Omental preservation versus omentectomy in curative-intent gastrectomy for gastric cancer: Swedish population-based cohort study

Abstract

Background

Omentectomy has traditionally been performed in gastric cancer surgery, but omental preservation has become increasingly common. It is unclear whether omentectomy leads to additional survival benefit compared with omental preservation. This nationwide population-based cohort study aimed to assess survival and surgical outcomes comparing omental preservation to omentectomy in curative-intent gastrectomy.

Methods

Patients were identified from the Swedish National Registry for Oesophageal and Gastric Cancer with inclusion between 2006 and 2022. The primary endpoint was overall survival assessed by a multivariable Cox proportional hazards model, adjusted for age, sex, American Society of Anesthesiologists physical status score, clinical T and N stage, type of gastrectomy, surgical approach, extent of lymphadenectomy, neoadjuvant chemotherapy, surgery year and regional cancer centre. Secondary endpoints were surgical outcomes including tumour-free resection margins, lymph node yield and postoperative complications.

Results

A total of 1615 patients were included, 517 (32.0%) underwent gastrectomy with omental preservation, and 1098 (68.0%) underwent gastrectomy with omentectomy. Overall survival after omental preservation was similar compared with omentectomy in the multivariable Cox model (HR 1.00, 95% c.i. 0.83 to 1.20; P = 0.967). Omental preservation also had similar surgical outcomes including lymph node yield and postoperative morbidity rate, compared with omentectomy.

Conclusions

Omental preservation was similar to omentectomy in terms of overall survival and surgical outcomes. The results suggest that omentectomy can safely be omitted in curative-intent gastrectomy for gastric cancer.

Introduction

The standard treatment for locally advanced gastric cancer consists of gastrectomy including D2 lymphadenectomy, and perioperative chemotherapy in Western countries^1–2 or adjuvant chemotherapy in Asian countries^3–4. Resection of the greater omentum and the omental bursa has been part of the Japanese radical gastrectomy concept, to minimize the risk of localized tumour seeding and subsequently prevent peritoneal recurrence^5–6. Bursectomy is no longer recommended since the Japanese randomized JCOG1001 trial showed that bursectomy did not improve survival⁷, whereas the value of omentectomy remains unclear.

The omentum plays an important role in the immune system, and it is also involved in intraperitoneal dissemination of tumour cells⁸. Milky spots, a type of secondary lymphoid organ, have been found predominantly in the omentum, but also in other locations such as the mesentery and the abdominal wall⁹. As milky spots may switch from an initially antitumourigenic role to a later protumourigenic role, removal of them by performing omentectomy is supported by animal studies¹⁰.

However, the effects of omentectomy have not been shown for gastric cancer patients, as previous retrospective cohort studies found no difference in overall survival (OS) or recurrence-free survival (RFS) comparing omental preservation to omentectomy^11–17. Currently, the European Society for Medical Oncology (ESMO) guidelines no longer include a recommendation regarding omentectomy¹, while there remains a weak recommendation for omentectomy in T3–4 gastric cancer in the Japanese guidelines³. There are two ongoing randomized clinical trials (RCTs), one Japanese¹⁸ and one Dutch¹⁹, with a non-inferiority hypothesis for omental preservation, but the results will not be available for several years to come.

In Sweden, omentectomy was routinely performed when open gastrectomy was the standard approach. When laparoscopic gastrectomy was gradually implemented during the past decade, omental preservation became more common, since omentectomy in the laparoscopic setting is more time-consuming. Results from the JCOG1001 trial⁷ showing that bursectomy could be omitted may also have promoted the trend of omental preservation, since omentectomy was a necessary first step in the bursectomy procedure. However, the clinical practice regarding omentectomy versus omental preservation varies across the six Swedish regional cancer centres that provide surgical treatment of gastric cancer. The choice between omentectomy and omental preservation could be based on local routines at the regional centres, as well as preference by the individual surgeons.

The aim of this study was to compare outcomes after omental preservation to those after omentectomy using a Swedish population-based cohort. We hypothesized that omental preservation is similar to omentectomy, in terms of survival, and surgical outcomes such as tumour-free resection margins (R0), lymph node yield and postoperative complications.

Methods

Study design

This cohort study included nearly all patients with gastric or gastro-oesophageal junction cancer Siewert type III, who underwent gastrectomy in Sweden between January 2006 and August 2022. All patients had histopathologically confirmed adenocarcinoma. The exclusion criteria were high-grade dysplasia (HGD), early gastric cancer (cT1N0), palliative gastrectomy, macroscopically non-radical (R2) resection or unknown resection margins, distant/oligo-metastatic (M1) disease, other known concomitant cancer, additional organ resection during gastrectomy including splenectomy, previous partial gastrectomy and unknown vital status. The study is reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines²⁰. Ethical approval was obtained from the Swedish Ethical Review Authority in Stockholm, Sweden (2013/596-31, with amendment 2020-06495). Informed consent was waived due to the observational study design and deidentified data.

Data source

Information on clinical and pathological characteristics, surgical procedures, oncological treatment and surgical outcomes was retrieved from the Swedish National Registry for Oesophageal and Gastric Cancer. The registry was launched in January 2006, and its data quality has been validated with a completeness rate of 95.5% and overall accuracy of 91.1%²¹. Data is reported directly online by the treating hospitals at initial staging, at the time of surgery and during postoperative follow-up. Vital status and date of death are monitored continuously through the Swedish National Population Register. Data monitoring is performed by trained staff at each of the six Swedish regional cancer centres.

Surgical and oncological treatment

In omental preservation, the greater omentum was typically divided at least 3 cm below the right and left gastroepiploic arteries, along the cranial border of the transverse colon, i.e. the gastrocolic ligament. The remaining omentum from the transverse colon and caudally was preserved. Omentectomy was defined as complete resection of the greater omentum. Both open and minimally invasive surgery were performed, with the minimally invasive technique being mainly conventional laparoscopy and in a few cases robotic-assisted. The extent of lymphadenectomy was classified into <D1+, D1+ and complete D2, based on detailed data of resected lymph node stations according to the sixth edition of Japanese guidelines³. Perioperative chemotherapy was provided according to national treatment guidelines, using epirubicin, oxaliplatin and capecitabine (EOX) or epirubicin, cisplatin and fluorouracil/capecitabine (ECF/ECX) until 2019, and thereafter fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT).

Outcomes

The primary endpoint was OS, from the date of diagnosis until death or censoring on 2 September 2022. Secondary endpoints were the R0 resection rate, lymph node yield, operative time, intraoperative blood loss, anastomotic leakage, aggregated surgical complications (anastomotic leakage, ileus, bleeding and intra-abdominal infection), aggregated non-surgical complications (cardiovascular, respiratory, thromboembolic and non-surgical infectious events), 30- and 90-day mortality rates.

Statistical analysis

For OS, Kaplan–Meier estimates were computed and compared using the log-rank test. A directed acyclic graph (DAG)²² was built to identify confounders and effect modifiers that were assumed to be causally associated with the exposure (omental preservation or omentectomy) and/or the outcome (death) (Fig. S1). Univariable and multivariable Cox proportional hazards models were constructed, incorporating a priori specified covariates in the main model: age (continuous), sex, clinical T and N stage, American Society of Anesthesiologists (ASA) physical status score²³, type of gastrectomy, surgical approach, extent of lymphadenectomy, neoadjuvant chemotherapy, year of surgery (quartiles of the study interval) and regional cancer centre. We detected a small violation of the assumption of proportional hazards for type of gastrectomy and neoadjuvant chemotherapy (global P = 0.320), which was handled by stratified analyses showing similar estimates as the main model (data available upon request). Tumour differentiation grade was adjusted for in an exploratory model, in addition to the aforementioned covariates, due to a large amount of missing data. Subgroup analyses were performed for patients with T3–4 tumours and for patients who underwent complete D2 lymphadenectomy, respectively. As an alternative method to multivariable models, propensity score matching was performed using the same covariates as the main Cox model. Patients treated with omental preservation were matched with patients treated with omentectomy, using the nearest neighbour method with a matching ratio of 1:2 without replacement and a calliper width of 0.2. After matching, all covariates had a standard mean difference <0.1, indicating adequate balance²⁴. For binary secondary outcomes, multivariable logistic regression models were constructed using the same covariates as the main Cox model, and the models were satisfactory when checked for collinearity and goodness-of-fit. Complete case analyses were applied for the multivariable models.

Continuous data were reported as median (interquartile range, i.q.r.) and compared using the Wilcoxon rank sum test. Categorical data were reported as numbers (percentages) and compared using the χ² test. A two-sided P value < 0.05 was considered statistically significant. Statistical analyses were performed using Stata²⁵ and R version 4.3.2²⁶ by B.H., and reviewed by two statisticians (R.M. and L.V.E.).

Results

A total of 2813 patients were identified and 1198 patients were excluded. Among the remaining 1615 patients fulfilling the inclusion criteria, 517 (32.0%) underwent gastrectomy with omental preservation and 1098 (68.0%) underwent gastrectomy with omentectomy (Figure 1). The distributions of age, sex, ASA score, clinical T stage and tumour differentiation grade were similar between the omental preservation and omentectomy groups. Compared with those treated with omentectomy, patients treated with omental preservation had a higher proportion of nodal negative (N0) disease (74.9% versus 70.3%), distal gastrectomy (69.6% versus 49.5%) and minimally invasive surgery (42.6% versus 12.0%), while neoadjuvant chemotherapy was less commonly administered (36.5% versus 45.2%) (Table 1). At the national level, omental preservation became more common in parallell with the implementation of minimally invasive gastrectomy during the study interval, but the clinical practice differed between the six regional cancer centres (Fig. 2).

Overall survival

Median follow-up time was 7.0 years in the omental preservation group and 9.3 years in the omentectomy group. The crude OS, as demonstrated by the Kaplan–Meier method, did not differ between the groups (P = 0.931). Median OS was 4.1 years after omental preservation and 3.8 years after omentectomy (Fig. 3). In the univariable Cox models, omental preservation versus omentectomy was not associated with OS (HR 0.99, 95% c.i. 0.87 to 1.14; P = 0.931). The multivariable Cox model confirmed that patients treated with omental preservation had similar OS compared with patients treated with omentectomy (HR 1.00, 95% c.i. 0.83 to 1.20; P = 0.967) (Table 2). In the exploratory model with tumour differentiation grade added as a covariate, the omental preservation group and the omentectomy group still had similar OS (HR 0.81, 95% c.i. 0.62 to 1.07; P = 0.140) (Table S1). In the subgroup analyses, OS was also similar among patients with clinical T3–4 tumours (HR 1.15, 95% c.i. 0.91 to 1.47; P = 0.239) and among patients who underwent complete D2 lymphadenectomy (HR 1.33, 95% c.i. 0.76 to 2.32; P = 0.322) (Table S1).

After propensity score matching, 274 patients treated with omental preservation and 472 patients treated with omentectomy were included for analysis (Table S2). Similar OS following omental preservation and omentectomy was found in the whole matched cohort (P = 0.866) (Fig. 4), as well as in a subgroup of patients with clinical T3–4 tumours (P = 0.383) (Fig. S2).

Surgical outcomes

The R0 resection rate was 89.6% for patients treated with omental preservation and 86.0% for those treated with omentectomy (P = 0.057). Lymph node yield was similar after omental preservation compared with omentectomy (median (i.q.r.) 21 (11–34) versus 21 (12–29), P = 0.220). Operative time for omental preservation was slightly longer compared with omentectomy (median (i.q.r.) 237 (180–300) versus 217 (166–296) min, P = 0.049). When stratified by surgical approach, there was no significant difference. Intraoperative blood loss was significantly lower for omental preservation compared with omentectomy (median (i.q.r.) 155 (50–400) versus 300 (150–600) ml, P < 0.001). Concerning postoperative morbidity and mortality rates, no significant differences were seen in anastomotic leakage (4.4% versus 5.5%, P = 0.353), aggregated surgical complications (15.3% versus 18.9%, P = 0.094), aggregated non-surgical complications (15.8% versus 18.5%, P = 0.198), 30-day mortality rate (2.1% versus 1.5%, P = 0.327) or 90-day mortality rate (3.9% versus 3.8%, P = 0.966) (Table 3).

In the multivariable logistic regression models, the probability of achieving R0 resection was higher after omental preservation (OR 2.04, 95% c.i. 1.24 to 3.37; P = 0.005). No significant differences were seen regarding risk of anastomotic leakage (OR 0.96, 95% c.i. 0.45 to 2.05; P = 0.913), aggregated surgical complications (OR 0.98, 95% c.i. 0.64 to 1.50; P = 0.925), aggregated non-surgical complications (OR 1.00, 95% c.i. 0.66 to 1.50; P = 0.985), 30-day mortality rate (OR 1.89, 95% c.i. 0.68 to 5.26; P = 0.226) or 90-day mortality rate (OR 0.90, 95% c.i. 0.43 to 1.88; P = 0.772) (Table S3).

Discussion

In this nationwide population-based cohort study, OS after omental preservation was similar compared with OS after omentectomy, for patients undergoing curative-intent gastrectomy. Omental preservation also showed similar surgical outcomes compared with omentectomy, including lymph node yield, and postoperative morbidity and mortality rates.

The comparable survival outcomes following omental preservation and omentectomy in this study are in line with previous studies^11–17. Some of these studies included only T3–4 tumours^12,14,15,17. Since advanced T stage is associated with a higher risk of peritoneal recurrence^27–28, we performed subgroup analyses focusing on patients with clinical T3–4 tumours, which also showed similar OS after omental preservation compared with omentectomy. Regarding oncological treatment, more than 40% of patients in the present study were treated with neoadjuvant chemotherapy. In contrast, all previous studies were from Asian institutions, where adjuvant instead of perioperative chemotherapy is the standard of care^3–4. Consequently, the previous studies either excluded patients undergoing neoadjuvant chemotherapy^12,15–17, or had only small numbers of patients undergoing neoadjuvant chemotherapy^11,14.

Concern about leaving positive lymph nodes and tumour deposits in the omentum has been raised as an argument against omental preservation. A Dutch study found omental lymph node metastases in 2% and omental tumour deposits in 8% of patients undergoing gastrectromy with omentectomy²⁹. A study from China found a similar incidence of omental tumour deposits at 11.2%³⁰. In another Dutch study, only 2 of 100 (2%) patients had lymph node metastases and 3 of 100 (3%) had tumour deposits in the resected omentum. The presence of omental metastases was associated with other negative prognostic factors such as microscopically non-radical (R1) resection and linitis plastica³¹. After 5 years, all five patients had died due to relapse except for one patient who died due to postoperative complications³². The presence of omental metastases should hence be considered distant metastatic disease, which may not benefit from extensive surgery.

These results suggest that omental preservation does not compromise pathological outcomes compared with omentectomy. The authors found similar lymph node yield, with a median of 21 harvested lymph nodes after both types of procedure, which is also comparable to previous studies including only omentectomy patients^29,31. The R0 resection rate was slightly higher after omental preservation in this study. This could be due to some residual confounding remaining even after multivariable adjustment. Omental preservation became more common in the latter half of the study interval, when advances in surgical techniques, oncological treatment and perioperative care also took place. For example, neoadjuvant chemotherapy, although adjusted for, was more frequently used in the omental preservation group, and improved R0 resection rates after neoadjuvant treatment are well documented³³.

The short-term surgical outcomes after omental preservation were for the most part comparable to omentectomy in this study. The authors found lower intraoperative blood loss after omental preservation, which is consistent with previous studies^11–12. On the other hand, omental preservation was associated with longer operative time, in contrast to what has been reported previously^11–13. This may partly be explained by a higher proportion of minimally invasive procedures in the omental preservation group and a learning curve for laparoscopic and robotic-assisted gastrectomy during the study interval. The difference in operative time was non-significant when analysing open and minimally invasive procedures separately. Furthermore, we found comparable levels of postoperative complications after omental preservation and omentectomy, in line with several previous studies^11,12,14,34. Other studies focusing on laparoscopic omentectomy have found increased risks of pulmonary complications¹⁶, as well as injuries to the spleen and mesocolon¹³. Open omentectomy has been associated with slightly increased risks of intra-abdominal abscess and adhesive ileus¹⁵.

To the best of the authors' knowledge, the present study is the first population-based cohort study to address the issue of omental preservation in comparison with omentectomy in gastric cancer surgery. Nearly all patients undergoing curative-intent gastrectomy in Sweden were included, which serves to minimize the risk of selection bias. Other strengths of the study include the close-to-complete OS follow-up and the large sample size. There are also some limitations that need to be acknowledged. First, certain variables were incorporated late or lacking in the registry and were therefore not available for analysis. These include recurrence patterns and the adjuvant part of perioperative chemotherapy. Second, this study included operations performed over a time interval of 16 years, during which both surgical technique and oncological treatment have evolved. The authors adjusted for surgical approach, neoadjuvant chemotherapy and surgery year to manage this issue. They also performed a subgroup analysis based on patients treated with D2 lymphadenectomy according to the current guidelines. Lastly, there is a risk of residual confounding due to the observational study design. For example, the surgeon may have an inclination intraoperatively to choose omentectomy in more advanced cases. To minimize this risk, they excluded advanced cases requiring multiorgan resection, performed multivariable adjustment in our models and used propensity score matching to balance confounding factors. The authors chose to use pre- and intraoperatively available covariates, including clinical T and N stage instead of their pathological counterparts, for multivariable adjustment as well as propensity score matching.

In conclusion, this large population-based cohort study showed that omental preservation was similar to omentectomy in terms of overall survival and short-term surgical outcomes for patients undergoing curative-intent gastrectomy. Findings from the present study suggest that omentectomy may safely be omitted in curative-intent gastrectomy, although this needs to be confirmed in the ongoing Japanese and Dutch RCTs.

Funding

This study was supported by the Swedish Cancer Society (J.H., CAN 2017/1086; I.R., 21 1382 Fk) and the Center for Innovative Medicine, Karolinska Institutet, Sweden (I.R., FoUI-961729). The funders had no involvement in study design, data collection, data analysis, manuscript preparation or publication decisions of the study.

Acknowledgements

The authors thank all the patients included in this study, all health professionals who took care of the patients and administrators who managed the data included in this study.

This study was not preregistered with an analysis plan in an independent, institutional registry.

Disclosure

The authors declare no conflict of interest.

Supplementary material

Supplementary material is available at BJS Open online.

Data availability

The study data is not openly available, but may be shared upon reasonable request and with permission from the Swedish National Registry for Oesophageal and Gastric Cancer.

Author contributions

Biying Huang (Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Visualization, Writing—original draft, Writing—review & editing), Chih-Han Kung (Conceptualization, Methodology, Writing—review & editing), Andrianos Tsekrekos (Methodology, Writing—review & editing), Raphaela Mayerhofer (Methodology, Writing—review & editing), Laura Vossen Engblom (Methodology, Writing—review & editing), Fredrik Klevebro (Data curation, Writing—review & editing), Mats Lindblad (Conceptualization, Data curation, Project administration, Writing—review & editing), Jakob Hedberg (Data curation, Writing—review & editing), Eva Szabo (Data curation, Writing—review & editing), David Edholm (Data curation, Writing—review & editing), Ulrika Smedh (Data curation, Writing—review & editing), Jan Johansson (Data curation, Writing—review & editing), Ioannis Rouvelas (Conceptualization, Data curation, Methodology, Supervision, Writing—review & editing) and Magnus Nilsson (Conceptualization, Data curation, Investigation, Methodology, Project administration, Supervision, Writing—original draft, Writing—review & editing)

References