Current debate in gastric cancer surgery: Omentectomy?

Abstract

Despite the advancement of technology and neoadjuvant/adjuvant chemotherapy, molecular targeted agents, gastrectomy, and D2 lymph node dissection are the only curative treatment option for advanced gastric cancer (GC). The most common sites of recurrence in patients with GC are the peritoneum and omentum. The omentum contains areas rich in lymphatic tissue (the milky area) that form the connection between the peritoneum and the lymphatic system. Tumor cells are often found in these areas. Therefore, omentectomy is added to radical gastric resection and modified D2 lymph node dissection in the treatment of GC. Total omentectomy is recommended by Western countries for GC diagnosed at T3-4 stage, while Japanese research suggests partial omentectomy at T1-2 stage and total omentectomy at T3-4 stage due to early diagnosis of GC. In addition to the differences in tumor biology, the fact that patients in Western countries are more likely to receive perioperative chemotherapy and the 5% incidence of omental metastasis in advanced disease has led to the belief that partial omentectomy is an adequate surgical procedure compared with total omentectomy. There are studies recommending total omentectomy for the removal of possible tumor foci, and there are some studies reporting that partial omentectomy is sufficient even in advanced GC. The aim of this review was to investigate whether total or partial omentectomy should be performed in patients with GC.

Key Words: Gastric cancer; Gastrectomy; Omentectomy; Partial omentectomy; Total omentectomy

Core Tip: Omentectomy is used to remove tumor cells or tumor deposits in gastrectomy for gastric cancer. However, it has not been shown to improve survival and is associated with perioperative problems. For this reason partial omentectomy or omentum preservation has been used in recent years.

INTRODUCTION

The omentum has a protective effect in preventing intra-abdominal infections and intra-abdominal adhesions. However, due to its role in the migration and trapping of immune cells, the omentum keeps cancer cells in the lymphatic channels. It is therefore thought to be responsible for the formation of microscopic cancerous foci. The omentum forms glomerular structures due to its very rich vascularization. It has a lethal effect on early-stage tumors with macrophages and lymphocytes collected in these perivascular areas. The omentum loses this effect in the late stages of the disease and becomes a source of nutrition for tumor cells with its structures called milky spots and lipid cells[1]. As an expected consequence of this process, it plays a role in the proliferation and peritoneal dissemination of gastrointestinal and ovarian cancer cells in particular[2].

Although the incidence of microscopic lymph node metastases or tumor deposits in macroscopically normal omentum is unknown, it has been reported to range from 3.5% to 31.3%. Experimental studies have shown that removal of the omentum affects the survival of intraperitoneal free malignant cells and reduces local recurrence. Because of this property, omentectomy has become a procedure used in radical surgery for gastric cancer (GC)[3]. In surgical practice the application of total omentectomy has gained importance due to the following findings: (1) The omentum is the seeding site for tumor cells in gastrointestinal malignancies; (2) Cancer cells growing in the omentum are shed into the peritoneal cavity; and (3) The omentum is the site of cancer recurrence.

Based on these clinical and experimental findings, studies conducted in later years have shown that total omentectomy, which is generally accepted, causes surgical problems in addition to its oncological uselessness. For this reason partial omentectomy is an option in some cases. Finally, the question of whether omentectomy is necessary has come to the forefront.

GENERAL EVALUATION OF CLINICAL TRIALS ON OMENTECTOMY

Approximately three decades after the first gastrectomy performed by Billroth in 1881, Groves[4] performed the first omentobursectomy in 1910. This procedure involved excision of the greater omentum from the transverse colon and dissection of the anterior membrane of the colonic mesentery and the upper capsule of the pancreas. Since then total omentectomy has been added to the surgical management of locally advanced GC in addition to radical gastric resection and modified D2 lymph node dissection because of its theoretical advantages. To ensure adequate survival after gastrectomy, the standard of care has been to remove adjacent tissues with lymphatic spread or containing occult metastases by extended lymphadenectomy, splenectomy, bursectomy, and omentectomy.

The Japanese Clinical Oncology Group (JCOG) reported in a controlled phase III trial (JCOG9501) that removal of lymph nodes beyond D2 dissection did not improve survival. Prophylactic splenectomy was later denied in the JCOG0110 trial. Kurokawa et al[5] and Nie et al[6] found no survival benefit between the groups of 600 patients who underwent bursectomy and 600 patients who underwent omentectomy alone in JCOG1001. They found that omentectomy alone was sufficient in addition to D2 lymph node dissection in cT3-T4 tumors. In Western countries total omentectomy is recommended because GC is diagnosed at an advanced stage. In countries such as Japan and South Korea, the early diagnosis of GC is facilitated by the implementation of comprehensive screening programs. However, in the West the diagnosis of GC is frequently made at advanced stages due to the absence of screening programs. In Japan partial omentectomy is recommended for T1-2 stages due to early diagnosis of GC, and total omentectomy is recommended for T3-4 stages[7].

Partial omentectomy is the preservation of the omentum by dissection at a distance of 3-4 cm on the greater curvature side, preserving the gastroepiploic arch. The Italian Research Group also shared a similar opinion to the Japanese Cancer Society. The European Society for Medical Oncology also recommended resection of the omentum in T1-2 patients. In later years, the Japanese GC Association recommended gastrectomy without omentectomy and D2 lymph node dissection as standard treatment. While the National Comprehensive Cancer Network recommended lesser and greater omental resection in 2010, omentectomy was not mentioned in the 2022 guidelines[8]. In addition to differences in tumor biology between Western countries, patients who received perioperative chemotherapy were more likely to be treated. Even in advanced disease the incidence of omental metastases was only 5%. These results led to the conclusion that partial omentectomy was not an inferior surgical procedure to total omentectomy.

Keywani et al[9] determined the predictive factors for omental metastases after a 5-year follow-up of 100 patients. These factors were: patients with N2; patients with T3-T4; patients with a tumor diameter over 5 cm; patients who underwent R1 resection; 1/3 proximal GC; and esophageal and duodenal involvement. However, as patients with omental metastases represent advanced stages and chemotherapy provides better results than surgery in the treatment of micrometastases, the need for omentectomy should be evaluated. While the survival time of patients with GC with omental metastases is short, omentectomy does not contribute to the survival time of patients without omental metastases. This conclusion was supported by the demonstration that there was no difference in survival between partial and total omentectomy. Therefore, in the current guidelines and clinical trials, total omentectomy and partial omentectomy without decreasing the curability of the disease and survival in GC surgery has become questionable (Table 1).

Table 1 Characteristics of the articles.

Ref.	Study design	Surgical procedures	Complications	5-year overall survival	3-year overall survival	5-year recurrence- free survival
Kurokawa et al[5]	Randomized controlled trial	Bursectomy; Omentectomy	NA	No differences	NA	NA
Sakimura et al[26]	Retrospective	Omentectomy; Non-omentectomy	NA	NA	No differences	NA
Zhang et al[34]	Meta-analysis	Partial omentectomy; Total omentectomy	No differences	No differences	NA	NA
Ishizuka et al[13]	Meta-analysis	Omentectomy; Non-omentectomy	NA	Significant differences	NA	No differences
Chai et al[21]	Meta-analysis	Partial omentectomy; Total omentectomy	NA	Significant differences	NA	No differences
Zhu et al[14]	Meta-analysis	Omentectomy; Non-omentectomy	No differences	Lower	Lower	No differences
Zizzo et al[25]	Meta-analysis	Omentectomy; Non-omentectomy	NA	Significant	Significant	NA
Lin et al[23]	Meta-analysis	Omentectomy; Non-omentectomy	No differences	No differences	NA	NA
Keywani et al[9]	Prospective cohort	Omentectomy	NA	NA	NA	NA

NA: Not available.

ONCOLOGICAL EFFECTS OF OMENTECTOMY

The main function of the omentum is to localize intra-abdominal infection. Its oncological importance was understood with the detection of metastasis and tumor deposits in the lymph nodes located in the omentum in pathological examinations. Haverkamp et al[10] demonstrated the oncological value of the omentum with the presence of 18% of lymph nodes and 8% of tumor deposits. However, the lack of a 1-year survival difference in patients with and without tumor deposits in the omentum showed that its clinical reflection was not significant. Studies conducted a decade ago have shown that preservation of the omentum did not increase recurrence in the peritoneum. Therefore, it has been suggested that the omentum can be preserved in advanced GC without serosa involvement[11,12].

Ishizuka et al[13] published a meta-analysis of retrospective studies including open and laparoscopic surgeries performed for advanced GC. They showed that omentectomy had no effect on 5-year overall survival, especially 5-year recurrence-free survival. Zhu et al[14] also published a meta-analysis of nine studies including 3329 patients. In this meta-analysis they examined the patient groups by separating them according to their low and moderate heterogeneity. In the patient group where the omentum was preserved, the 5-year survival was found to be better in low heterogeneity, while they did not find any difference between 3-year and 5-year survival in moderate heterogeneity.

In some studies where the omentum was preserved, overall survival was found to be good, but no improvement in recurrence-free survival was shown. However, results with a longer 5-year recurrence-free survival have been reported[15-17]. Paul et al[18] reported that 12.7% of omental metastases in T3-4 tumors were associated with peritoneal recurrence and that these patients had a poor prognosis and low survival despite total omentectomy. They showed that omentectomy was not necessary in T1-2 tumors because no metastases were found. In a Dutch study no 5-year survival was seen in omentum with metastases, whereas this rate was 44.2% in those without omental metastases. The conclusion of this study was that omentectomy is useless because omental metastases are a sign of advanced disease[9].

Ishizuka et al[13] in a systemic review and meta-analysis of eight retrospective studies including 2658 cases emphasized that the number of lymph nodes removed after total omentectomy was high. It was expected that local recurrences would decrease with the hypothesis that metastatic lymph nodes could also be removed, but they reported that no difference in overall and disease-free survival was found between partial and total omentectomy[13]. The first of two South American studies was a prospective study that excluded patients with macroscopic omental involvement. In patients who underwent omentectomy in addition to gastrectomy, the presence of lymph node metastases in the omentum was found to be associated with disease recurrence[19]. The second study compared patients with advanced GC who underwent omentectomy or omentum preserving procedures. It was found that omentectomy had no effect on overall survival, recurrence-free survival, peritoneal recurrence, and operation time[20].

Although omental lymph node metastases and tumor deposits are not significant risk factors, postoperative bleeding, anastomotic leakage, and intra-abdominal infections affect patient survival by delaying adjuvant chemotherapy. Neoadjuvant treatment reduces microscopic metastases, lowers tumor stage, and increases the rate of benefit from surgery. Chai et al[21] evaluated the effect of neoadjuvant treatment in nine trials involving 1043 patients with partial omentectomy and 1995 patients with total omentectomy. Although total or partial omentectomy did not result in different oncological outcomes in patients who responded well to neoadjuvant treatment, total omentectomy was recommended in patients who responded poorly to treatment. Although total omentectomy is thought to have a positive effect on survival in advanced GC, disease-free survival was similar and overall survival was better in patients with partial omentectomy. To achieve this result, it is important that a higher number of lymph nodes are removed in patients who have undergone total omentectomy. However, it should not be overlooked that the factors affecting survival are the neoadjuvant or adjuvant chemotherapy with or without radiotherapy given to the patient with GC.

SURGICAL IMPLICATIONS OF THE TYPE OF OMENTECTOMY

The heterogeneity of the studies, differences in stage, open vs minimally invasive surgery, and the use of energy devices led to different results in the evaluations. In general total omentectomy is associated with longer operative times and more intraoperative blood loss[14,22,23]. No difference was found between partial and total omentectomy in patients with a Clavien-Dindo score of 3. The most important complication that delays the start of effective chemotherapy in patients undergoing gastrectomy is anastomotic leakage. However, in patients with a high ASA score, low serum albumin level and high Charlson comorbidity score, which are predictive factors for anastomotic leakage, partial omentectomy may be beneficial because the remaining omentum closes the leakage site[21]. The surgical outcomes were found generally similar in the last 5 years. A Japanese study with a large number of patients found no difference in 5-year overall survival and 5-year recurrence-free survival between the omentectomy and non-omentectomy groups, but surgical complications were 27.5% and 14.4%, respectively, and were not found to be statistically significant[13].

It has been shown that postoperative complications are high in patients who have undergone total gastrectomy and D2 lymph node dissection combined with omentectomy. The most common complication is small bowel obstruction due to adhesions. Chen et al[24] found that the 3-year and 5-year overall survival was longer in patients who underwent omentectomy than in those who did not. Zizzo et al[25] conducted a meta-analysis of eight trials conducted between 2000 and 2018 and did not show a significant difference in long-term overall survival, recurrence-free survival, and disease-free survival. In the pooled analysis of the trials, a long overall survival was found. In the long-term meta-analysis, major complications were similar, and postoperative mortality was very low and similar in both groups.

Sakimura et al[26] from Japan showed that omentum preservation had no effect on 3-year follow-up and recurrence-free survival. The TOP-G trial compared short-term outcomes in patients who did not receive neoadjuvant therapy with those who underwent open gastrectomy. While omentectomy resulted in longer operating times and increased blood loss, there was no significant difference in morbidity[9]. Using metabolic indicators, gastrectomy reduced body mass index, and no difference was found in triglyceride, low-density lipoprotein, and high-density lipoprotein levels between patients who underwent omentectomy and non-omentectomy[27].

OMENTECTOMY IN OPEN AND MINIMALLY INVASIVE PROCEDURES

Trials have generally evaluated open and minimally invasive procedures together, and omentectomy is associated with perioperative problems, especially in patients with obesity. Based on the oncological results of the trials, it is preferable not to perform partial omentectomy or omentum resection in laparoscopic procedures. In patients with serosa-negative T3 GC, total omentectomy in laparoscopic gastrectomy caused injury to the spleen and mesocolon. Lee et al[28] found no difference in clinicopathological and short-term surgical outcomes in the series where laparoscopic distal gastrectomy was performed. While tumor recurrence in the peritoneum was found to be 12.0% and 4.7% for total and partial omentectomy, respectively, no difference was found in recurrence-free survival of the patients. The authors stated that partial omentectomy can be used in laparoscopic distal gastrectomy for T3-4 tumors that do not penetrate the serosa.

Jongerius et al[29] found no benefit of total omentectomy for systemic disease in 100 cases; omentectomy was not defined as routine practice. However, lymph nodes outside the dissection margin in patients undergoing partial omentectomy for distal GC may be metastatic[30]. In patients who underwent laparoscopic distal gastrectomy, operative time and blood loss were found to be low, and overall recurrence and 2-year survival were similar compared with total omentectomy[31]. There was no difference in disease-free survival and the recurrence rate was 17.5% for total omentectomy and 7.6% for partial omentectomy.

In addition to the shorter operative time with partial omentectomy, pulmonary complications were found to be less frequent in the 30-day postoperative period[32]. The low serum amylase level on the first day after surgery in patients who underwent partial omentectomy also suggests that the surgical stress was less. Although it has been reported that infarction due to omental ischemia may occur as a postoperative complication, its incidence is 2.3%[33]. In a study including laparoscopic and open surgery, no difference in 3-year recurrence-free survival was found between total and partial omentectomy[11].

Zhang et al[34] investigated the safety of total and partial omentectomy in a meta-analysis of 2031 patients of whom 574 underwent partial omentectomy. They found no difference in 5-year recurrence-free survival, number of lymph nodes removed, complications, and hospital stay, while the duration of surgery was significantly shorter in patients who underwent partial omentectomy. In addition to the shorter operative time in patients who underwent laparoscopic partial omentectomy, the postoperative albumin level on day 1 was found to be higher in patients who underwent laparoscopic partial omentectomy[2]. Kim et al[35] found no difference in disease-free survival and disease-specific survival between total and partial omentectomy groups in T2 and T3 tumor groups in patients who underwent laparoscopic gastrectomy alone. They also found no difference in the development of peritoneal carcinomatosis in patients who developed recurrence. In these studies the type of omentectomy was not found to be a risk factor for the development of recurrence.

The ongoing JCOG1711 trial, which is a gastrectomy without omentectomy trial, the DRAGON 05 trial, which is an omentum-preserving gastrectomy trial, the long-term results of the TOP-G trial, and the results of the OMEGA trial will shed light on whether omentectomy should be performed in GC[9,36-38]. The initial two studies examined the surgical and oncological outcomes of omentectomy and partial omentectomy without omentectomy.

In the TOP-G trial, short-term results have been published previously, and the investigation is ongoing as to whether omentum preservation is an inferior operation in comparison with omentectomy over an extended time period. In the OMEGA study the 3-year survival rate will be examined by means of a comparison between omentum preservation and omentectomy. The results of the ongoing trials are being awaited with keen interest.

CONCLUSION

Since the tumor frequency in the omentum is 5% in T3/T4 tumors in locally advanced GC, omentectomy is not an additional procedure to gastrectomy. Theoretically, the omentum can be preserved as omental involvement is not expected in cases where GC does not involve the serosa. Although the aim of total omentectomy is to prevent microscopic metastases, it has no effect on preventing recurrence and mortality and has disadvantages such as prolonged operation time and perioperative blood loss. The addition of total omentectomy to gastrectomy has been reported to have no metabolic effects and no effect on peritoneal recurrence and overall survival. When partial and total omentectomy were compared, there was no difference in 3-year and 5-year overall survival. In minimally invasive surgery partial omentectomy was preferred in early-stage cancers.