Aliment Pharmacol Ther 2004; 20: 719732.

doi: 10.1111/j.1365-2036.2004.02149.x

Review article: the role of the hiatus hernia in gastro-oesophageal reux disease
C. GOR DON, J. Y. KAN G, P. J. NEILD & J. D. MAX WELL Department of Gastroenterology, St Georges Hospital, London, UK
Accepted for publication 26 June 2004

SUMMARY

A sliding hiatus hernia disrupts both the anatomy and physiology of the normal antireux mechanism. It reduces lower oesophageal sphincter length and pressure, and impairs the augmenting effects of the diaphragmatic crus. It is associated with decreased oesophageal peristalsis, increases the cross-sectional area of the oesophago-gastric junction, and acts as a reservoir allowing reux from the hernia sac into the oesophagus during swallowing. The overall effect is that of increased oesophageal acid exposure. The presence of a hiatus hernia is associated with symptoms of gastrooesophageal reux, increased prevalence and severity of

reux oesophagitis, as well as Barretts oesophagus and oesophageal adenocarcinoma. The efcacy of treatment with proton pump inhibitors is reduced. Our view on the signicance of the sliding hiatus hernia in gastrooesophageal reux disease has changed enormously in recent decades. It was initially thought that a hiatus hernia had to be present for reux oesophagitis to occur. Subsequently, the hiatus hernia was considered an incidental nding of little consequence. We now appreciate that the hiatus hernia has major patho-physiological effects favouring gastro-oesophageal reux and hence contributing to oesophageal mucosal injury, particularly in patients with severe gastro-oesophageal reux disease.

INTRODUCTION

Winklestein rst described gastro-oesophageal reux disease (GERD) in 1935,1 and Allison2 highlighted the association between oesophagitis and hiatus hernia. For many years it was thought that a hiatus hernia had to be present for reux to occur.3 In 1972, Cohen et al. drew attention to the role of a persistently hypotensive lower oesophageal sphincter (LOS) in patients with GERD.4 However, many patients with GERD were then found to have basal LOS pressure within the normal range.5 In 1982, Dodds et al.6 emphasized transient lower oesophageal sphincter relaxations (TLOSRs) not associated with swallowing and their role in the
Correspondence to: Dr J. Y. Kang, Department of Gastroenterology, St Georges Hospital, Blackshaw Road, London SW17 0QT, UK. E-mail: jykang@sghms.ac.uk 2004 Blackwell Publishing Ltd

aetiology of GERD. Subsequent studies have shown that TLOSRs are in fact physiological,7, 8 and they underlie the majority of reux events in healthy subjects.9 The pathogenesis of GERD is now recognized to be multifactorial, involving the LOS, diaphragmatic crus, oesophageal acid clearance, gastric acid secretion, gastric emptying and intra-abdominal pressure. But what of the hiatus hernia? The association between hiatus hernia and GERD has long been recognized.2, 10 Much work has been done recently to elucidate the effect of the hiatus hernia in the pathophysiology of GER, and we are now beginning to understand this complex relationship.11 The pendulum has swung back, and like ared trousers and other icons of the 1960s, the hiatus hernia is coming back into fashion. This review looks at how the hiatus hernia inuences antireux mechanisms, GERD and its complications in adults.
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METHODS

A Medline search was performed, limited to English language, using keywords: hiatus hernia/gastro-oesophageal reux disease/aetiology/prevalence/classication/ diagnosis/Barretts/proton pump inhibitors/oesophageal neoplasia/genetics/therapy, from the 1966 to 2003 database and PreMedline. Other relevant publications known to the authors were also reviewed. Studies on paediatric subjects were not included.
OESOPHAGEAL ANATOMY AND PHYSIOLOGY IN NORMAL SUBJECTS

a pressure of 6 mmHg or less is required for GER,18 although there is a great deal of overlap and many patients with milder forms of GERD will have normal LOS pressure. The LOS is approximately 4 cm long, 2 cm of which lies intra-abdominally. The intrinsic muscles of the distal oesophagus and the proximal stomach, with the sling bres of the cardia, form the intrinsic part of the LOS. This is augmented externally by a number of adjacent structures: 1 The crural diaphragm forms a sling around the GOJ and has been shown to have a sphincteric action distinct from that of the LOS.19, 20 It enhances the LOS pressure,21 and augments the oesophago-gastric junction (OGJ) when abrupt rises in intra-abdominal pressure occur, such as coughing or abdominal straining.22 2 The angle of His is the acute angle formed between the greater curvature of the stomach and the oesophagus, and this is thought to function as a valve.23, 24 If the angle becomes less acute then reux is more likely to occur.25 3 The distal portion (approximately 2 cm) of the oesophagus is thought to act as a valve. This portion of the oesophagus is within the abdominal cavity, and thus any increase in intra-abdominal pressure will be transmitted equally to the stomach and the intra-abdominal oesophagus.26, 27 Thus, as long as the LOS maintains an intraluminal pressure increment greater than intragastric pressure, the reux barrier is maintained. 4 The phrenoesophageal ligament inserts circumferentially into the oesophageal musculature close to the squamo-columnar junction,16 and contributes to the competence of the GOJ.28, 29 In patients with hiatus hernia, the phrenoesophageal ligament is stretched in an orad direction, forming a sac which contains part of the proximal stomach and distal oesophagus. DeMeester et al. proposed that this functions as an extension of the abdomen into the mediastinum, and allows for transmission of intra-abdominal pressure to that portion of the LOS contained within the sac.30 The importance of the length of oesophagus within the hernia sac is seen in the autopsy study of 55 patients by Bombeck et al.28 Eight patients had a hiatus hernia, ve of whom had no evidence of oesophagitis (and hence a competent cardia). The phrenoesophageal membrane in these ve patients
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The oesophagus is a hollow muscular tube extending from the pharynx to the stomach. It is composed of both striated and smooth muscle and functionally comprises three portions: (i) posterior cricoid portion contains striated muscle under voluntary control, and initiates swallowing; (ii) body of the oesophagus smooth muscle which propagates peristalsis under control of both the extrinsic (vagus) and intrinsic (Auerbachs) plexus; and (iii) the LOS. The distal end of the oesophagus is anchored to the diaphragm by the phreno-oesophageal ligament/membrane, which is formed by the fused endothoracic and endoabdominal fascia.12 The longitudinal muscles of the oesophagus shorten during swallowing,13, 14 and the gastric cardia tents through the diaphragmatic hiatus,13 but reduces afterwards. This is commonly seen on barium studies, provided a careful examination is performed,15 and is termed the phrenic ampulla. Traditionally, it was regarded as part of the oesophagus and hence a physiological nding. However, simultaneous uoroscopic and manometric studies of the gastro-oesophageal junction (GOJ) by Lin et al.16 suggested that the phrenic ampulla is physiologically distinct from the oesophagus, and is analogous to a small reducing hiatus hernia.16 The LOS is a manometrically distinct entity, identied by a rise in pressure over the gastric baseline pressure as a pressure transducer is withdrawn from the stomach to the oesophagus. It is a functional barrier with no anatomical landmarks, and represents an intraluminal zone with a basal pressure greater than that of the stomach and oesophagus. In adults, this zone has a pressure of approximately 20 mmHg (in one study with a range of 1035 mmHg17). It has been suggested that

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inserted a mean of 3.6 cm above the GOJ. In the three patients with oesophagitis (and hence an incompetent cardia), the ligament inserted a mean of 0.5 cm above the GOJ. This difference was signicant and emphasizes the importance of an adequate length of intra-abdominal oesophagus in maintaining a competent antireux mechanism, even in patients with a hiatus hernia. Transient lower oesophageal sphincter relaxations The TLOSRs are spontaneous relaxations to baseline of LOS pressure, and are distinct from swallow-induced LOS relaxations. In normal subjects, they allow belching to occur.7, 8 They underlie the majority of reux events in healthy individuals and patients with mild GERD, i.e. those with normal basal LOS pressure.5, 31, 32 In patients with severe GERD other factors such as low basal LOS pressure, defective LOS function, or a hiatus hernia, are more important.32, 33 Over the whole spectrum of GERD, the proportion of reux episodes that can be ascribed to TLOSRs varies inversely with the severity of the disease.34
PATHOPHYSIOLOGICAL MECHANISMS UNDERLYING GERD IN SUBJECTS WITHOUT HIATUS HERNIA

in age-matched controls,39 it can be doubled by chewing gum, and this has been proposed as a nonpharmacological treatment for GERD.40 Delayed emptying of the proximal stomach may make reux more likely due to a pressure backow effect. Many patients with GERD have an enhanced or prolonged postprandial fundic relaxation, with delayed emptying of the proximal stomach.41, 42 Gastric outlet obstruction, as in peptic ulcer disease43, 44 and delayed gastric emptying, as in diabetes,44 can be associated with GERD.
HIATUS HERNIA

Hiatus hernia refers to the herniation of parts of the abdominal contents through the oesophageal hiatus of the diaphragm. There are three recognized types:45, 46 Type I This is the commonest type, and is characterized by widening of the muscular hiatal aperture of the diaphragm, with laxity of the phrenoesophageal membrane, allowing some of the gastric cardia to herniate upwards. Type II A type II hernia results from a localized defect in the phrenoesophageal membrane. The GOJ remains xed to the preaortic fascia and the arcuate ligament, and the gastric fundus forms the leading part of the herniation. Type III Type III hernias are mixed types I and II, with a sliding element to the type II hernia. Type III hernias associated with a large defect can allow other organs to herniate, e.g. spleen, pancreas. The remainder of this review will concentrate on the type I hiatus hernia, as it accounts for about 90% of the hiatal hernias seen in clinical practice.47
DIAGNOSIS

Gastric acid is kept in the stomach by a combination of oesophageal motility, LOS function and gastric emptying. Coordinated peristaltic waves deliver the food boluses to the distal oesophagus from the mouth. This is achieved by voluntary (pharyngeal) and involuntary (oesophageal) muscle, coordinated by the Auerbachs plexus. Oesophageal peristalsis can be primary (initiated by a swallow), or secondary (initiated by distension of the oesophagus because of retained food or reuxed material). Tertiary contractions refer to non-peristaltic oesophageal activity. The LOS relaxes completely during swallowing to allow passage of the ingested material. As mentioned earlier, a low LOS pressure is an important determinant of GERD. LOS pressure is reduced by cigarette smoking,35 alcohol36 and by some foods, e.g. peppermint. In adults about 10001500 mL of saliva is secreted per day, with a pH of approximately 7.0.37 This large volume of saliva contributes to the buffering of reuxed acid, and induces primary peristalsis.38 Although salivary ow in patients with GERD is similar to that
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The GOJ moves during swallowing in relation to the diaphragmatic crus. While large hiatal herniae are easily identied in radiological, endoscopic and manometric

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studies, the diagnosis of a small hiatus hernia is not well-standardized. Radiography On barium studies, the lower oesophageal mucosal ring demarcates the union of the oesophagus with the stomach,48 and thus its presence above the diaphragmatic hiatus is used as a sign of a hiatus hernia. As discussed previously, the distal oesophagus and gastric cardia move cranially during swallowing and form the phrenic ampulla. There is no precise consensus regarding the differentiation of a phrenic ampulla, which is physiological, from a hiatus hernia, which is pathological. Most authors agree that the lower oesophageal ring must be at least 12 cm above the level of the diaphragmatic hiatus to diagnose a hiatus hernia,45 although in practice the distinction can be quite arbitrary. In particular, there is no standardized protocol in assessing and recording the reducibility of a hiatus hernia in between swallows or when getting upright from the supine position. Upper gastrointestinal endoscopy At upper GI endoscopy, the GOJ is recognized as the Z-line, where the dark pink columnar stomach mucosa changes to the lighter pink squamous oesophageal mucosa above the visible stomach folds. In a normal subject, the GOJ is usually seen just above the diaphragmatic crus.49 Most authors consider a hiatus hernia to be present if diaphragmatic indentation is seen 2 cm or more distal to the Z-line and the top of the stomach mucosal folds.46, 49 The current practice of diagnosing a hiatus hernia and measuring its size using the centimetre markings on the endoscope is inaccurate. There is no standardization regarding the degree of air insufation or which phase of respiration the measurement is made at.49 It is also difcult to be certain that the tip of the endoscope is precisely at the Z-line or diaphragmatic crus while the distance from these landmarks to the incisors can vary circumferentially. There are few published data on the correlation between upper endoscopy and barium studies in the diagnosis of hiatus hernia. Panzuto et al. studied 21 patients with large hiatus hernias, using both upper GI endoscopy and barium studies.50 They noted that upper GI endoscopy signicantly underestimated the

size of hiatus hernias compared with barium studies. Small hiatus hernias were not included in this study. In contrast, of 34 patients in whom hiatus hernias were diagnosed at upper GI endoscopy, only 20 met the radiological criteria for hiatus hernia.51 At present, radiology is the only accurate method of measuring hiatus hernia size. However, upper GI endoscopy is now the standard tool for assessing upper GI symptoms. If a simple, standardized, endoscopic method of diagnosing a hiatus hernia and measuring its size could be developed, our knowledge of the role of the hiatus hernia in GERD could be much advanced. Oesophageal manometry When the manometry probe is in the stomach, a deep inspiration is recorded as a positive deection, as abdominal pressure rises. When the probe is in the thoracic cavity a deep inspiration causes a negative deection as thoracic pressure is lowered. When the probe is at the level of the diaphragm, deep inspiration causes a positive deection followed by a negative deection, as the probe lying in the stomach moves into the oesophagus as the diaphragm descends. This is called the respiratory reversal point. The LOS is identied as a pressure rise above gastric baseline as the probe is pulled back from the stomach to the oesophagus this falls back to baseline during swallows and periodically after eating (TLOSRs). In a normal subject, the distal border of the LOS is below the respiratory reversal point, and hence part of the LOS appears intra-abdominal. With a small hiatus hernia, an accurate measurement can be difcult because the diaphragm changes position with respiration. It is only in large hernias that the LOS is proximal to the respiratory reversal point. Therefore, manometry is not a sensitive tool for the diagnosis of a hiatus hernia.46
AETIOLOGY

Simplistically, the hiatus hernia can be caused by one or more of three mechanisms: (i) widening of the diaphragmatic hiatus, (ii) pulling up of the stomach by oesophageal shortening, and (iii) pushing up of the stomach by increased intra-abdominal pressure.52 During a normal swallow, the oesophagus shortens by up to 2 cm. The elasticity of supporting structures, especially the phrenoesophageal ligament, returns the anatomy to its normal position.46 Age-related wear and tear of the phrenoesophageal ligament could loosen the
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attachment of the GOJ to the diaphragmatic crus,16 and thus over time contribute to the formation of a hiatus hernia. Intraoesophageal acid perfusion causes proximal migration of the LOS.53 Mittal46 proposed a unifying hypothesis relating GER and oesophagitis to the pathogenesis of hiatus hernia. Frequent TLOSRs with resultant acid reux could be the initiating factor causing oesophagitis, which leads secondarily to oesophageal shortening through acid-induced contraction of the longitudinal muscles. This may lead to subsequent brosis, exacerbated by age-related loss of elasticity of the surrounding structures. A hiatus hernia then results, which in turn enlarges the oesophageal hiatus, impairing the sphincter function of the crural diaphragm. The development of hiatus hernia and crural diaphragmatic incompetence introduces further mechanisms of GER leading to exacerbation of oesophagitis and setting up a vicious cycle.54 A high prevalence of hiatus hernia of up to 80%55 amongst power athletes suggests a role for raised intraabdominal pressure.55, 56 However, the extreme intraabdominal pressures seen in this setting (up to 365 mmHg amongst those who wear a lifting belt55) is far beyond that normally encountered in the normal subjects, and thus is unlikely to be a major factor in the causation of hiatus hernia in the general population. Familial clusters of hiatus hernia have been des cribed.5759 In a recent study by Carre et al.,60 38 members of a family pedigree across ve generations were studied. Twenty-three had radiological evidence of a hiatal hernia. No individual with a hiatus hernia was born to unaffected parents. In one case direct maleto-male transmission was shown. This raises the possibility of genetic inheritance, which Carre proposed 60 occurs in an autosomal dominant fashion. However, since the frequency of hiatus hernia in the general population is still not clear, it is difcult to draw denite conclusions from these data.
OBESITY AND HIATUS HERNIA

the risk of reux oesophagitis on the basis of their body mass index61 and showed that obesity is a signicant risk factor for oesophagitis. Excessive body weight was also signicantly associated with the presence of hiatus hernia, the probability of hiatus hernia increasing with each level of obesity. Wilson et al.61 proposed that although obesity was a signicant risk factor for oesophagitis, it was largely through an association with hiatus hernia, a view shared by Barak et al.62 Logistic regression analysis of 385 dyspeptic patients in the UK and Singapore showed that body mass index was an independent risk factor for both hiatus hernia and reux oesophagitis.63 Stein-Larson et al. also described an association between obesity and the occurrence of both hiatus hernia and reux oesophagitis in a prospective study of 1224 patients undergoing upper endoscopy.63 Wu et al. examined the relationship between hiatus hernia, reux symptoms and body size as part of a population-based, casecontrol study of the risk of upper GI cancers.64 A positive trend was found between increasing body size and hiatus hernia presence, although this did not reach statistical signicance. There is therefore an association between obesity and hiatus hernia, but the nature of this association is unclear. Is it a pure pressure effect? Or is it related to a lax hiatal orice? It would be interesting to study the effect of weight loss on the size of a hiatus hernia.
PREVALENCE AND INCIDENCE OF HIATUS HERNIA

It is commonly thought that obesity is a risk factor for reux symptoms, and indeed weight loss forms part of the lifestyle advice given to patients with GERD. However, it is unclear whether obesity in itself increases the risk for GERD,47 whether the association arises through the types of food obese people eat, or by a common relationship with hiatus hernia. In a retrospective casecontrol study of 1205 patients who underwent upper endoscopy, Wilson et al. analysed
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The frequency of hiatus hernia, like that of oesophagitis, increases with age.6567 There is, however, no denite gender effect, different series showing male predominance,68 female predominance,69 or no difference.6567 Prevalence data relating to the hiatus hernia are difcult to interpret. They generally relate to patients attending for upper endoscopy rather than community subjects, and as selection criteria for this procedure vary, such data are not strictly comparable across series. Details such as age and body mass index are seldom presented. Furthermore, diagnostic criteria for hiatus hernia vary between studies, and in some reports are not even described. While there is geographical variation in the prevalence of hiatus hernia, it is uncertain if these differences are genuine, because of genetic or lifestyle variations, or whether they merely reect variability in patient selection and diagnostic criteria. In a literature review by Pridie,70 the frequency of hiatus hernias found incidentally during barium studies

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varied widely depending on when the studies were performed. Throughout the 1930s and 1940s, the reported prevalence was between 0.8 and 2.9%. However, in the 1950s and early 1960s, when abdominal pressure was routinely applied during barium examinations, the prevalence rose to between 11.8 and 29.6%.70 The GERD is generally thought to be uncommon in the Far East, and the prevalence of hiatus hernia seems to follow this trend. Of patients undergoing upper endoscopy, the proportion with a hiatus hernia was 2.2% of 2044 subjects71 and 7% of 464 subjects72 in Taiwan, 2.9% of 11 943 subjects in Singapore,73 and 4.1% of 1010 patients in Korea.68 In a recent Japanese series of 6010 individuals undergoing upper endoscopy between 1996 and 1998, 17.5% had a hiatus hernia.65 This prevalence is higher than that shown by other studies in Far Eastern populations, and may reect the fact that the frequency of GERD is thought to be increasing in the East in recent years.74 However, for this study, the diagnostic criteria for hiatus hernia were not described. Higher frequencies of hiatus hernia have been reported in Western populations. For example, 16.6% of 670 subjects (Norway),75 22% of 293 subjects (USA),10 and 14.5% of 1000 subjects (Sweden)76 undergoing upper endoscopy were found to have a hiatus hernia. A comparative study by a single endoscopist between English and Singaporean patients with dyspepsia found that the proportion of patients with hiatus hernia was 49% and 4% respectively (P < 0.005).66 Loffeld and Van der Putten67 calculated the incidence of hiatus hernia for a cohort of patients with a normal index upper endoscopy, who had a second procedure (for newly developed or recurrent symptoms) over a study period of up to 8 years. Ninety of 353 patients developed a hiatus hernia, dened as a distance of more than 2 cm between the OGJ and the diaphragmatic indentation. The incidence of hiatus hernia in this highly selected group of patients was 19.9%. Patients who developed hiatus hernia were older, more likely to be female and had a higher incidence of reux oesophagitis or Barretts metaplasia compared with those who did not develop a hiatus hernia. However, an annual incidence of 19.9% seems high. The reproducibility of the endoscopists diagnosis of hiatus hernia was not assessed, and it was not stated if any of the patients with a hiatus hernia at the index upper endoscopy were found not to have a hiatus hernia at a subsequent upper endoscopy.

The frequency of hiatus hernia in asymptomatic individuals would be of great interest, but reliable data are unavailable. Most studies relate to symptomatic subjects undergoing investigation, rather than community subjects or asymptomatic individuals. One radiological study reported a 33% prevalence of hiatus hernia in asymptomatic individuals,15 but the protocol included the application of abdominal pressure, a practice which is now obsolete, and thus the results are difcult to interpret. In the Far East, upper GI endoscopy is frequently performed as part of a routine medical check up. Hiatus hernia has been reported in about 11% of such individuals in one Korean series, most of whom were asymptomatic.77 However, these subjects represent a self-selected group who may not be comparable with community subjects.

PHYSIOLOGICAL EFFECTS OF HIATUS HERNIA

LOS function In a patient with a hiatus hernia, the portion of the LOS exposed to intra-abdominal pressure is shorter.30, 78, 79 LOS pressure is reduced,80 and this is proportional to the size of the hiatus hernia.79 These changes in LOS pressure and function seem to be due to the spatial separation of the pressure components derived from the intrinsic LOS and compression of the oesophagus within the hiatal canal.80 Impairment of the diaphragmatic sphincter A hiatus hernia compromises the diaphragmatic sphincter independently of its effects on the LOS. A patient with a hypotensive LOS and a large hiatus hernia is more likely to develop GER during straining manoeuvres compared to a patient with a hypotensive sphincter alone.51 Similarly, the presence of a hiatus hernia is an independent risk factor, in addition to a defective LOS, for abnormal oesophageal acid exposure.78 It has been proposed that in the presence of a structurally normal LOS, a hiatus hernia alters the anatomy of the cardia and facilitates the ability of the gastric wall tension to pull open the LOS.78 Oesophageal peristalsis The presence of a large hiatus hernia is associated with decreased peristaltic amplitude in the distal
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oesophagus.78, 79 This may impair the clearance of reuxed acid.81 It is uncertain whether this defective peristalsis is caused by the hiatus hernia, or if it is secondary to oesophageal damage because of GER. Transient lower oesophageal sphincter relaxations What about the effect of a hiatus hernia on TLOSRs? Van Herwaarden et al.5 studied GERD patients with and without hiatus hernia. While those with a hiatus hernia had greater oesophageal acid exposure and more reux episodes, the frequency of TLOSRs and proportion associated with acid reux was similar in the two groups. However, patients with hiatus hernia did have more reux associated with low LOS pressure, swallowassociated LOS relaxations and straining during periods with low LOS pressure. Kahrilas et al.82 studied the effects of gastric distension (by gaseous infusion) on TLOSRs in GERD patients. While the amount of reux and frequency of TLOSRs at baseline were unaffected by the presence of a hiatus hernia, gastric distension elicited a greater increase in the frequency of TLOSRs in patients with a hiatus hernia compared to those without. The resultant TLOSR frequency was proportional to the size of the hiatus hernia. The conicting conclusions reached by these two studies could be due to differences in study design. Van Herwaardens subjects were semiambulant, had small standardized meals and were studied over 24 h. Kahrilas et al.82 performed their study in recumbent patients over 21 h, with the stomach distended with 2 200 mL saline and 1800 mL air. More work needs to be done to determine if TLOSRs are a signicant cause of GER in the presence of a hiatus hernia. Cross-sectional area of the gastro-oesophageal junction Using a barostat lled with radioactive contrast, Pandalno et al.83 were able to study the opening of the GOJ and to measure its cross-sectional area and compliance during low pressure distension. Compliance was increased in GERD patients compared with controls. The cross-sectional area was greater in patients with a hiatus hernia and GERD than in patients with GERD but no hiatus hernia, and this in turn was greater than that in normal subjects. The larger cross-sectional area could allow reux of uid rather than gas, and possibly a higher volume of reuxate.

Oesophageal acid clearance In a study combining barium examinations with oesophageal pH studies, Ott et al. showed that patients with larger (>2 cm) hiatus hernias were more likely to have abnormal results on 24 h pH monitoring, compared with normal subjects and those with hiatus hernias <2 cm.84 The increase in oesophageal acid exposure with hiatus hernia is not just due to increased frequency and volume of reuxate. Mittal et al. instilled acid into the oesophagus of patients with and without hiatus hernia.85 In the absence of a hiatus hernia, a single swallow resulted in restoration of a normal oesophageal pH. However, patients with a hiatus hernia showed a biphasic response an initial episode of acid reux, seen as a fall in pH, followed by restoration of pH towards normal. Simultaneous radionuclide studies showed that the initial drop in pH coincided with reux from the hiatus hernia proximally. Mittal et al.85 proposed that gastric contents could be trapped in the hiatus hernia limited by the LOS proximally and the crural diaphragm distally. These contents could then reux into the oesophagus when the LOS relaxed during swallowing. Using concurrent videouoroscopy and manometry, Sloan and Kahrilas studied asymptomatic volunteers and patients with symptomatic GERD who had hiatus hernias noted during upper endoscopy. Ten of the 22 patients had endoscopic oesophagitis. In 10 of the patients, the hiatus hernia was reducing while in the other 12 it was non-reducing.86 Complete oesophageal emptying without retrograde ow was seen in 86% of test swallows in controls, 66% of swallows in the reducing hiatus hernia group, and in 32% of swallows in the non-reducing group. Both these studies suggest that a hiatus hernia acts as a reservoir, from which acid can reux during a swallow, thus contributing to the increased acid exposure time seen in these patients. In a detailed pathophysiological study of nine controls and 38 patients with GERD, increasing hiatus hernia size was associated with greater oesophageal acid exposure, more prolonged episodes of reux and longer acid clearance times.87 However, Massey argued that the presence of a hiatus hernia is more important than its size in its effects on GERD.88

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Reducibility of hiatus hernia Mattioli et al.8991 recently drew attention to hiatus hernia which reduce when the patient is in the upright position. For this group of patients both the LOS pressure, and the percentage time during which the lower oesophageal pH is <4, are between those for healthy volunteers and patients with irreducible hernias. They suggested that hiatus hernias that reduce in the upright position represent a stage in the development of xed hiatus hernias. They did not, however, report on the effect of swallowing on the reducibility of hiatus hernias. In contrast, Sloan and Kahrilas dened reducing hiatus hernias as those occurring only during mid-swallows, but reducing between swallows.86 The frequency of incomplete oesophageal emptying during swallows in these subjects was intermediate between healthy controls and those with irreducible hiatus hernias. In a later study,51 the same authors considered these same subjects not to have hiatus hernias. Sloan and Kahrilas86 studied patients only in the supine position so the reducibility of hiatus hernias in the upright position was not assessed. In practice, there is no uniformity in the assessment or reporting of the reducibility of hiatus hernias between swallows and in the upright position during barium studies. Furthermore endoscopy, which is always carried out in the supine position and in which the effects of swallowing are not assessed, is now the standard modality of investigating upper GI anatomy. Thus, although the reducibility or otherwise of hiatus hernias is potentially important in terms of pathophysiological considerations, its clinical effects cannot be studied easily. In summary, a hiatus hernia reduces LOS length and pressure, impairs the augmenting effect of the diaphragmatic sphincter, is associated with decreased

oesophageal peristalsis, affects the opening characteristics of the OGJ and acts as a reservoir allowing GER during swallowing. The overall effect is that of increasing oesophageal acid exposure and decreasing oesophageal acid clearance.

CLINICAL EFFECTS OF HIATUS HERNIA

Reux symptoms and hiatus hernia In a study of 57 healthy subjects by Stal et al.,92 62% with GER symptoms at computer interview had a hiatus hernia at upper endoscopy, compared with only 14% of asymptomatic subjects (P < 0.01). Subjects with GERD had predominantly non-erosive disease: only one quarter had oesophageal erythema or erosions. Peterson et al.93 investigated 930 successive patients who underwent endoscopy because of dyspepsia, and looked at both GERD and non-erosive reux (NERD) patients. Even with exclusion of 131 patients with reux oesophagitis, patients with a hiatus hernia were signicantly more likely to have heartburn and regurgitation compared to those without. Thus, it can be seen that reux symptoms are more common in subjects with a hiatus hernia than in those without, even when reux oesophagitis is not present at upper endoscopy, i.e. non-erosive disease. Oesophagitis and hiatus hernia The relationship between oesophagitis and hiatus hernias has been recognized as far back as 1951.2 Both the presence and size of the hiatus hernia are important.75, 88 Table 1 summarizes the results of various studies in which this relationship was analysed by univariate
Table 1. Prevalence of hiatus hernia in patients with and without oesophagitis

Frequency of hiatus hernia Location of study Kang and Ho66 Yeom et al.68 Kang et al.73 Stein-Larson et al.63 Berstad et al.75 Wright and Hurwitz10 Cronstedt et al.76
* Statistically signicant.

Patients without Number of Patients with oesophagitis (%) oesophagitis* (%) patients 64 32 13 68 63 84 72 6 3 2 11 8 13 9

UK/Singapore 383 Korea 1010 Singapore 11 943 Norway 1224 Norway 670 USA 293 Sweden 1000

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Table 2. Factors contributing to the antireux mechanism in normal subjects Lower oesophageal sphincter (LOS) Crural diaphragm Angle of His Intra-abdominal portion of the LOS Phrenoesophageal ligament Oesophageal peristalsis Saliva

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Table 3. Pathophysiological effects of a hiatus hernia Decrease in intra-abdominal length of the lower oesophageal sphincter (LOS) Decreased LOS pressure Impairment of the diaphragmatic sphincter Impairment of oesophageal peristalsis Increased cross-sectional area of the gastro-oesophageal junction (GOJ) Decreased oesophageal acid clearance Increased oesophageal acid exposure

associated with a hiatus hernia, more reux episodes, and excess smoking and alcohol.96 Cameron looked at the prevalence and size of hiatus hernia in Barretts oesophagus.97 A hiatus hernia was found in 96% of patients with classical Barretts oesophagus, 72% of patients with short segment (<2 cm) Barretts oesophagus, 71% of patients with oesophagitis, and 29% of controls with no oesophagitis. Among patients with hiatus hernias, those with Barretts oesophagus had wider hiatal orices, and longer hiatal hernias compared to patients without Barretts oesophagus. Weston et al. prospectively followed up 99 patients over a period of 24106 months, and identied seven in whom complete regression of the Barretts occurred. Stepwise logistic regression analysis showed that only the absence of a hiatus hernia and length of Barretts <6 cm were signicantly and independently predictive of complete regression of the Barretts segment.98 Oesophageal adenocarcinoma and hiatus hernia

analysis. These studies included patients who had an upper GI endoscopy done for a variety of indications,10, 63, 68, 73, 75, 76 or for dyspepsia only.66 The association between hiatus hernia and reux oesophagitis is signicant across different countries, irrespective of the background prevalence of this condition. Using multivariate analysis, Sontag et al. demonstrated that the presence of a hiatus hernia was a more important predictor of reux oesophagitis than LOS pressure.94 Jones et al. showed that increases in hiatal hernia size were signicantly correlated with total oesophageal acid-exposure, acid clearance time and oesophagitis severity,87 although the effect of presence or absence of a hiatus hernia was not analysed. In a third study by Cadiot et al.,95 the relationship between hiatus hernia and reux oesophagitis was not statistically signicant on multivariate analysis, although an association was demonstrable on univariate analysis. Barretts oesophagus and hiatus hernia Barretts oesophagus is associated with male sex, older age, excess alcohol, cigarette smoking and frequent reux episodes. In a study of 229 patients with Barretts oesophagus and 229 patients with non-erosive GERD, the presence of Barretts oesophagus was strongly
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There is an established association between GERD and oesophageal adenocarcinoma,99 but few studies specifically examined the relationship between hiatus hernia and oesophageal carcinoma. Chow et al. performed a medical record based casecontrol study of 196 patients with oesophageal adenocarcinoma and 196 controls, and showed that the presence of a hiatus hernia doubled the risk of oesophageal carcinoma. There was also a cumulative increase in risk with a history of reux, dysphagia and previously documented oesophagitis.100 In a population-based, casecontrol study of patients with oesophageal adenocarcinoma (n 222), both hiatus hernia and reux symptoms emerged as signicant risk factors. The risk was increased threefold in those with reux symptoms but no hiatus hernia, sixfold in those with a hiatus hernia but no reux symptoms, and eightfold in those with both reux symptoms and a hiatus hernia.64 Avidan et al. reviewed 131 patients with high-grade dysplasia or oesophageal adenocarcinoma, 2170 patients with no GERD, and 1189 patients with Barretts oesophagus but no dysplasia. Logistic regression analysis showed the risk of high-grade dysplasia or esophageal adenocarcinoma to be proportional to the size of hiatus hernia and length of Barretts oesophagus. Patients with high-grade dysplasia or oesophageal adenocarcinoma shared many characteristics with

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other forms of severe GERD, such as older age, male gender and white ethnicity.101 Weston et al. prospectively followed up 108 patients with Barretts oesophagus.102 Stepwise logistic regression analysis showed that progression to high-grade dysplasia and oesophageal adenocarcinoma were signicantly and independently associated with hiatal hernia size, dysplasia at diagnosis and the length of the Barretts segment. The association between hiatus hernia, and Barretts oesophagus and oesophageal adenocarcinoma is consistent with a promoting effect of the hiatus hernia on GERD, and not necessarily by the presence of the hiatus hernia per se. Acid suppression treatment and hiatus hernia Frazzoni et al. studied lower oesophageal pH in 50 patients with complications or atypical manifestations of GERD, who had been referred for upper GI endoscopy. A 30 mg dose of lansoprazole normalized oesophageal acid exposure in 70% of subjects, whereas a 60 mg daily dose was necessary in the remainder. The two groups differed only in the presence of hiatal hernia (28% vs. 100% respectively). However, hiatal hernia size was not studied.103 Said et al. examined predictors of early recurrence of peptic oesophageal strictures after initial dilatation in 67 patients over a 1-year period. Continued acid suppression was used in 94% of patients. Both the presence and size of a hiatus hernia were signicantly associated with early recurrence on multivariate analysis.104 Both these studies suggest that a hiatus hernia affects the ability of acid suppressing medication to normalize intraoesophageal pH. This could be due to the promoting effect of hiatus hernia on GER. It has been shown that on standard doses of PPIs, nocturnal acid breakthrough commonly occurs,105 and it may be that this residual acid reuxes more easily in the presence of a hiatus hernia. Surgical and endoscopic therapy for GERD in the presence of hiatus hernia In the infancy of antireux surgery, it was thought that a hiatus hernia was the only causative factor leading to GERD. Thus, early surgery was designed only to treat the hernia itself and was often ineffective for reux oesophagitis.106 We now know that the aetiology of GERD is multifactorial, and an ideal operation, whether

open or laparoscopic, should address all the various aspects,106 including (i) restoration of the intra-abdominal oesophagus, (ii) reconstruction of the diaphragmatic hiatus (with reduction of a hiatus hernia if present) and (iii) reinforcement of the LOS by fundoplication.107 The operation most commonly used today is a modication of the operation described by Nissen in 1956.106 During surgery the oesophagus is mobilized in the thorax so that it can be brought down sufciently to restore the intra-abdominal portion. This reduces tension on the repair, and reduces the risk of late failure.108 However, in the context of a large or irreducible hiatus hernia, there may be a short oesophagus despite adequate mobilization.108111 Oesophageal lengthening (Collis gastroplasty) combined with fundoplication can be performed during laparoscopic112 surgery, but may require an open operation.107 A large hiatus may be seen in patients with a large hiatus hernia,97 and reconstruction of the diaphragmatic hiatus is an integral part of antireux surgery.107, 113 Both the reconstruction of the oesophageal hiatus and oesophageal lengthening can be achieved laparoscopically,107, 112 but the presence of a large hiatus hernia might inuence the surgeon to consider an open operation.107 Antireux surgery is indicated in patients affected by severe GERD who are (i) not compliant with long-term medical therapy, (ii) who require high doses of drugs and (iii) who wish to avoid lifetime medical treatment.114 While the presence of a large hiatus hernia is associated with severe GERD symptoms, erosive oesophagitis and poorer response to treatment, a sliding hiatus hernia per se is not an indication for surgery. In contrast, surgery is recommended for para-oesophageal hernias because, if left untreated, approximately 33% will suffer complications such as intrathoracic incarceration of the stomach, bleeding, strangulation or perforation115 A number of novel endoscopic techniques have recently been described for the treatment of GERD.116 These include (i) endoscopic plicators which place sutures around the LOS, (ii) bulking techniques in which inert substances are injected into the lower oesophagus, and (iii) the STRETTA procedure in which radiofrequency energy is delivered to the LOS and gastric cardia. To date subjects with hiatus hernia have not been included in the case series that have been published. However, none of these techniques correct the anatomical abnormality, and thus are unlikely to be effective in patients who have signicant hiatus hernias.
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Our view of the role of the hiatus hernia in GERD has changed in recent decades. Initially thought to be synonymous with GERD, then in the 1970s and 1980s regarded as an incidental nding, the hiatus hernia is now recognized to be an important aetiological factor at the more severe end of the GERD spectrum. A hiatus hernia impairs LOS competence, reduces LOS pressure and length and alters the opening characteristics of the GOJ, resulting in delayed oesophageal acid clearance and increased oesophageal acid exposure. Numerous studies have shown that hiatus hernia is associated with GERD symptoms, endoscopic oesophagitis, Barretts oesophagus and oesophageal adenocarcinoma. Among patients with GERD, patients with hiatus hernia have more severe disease and poorer response to treatment. Studies on hiatus hernia are hampered by a lack of standardized diagnostic criteria, and hiatal hernia size is frequently not taken into account. This may hamper our understanding of the contribution of the hiatus hernia to GERD, and thus prevent us from effectively managing the condition. Development of a simple method of diagnosing, measuring and reporting a hiatus hernia endoscopically would help to advance our understanding of this important subject. The hiatus hernia is again emerging as an important factor in the pathogenesis of GERD. Although our understanding of its contribution to this condition has advanced, we are still not seeing the full picture. Further work is needed to understand how the hiatus hernia inuences the pathogenesis of GER, progression of GERD and its complications, and the effects of therapy. At the present time, the hiatus hernia is a marker of severe GERD, but its presence per se does not alter management strategies.
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