Gastric cancer is one of the most common cancers worldwide. Approximately 10% of patients have tumors that perforate the serosa and extend to adjacent organs [3, 4]. The transverse colon is the most common organ involved with gastric cancer; however, whether or not the patients with tumors invading the colon have improved survival than those with tumors invading other organs is still unknown. Some studies reported that there is no correlation between survival rate and which organ is invaded [5–7]. Pacelli et al. also found that patients with colon invasion had no survival advantage over those with other organ invasions [8]. Although Dhar et al. reported that patients with colon or mesocolon invasion had better survival rates than patients with other organ invasion based on univariate analysis; however, colon or mesocolon invasion was not a significant factor based on multivariate analysis [9]. These results indicated the prognosis of patients with invasion to the transverse colon was comparable to the prognosis of patients with invasion to other organs.
In our study, the 5-year overall survival rate was 36.9%, with a complication rate of 12.5%, which is considered acceptable. Fukuda et al. reported that the 5-year survival rate in T4 gastric cancer patients undergoing curative gastrectomy was 34.1% and the morbidity rate was 26.8% [4]. Brar et al. reviewed a total of 17 studies, including 1343 patients with locally advanced gastric cancer, and observed that the 5-year survival rate after R0 resection was 32%-35% and the overall complication rates ranged from 11.8%-90.5% [2]. In a recent study, the 3-year survival rate of 47.7% and complication rate of 37.9% were obtained from patients with clinical T4b gastric cancer [10]. Thus, the long-term outcomes in our study were similar to those in previous studies. However, we achieved a less complication rate compared with previous studies,which could be attribute to only colon resection in our study. Kasakura et al. found that patients with additional organs resection had a higher complication rate compared with patients undergoing gastrectomy alone [11], and Ozer et al. found that patients who underwent MVR with 2 or more organs had a higher surgical morbidity [12]. Based on these considerations, we suggest that extended gastrectomy with involved colon resection can be performed with minimal morbidity and can improve the probability of overall survival in T4 gastric cancer extending to the transverse colon.
The most commonly reported prognostic factors of T4 gastric cancer patients are curability, the depth of tumor invasion, and lymph node metastasis. Curative resection offers the likelihood for cure, and non-curative resection is usually adopted in patients with peritoneal carcinomatosis and distant metastasis for palliative. Survival in patients who underwent multi-visceral resection without a complete resection was demonstrated to be significantly diminished compared to those patients had R0 resections [13, 14]. Dhar et al. treated 150 patients with T4 gastric cancer and reported that curative patients had survival benefit over non-curative patients [9]. Furthermore, Mita et al. concluded that extended multi-organ resection could be beneficial only if curative surgery was performed [15]. Therefore, our study was limited to patients without distant metastasis who were treated with curative resection. Our results further demonstrated that R0 resection resulted in favorable survival.
The present study revealed that advanced T stage was an unfavorable prognosis factor for overall survival. In fact, it is difficult to identify the T stage when tumors extend to adjacent organs. The positive predictive values of preoperative computed tomographic scans in assessing T4 stage were only 50% [16]. Furthermore, intraoperative assessment of true invasion into adjacent organs may be challenging. Mita et al. reported that 19 of 41 (46.3%) T4 gastric cancer patients had pathologically-confirmed inflammatory adhesions [15]. Similarly, 45% of patients in our study had tumor adhesions to the colon (pT4a) rather than invasion to the colon (pT4b). It is unclear if the involved organs require resection when patients have pT4a (cT4b) gastric cancer. In a previous study, Cheng et al. treated 179 patients with T4 gastric cancer and observed that combined resection achieved a better survival whether or not the tumors are adhere to or invade the adjacent organs [17]. Therefore, extended multi-organ resection is recommended for patients with T4 gastric cancer for curative resection.
Lymph node metastasis is common in T4 gastric cancer. The lymph node metastasis rate in the current study was up to 72.5%. Lymph node metastasis is a commonly reported prognostic factor for poor outcome in patients with T4 gastric cancer. Ozer et al. reported that lymph node metastasis is an independent poor prognostic factor in patients with locally advanced gastric cancer [12]. Jeong et al. revealed that lymph node metastasis (greater than pN3) is an independent poor prognostic factor for patients with T4 gastric carcinoma who underwent curative surgery [18]. Further, it was observed that patients with extensive lymph node metastasis (N2 or N3) had a significantly poorer prognosis compared to patients with limited lymph node metastasis (N0 or N1) [4, 7]. Cheng et al. regarded T4 gastric cancer with N2 or N3 nodal disease as incurable and a contraindication for extensive surgery [17]. In agreement with previous observations, lymph node metastasis, as well as grade of lymph node metastasis, were associated with poorer overall survival in T4 gastric cancer extending to the transverse colon. Taken together with our present results, we recommend preforming extended multi-organ resection in T4 gastric cancer patients with limited lymph node metastasis.
Neoadjuvant therapy is increasingly advocated in patients with locally advanced gastric cancer. In the MAGIC randomized trial, 503 patients with gastroesophageal cancer were assigned to perioperative-chemotherapy and surgery (n = 250 patients) or surgery (n = 253 patients) [19]. In this study, perioperative-chemotherapy and surgery improved overall survival and local control compared with surgery. In the French FFCD 9703 multicenter phase-Ⅲ trial [20], 224 patients with resectable adenocarcinoma of the lower esophagus, the gastroesophageal junction, or the stomach were randomly assigned to receive surgery and perioperative chemotherapy or surgery alone. Higher R0 resection rates and improved overall survival were achieved in the perioperative chemotherapy group compared with surgery alone group. However, perioperative chemotherapy was not significantly effective for patients with gastric cancer in the multivariate analysis. Another randomized trial (EORTC 40954) including 144 patients with locally advanced adenocarcinoma of the stomach or esophagogastric junction showed that neoadjuvant chemotherapy increased R0 resection rate but failed to improve overall survival compared with surgery alone [21]. The aforementioned studies demonstrate that neoadjuvant chemotherapy can decrease the T and N stage and increase R0 resection rate, whereas a survival benefit from neoadjuvant chemotherapy in distal gastric cancer remain vague. A retrospective analysis from National Cancer Data Base (1998–2011) indicated that neoadjuvant therapy may allow for improved overall survival in patients with T4 gastric cancer [22]. However, only 61.7% (648/1049) of the patients who underwent surgical resection received R0 resection. Also, it was not described whether D2 or D1 lymph node dissections were performed. Thus, RCT studies are required to demonstrate a survival benefit from neoadjuvant therapy in distal gastric cancer.