**Robotic Surgery and Functional Esophageal Disorders: A Systematic Review and Meta-Analysis**

**Sara Vertaldi 1,\* , Anna D'Amore <sup>1</sup> , Michele Manigrasso <sup>2</sup> , Pietro Anoldo <sup>2</sup> , Alessia Chini <sup>1</sup> , Francesco Maione <sup>1</sup> , Marcella Pesce <sup>1</sup> , Giovanni Sarnelli <sup>1</sup> , Giovanni Domenico De Palma <sup>1</sup> and Marco Milone <sup>1</sup>**

	- **\*** Correspondence: vertaldisara@gmail.com; Tel.: +39-340-86-03-360

**Abstract:** The functional disease of the esophago-gastric junction (EGJ) is one of the most common health problems. It often happens that patients suffering from GERD need surgical management. The laparoscopic fundoplication has been considered the gold standard surgical treatment for functional diseases of the EGJ. The aim of our meta-analysis is to investigate functional outcomes after robotic fundoplication compared with conventional laparoscopic fundoplication. A prospective search of online databases was performed by two independent reviewers using the search string "robotic and laparoscopic fundoplication", including all the articles from 1996 to December 2021. The risk of bias within each study was assessed with the Cochrane ROBINS-I and RoB 2.0 tools. Statistical analysis was performed using Review Manager version 5.4. In addition, sixteen studies were included in the final analysis, involving only four RCTs. The primary endpoints were functional outcomes after laparoscopic (LF) and robotic fundoplication (RF). No significant differences between the two groups were found in 30-day readmission rates (*p* = 0.73), persistence of symptomatology at follow-up (*p* = 0.60), recurrence (*p* = 0.36), and reoperation (*p* = 0.81). The laparoscopic fundoplication represents the gold standard treatment for the functional disease of the EGJ. According to our results, the robotic approach seems to be safe and feasible as well. Further randomized controlled studies are required to better evaluate the advantages of robotic fundoplication.

**Keywords:** robotic fundoplication; laparoscopic fundoplication; reflux; hiatal hernia; functional outcomes

### **1. Introduction**

The functional disease of the esophago-gastric junction (EGJ) is one of the most common health problems, affecting more than 50% of the world's population and resulting in a serious deterioration of quality of life with important economic implications [1]. Medical treatment with a proton pump inhibitor (PPI) can help control reflux symptoms, but on the other hand, it implies cost-effective, long-lasting medicine-based treatment. It often happens that GERD patients do not achieve complete control of the symptoms, needing surgical management [2].

The laparoscopic fundoplication has been performed with patient satisfaction since its introduction during the twentieth century, becoming the gold standard for the surgical treatment of functional disease of the EGJ [3,4].

Additionally, after the first robotic-assisted Nissen fundoplication (RALF) reported by Cadiere in 1999 [5], it has been debated if the robotic approach could improve surgical outcomes due to the three-dimensional view and the enhanced manipulation of instruments [6] compared with the conventional laparoscopic fundoplication (CLF). Several previous studies have demonstrated the safety and feasibility of a robot-assisted approach in this setting [7–10].

The aim of our meta-analysis is to investigate the functional outcomes after minimally invasive surgery, both laparoscopic and robotic, for the treatment of functional disease of the EGJ.

**Citation:** Vertaldi, S.; D'Amore, A.; Manigrasso, M.; Anoldo, P.; Chini, A.; Maione, F.; Pesce, M.; Sarnelli, G.; De Palma, G.D.; Milone, M. Robotic Surgery and Functional Esophageal Disorders: A Systematic Review and Meta-Analysis. *J. Pers. Med.* **2023**, *13*, 231. https://doi.org/10.3390/ jpm13020231

Academic Editor: Marijn Speeckaert

Received: 30 October 2022 Revised: 7 January 2023 Accepted: 22 January 2023 Published: 27 January 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

#### **2. Materials and Methods**

#### *2.1. Literature Search and Eligibility Criteria*

This systematic review complied with PRISMA (preferred reporting items for systematic reviews and meta-analyses) reporting standards [11] and was developed in line with MOOSE (meta-analysis of observational studies in epidemiology) guidelines [12].

A prospective search of Embase, PubMed, SCOPUS, and Web of Science was performed using the search string "robotic and laparoscopic fundoplication".

The analysis included all the articles from 1996 to December 2021. The last search was performed in January 2022.

Case reports, case series without a control group, indexed abstracts of posters and podium presentations at international meetings, and non-English articles were excluded. Systematic reviews and meta-analyses were only consulted to identify additional studies of interest. In addition, the reference lists of the retrieved studies were manually reviewed. In cases of overlapping series in different studies, only the most recent article was included. Publications with no data about functional results after minimally invasive fundoplication were also excluded.

The research question was structured using the PICO (problem/population, intervention, comparison, and outcome) framework. The populations of interest included patients affected by functional esophageal disease (GERD, hiatal hernia, or paraesophageal hernia). The intervention was robotic fundoplication, and the comparator was laparoscopic fundoplication. The functional outcomes after surgery were analyzed: 30-day readmission; persistent symptomatology at follow-up, including delayed gastric emptying; postoperative pyrosis or dysphagia; disease recurrence; need for reintervention.

The literature search and study selection were performed independently by two reviewers (S.V. and A.D.), showing a high level of inter-reader agreement (κ = 1). In case of disagreement, a third investigator (Mi.Ma.) was consulted, and an agreement was reached by consensus.

#### *2.2. Data Extraction and Assessment of Risk of Bias in Included Studies*

The titles and abstracts were screened and reviewed independently by S.V. and A.D., followed by full-text reading. In addition, ineligible studies were excluded after full-text reading. The data extraction was conducted independently and in duplicate by the two reviewers. Further, the data extraction form was created in accordance with the guidelines in the Cochrane Handbook for systematic reviews of interventions by the consensus of both reviewers.

The following data were extracted from each included study: first author, year of publication, study design, period of study, surgical indication, sample size, number of patients in each surgical group, gender, mean age, mean BMI, type of intervention (Nissen, Dor, Toupet, or no fundoplication), redo surgery, operative time, 30 days readmission, mean follow-up, persistence of symptomatology at follow-up, complaining of delayed gastric emptying, pyrosis, or dysphagia, needing of reintervention. The data extracted from studies were then separated into the following sections: study characteristics, population characteristics, intervention characteristics, and functional outcomes.

Additionally, after data extraction was completed, the risk of bias within each study was assessed.

The Cochrane ROBINS-I (Risk of Bias in Non-randomized Studies of Interventions) tool [13], which is a risk of bias tool to assess the quality of non-randomized studies of interventions, was adopted to evaluate the methodological quality of each cohort-type study. The scoring system encompasses seven domains. The first two domains, covering confounding and selection of participants into the study, address issues before the start of the interventions that are to be compared ("baseline"). The third domain addresses the classification of the interventions themselves. The other four domains address issues after the start of interventions: biases due to deviations from intended interventions, missing data, measurement of outcomes, and selection of the reported result. The categories for

risk of bias judgments are "low risk", "moderate risk", "serious risk", "critical risk", and "no information" when insufficient data are reported to permit a judgment.

In cases of randomized controlled trials (RCTs), the risk of bias was evaluated using the revised Cochrane Risk of Bias tool (RoB 2.0) [14]. According to this scoring system, seven domains were evaluated as "low risk of bias", "high risk of bias", or "unclear" according to the reporting on sequence generation, allocation concealment, blinding of participants, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, and other potential threats to validity.

### *2.3. Statistical Analysis*

The statistical analysis was performed using Review Manager (RevMan Version 5.4, Copenhagen, Denmark: The Nordic Cochrane Centre, The Cochrane Collaboration, 2020).

The primary outcomes of this study were the functional results after robotic fundoplication in patients suffering from GERD, hiatal hernia, or paraesophageal hernia compared to a laparoscopic approach. In addition, the differences among cases and controls were expressed as risk difference (RD) with pertinent 95% CI for dichotomous variables, to maintain analytic consistency and include all available data, according to Messori et al. [15]; the differences among cases and controls were expressed as mean difference (MD) with pertinent 95% confidence intervals (95% CI) for continuous variables. The risk difference represents the difference between the observed risks (proportions of individuals with the outcome of interest) in the two groups. If studies reported only the median, range, and size of the trial, the means and standard deviations were calculated according to Luo et al. and Wan et al. [16,17]. When studies reported only means for continuous variables and the sample size of the trial, a standard deviation was imputed, according to Furukawa et al. [18].

The overall effect was tested using Z scores, and significance was set at *p* < 0.05. Statistical heterogeneity between studies was tested by the Q statistic and quantified by the I 2 statistic, a measurement of the inconsistency across study results and a description of the proportion of total variation in study estimates, that is due to heterogeneity rather than sampling error. In detail, an I<sup>2</sup> value of 0% indicates no heterogeneity, 25% low, 25–50% moderate, and >50% high heterogeneity [19].

According to DerSimonian and Laird [20], the random-effects model was used for all analyses to account for the heterogeneity among included studies.

The presence of publication bias was investigated through a funnel plot, where the summary estimate of each study (Risk Difference) was plotted against a measure of study precision (Standard Error). In addition to visual inspection and the funnel plot, symmetry was tested using Egger's linear regression method. [21] *p* values < 0.05 were considered statistically significant.

#### **3. Results**

#### *3.1. Study Selection*

A total of 339 articles were identified from electronic databases. After the removal of duplicate studies, 287 publications were screened according to the PRISMA flowchart (Figure 1).

Of the 72 articles that were selected for the title and abstract, 51 studies were excluded because they did not meet the inclusion criteria. Furthermore, the online full version of five articles was not available, and it was not possible to extract data from the abstract. The remaining 16 studies [22–37] were selected as they met the eligibility criteria and were included in the final analysis.

(Figure 1).

A total of 339 articles were identified from electronic databases. After the removal of duplicate studies, 287 publications were screened according to the PRISMA flowchart

**Figure 1.** PRISMA 2020 flow diagram **Figure 1.** PRISMA 2020 flow diagram.

#### Of the 72 articles that were selected for the title and abstract, 51 studies were excluded *3.2. Baseline Characteristics of the Included Studies*

Major characteristics of the studies are shown in Table 1

because they did not meet the inclusion criteria. Furthermore, the online full version of five articles was not available, and it was not possible to extract data from the abstract. The remaining 16 studies [22–37] were selected as they met the eligibility criteria and were included in the final analysis. *3.2. Baseline Characteristics of the Included Studies* This meta-analysis included 16 monocentric studies published between 2002 and 2021, involving 1064 patients suffering from GERD, hiatal hernia, or paraesophageal hernia, whereof 618 underwent laparoscopic and 445 robotic fundoplication, respectively. There were 4 RCT [27,32–34], 10 retrospective [22–26,28–30,35,36], and 2 prospective [31,37] trials. The number of patients ranged between 12 and 687, the mean age was between 3.8 and 72.5 years, and the mean BMI varied from 10.1 kg/m<sup>2</sup> to 37.0 kg/m<sup>2</sup> .

Major characteristics of the studies are shown in Table 1.

This meta-analysis included 16 monocentric studies published between 2002 and 2021, involving 1064 patients suffering from GERD, hiatal hernia, or paraesophageal hernia, whereof 618 underwent laparoscopic and 445 robotic fundoplication, respectively. There were 4 RCT [27,32–34], 10 retrospective [22–26,28–30,35,36], and 2 prospective [31,37] trials. The number of patients ranged between 12 and 687, the mean age was between 3.8 and 72.5 years, and the mean BMI varied from 10.1 kg/m<sup>2</sup> to 37.0 kg/m<sup>2</sup> . Intervention characteristics are described in detail in Table 2. Nissen fundoplication (360◦ ) was performed in fourteen studies [22,24–28,30–37], Toupet fundoplication (270◦ ) was reported in seven papers [23,25,29,31,35–37], Dor fundoplication (180◦ ) was described in two articles [29,36], while in only one study [35] Watson partial anterior fundoplication was performed. Only two studies [22,36] included redo fundoplications.

*J. Pers. Med.* **2023**, *13*, 231









