfunction in patients with achalasia of the esophagus.

Swallowing complaints are common and may have significant consequences for nutrition and pulmonary health. Etiology varies and different aspects of the deglutitive system may be affected. A thorough assessment from the oral cavity to the stomach will provide physiologic information that enables specific targeted management plans to be devised. Although the swallow trajectory bridges anatomic areas, there has previously been a tendency to compartmentalize assessment and treatment by arbitrary anatomic boundaries. It is now clear that this approach fails to appreciate the complexity of swallow mechanics and that systems (oral, pharyngeal, esophageal, and pulmonary) are intertwined and codependent. Swallowing specialists from different backgrounds and with complementary skill sets form a multidisciplinary team that can provide insight and address multiple areas of management. With the advent of new tools for instrumental evaluation, such as manometry, targeted rehabilitative strategies can be informed by physiology, increased in precision and breadth, and assessed quantitatively. Surgical approaches have evolved toward endoscopic techniques, and food technology is expanding options in dietary management. The multidisciplinary team is core to managing this varied and often neglected patient population. This review is for clinicians treating swallowing disorders and will explore the selected aspects of the assessment and management of pharyngoesophageal swallowing disorders.