Frailty predicts recurrence after laparoscopic Nissen fundoplication with mesh cruroplasty for giant sliding hiatal hernia with severe reflux esophagitis in elderly patients: a multicenter retrospective study

This retrospective multicenter study evaluated 266 consecutive elderly patients aged ≥ 60 years [https://www.who.int/news-room/fact-sheets/detail/ageing-and-health]. The inclusion criteria included elderly patients who underwent LNF with mesh cruroplasty for giant (> 5 cm) [24] sliding HH with severe GERD (DeMeester score > 100) and refractory symptoms despite optimal medical therapy and were treated between March 2016 and March 2022. Patients were stratified into two groups based on HH recurrence: non-recurrent (n = 241), and recurrent (n = 25). The inclusion criteria were formulated according to the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) guidelines for GERD surgery for type I HH [25, 26]. The inclusion and exclusion criteria for the study participants are shown in Fig. 1. All participants exhibited a hypotensive lower oesophagal sphincter (LES) on high-resolution manometry (HRM) and abnormal pH impedance testing (DeMeester score > 100). Furthermore, the patients were surgically fitted, and informed consent was obtained prior to the procedure. The study participants completed a standardized three-year follow-up period. The study protocol was approved by the Institutional Ethics Committee and conducted in accordance with the principles of the Declaration of Helsinki, with registration in a clinical trial (NCT06935617).

The primary outcome was the incidence of postoperative recurrent sliding HH confirmed via clinical symptoms, barium swallow, endoscopy, or high-resolution manometry (HRM). Recurrence was defined as proximal displacement of the Z-line and gastric folds ≥ 2 cm above the diaphragmatic hiatus. The term ‘giant or large HH’ was defined as HH > 5 cm, with intraoperative crural defect size measured using sterile tape or calibrated graspers [27]. The secondary outcome was the association between frailty and HH recurrence assessed using the Clinical Frailty Scale (CFS).

The modified DeMeester scoring system evaluates typical symptoms, including heartburn (HB), regurgitation, and dysphagia [28]. GERD severity was evaluated using the modified DeMeester score (DMS). DMS < 14.72: No GERD. DMS 14.72–50: Mild GERD. DMS 51–100: Moderate GERD. DMS > 100: Severe GERD. Testing was performed after discontinuation of acid-suppressive therapy. HRM was conducted to assess the LES pressure and configuration [29]. The severity of esophagitis was graded using the Los Angeles classification [30]. Failed fundoplication was classified according to Horgan criteria [31]. Intraoperative endomanometric evaluation of LES pressure and configuration was performed as previously described [32]. The Clinical Frailty Scale (CFS) was used to evaluate frailty as it is a validated tool for assessing functional decline in elderly surgical patients [33].

Age, gender, smoking, diabetes mellitus (DM), coronary heart diseases (CHD), hypertension (HT), body mass index (BMI), ASA, Charlson comorbidity index, Frailty index, Times with symptoms before surgery (months), Response to acid reducing medications before surgery, Haitus hernia size cm, Preoperative initial symptoms, Modified demeester score of severity of initial symptoms, Preoperative esophagitis grading, Preoperative lower esophageal sphincter manometry (mmhg), Preoperative DeMeester score, Operative time (min), use of intraoperative endomanometry, Intraoperative esophageal sphincter manometry (mmhg), time taken to perform intraoperative manometry(min), time taken to perform intraoperative endoscope(min), Intraoperative complications, Endomanometry related complications, Dealing with intraoperative complications, Postoperative length of hospital stay, Early Postoperative complications, Clavien-Dindo (CD) classification, readmission within 30days, Dealing with early postoperative complications, 30 days mortality, Causes of mortality, Size of recurrent hernia (cm), time from surgery to recurrence(months)(median, IQR), Clinical Forms of recurrence, Treatment of recurrent HH, Causes of recurrence detected during reoperation, surgery for recurrent HH, Postoperative recurrent symptoms, Types of postoperative recurrent symptoms, Severity of recurrent GERD, DeMeester score of severity of recurrent symptoms, Appearance of new postoperative symptoms, Postoperative dysphagia score, Postoperative esophagitis grading, Lower esophageal manometry at the end of the study.

All patients received Premedication: Oral flunitrazepam (1 mg), Induction: Etomidate (0.3 mg/kg) + fentanyl (2 µg/kg), Maintenance: Isoflurane (1–1.5 MAC) + fentanyl bolus (1 µg/kg/h), and neuromuscular blockade: Atracurium (0.5 mg/kg). All patients underwent hiatal hernia mesh cruroplasty with concomitant laparoscopic Nissen fundoplication (LNF), which is a well-established approach for managing giant sliding hiatal hernias (HH) with severe GERD in our centers. LNF is routinely performed alongside hiatal closure and mesh fixation in patients with HH to address both anatomical (hernia reduction, crural repair) and functional (anti-reflux) components. Operative steps were performed as previously described [24, 32, 34]. Dissection of the diaphragmatic hiatus to detect giant hiatal defect [Supplementary Fig. 1]. Mediastinal dissection was completed to obtain at least 3 cm of intraabdominal esophagus without tension. Posterior hiatoplasty was done by approximation of the diaphragmatic crura posterior to the esophagus using 3–4 interrupted non-absorbable braided polyester sutures (Ethibond Excel, Ethicon Inc., Somerville, NJ, USA) [Supplementary Fig. 2]. The sutures were deeply placed, including the subdiaphragmatic fascia, immediate sequential suture tying to prevent fouling, and objective hiatal calibration. When difficult crural defects are closed with poor tissue quality characterized by attenuated muscular fibres and minimal fascial components, a primary tension-free crural approximation is often unachievable. To facilitate medial crural mobilization, we made right-sided lateral relaxing incisions. In order to avoid postoperative dysphagia, the cura was closed leaving almost 5 mm between the apex of the cruroplasty and the posterior wall of the esophagus. After crural repair, the diaphragmatic defects were reinforced with a U-shaped fenestrated polypropylene-based composite mesh (Ventralight™ ST Mesh, C.R. Bard, Inc.; Product #5954113) secured to the approximated crura using interrupted non-absorbable polypropylene sutures (2 − 0), or titanium helical tackers [Supplementary Fig. 3]. A 360° Nissen fundoplication was then constructed using 2–3 interrupted non-absorbable sutures (Ethibond™ 2 − 0, Ethicon) to create a 2-cm posterior wrap. Before fundoplication, oesophagal calibration was performed using a 52-French bougie to ensure the appropriate wrap dimensions. After LNF wrap formation, intraoperative HRM and endoscopy were performed only in the patients with endomanometric LNF. Postoperative admission to the intensive care unit (ICU) was performed when clinically indicated. All patients underwent transthoracic echocardiography within 6 h postoperatively to evaluate pericardial effusion, which was performed by certified cardiac sonographers.

Patient Characteristics and Preoperative Data are summarized in Table 1. Our study included 266 patients who underwent LNF, with 241 (90.6%) maintaining a successful repair and 25 (9.4%) developing recurrent HH. The baseline characteristics were similar between the groups, except for frailty status (p = 0.02) and duration of preoperative symptoms (p = 0.03), which showed statistically significant differences. Clinical data before surgery showed no significant differences in mean age (66.92 ± 4.3vs 67.79 ± 3.7 years, p = 0.25); the majority of patients in both groups were female (72.6% vs. 80%, p = 0.4), The mean BMI (31.36 ± 3.4 vs. 31.7 ± 3.9, p = 0.62), HB (73.4% vs. 68%, p = 0.4), regurgitation (20.8% vs. 32%, p = 0.3), hernia size (6.5 ± 0.8 cm vs. 6.4 ± 0.7, p = 0.31), mean Charlson comorbidity index (6.5 ± 1.7 vs. 6.7 ± 2.2, p = 0.58) and, grade C esophagitis (63.9% vs. 68%, p = 0.4) in the non-recurrence and the recurrence group, respectively. The frailty index was significantly associated with recurrence, with a higher proportion of patients with moderate and severe frailty in the recurrence group (44% vs. 17% and 20% vs. 13.3%, respectively; P = 0.02). Most preoperative initial symptoms were heartburn (HB) (73.4% vs. 68%, p = 0.2), with grade III HB being the most common Modified DeMeester score in both groups (51.5% vs. 48%). The median Preoperative DeMeester scores were 114(107–122) and 110(105–120) (p = 0.23) in the two groups, respectively.

All procedures were completed laparoscopically without major complications. The median operative time was significantly longer in the recurrence group (71 [57–110] min vs. 57 [55–70] min; p = 0.009). The use of intraoperative manometry differed significantly between groups (47.7% vs. 20%, p = 0.008). Three patients (1.2%) in the recurrence group experienced HRM/endoscopy-related complications: esophageal wall bleeding (n = 2, 8%) managed with argon plasma coagulation and epistaxis (n = 1, 4%) controlled with nasal packing. The mean duration of HRM (32.5 ± 4.6 vs. 35.8 ± 5.2 min, p = 0.11) and endoscopy (20 [16–24] vs. 18 [15–23] min, p = 0.42) did not differ significantly between groups. The mean postoperative hospital stay was significantly longer in the recurrent group (2.4 ± 0.5 vs. 2.7 ± 0.5 days, p = 0.01). Superficial surgical site infections (0.4% (n = 1) vs. 4% (n = 1), p = 0.2), organ/space infections (8% (n = 2) vs. 0%), and 30-day mortality rates (2.5% (n = 6) vs. 4% (n = 1), p = 0.6) were observed in the recurrent and nonrecurrent groups, respectively.

The median size of the recurrent HH was 5.2 cm (IQR 4.1-6.0), with recurrence occurring at a median of 16 months (IQR 13–20) postoperatively. While most recurrences were symptomatic (88%(n = 22]), we identified three asymptomatic patients (12%) through routine imaging. Nearly half of the recurrent cases (n = 12, 48%) required reoperation primarily through laparoscopic approaches (n = 8, 32%). Intraoperative findings during revision surgery revealed several failure mechanisms, including crural closure failure (n = 4, 16%), suture breakdown (n = 5, 20%), mesh disruption (n = 1, 4%), and type IA herniated fundoplication (n = 1, 4%). Postoperatively, recurrent GERD symptoms were significantly more prevalent in the recurrence group (88% vs. 0.8%, p < 0.001), with HB (n = 14, 56%) and regurgitation (n = 8, 32%) being the most common. The objective assessment revealed severe GERD (DeMeester score > 100) in 48% (n = 12) of recurrent patients. High-resolution manometry demonstrated lower LES pressures in the recurrence group (15–16 mmHg vs. 15–19 mmHg, p = 0.02), while 24-hour pH monitoring showed significantly greater acid exposure (total time pH < 4:23 vs. 3, p < 0.001; supine reflux: 16 vs. 3, p < 0.001). Endoscopic evaluation revealed higher grades of esophagitis (LA classification grade C/D, 48%) in the recurrent patients.

Multivariate analysis confirmed that the frailty index (odds ratio [OR], 1.4; 95% CI, 1.003–1.982, p = 0.04) and postoperative length of hospital stay (OR, 3.6; 95% CI, 1.4–9.1, p = 0.005) were independent risk factors for recurrence (Table 4).

Our study addresses a critical knowledge gap by demonstrating that frailty independently predicts recurrence in EP with large HH (> 5 cm) and severe GERD (DeMeester > 100), showing a 9.4% recurrence rate, which compares favorably with published rates of 10.1–42% [35‐38] and higher than other study [39]. Multivariate analysis confirmed frailty as a key determinant, with survival curves revealing that moderately/severely frail patients experienced 80–90% 1-year recurrence versus > 50% 2-year recurrence-free survival in fit patients, whereas the median time-to-recurrence decreased progressively from > 23 months to 9 months across frailty strata. The predominant failure mechanism, crural suture breakdown, aligns with prior reports [40]. Our reduced incidence of recurrent sliding HH was likely due to rigorous preoperative smoking cessation, aggressive antiemetic/antitussive protocols, and meticulous surgical techniques. Polypropylene-based composite mesh reinforcement (U-shaped configuration with a preserved esophageal cuff) provides additional durability benefits through circumferential tissue contact and overlap, which is consistent with biomechanical principles. Mesh-related complications can be avoided by careful tissue spacing [41‐43]. These findings underscore the interplay between patient factors (particularly frailty) and technical precision in determining surgical outcomes in this complex population.

Our findings establish frailty as a critical, modifiable risk factor for recurrent HH, distinct from the traditional anatomical or technical considerations. A striking dose-dependent relationship was observed, where moderate/severe frailty predicted a high recurrence rate. Conventional paradigms have focused solely on BMI, hernia size, or transient stressors [16, 37, 44]. We recommend routine frailty screening for patients with giant HH. These results are consistent with those of a previous study linking frailty to poor surgical outcomes [45]. A gradual decrease in physiological reserve occurs with aging; however, this decrease is accelerated in frailty, and homoeostatic mechanisms begin to fail [46]. Therefore, an important aspect of frailty is how the complex mechanisms of aging promote a cumulative decline in several physiological systems, subsequent depletion of homoeostatic reserves, and vulnerability to disproportionate changes in health status after minor stressor events [47].

Frailty arises from cumulative dysfunction across the neurological, endocrine, immune, and musculoskeletal systems, impairing stress response and tissue repair. Neurologically, frailty-associated hippocampal dysfunction promotes chronic glucocorticoid excess [48], inducing diaphragmatic sarcopenia and connective tissue catabolism, which in turn promotes muscle catabolism (sarcopenia), weakens the diaphragmatic crura and LES, and increases the risk of HH recurrence. Dysautonomia may disrupt gastroesophageal motility and exacerbate gastroesophageal reflux disease (GERD) and mechanical stress during crural repair. Neuroinflammatory mediators (elevated IL-6/TNF-α) increase in frail persons [49] and impair wound healing through matrix metalloproteinase activation, which impairs postoperative healing of the fundoplication site and reduces diaphragmatic strength. Additionally, delirium risk compromises postoperative compliance with postoperative restrictions (e.g., lifting, bending), aspiration risk due to impaired swallowing coordination, prolonged immobilization, delayed recovery, stress of repair and modifications (e.g., avoiding large meals), medication regimens (e.g., PPIs and prokinetics), and lifestyle restrictions (e.g., weight management and smoking cessation) [50]. Immunologically, the pro-inflammatory mediator associated with frailty generates glycation endproducts that disrupt crural collagen integrity [51]. Muscularly, sarcopenia is defined as the progressive loss of skeletal muscle mass, strength, and power and is regarded as a key component of frailty [52]. Loss of muscle strength and power may be more important than changes in muscle mass [53]. Under normal circumstances, muscle homeostasis is maintained through a delicate balance between new muscle cell formation, hypertrophy, and protein loss. This balance is coordinated by the brain, endocrine system, and immune system and is affected by nutritional factors and the amount of physical activity. The adverse neurological, endocrine, and immune components of frailty have the potential to disrupt this delicate homoeostatic balance and accelerate the development of sarcopenia. Loss of muscle mass and strength compromises crural integrity, reduces functional ability, and increases mechanical strain during repair. Our results align with evolving geroscience frameworks [45‐46] while offering specific clinical applicability; frailty assessment better predicts vulnerability than chronological age or isolated risk factors.