Gastroesophageal reflux disease – from the point of view of a gastroenterologist, otolaryngologist and surgeon

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Gastroesophageal reflux disease from the

point of view of a gastroenterologist, an

otolaryngologist, and a surgeon

Dariusz Jurkiewicz

¹

, Dorota Waśko-Czopnik

²

, Wioletta Pietruszewska

³

, Wiesław Tarnowski

⁴

, Magda Barańska

³

,

Magdalena Kowalczyk

³

, Paweł Jaworski

⁴

1Department of Otolaryngology and Oncological Laryngology with Craniomaxillofacial Surgery Unit, Central Clinical Hospital of the Ministry of National Defense, Military Institute of Medicine, Warsaw, Poland; Head: Prof. Dariusz Jurkiewicz MD PhD

2Department and Chair of Gastroenterology and Hepatology, Wrocław Medical University, Poland; Head: Prof. Elżbieta Poniewierka MD PhD

31^st Chair of Otolaryngology, Department of Otolaryngology and Head and Neck Oncology, Medical University of Lodz, Poland; Head: Prof. Wioletta Pietruszewska MD PhD

4Department of General, Oncological, and Gastrointestinal Surgery, Centre of Postgraduate Medical Education, W. Orłowski Hospital in Warsaw, Poland;

Head: Prof. Wiesław Tarnowski MD PhD

Article history: Received: 02.04.2021 Accepted: 22.04.2021 Published: 22.04.2021

SUMMARY: Gastrooesophageal reflux disease is the regurgitation of stomach contents into the esophagus, which causes troublesome symptoms or complications for the patient. Before starting the treatment, it is always necessary to objectively confirm gastroesophageal reflux disease, especially in correlation with ENT symptoms, as extra esophageal complications.

In diagnostics, the "gold standard" is a 24-hour impedance-pH supplemented with endoscopy. Treatment without objective confirmation of the disease is not recommended, the more so that non-acid gas proximal reflux, detectable only in the MII- pH test, causes the greatest number of laryngological complications. It is important to confirm the coexistence of clinical symptoms of GERD with ESS. Considering the time of treating the disease and its consequences, it is worthwhile to be cautious and careful with the diagnosis of the disease, and the treatment should be carried out for a long time in relation to the recommendation, preferably in cooperation with an ENT specialist and gastroenterologist. The greatest therapeutic effectiveness is achieved by combining PPI with itopride while maintaining the appropriate doses of drugs and observing a sufficiently long duration of treatment, while maintaining the correct dose reduction and drug discontinuation regimen.

In case of failure of pharmacological treatment, antireflux surgery should be take into consideration.

KEYWORDS: diagnosis, gastroesophageal reflux disease, pharmacological and surgical treatment

ABBREVIATIONS

BMI – body mass index

FDA – Food and Drug Administration

GERD – erosive gastroesophageal reflux disease LPR – laryngopharyngeal reflux

MII – multichannel intraluminal impedance NCCP – non-cardiac chest pain

NERD – non-erosive reflux disease PPI – proton pump inhibitor.

RFS – Reflux Finding Score RSI – Reflux Syndrome Index

Contrary to all appearances, not everything has already been learned about gastroesophageal reflux disease (GERD), and its diagnostics and treatment are still associated with certain difficulties.

Recent epidemiological data indicate that the global incidence of the disease is on the increase. According to current estimates, nearly 30% of global population suffers from GERD symptoms at least once a week [1]. Moreover, GERD is a condition which sig- nificantly affects the quality of life of patients in virtually every as- pect by impairing the physical and mental well-being and vitality,

disturbing the emotional sphere, and affecting social and general functioning leading to absence leaves and generating significant costs associated therewith [2].

Firstly, it is worth pointing out that regurgitation of gastric contents into the esophagus is a physiological phenomenon in healthy peo- ple. It is considered normal for a person to experience a total of not more than 20 reflux incidents per day, lasting not more than 5 minutes and presenting with no clinical symptoms or complications. If significant quality of life reduction occurs as a consequence of clinical symptoms of gastric contents being refluxed into the esophagus, esophageal mucosal lesions or extraesophageal complications de- velop, or the duration of reflux is increased to more than 5 minutes, the condition is referred to as reflux disease. From a gastrologist’s point of view, the disease may present itself as either erosive gastroesophageal reflux disease (GERD) or non-erosive reflux disease (NERD), with gastroscopy being the main diagnostic tool used to differentiate between two forms. The diagnosis is straightforward if esophageal erosions are found in panendoscopic examinations whereas in cases when clinical symptoms are present without signs of esophagitis, additional diagnostic examinations are recommended, including 24-hour impedance-pH testing and esophageal manometry, preferably high-resolution esophageal manometry.

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Fig. 1. Esophageal and extraesophageal symptoms of esophageal reflux disease [24].

and endoscopy are used [4]. Twenty-four-hour intraesophageal impedance-pH testing is the gold standard in the diagnostics of reflux disease. The measurements are made using a catheter con- taining a pH-metric channel being placed along with impedance rings 5 cm above the inferior esophageal sphincter. The measurement of the difference of potentials between the two electrodes upon the electrical circuit being closed by ambient ions results in a change in impedance, facilitating the determination of the movement of gastrointestinal bolus as well as to precisely differentiate the nature of reflux depending on its chemical composition (acidic, non-acidic, or weakly acidic) and physical state (liquid, mixed, or gaseous). Esophageal manometry is a complementary test used in the diagnostics of GERD; it facilitates evaluation of the activity of individual esophageal trunk segments, the parameters of the superior and the inferior esophageal sphincter, and motor disturbances. Examination should always precede elective procedures within the esophagus. Panendoscopy is another auxiliary tool used in the diagnostics of GERD. GERD is confirmed only in its erosive form, whereas esophagitis indicative of gastroesophageal reflux is detected in 30% of patients with typical symptoms.

Endoscopy is an invaluable tool for the assessment of esophageal complications such as inflammation, ulceration, stenosis, and Bar- rett’s esophagus. In GERD patients, it should be only performed once, with no need to repeat the examination upon the recurrence of symptoms. When is a diagnosis of GERD likely? A diagnosis of GERD is likely when the impedance-pH testing reveals a correlation between the laryngological symptoms and GERD, since extraesophageal complications without any typical complaints and symptoms are encountered in very rare cases. The improvement in patient’s well-being after initial PPI treatment lacks sensitivity, as relief is also experienced in other diseases such as dyspepsia, functional heartburn, eosinophilic esophagitis, esophageal hyper- sensitivity, etc. It is important that other causes of pharyngitis are Reflux disease is associated not only with symptomatic esopha-

geal syndromes such as the reflux syndrome or the non-cardiac chest pain (NCCP) syndrome, but also with syndromes involving esophageal damage (inflammation, stenosis, Barrett’s esophagus, esophageal adenocarcinoma), and numerous extraesophageal syndromes presented at Fig. 1., including ENT complications [3].

In relation to the etiological factors of GERD other than overproduction of gastric juice, a number of components are conducive to the development of the disease as being related to esophageal, gastric, or duodenal dysfunction. The important elements include disturbed esophageal clearance, inefficiency of cardia, transient inferior esophageal sphincter relaxation, hiatal hernia, disturbed gastric emptying, or duodenogastric reflux. Taking into account the elements described above, an ideal pattern for causal treatment of reflux disease consists not only in inhibiting the overproduction of hydrochloric acid by using proton pump inhibitors (PPIs), but also in a prokinetic medication being added to improve the motor properties of the upper gastrointestinal tract.

The diagnosis of GERD based on typical clinical symptoms is straightforward; however, it should be borne in mind that the spectrum of complaints can be broad. Besides the most common symptoms such as heartburn, burning sensation, pyrosis, and regurgitation, alarming symptoms including e.g. dysphagia or ody- nophagia may be encountered thus requiring the scope of diagnostics being extended to exclude proliferative lesions despite the fact that these symptoms may as well accompany severe esophageal inflammation of LA grades C and D. In young patients presenting with typical symptoms, no alarming complaints, and no family history, endoscopic examinations are not required. It is important to extend the scope of diagnostic examinations upon the presence of atypical reflux symptoms, NERD, or extraesophageal complications. To this end, impedance-pH testing, esophageal manometry,

Extraesophageal syndromes Esophageal syndromes

Symptomatic:

- typical reflux syndrome;

- chest pain syndrome.

With esophageal damage:

- esophagitis;

- esophageal stenosis;

- Barrett’s esophagus;

- esophageal adenocarcinoma.

Documented relationship:

- GERD-related cough;

- laryngopharyngeal reflux;

- GERD-related asthma;

- GERD-related dental erosion.

Possible relationship:

- pharyngitis;

- paranasal sinusitis;

- idiopathic pulmonary fibrosis;

- otitis media.

Gastroesophageal reflux disease

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4 reaching the level above the inferior esophageal sphincter every day, particularly after meals. Each episode involving the gastroduodenal contents being regurgitated beyond the superior esophageal sphincter is considered pathological. Even a small number of such events may lead to chronic inflammation of laryngeal mucosa which may last for several weeks, or even persists forever [11].

Typical symptoms of GERD include heartburn, belching, epigas- tric and/or retrosternal pain, and acidic contents being regurgitated from stomach to esophagus. The symptoms of LPR are completely different, and patients may not experience retrosternal burning and esophagitis required as a sine qua non condition of GERD diagnosis. It is estimated that only about one half of the patients with LPR present with disease-specific symptoms such as heartburn and regurgitation [12]. The most common symptoms of LPR include throat clearing, hoarseness, coughing after meals and when adopting horizontal position, secretion flowing down the posterior wall of the throat, sensation of a foreign body within the throat, and morning voice disturbances. The symptoms are not specific and even when typical lesions are observed in laryngoscopic examination, the clinician should be vigilant to exclude any malignant processes in the first place.

To date, no gold standard has been established for the diagnostics of LPR. For this reason, different methods are used in clinical practice depending on the individual case, from clinical evaluation of disease symptoms, videoendoscopy and trial PPI treatments, to 24-hour esophageal pH monitoring and multichannel intraluminal impedance (MII) measurements. Laryngological diagnostics is based mainly on thorough interview and ENT examination, fre- quently complemented by gastroenterological diagnostics.

In order to facilitate early diagnosis, two questionnaires were introduced to assess the incidence and severity of LPR symptoms. Based on the conducted laryngoscopic study, the ENT specialist/phoniatri- cian assesses the clinical advancement of the disease using the Reflux Finding Score (RFS) scale. The scoring system involves the evaluation of eight characteristics including subglottic edema, ventricular oblit- eration, erythema/hyperemia, vocal fold edema, diffuse laryngeal edema, posterior commissure hypertrophy, granuloma/granulation, and thick endolaryngeal mucus. The final score ranges from 0 (best) to 26 (worst). Results of above 13 points are indicative of the initial diagnosis of LPR. The other questionnaire useful in early diagnostics, namely the Reflux Syndrome Index (RSI), is completed by the patient who specifies the symptoms he/she is experiencing. The score of more than 7 constitutes the threshold suggestive of LPR. The greatest drawback to the clinical utility of the above questionnaires consists in the fact that they both rely on subjective judgments of individuals – the physician and patient, respectively [13]. The translation of the original version of the questionnaire may also negatively impact its efficiency due to linguistic as well as cultural differences such as the perception of a “serious health problem” within a particular society.

While full applicability has been established for the Greek and Ital- ian translations, the current Polish translation seems insufficient for a consistent and reliable assessment. Studies suggest that the Polish version measures concepts and aspects other than those assessed by verified questionnaires in other language versions [14]. Fig. 2. pres- ents a comparison of GERD vs. LPR symptoms.

excluded, including working with one's voice, allergies, habitual throat clearing, allergic rhinitis, eosinophilia, infection, environmental irritants (dust, smoke, smoking). If no typical GERD symptoms are observed, the diagnosis of laryngological complications is very unlikely unless confirmed by impedance-pH testing. These conclusions were confirmed by numerous studies which showed that impedance-pH testing confirmed GERD in less than 40% of patients with the diagnosis of laryngopharyngeal reflux disease as being suggested by laryngologists, corresponding to a very low sensitivity of lesions detected in laryngological examination [5].

Laryngopharyngeal reflux disease (LPR) is the most common extraesophageal laryngological symptom. According to the estimates, as many as 10% of all patients reporting to an ENT specialist present with GERD symptoms [6]. On the other hand, the prevalence of LPR frequency is disputable. For the population of northern and central Europe, it is estimated at around 1%; however, symptoms suggesting LPR are reported by up to 35% of adults [7, 8]. The risk factors of LPR include the frequent use of voice, smoking, frequent respiratory infections, allergies, pet animals, chronic exposure to air conditioning, secretions flowing down the posterior wall of the throat (symptoms of chronic paranasal sinusitis), environmental conditions, and positive history of GERD [9].

The clinical presentation, and therefore the diagnosis and treatment of LPR are different from those of GERD while sharing certain pathophysiological mechanisms. Regurgitating gastroduodenal contents directly and indirectly irritate upper respiratory tract tissues leading to the development of morphological lesions. Within the larynx, the largest pathological lesions are caused by the damaging effects of pepsin and bile salts [10]. In addition, the mucous membrane lining the throat and the larynx is much more sensitive to damage due to the irritation by gastroduodenal contents than the membrane lining the esophagus, and the damage to the former is irreversible. It is believed that a healthy human experi- ences up to 50 physiological episodes of reflux with pH of below Fig. 2. Comparison of the main characteristics of GERD vs. LPR [10, 11, 49].

GERD LPR

heartburn, regurgitation throat clearing, hoarseness daytime or nighttime reflux

episodes, horizontal position daytime episodes, vertical position inferior esophageal sphincter

failure gastric content regurgitated above the

superior esophageal sphincter esophageal motility

predominantly abnormal esophageal motility predominantly normal

low risk of mucosal damage from

up to 50 episodes/day any exposure to the gastroduodenal contents leads to mucosal damage;

laryngeal and pharyngeal mucosa more sensitive to the damaging effect damaging effect of gastric acid,

pepsin, and bile salts damaging effect of gastric acid, pepsin, and bile salts, the latter two being the predominant factors

features of esophagitis present features of esophagitis possible

common comorbid overweight

status or obesity normal body mass predominant

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a probable risk factor for laryngeal cancer, albeit its role in its development requires further confirmation in more studies [17, 18].

The management of reflux disease includes recommendations for lifestyle changes and pharmacological treatment including causal treatment with prokinetic medicines regulating the mobility of the upper section of the digestive tract in addition to PPIs which reduce the volume of the gastric contents by reducing the produc- tion of hydrochloric acid. Notably, at least 1 in 4 patients is not able to achieve full satisfaction with the PPI treatment and needs to be treated in a case-by-case manner [19].

The efficacy of PPIs in the treatment of GERD, including its extraesophageal complications, is confirmed by numerous randomized studies and meta-analyses; the studies indicate that better control of symptoms is achieved when PPIs are combined with other management strategies such as lifestyle modifications [20]. An even greater efficacy can be achieved using a combination of itopride – a novel generation prokinetic drug – with PPIs. Itopride pres- ents a save alternative to other drugs in this group. Itopride has a dual mechanism of action as it blocks the release of dopamine and inhibits the secretion of acetylcholine to increase its levels in smooth muscle tissues, thus improving contraction strength and motor activity of the gastrointestinal tract. As the result, it stim- ulates the esophageal peristalsis, increases the inferior esophageal sphincter contraction strength, inhibits transient relaxation of cardia, accelerates gastric emptying and contributes to stimu- lated motility of the colon which is important in cases of overlap Laryngoscopic evaluation reveals swelling and congestion of ar-

ytenoid cartilage region and the interarytenoid fold, swelling of the posterior commissure, congestion and swelling of vocal folds, subglottic swelling (pseudosulcus), vocal process adenomas, con- tact ulcerations, thick mucus accumulation and shallow laryngeal ventricles (Fig. 3.). Uncomplicated LPR is diagnosed when no concomitant laryngeal stenosis, tumor, leukoplakia, paradoxical vocal fold movement, or granulomatous lesions are observed [13].

Multichannel intraluminal impedance (MII) measurements taken together with 24-hour esophageal pH monitoring constitute the gold standard of GERD diagnostics as they facilitate all reflux episodes being observed. Unfortunately however, in patients reporting symptoms typical of LPR, it is not always possible to obtain satisfactory results which correlate with clinical presentation. It was hoped that extraesophageal reflux diagnostics could be sup- ported by airway pH measurements taken using a special system to monitor the pH within the oropharynx (Dx-pH Measurement System). Unfortunately, the applicability of the tool in diagnostic examinations is disputable, and some researchers question all di- agnoses made using this system [15, 16].

In all cases involving the diagnosis of LPR, treatment should be initiated not only in order to improve the patient's quality of life by relieving the patient from persistent symptoms, but also in order to prevent disease recurrence so as to avoid serious complications.

The most dangerous of these complications consists in malignant transformation of the irritated mucous membrane. LPR itself is

Fig. 3. Videofiberolaryngoscopy images revealing typical lesions observed in laryngopharyngeal reflux disease: (A), (D) – hyperplasia of the posterior commissure with granuloma in the right arytenoid cartilage region; (B), (E) – edema and hyperplasia of the posterior commissure region; (C) edema and congestion of posterior commissure with a developing granuloma in the right arytenoid cartilage region.

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a prospective, double-blind, randomized observational study to evaluate the efficacy of itopride as a prokinetic agent in the treatment of LPR by assessing the changes in the severity of laryngeal symptoms before and after the treatment as well as the indicators of symptom recurrence and to compare the itopride/pantoprazole combination versus pantoprazole/placebo [33]. Inclusion of itopride in PPI-based treatment of LPR has been shown to reduce the severity of symptoms such as heartburn, regurgitations, cough, throat clearing, throat obstruction (RSI), as well as to improve certain morphological lesions within the larynx such as edema, erythema, granulomas (Belafsky’s RFS). A reduction in LPR symptom recurrence rates was also demonstrated for itopride being added to PPI treatment. In addition, itopride reaches its maximum se- rum concentration after 35 minutes (as compared to 60 minutes for cisapride) and its absorption is not related to food intake [34].

Moreover, itopride is not responsible for any changes within the nervous system as its polarity prevents it from crossing the blood- brain barrier; the drug does not elongate the QT segment and only slightly increases the prolactin levels [35].

One should keep in mind that treatment is not always possible without extended diagnostics. In the case of “red flags” such as symptoms developing in patients abusing alcohol or smok- ers, history of head and neck cancers, symptoms lasting more than 3 weeks, lymph node enlargement, weight loss, lung infections, severe dysphonia, hemoptysis and dyspnea, patient should be referred to laryngological consultation to exclude a malignant tumor.

In patients in whom no improvement was observed despite the above regimen being introduced, compliance should be assessed as the first measure since nearly 63% of patients fail to take their medications appropriately [36]. Then, extensive differential diagnostic examinations should be carried out, particularly toward gastrointestinal diseases. Additional tests such as gastrointestinal endoscopy or manometry are also recommended.

The efficacy of the treatment should be assessed not earlier than 8 weeks after implementation to allow for mucous membrane healing. However, reevaluation is recommended after 3 months to allow for possible modification of treatment being delivered over the next 3-month period. Due to the chronic nature of the disease, maintenance of modified diet and physical activity is recommended. On the other hand, chronic use of PPIs should be avoided and attention should be paid to their side effects such as the risk of malignant lesions within the gastrointestinal tract, acute inter- stitial nephritis, dementia, or pneumonia in elderly patients [37].

For this reason, treatment of patients with mild reflux symptoms should be focused on behavioral management. Family physicians play the primary role in strengthening the adequacy of diet and lifestyle of LPR patients, as they are able to educate patients on methods to avoid stressful situations and nutritional errors. In recent years, scales have been developed allowing patients to deter- mine the nutritional potential of their meals or diet, thus assisting them in changing their eating habits [38].

If no improvement is found following conservative treatment, surgical treatment of reflux should be considered.

syndromes [21]. Randomized studies confirm the efficacy of itopride polytherapy in reducing esophageal and extraesophageal symptoms and preventing the recurrence of GERD. In randomized studies, the addition of itopride to a PPI, regardless of its type, always improved the efficacy of treatment, allowing for proven PPIs being used throughout the treatment [22].

Both behavioral and pharmacological techniques are used in the treatment of LPR. The long-term reflux control requires a switch to a low-fat, high-fiber diet and moderate aerobic physical exercise [23, 24]. Compliance with medical recommendations regarding lifestyle changes to reduce LPR symptoms remains low [25]. Typi- cal recommended pharmacological treatment of LPR includes the use of PPIs leading to clinical improvement in selected patients.

This has been demonstrated e.g. in the study by Jin et al. who assessed the acoustic parameters in dysphonic reflux before and after a 3-month treatment to observe a significant improvement in the quality of voice as expressed using the jitter and shimmer parameters [26]. However, studies indicate that only diet modifications combined with PPIs lead to satisfactory results, even in patients with PPI monotherapy-resistant reflux [27]. Recent hypotheses suggest that the LPR modifies the microbiota of mouth and the oropharynx, and therefore beneficial results may be achieved by adopting a diet modifying the microbiotic composition [28]. A retrospective study comparing the efficacy of the diet and PPIs revealed no significant differences between any of these treatments, with a small advantage being observed for the dietary approach [29]. In addition, PPI monotherapy has only a small and controversial advantage over placebo. However, it should be noted that this finding may be due to the heterogeneity of LPR patients. Given the presence of both acidic and nonacid reflux, PPIs are questionable in patients presenting with the latter as they may even increase the severity of the disease. In such cases, symptoms may be reduced using alginate drugs or magaldrate combined with alginate drugs administered before sleep. In acidic reflux, PPIs administered twice a day may lead to clinical improvement.

Recent reports describe the role of oral hyaluronic acid and chondroitin sulphate combined with bioadhesive poloxamer in sig- nificantly reducing the symptoms of laryngopharyngeal reflux, particularly in patients with chronic cough, throat clearing, and hoarseness. By lining the mucosal membranes of the throat and the larynx with a protective layer, the product facilitates better hydration as well as faster healing and regeneration of the mucosal membrane, usually leading to a reduction or resolution of morphological changes within the larynx [9]. The product is used in the treatment of laryngopharyngeal reflux either as standalone monotherapy or as an adjunct to PPIs. Other medications used in the treatment include formulations accelerating gastric motility and increasing the inferior esophageal sphincter pressure such as dopamine receptor D2 antagonists, serotonin receptor 5-HT4 antagonists [24]. Some formulations within the aforementioned drug classes are associated with risk of neurological symptoms (metoclopramide) or symptoms of cardiac conduction system disturbances (cisapride) [30, 31]. Itopride administered three times a day in combination with PPIs may provide an alternative to the aforementioned agents as it accelerates the relief of reflux symptoms in LPR patients [32, 33]. Ezzat et al. carried out

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of the esophagus to gastric acid was much lower following the surgery whereas the inferior esophageal sphincter pressure was much higher. More than 62% of patients are capable of completely discontinuing acid inhibitors following the surgery. One should also remember that fundoplication leads only to elimination of esophageal regurgitation; it has no effect on inflammation within the stomach or duodenum. A large proportion of patients who resume medications after the surgery do so in relation to other disorders rather than esophageal regurgitation. In summary, the efficacy of surgical treatment in the group of patients with gastroesophageal reflux disease as confirmed using objective diagnostic methods is at the level of 85–93% [40]. This is slightly different in the group of patients whose treatment with proton pump inhibitors failed to reduce the reflux symptoms. In this group, the efficacy of surgical treatment is 50% [41]. Similarly, in the group of patients with extraesophageal symptoms such as cough or snoring, reduction of symptoms is at the level of 69% over 69 months of follow-up [42]. Barret's esophagus is a separate indication for antireflux surgery. Concomitance of GERD and Barrett's esophagus is an obvious indication for surgical treatment. Surgery may lead to regression of esophageal lesions. Thus, the study by Hof- stetter revealed that low-degree dysplasia regressed in 44% of cases while intestinal metaplasia regressed in 14% of cases [43]. No similar results could be obtained in the group of patients receiving conservative treatment.

Despite their high therapeutic efficacy, antireflux surgeries are also associated with some adverse effects. The most common ones include swallowing disorders (dysphagia), abdominal distension, early satiety after a meal, and inability to belch or vomit. Early post- operative dysphagia occurs in up to 76% of patients. One year after surgery, up to 20% of patients complain about swallowing disorders of varying severity. As many as 5–8% continue to experience this problem in long-term follow-up [39].

In 2012, in search for novel methods for the surgical treatment of GERD, the Food and Drug Administration (FDA) approved the use of the Linx™ Reflux Management System. The system consists of a ring comprising 10 or more magnetized beads connected with a titanium wire and being implanted by laparoscopy onto the inferior esophageal sphincter to increase the pressure within the lower esophagus and thus prevent regurgitation of gastric contents into the esophagus. The treatment is indicated in chronic reflux disease in a patient with normal esophageal motility, body weight index (BMI) of < 35 kg/m², with or without a small (< 3 cm) hiatal hernia and no history of surgeries within the upper gastrointestinal tract. The efficacy of this new therapy in GERD treatment has been shown to be very high. Bonavina et al., who had conducted a study in a group of 100 patients, concluded that 6 years after the implantation of the Linx system 85% of patients discontinued their medicines, their quality of life being improved in a statisti- cally significant manner [44]. The high efficacy of the method was also reported in other publications. In 2015, Saino et al. observed a significant improvement in pH measurement results in 70% of patients, with 87,8% of patients discontinuing proton pump inhibitors, and the quality of patients’ lives being improved in a sta- tistically significant manner [45]. However, there are also some disadvantages to the use of the Linx system. In their study carried According to the SAGES guidelines, indications for surgical treat-

ment include:

•

inefficacy of conservative treatment, i.e. insufficient control of symptoms and regurgitation despite pharmacotherapy or adverse effects of pharmacotherapeutic agents;

•

decision to carry out surgery despite the effectiveness of conservative treatment – related to the need for chronic use of medications, significant impairment of the quality of life, and patient’s socioeconomic situation in relation to the expenditure on medicines;

•

GERD complications – post-inflammatory esophageal stenosis, Barrett’s esophagus;

•

Extraesophageal symptoms – asthma, snoring, cough, chest pain, choking on food or drinks [39].

Regardless of the method, antireflux surgery should include the following elements:

1. dissection and suturing of crura;

2. elongation of the abdominal segment of the esophagus;

3. full (360°, Nissen) or partial (270°, Toupet) fundoplication.

Currently, Nissen fundoplication (360°) is the most common surgical approach. Standardization of surgical approach is important for comparability of operative outcomes between sites. Accord- ing to SAGES, Nissen fundoplication should involve the following elements:

•

opening of the phrenoesophageal ligament in a left to right fashion;

•

preservation of the hepatic branch of the anterior vagus nerve;

•

dissection of both crura;

•

transhiatal mobilization to allow approximately 3 cm of intraabdominal esophagus;

•

short gastric vessel division to ensure a tension-free wrap;

•

crural closure posteriorly with nonabsorbable sutures;

•

creation of a 1.5 to 2-cm wrap with the most distal suture incorporating the anterior muscular wall of the esophagus;

•

bougie placement at the time of wrap construction [39].

Proper execution of individual procedure stages should ensure a good operative outcome. However, adequate surgeon training is required. A surgeon is considered being able to perform these surgeries on their own after a total of 15–20 supervised surgeries.

As mentioned earlier, gastroesophageal reflux disease should be treated conservatively in most cases. Literature contains many comparisons of conservative vs. surgical treatment. Thus, a 10- year observational study revealed that surgical treatment was an effective alternative to conservative treatment [39]. Surgical treatment is considered effective if the patient does not need to use gastric acid secretion inhibitors after the surgery. Assessment of the outcomes of antireflux surgeries using pH monitoring and esophageal manometry led to clear conclusion that the exposure

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treatment of gastroesophageal reflux disease, with the Linux system being associated with lower rates of swallowing problems or abdominal distension.

In conclusion, gastrointestinal reflux disease should always be objectively confirmed prior to the treatment, particularly as related to laryngological complaints as extraesophageal complications. Twenty-four-hour intraesophageal impedance-pH testing supplemented by endoscopic examination is the gold standard in the diagnostics of GERD. According to literature data, initiation of treatment is not recommended prior to objective confirmation of the disease, the more so that the greatest number of laryngological complications is caused by proximal nonacidic gaseous reflux detectable only in the MII-pH test. It is important to confirm the coexistence of clinical symptoms of GERD with extraesophageal symptoms. Considering the duration of disease treatment and its consequences, it is worthwhile to approach the diagnosis in a cautious and careful manner; the treatment should be delivered for an appropriately long time, as recommended, preferably in cooperation with an ENT specialist and gastroenterologist. The greatest therapeutic effectiveness is achieved by combining a PPI with itopride at appropriate doses and observing the sufficiently long duration of treatment while maintaining the correct dose reduction and drug discontinuation regimen. In the case of a failure of pharmacological treatment, antireflux surgery should be considered.

out in a group of 1000 patients, Lipham et al. observed that 5.6%

of patients required endoscopic expansion of the esophagus due to dysphagia, the Linx system had to be removed in 3.4% of patients, and 1.3% of patients were hospitalized again due to epigas- tric pain, dysphagia, nausea and vomiting. To date, many studies have been published assessing the efficacy of the method in the treatment of esophageal reflux [46]. When comparing the efficacy of Nissen fundoplication vs. the Linx system in 64 patients (32 fundoplication, 32 Linx), normalization of pH at < 4 was observed in both groups, albeit with statistical difference being observed in Nissen fundoplication group only. The improvement in the quality of life was significant in both groups. On the other hand, abdominal distension rates were much lower in the Linx group as compared to fundoplication group. Likewise, the ability to belch was maintained at 67% in the Linx group as compared to 0% in the Nissen surgery group [47]. Having conducted a meta- analysis including the assessment of 273 patients having undergone Nissen fundoplication and 415 patients having undergone implantation of the Linx system, Skubleny et al. concluded that the ability to belch and vomit was retained in 95.2% of patients in the Linx group and 65.9% of patients in the Nissen group, with no significant differences being observed in relation to abdominal distension or swallowing problems. Similarly, the PPI discontinuation rates both groups amounted to 81.4% and 81.5% [48]. There- fore, it appears that both procedures have similar efficacy in the

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The full terms of this license are available on: https://creativecommons.org/licenses/by-nc/4.0/legalcode Dorota Waśko-Czopnik MD PhD; Department and Chair of Gastroenterology and Hepatology, Wrocław Medical University, Poland; Borowska street 213, 50-556 Wroclaw, Poland; Phone: +48 71 733 21 20; E-mail: dczopnik@gmail.com Jurkiewicz D., Wasko-Czopnik D., Pietruszewska W., Tarnowski W., Baranska M., Kowalczyk M., Jaworski P.: Gastroesophageal reflux disease – from the point of view of a gastroenterologist, otolaryngologist and surgeon; Otolaryngol Pol, 2021: 75 (2): 42-50

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