Abstract】Objective To investigate the efficacy of laparoscopic esophageal hernia (HH) repair with fundoplication on GERD combined with HH and asthma symptoms. Methods Patients with GERD combined with HH admitted to the Second Artillery General Hospital from January 2008 to January 2012 were collected. Questionnaires were used to follow up and evaluate the typical symptoms of GERD and asthma symptom scores and complications before and after surgery. Results A total of 476 cases were included and successfully followed up, of which 90.8%, 1.1%, 5.9%, and 2.3% were type I, II, III, and VI HH, respectively. Patch implantation was performed in 56 cases, and Nissen and Toupet fundoplication were performed in 310 and 166 cases, respectively. The mean follow-up was (4.4±1.3) years, with no serious postoperative complications or deaths. The overall surgical efficiency was 95.5%, and the typical symptom scores of GERD and asthma decreased from (13.4 ± 2.0) and (18.2 ± 2.9) to (3.1 ± 1.7) and (5.2 ± 5.0), respectively (P < 0.001), with postoperative symptom score remission rates of 76.9% and 71.4%, respectively. Conclusion Laparoscopic HH repair with fundoplication is effective in controlling the typical symptoms of GERD and asthma and has a good safety profile. The correlation between GERD, esophageal hiatal hernia and asthma is worth further investigation and study. Keywords: hernia, esophageal hiatus; GERD; asthma; hernia repair; fundoplication GERD is a common disease with a prevalence of about 10%-20% of the population in Western countries [1] and 6%-10% in Asia [2]. Esophageal hiatal hernia (HH) can cause gastroesophageal reflux by weakening the anti-reflux barrier at the diaphragmatic-esophageal junction and esophageal clearance [3].HH, especially in elderly patients [4], has a higher rate of GERD and esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. Patients with GERD have a higher proportion of combined HH than patients without GERD [5-7]. Patients with large HH have more significant acid exposure and reflux symptoms compared to patients with small HH [8]. GERD with combined HH often requires higher doses of anti-reflux medication [9].GERD with combined HH and/or respiratory symptoms is considered an indication for surgery [10-12]. Since laparoscopic fundoplication for GERD with asthma and other respiratory symptoms as the main manifestation was performed in 2008, our center has gradually recognized the important role of HH in the development of GERD GI symptoms and even extraesophageal symptoms, especially GERD-associated asthma. In this study, we investigated the surgical efficacy of laparoscopic HH repair with fundoplication for the treatment of GERD combined with HH and asthma symptoms to provide a clinical basis for improving the diagnosis and treatment of such individuals. Data and methods I. General data From January 2008 to January 2012, 1,869 consecutive patients with GERD admitted to the Second Artillery General Hospital were selected, including 497 (26.6%) patients with HH. The patients were >18 years old and met the following criteria: (1) they had typical GERD symptoms such as significant reflux (acid reflux and/or regurgitation), heartburn or chest pain, combined or not with asthma symptoms such as cough, wheezing and chest tightness. (2) All had a GERD diagnosis confirmed by preoperative evaluation of GERD at our center. (3) All were diagnosed with HH by preoperative gastroscopy and upper gastrointestinal barium angiography.(4) All underwent HH repair and fundoplication (Toupet or Nissen). 2. Methods 1. Surgical methods: All patients underwent laparoscopic HH repair plus Nissen or Toupet fundoplication. Tracheal intubation and general anesthesia were performed. The patient was placed in a supine position with the head high and feet low, and the operator stood between the patient’s legs. A pneumoperitoneum is established and two 10 mm and three 5 mm trocar needles are placed at different locations in the epigastrium. The ligament between the esophageal cardia and the liver was dissociated with an ultrasonic knife, the right diaphragmatic foot and the anterior esophageal peritoneum were free, the ligament between the stomach and the superior pole of the spleen and the short gastric vessels were dissociated, the gastric diaphragm and the esophageal diaphragmatic ligament were cut free, and the left diaphragmatic foot was exposed; the esophagus was free for ≥3 cm to create a posterior esophageal hiatus. The esophageal fissure is narrowed with 2-0 silk interrupted sutures of 2-4 stitches on both sides of the diaphragmatic foot. If the fissure is >5 cm, the diaphragmatic foot is obviously weak or the direct suture tension is too high, the HH patch is used to repair and strengthen both sides of the diaphragmatic foot, and the patch is fixed with sutures or staple gun (titanium) stapling; the fundus of the stomach is pulled from the posterior esophagus through the right side to the anterior esophagus and sutured to the right anterior wall of the esophagus, and the fundus of the left side of the esophagus is sutured to the left anterior wall of the esophagus. A loose fold of 270° is formed (Toupet). Alternatively, the gastric fundus is drawn around the posterior aspect of the esophagus and the fundus wraps around the esophagus 360° (Nissen), with silk sutures securing the folded flap and the esophagus. 2-0 silk sutures are interrupted to secure the folded flap and the diaphragmatic foot for 2 stitches (Figure 1 ). 2. Observation items and criteria: Before and after the anti-reflux surgical treatment, a centralized questionnaire telephone follow-up was performed, and the observation and assessment items were as follows. (1) Preoperative assessment: upper gastrointestinal imaging was performed using upright, semi-recumbent, recumbent, multi-axial and prone head-low-foot-high (foot elevated 10-15°) positions to observe upper gastrointestinal mucosal contours, esophageal morphology, contrast passage and intrathoracic hernia sac. Gastroscopic observation of esophageal mucosa, esophagitis was performed using Los Angeles grading criteria (LA): normal as no esophageal mucosa breakage; LA-A as 1 or more mucosal breaks with ≤5 mm long diameter; LA-B as 1 or more mucosal breaks with >5 mm long diameter but no fused lesions; LA-C as mucosal breaks with fusion but <75% of esophageal circumference; LA-D as mucosal breaks with fusion and The diagnosis was confirmed by biopsy in patients with suspected Barret's esophagus. 24-h esophageal pH monitoring with DeMeester score >14.72 was considered pathologic acid reflux. High-resolution manometry was used to measure the mean lower esophageal sphincter resting pressure (MLESP) with a normal reference value of 13-43 mmHg (1 mmHg=0.133 kPa). (2) Symptom scoring: A self-administered questionnaire grading symptom scoring system was used. Onset frequency score: 0 as no symptoms; 1 as episodes <1/week; 2 as episodes 1-2/week; 3 as episodes 3-4/week; 4 as episodes 5-6/week; 5 as episodes >6/week. Symptom severity score: 0 for no symptoms; 1 for mild symptoms; 2 for mild, with discomfort but not affecting normal life; 3 for moderate, affecting normal life and work; 4 for severe, with great discomfort and partial inability to take care of oneself; 5 for very severe, with inability to take care of oneself or life-threatening, even requiring one or more resuscitations. The frequency of onset score + severity of symptoms score is 0 to 10. Esophageal symptoms included 3 items such as reflux, heartburn and chest pain, with a score range of 0 to 30; asthma symptoms included 3 items such as cough, wheezing and chest tightness, with a score range of 0 to 30. For details of the questionnaire, please refer to the Reflex Diagnostic Questionnaire (RDQ) [13]. The preoperative and postoperative symptom scores were compared and the symptom score remission rate was calculated (the formula is as follows) (3) Evaluation of asthma symptom efficacy [14]: ①Cure: complete disappearance of respiratory symptoms after surgery and complete discontinuation of anti-asthma medication. (ii) Excellent: occasional mild or below symptoms, complete discontinuation of anti-reflux medication or medication reduction more than half the amount before surgery. (③Good: moderate or less frequent asthma symptoms less than 1 time per week. Anti-asthma medications have been reduced to varying degrees. ④ Fair: The severity or frequency of symptoms is reduced by only 1 to 2 points, and the patient continues to have severe or moderate symptoms on a weekly basis. Anti-asthma medication is reduced by less than half a dose. (5) Ineffective: No change in both symptoms and anti-asthma medication. III. Statistical treatment SPSS 13 was used, and paired t-test was used for pre- and post-data comparison, and independent t-test was used for comparison of continuous variables between different groups, and P<0.05 was considered a statistically significant difference. Results I. Clinical data 476 cases were successfully followed up after surgery, 275 males and 201 females; age 21-84 years, mean 50.1 years; 87 smokers and 389 non-smokers; their examination results were compiled (Table 1). 2 to 50 years of GERD, mean (14.7±13.7) years. The follow-up ranged from 2 to 6 years, with a mean of (4.4±1.3) years. 432 (90.8%) of the 476 HH patients had type I (sliding type), 5 (1.1%) had type II (paraesophageal type), 28 (5.9%) had type III (mixed type), and 11 (2.3%) had type VI (combined with herniation of other abdominal organs into the thoracic cavity). A total of 208 cases (43.7%) presented with simple GI symptoms, 47 cases (9.9%) presented with simple asthma symptoms, and 221 cases (46.4%) presented with GI symptoms combined with asthma symptoms, for a total of 268 patients (56.3%) with asthma symptoms. A total of 57 patients (12.0%) had a combination of dysphagia of varying degrees. Patch implantation was performed in 56 cases (11.8%), Nissen fundoplication in 310 cases, and Toupet fundoplication in 166 cases. The overall effective rate of postoperative follow-up was 95.6%, and the scores of digestive symptoms and asthma symptoms in patients with anti-reflux surgery were significantly lower than those before treatment (Table 2), with the efficacy of surgery on asthma grouped as 9.0% cured, 53.6% excellent, 24.3% good, 8.6% fair and 4.5% ineffective. There was no statistical difference between the remission rate of digestive symptoms (reflux, heartburn and chest pain) in patients with combined asthma and the remission rate of digestive symptom scores in patients presenting with digestive symptoms alone (p=0.67) III. Recurrence and complications (Table 3): 24 cases (5.0%) had varying degrees of symptomatic or anatomical recurrence (Figure 2), mostly in patients who had earlier surgery. None of the group with implanted patches had recurrence. Seven of these patients were surgically corrected after a second evaluation with good results. One patient in this group should have splenic hemorrhage in transit to open abdomen, with no serious complications or death. Patients with intraoperative vagus nerve injury are mostly obese, herniation contents contain more tissues, and occur when the surgical field is poorly exposed and adipose tissue is removed; no complications were observed in this group of patients with vagus nerve dissection at follow-up; mural pleura mostly occurs when separating the deep mediastinal esophagus is, and closed drainage is not placed postoperatively, and it mostly heals within 1 week. The pneumoperitoneum-related subcutaneous emphysema of the chest or neck often accompanied by shoulder and back pain mostly resolved within 1 week after surgery and persisted for several weeks after discharge in a few patients; the degree of postoperative dysphagia ranged from choking when eating too fast, too large or too hard food masses to significant difficulty in eating liquid food, which appeared in some patients immediately after surgery and in most patients 5-7 days after surgery and resolved 1 to 2 months after discharge, and 14 patients with significant dysphagia or unsatisfactory relief within several months were discharged from the hospital. The 14 patients with significant dysphagia or unsatisfactory relief within a few months improved significantly after postoperative gastroscopic exploration alone or dilatation with a gastroscopic probe, and the two patients with ineffective dilatation were relieved after secondary surgery to release the fibrous growth of the esophageal fissure and enlarge the fissure; and the preoperative combined dysphagia symptoms were mostly relieved well after surgery. Only a few patients had increased abdominal distension or newly developed abdominal distension, and a few patients had increased gas and intermittent diarrhea or constipation after surgery, which improved to varying degrees after improving gastrointestinal dynamics, regulating intestinal flora or Chinese herbal medicine treatment. Discussion HH and GERD intersect with each other but are not equivalent. More than 95% of HH is type I HH (sliding type) [15]. Asymptomatic sliding HH is not indicated for surgery, but when it causes GERD and complications, it is indicated for surgical repair, and fundoplication should be performed at the same time [11]. Type I HH was also predominant in this group of patients (90.8%). In some cases, HH may also turn into strangulated hernia and require emergency surgery, where type II HH is considered to be prone to incarcerated strangulation and should be more aggressively treated surgically. The Skinner study in the 1960s found a mortality rate of 29% for type II HH with non-operative treatment of intussusception [16]. With the improvement of medical treatment, the mortality rate of type II HH has decreased significantly [17]. None of the patients in our group with type II and type III HH had a history of embedded strangulation. Similar to GERD without HH, indications for surgery in GERD with combined HH include (1) failure of anti-reflux medication (still uncontrolled reflux, or adverse drug reactions), (2) complications of GERD (e.g., Barrett's esophagus, peptic stricture, etc.), and (3) to improve quality of life (not wanting to take medication for a long time or for life, or to bear the ongoing cost of medication) [18 -20]. Patients with combined giant HH often have significant typical GERD symptoms, such as acid reflux and heartburn, and are additionally prone to dysphagia, vomiting, and anemia [16, 17, 21-24]. These hernia-related symptoms are also indicative of surgery. In terms of technical difficulty, small (<3 cm) and moderate HH (3-5 cm) are almost as difficult to operate as GERD without combined HH. In contrast, large HH (>5 cm), especially giant HH (no uniform definition, at least >30% or 50% of the stomach herniated into the thorax, usually type III and VI HH) is the difficult part of anti-reflux surgery. The reasons for this are the markedly enlarged and weak cleft, the markedly abnormal anatomy, the complex and hyperplastic adhesions of the hernia contents, and the tendency to combine with a short esophagus. The short esophagus is considered to be <2-2.5 cm in length after intraoperative separation and release of the abdominal segment, which is difficult to determine accurately preoperatively with the current examination. The true short esophagus (a true short esophagus, but the ventral segment of the esophagus can exceed 2.5 cm after a reasonable release); and the true non-extendable short esophagus (a true short esophagus, but the ventral segment of the esophagus cannot reach 2.5 cm after a release). Short esophagus can cause difficulties in completing a fundoplication with suitable tension, which is very important and has a great impact on the surgical outcome, postoperative discomfort and postoperative recurrence. This study contains 39 cases of type III and VI HH, and the presence of insufficient length of ventral segment esophagus after lower esophageal freeing in early cases is an important reason why more recurrent cases in this group are patients operated in early years. In this group of late cases (after 2009), all ventral segments of the esophagus could reach the required length after adequate release freeing. There is no consensus on the indication for patch implantation, which is generally considered to be applicable to giant hiatal hernias. Zhang Cheng et al [27] used it for patients with a hiatal hernia >5 cm, or with excessive direct suture tension, and achieved good results. Both permanent (non-absorbable) and biological (absorbable) patches are safe and help to reduce the recurrence of HH [28]. Only a few patients developed complications such as esophageal erosion and lower esophageal obstruction after implantation of permanent patches [29]. In our group, there was no case of esophageal erosion or long-term severe dysphagia due to patch implantation. The technique and method of implantation are important factors in the occurrence of patch-related complications. A patient with lower esophageal obstruction due to improper method of permanent patch implantation in an outside hospital was admitted to our center and was given a partial resection of the patch with relief of symptoms [30]. A recent study by Schmidt et al [31] found that implantation of a biopatch in small esophageal hiatal hernias (<125px) significantly reduced the recurrence rate at 1 year postoperatively (0%:16%) compared to diaphragmatic pedicle suturing alone. Currently, a wide variety of esophageal hiatal hernia patches are commercially available, but most are expensive, which is an important factor in increasing the cost of the procedure, and adequate informed patient consent should be obtained preoperatively. Proton pump inhibitors (PPIs) are widely used clinically to treat esophageal symptoms of GERD and have been shown to be effective [32]. However, the efficacy of PPIs for GERD-related asthma is currently controversial, with several randomized controlled trials showing limited anti-asthmatic effects of PPIs compared with placebo [33]. However, PPI still has a high value for well-selected patients with asthma combined with GERD. We believe that the inability of PPI to improve barrier defects in the esophagus, such as HH and its resulting reflux of gastric contents, is an important reason for the limited effect on GERD-associated asthma. Surgery can reconstruct the anti-reflux anatomy and function of the esophagus and reduce the invasion and reflexes caused by reflux in terms of time, frequency, volume and height of reflux. Fundoplication has been shown to be effective in controlling the classic symptoms of GERD [19], and anti-reflux surgery for extraesophageal symptoms of GERD has shown encouraging results [34-35]. Our group mainly presented with asthmatic symptoms in 268 cases, most of whom had severe symptoms and poor results with long-term anti-asthmatic medication. However, these patients showed significant improvement in both esophageal symptoms and asthma symptoms after anti-reflux treatment. This study and previous work have shown that if a patient's respiratory symptoms such as asthma are proven to be related to their GERD, effective control of asthma symptoms may be achieved with effective anti-reflux therapy such as HH repair with fundoplication [14, 36-39]. Patients may require secondary surgery (incidence 0-15%) for recurrence of symptoms and complications due to herniation of the folded flap into the chest after anti-reflux surgery, slipped folded flap, overtightened fold, paraesophageal hernia and poorly positioned fold [40]. Secondary evaluation and surgery remain safe and effective [41], as confirmed by the present study. Common complications of laparoscopic HH repair surgery include visceral injury, bleeding, postoperative dysphagia, and gastrointestinal dysfunction. In the literature, the incidence of postoperative dysphagia ranges from 10% to 50% in the early stage and 3% to 24% in the late stage, the incidence of gastric distention syndrome ranges from 1% to 85%, the incidence of diarrhea ranges from 18% to 33%, the incidence of intermediate open abdomen ranges from 0 to 24%, the incidence of reoperation ranges from 0 to 15%, and the mortality rate is <1%. The vast majority of complications resolved within 3-6 months after surgery, and postoperative dietary modification, pharmacological modifications, and esophageal dilatation therapy were beneficial in relieving complications [40]. There were no cases of intermediate opening and death in our patients, with the highest incidence of short-term postoperative dysphagia (34.7%), mostly aggravated 5-7 d postoperatively when folded flap edema was most pronounced. Most patients can be relieved on their own, and those with significant swallowing difficulties or unsatisfactory time relief can be significantly improved after simple gastroscopic exploration, gastroscopic probe expansion or secondary surgical release. Abdominal distension and diarrhea also improve to varying degrees with improved gastrointestinal dynamics, regulation of intestinal flora or Chinese herbal medicine. It should also be emphasized that complications are prevention-oriented, and preoperative evaluation should be improved, surgical skills should be improved, and intraoperative and postoperative complications should be managed promptly [31, 42-43]. HH repair with fundoplication is safe and effective for the treatment of GERD combined with HH and asthma symptoms, and both their GI symptoms and asthma symptoms can be significantly relieved, which is worthy of further promotion and application. Patients with asthma who do not respond well to respiratory medications should be encouraged to undergo gastroesophageal reflux evaluations, and the results of these evaluations may suggest an indication for anti-reflux therapy. This study is a single-center non-randomized controlled study, which is methodologically deficient, but this study has important value in suggesting a correlation between HH, GERD and asthma, and is a guide for further studies.