Factors Related to Textbook Outcome in Laparoscopic Liver Resections: a Single Western Centre Analysis

Introduction The selection of the most informative quality of care indicator for laparoscopic liver surgery (LLS) is still debated; among those proposed, textbook outcome (TO) seems to provide a compositive measure of the outcomes of surgery. The aim of this study was to investigate the factors related with the TO in a cohort of patients who underwent LLS. Methods Patients who underwent LLS from 2014 to 2021 were included. TO for LLS (TOLLS) was defined as: R0 resection, absence of intraoperative incidents, severe complications, reintervention, 30-day readmission and in-hospital mortality. When also considering no prolonged length of hospital stay (LOS), the outcome was called TOLLS+. Results Four hundred twenty-one patients were included; TOLLS was achieved in 80.5%, TOLLS+ in 60.8% cases. R0 resection was obtained in 90.2% cases, intraoperative incidents occurred in 7.8%, severe complications in 5.0%, reintervention in 0.7%, readmission in 1.4% and in-hospital mortality in 0.2%. 32.5% of patients showed prolonged LOS. After univariate and multivariate analysis, factors influencing TOLLS were age (OR 0.967; p=0.003), concomitant surgery (OR 0.380; p=0.003), operative time (OR 0.996; p=0.008) and blood loss (OR 0.241; p<0.001); factors influencing TOLLS+ were ASA-score (OR 0.533; p=0.008), tumour histology (OR 0.421; p=0.021), concomitant surgery (OR 0.293; p<0.001), operative time (OR 0.997; p=0.016) and blood loss (OR 0.361; p=0.003). Conclusions TOLLS can be achieved in most patients undergoing LLR, and it seems to be influenced mostly by surgery-related factors; conversely, TOLLS+ is achieved less frequently and seems to be influenced also by patient- and tumour-related factors. Supplementary Information The online version contains supplementary material available at 10.1007/s11605-022-05413-x.


Background
In the last decades, laparoscopic liver surgery (LLS) has proven to be feasible and safe for the treatment of both benign and malignant liver diseases, showing benefits when compared with open surgery, especially in terms of postoperative morbidity and length of hospital stay. 1 Alongside the worldwide spread of LLS, surgical quality assessment is becoming crucial; although surgical outcomes have been used as a tool for assessing quality, they typically do not reflect the multidimensionality of the surgical process. Moreover, the reliability of single-risk-adjusted outcome measure reported to be low for differentiating hospital performance. 2,3 Given these reasons, the identification of the most informative quality of care indicator is still a matter of debate in literature.
Composite outcomes have been proposed to avoid these limitations, combining multiple outcomes into a single summary measure. 3 The most known and used combined measure is called textbook outcome (TO), an all-or-none combined outcome tool that includes peri-operative outcomes indexes of an optimal peri-operative care. While TO was evaluated in many surgical areas and disciplines, [4][5][6] a proper definition and evaluation for LLS is still lacking; furthermore, analysis of factors influencing TO is still controversial.
In a recently published, multicentric study, Görcec et al. tried to give a definition of textbook outcome for laparoscopic liver surgery (TOLLS) based on an internationally conducted survey involving members of the European-African and International Hepato-Pancreato-Biliary Association and identified the most important influencing factors. 7 The aims of this study are to evaluate and validate the so-defined TOLLS on a western tertiary HPB referral centre case-series, and to analyse the factors related with its achievement.

Data Source and Study Population
Patient data were obtained from a prospectively maintained, anonymized database of all the patients undergoing LLS at General and Hepatobiliary Surgery Division of University of Verona, Italy. All patients who underwent surgery between January 2014 and June 2021 were considered for the study. Inclusion criteria were age ≥ 18 years, at least one laparoscopic liver resection performed, 90-day follow-up and the availability of data regarding intra-operative events, post-operative complications, length of hospital stay, postoperative readmission or mortality and state of the resection margins. Patients undergoing cyst fenestration or tumour ablation were excluded; all patients missing one or more data needed to evaluate the TO were excluded. This study was reviewed and approved by the Ethics committee of our institution.

Data Collection
Demographic and clinical data analysed included were gender, age, body mass index (BMI), American Society of Anaesthesiologists (ASA) class, Charlson comorbidity score (CCs), liver disease, the presence of clinical portal vein hypertension (assessed by spleen diameter, presence of gastro-oesophageal varices or platelets count ≤ 100,000), platelets count, pathological diagnosis of the liver tumour, number of tumours, size of the main lesion and its proximity to major vessels. Moreover, we considered previous abdominal non-hepatic or hepatic surgery and neo-adjuvant chemotherapy, concomitant surgical procedures (small or large bowel resection, hepatic hilar and local lymphadenectomy, main bile duct resections and biliary-jejunal reconstruction). Minor surgical procedures as cholecystectomy or ventral/inguinal hernia repair were not considered. The types of resections were categorised (minor vs technically and anatomically major resections) according to the Brisbane nomenclature and the Southampton guidelines for laparoscopic liver surgery statements; 1,8 in particular, while anatomically major resections were defined as resections of three or more Couinaud segments, whereas technically major resections as anatomical resections of one or two liver "difficult segments" (I, IVa, VII and VIII). The Iwate difficulty scoring systems (DSS) for LLS was also calculated in all cases. 9 The following intra-operative aspects were considered: operative time, hilar clamping, blood losses and peri-operative (within 24 h) blood transfusions. Finally, length of hospital stay (LOS) was considered, divided in categories based on the extent of resection performed (minor and technically/anatomically major); prolonged hospital stay was defined as hospital stay equal or longer than the 75th percentile for every category.

Textbook Outcome
In a recently published multicentric study, Görcec et al. proposed a definition of textbook outcome for laparoscopic liver surgery (TOLLS): 7 the authors developed a survey including individual surgical outcomes and submitted to the European-African and International Hepato-Pancreato-Biliary Association (E-AHPBA, I-HPBA) members. Parameters included in the definition were the following: absence of grade II or III intra-operative events according to the Oslo classification; this is a classification that divides peri-operative events into three classes: I, incidents managed without changing the operative approach and without further consequences for the patient; II, incidents with further consequences for the patients (i.e. excessive blood losses, and for endoscopic surgery, anything requiring unplanned conversion) and III, incident leading to significant consequences for the patient (i.e. intra-operative death); 10 no severe post-operative complications, classified according to the Clavien-Dindo classification 11 as grade III or higher; no readmission within 30 days, no in-hospital mortality and R0 resection margins (defined as tumourfree margin of 1 mm or more). In the present study, it was applied this definition of TOLLS. Moreover, according to Görcec et al., an extended definition of TOLLS was created also considering the length of hospital stay (LOS); this enriched definition of TOLLS has been named as TOLLS+ ( Figure 1).

Statistical Analysis
Categorical variables were presented as frequency, while continuous variables were expressed as median and interquartile range (IQR). To investigate possible association among patients, tumour and operative characteristics and TOLLS both a univariate and a multivariate logistic regression analysis were performed. Factors that resulted significant after univariate analysis were considered for multivariate analysis. The same analysis was performed for TOLLS+. A p value of <0.05 was considered as significant. All statistical analyses were performed using SPSS (IBM Corp.

Textbook Outcome
The frequencies of every single surgical outcome included in TOLLS and TOLLS+ were absence of in hospital mortality in 99.8%, no 30-day readmission in 98.6%, no severe (CD≥3) complications in 95%, no grade 2-3 intra-operative events in 92.2% and R0 resection in 90.3%. Overall, TOLLS was achieved in 80.5% of patients. When considering prolonged length of hospital stay (LOS) in calculating TOLLS+, no prolonged LOS was achieved in 67.5%; consequently, TOLLS+ was achieved in 60.8% (Fig. 2).

Factors Associated with TOLLS
Results of univariate analysis for TOLLS are shown in Table 2 (Table 4). Age, while reaching significance after univariate analysis, was not included in multivariate analysis since increasing age was associated with increasing ASA score, thus invalidating the analysis.
A subset analysis comparing major (technically and anatomically) and minor resections has been carried out and the results can be found in the supplementary material ( Supplementary  Tables 1, 2, 3 and 4).

Discussion
Quality assessment in surgery has become of paramount importance, especially in a novel and improvable field such as LLS. Traditionally, quality assessment relied on the analysis and comparison of a single simple surgical outcome, such as mortality, morbidity, hospital stay or readmission; 12-14 many authors  The use of composite outcomes has been suggested to properly analyse and compare performances. Among these, textbook outcome (TO) has been indicated as the best tool for evaluating surgical outcomes. Moreover, TO, an Signifcant p values (p < 0.05) are reported in italics  all-or-none composite outcome tool, combines multiple single binary outcomes and can be achieved only when all outcomes are achieved. This is a more comprehensive patientfocused evaluation of the surgical performance because a favourable outcome is obtained only when all the items are satisfied. The TO has been defined and validated for many surgical procedures, including liver surgery, but a specific TO definition for LLS still lacking. Görcec et al. 7 performed a survey among experts in this branch of surgery, in order to develop a new definition of TO that should be better suited for LLS. In our study, we applied this definition of TO for LLS (TOLLS) in a cohort of patients undergoing LLS in a single, tertiary referral HPB Western centre; moreover, we aimed to validate its performance and identify factors influencing TOLLS achievement. In our case series, 80.5% of patients reached TO, a value which is in line with the recent published data, Görcec et al. 7 in a multicentric study reported a rate ranging from 60. 6 18 In our results, radicality of the resection was the factor with the most negative impact on TOLLS achievement; the observed R0 resection rate of 90.3% is similar to other reports in literature. Görcec et al. 7 and Tsilimigras et al. 16 reported an R0 rate of 87.4% and 89%, respectively, and they confirmed that it was the most limiting factor in achieving TOLLS also in their experience. Conversely, in other case series, severe post-operative complications were the most negatively influencing TO for open or laparoscopic liver surgery, excluding LOS; specifically, Tsilimigras et al. reported a frequency of 14% of severe complications, while Azoulay et al. reported a frequency of 27%. 16,19 Many factors have been found to influence the chance to achieve TO in published reports; in gastrointestinal surgery, three groups of factors have been reported: patient-related factors (age, comorbidities), tumour-related factors (stage of the tumour, dimension) and surgery-related factors (such as type of surgery). 4,5 When considering TO for liver surgery, Tsilimigras et al. found similar results, identifying that patient-related (age, ASA score≥3), tumour-related (histology, vascular invasion) and surgery-related (type of liver resection) factors have a statistically significant relation with TO achievement. 16 These results were partially confirmed for LLS; TOLLS achievement seems to be less likely in advanced age, higher ASA class, previous abdominal surgery, malignant histology, tumour size and type of liver resection. 7 In our report, we found that factors associated with a reduced chance of TOLLS achievement were mostly associated with the complexity of surgical procedure (concomitant surgery, blood losses and operative time). Not surprisingly, both TOLLS and TOLLS+ were negatively influenced by higher risk classes of Iwate DSS and the need of concomitant surgery.
In our study, when LOS is included in the definition of TOLLS, it becomes the outcome with the higher negative impact: 7,16,20 TOLLS plus LOS (TOLLS+) was achieved in 60.8%, since prolonged LOS had a rate of 32.5%. This is comparable to other rates reported in literature: for example, in a recent multicentric study on liver resection for malignancies, a rate of prolonged LOS varied from 33.3 to 74.3%. 21 Prolonged LOS has been deemed surrogate of many surgical outcomes such as post-operative complications, and that is why in many definitions of TO for complex surgeries, like colorectal or hepato-pancreatobiliary surgery, prolonged LOS was included. [4][5][6][7]16,20 Many authors, on the other hand, believe that LOS is too susceptible to cultural or socio-economic factors with high variation rate among different countries and centres, implying it should not be included in the TO definition; Merath et al., 21 for example, that there are significant differences in prolonged LOS incidence between Eastern and Western hospital, suggesting that this may have cultural and organisational reasons, but maybe also reasons linked to economic interests and founding mechanisms. Given this dichotomy, we decided to test both definitions of TOLLS, with and without prolonged LOS, to highlight difference in factors limiting their achievement. Our results seem to suggest that when LOS is included in TOLLS definition, patient-and tumour-related factors have a somewhat higher impact in determining TO achievement, even if surgical complexity factors remain the ones with the bigger impact. Therefore, it is possible that TOLLS + could be more useful for proper and more accurate patient preselection and risk classification than TOLLS alone, even if this means achieving it in a lesser number of cases.
The results of this study should be evaluated in light of some limitations: firstly, its retrospective nature, although data were collected in a prospectively maintained database and in a short time of observation; secondly, we applied the definitions of TOLLS proposed by Görcec et al. that 7 that have not still been externally validated; finally, the mono-centricity nature of our study, whereas standardisation of treatment (no variations in patient selection criteria, pre-and post-operative management, only three senior surgeons performed all the laparoscopic liver resections), may increase the value of our analysis.

Conclusions
Textbook outcome is a simple, patient-centred tool to evaluate surgical performance also for LLS. According to our results, TOLLS can be achieved in most patients undergoing LLS, and it seems to be influenced mostly by surgery-related factors; conversely, when also LOS is considered, TOLLS+ is achieved less frequently and seems to be influenced by both patient-and tumour-related factors.
Author Contribution AR and EP made substantial contribution to the study conception, acquisition of data, analysis, and interpretation of data. All the authors have been involved in drafting the manuscript and revising the content. All authors read and approved the final manuscript.
Funding Open access funding provided by Università degli Studi di Verona within the CRUI-CARE Agreement.

Data Availability
The database gathering all data used for this article is available for the Editor of this article for review.

Declarations
Ethics Approval and Consent to Participate The present study was approved by the ethics committee of Verona and Rovigo.

Consent for Publication
Written informed consent for the gathering and use of clinical data and its publication were obtained from the participants. A copy of said consent is available for review by the Editor of this article.

Competing Interests
The authors declare no competing interests.
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