Three-Port Laparoscopic Exploration is not Sufficient for Patients with T4 Gastric Cancer

Gastric cancer is the second leading cause of cancerrelated deaths worldwide (Bertuccio et al., 2009; Strong et al., 2012; Jemal et al., 2013). Surgical resection remains the only curative treatment for patients with gastric cancer. However, surgical resection is dependent on the accuracy of the disease staging. Accurate preoperative staging can help reduce the number of unnecessary surgeries and decide other options of treatment. Computed tomography (CT) is a routine preoperative investigation. But CT scan does not totally exclude liver and peritoneal metastasis (Kapiev et al., 2010; Makino et al., 2011). Technique of laparoscopy-assisted gastric cancer resection was reported widely (Zhang et al., 2014). Laparoscopy may detect occult metastatic diseases and spare the patient an unnecessary laparotomy, result in fewer complications, and reduce the substantial morbidity and mortality associated with nontherapeutic laparotomy (Karanicolas et al,. 2011). The liver, diaphragm, serosal surfaces, peritoneum, omentum, and pelvic organs can be systematically inspected. Most of the anterior wall of the stomach can be inspected


Introduction
Gastric cancer is the second leading cause of cancerrelated deaths worldwide (Bertuccio et al., 2009;Strong et al., 2012;Jemal et al., 2013). Surgical resection remains the only curative treatment for patients with gastric cancer. However, surgical resection is dependent on the accuracy of the disease staging. Accurate preoperative staging can help reduce the number of unnecessary surgeries and decide other options of treatment. Computed tomography (CT) is a routine preoperative investigation. But CT scan does not totally exclude liver and peritoneal metastasis (Kapiev et al., 2010;Makino et al., 2011). Technique of laparoscopy-assisted gastric cancer resection was reported widely (Zhang et al., 2014). Laparoscopy may detect occult metastatic diseases and spare the patient an unnecessary laparotomy, result in fewer complications, and reduce the substantial morbidity and mortality associated with nontherapeutic laparotomy (Karanicolas et al,. 2011). The liver, diaphragm, serosal surfaces, peritoneum, omentum, and pelvic organs can be systematically inspected. Most of the anterior wall of the stomach can be inspected RESEARCH ARTICLE

Three-Port Laparoscopic Exploration is not Sufficient for Patients with T4 Gastric Cancer
Hua Huang 1,2 , Jie-Jie Jin 1,2 , Zi-Wen Long 1,2 , Wei Wang 3 , Hong Cai 1,2 , Xiao-Wen Liu 1,2 , Hong-Mei Yu 1,2 , Li-Wen Zhang 1,2 , Ya-Nong Wang 1,2 * without further manipulation (Coburn et al., 2010). But the three-port laparoscopic exploration is difficult to define evaluation of posterior infiltration of the tumor. More often than not, when the tumor originates from the posterior wall or a posterior fixity is suspected, gastrocolic ligament must be scissored in order to penetrate the lesser sac. In this study, we evaluated the usefulness of five-port anatomical laparoscopic exploration to decide the resectability of gastric cancers.

Materials and Methods
This was a retrospective study based on 126 gastric cancer (GC) patients operated at the Department of Gastric Cancer and Soft Tissue Sarcoma, Fudan University Shanghai Cancer Center from Apr. 2011 to Apr. 2013. Data were retrieved from patient charts and a computerized database. The study was approved by the Institutional Review Board. All patients were preoperative staging T4 according to the 7 th edition of the Union for International Cancer Control (UICC) by enhanced CT scan with the same setting. Patients with proven adenocarcinoma of the stomach after diagnosis were included. Patients with obvious unresectable diseases, e.g., liver metastases, ascites, and patients with obvious resectable diseases were excluded following CT scan. A total of 126 patients were included in this study. This represented 9.38% (126/1343) of all patients operated on for gastric cancer during this period. Table 1 summarizes the patients and clinicopathological characteristics of the patients. Demographic data, pathologic data, and follow-up data were entered into a prospective gastric database at the Department of Gastric Cancer and Soft Tissue Sarcoma, Fudan University Shanghai Cancer Center. The written informed consent had been obtained from all the patients, and this study was approved by the Ethical Committee of Shanghai Cancer Center of Fudan University. A retrospective review was performed analyzing the results of exploration, curative intent, postoperative length of stay, complications, operative times, and subsequent operation. Statistical analysis of means between groups was calculated using a one-way analysis of variance. The association between different parameters was computed with the x 2 -test and the Fisher's exact test. A p-value of less than 0.05 was considered to be statistically significant. SPSS 17.0 (SPSS Inc.) was used for analysis.

Operative technique
Patients underwent exploration under general anaesthesia. In the laparotomy exploration group (Group I): Upper abdominal midline incision about 15 cm was chosen ( Figure.1A). The parietal and serosal surfaces of the peritoneum were inspected initially for malignant implants. The liver, diaphragm, serosal surfaces, peritoneum, omentum, and pelvic organs were systematically inspected. Then gastrocolic ligament was opened in order to penetrate the lesser sac. If the disease was identified to be resected upper abdominal midline incision was extend to 18-20cm. In three-port laparoscopic exploration (Group II): The patients are placed in supine "scissor" position, and a 12-mm trocar is inserted into the subumbilical region. A telescope angled at 30 is used to inspect the peritoneal cavity. Another trocar, 12 mm, is inserted into the left subcostal region, and the other trocar, 5 mm is inserted into the right subcostal region ( Figure 1B). (Burke et al.,1997). If the disease was identified to be curatively resectable, upper abdominal midline incision about 18-20cm was made .The parietal and serosal surfaces of the peritoneum were inspected initially for malignant implants. The liver, diaphragm, serosal surfaces, peritoneum, omentum, and pelvic organs were systematically inspected. But do not enter the lesser sac for inspection. In the five-port anatomical laparoscopic exploration group (Group III): Five trocars were under direct vision in the patient. A 30-degree telescope was used for exploration ( Figure 1C). The parietal and serosal surfaces of the peritoneum were inspected initially for malignant implants. The liver, diaphragm, serosal surfaces, peritoneum, omentum, and pelvic organs were systematically inspected. We routinely scissored gastrocolic ligament in order to penetrate the lesser sac. The posterior walls of stomach and pancreas were inspected. If the disease was identified to be curatively resectable, upper abdominal midline incision about 18-20cm was made for D2 resection.
The peritoneal cavity was insufflated to 12-15 mmHg. Any suspicious lesion was biopsied. After the exploration was conducted and we deemed it resectable laparotomy was proceeded. If there are suspicious lesions, we do not proceed for resection till confirmatory results are available.

Results
One hundred twenty-six patients underwent exploration for evaluation of gastric adenocarcinoma. There are 54 patients in the laparotomy exploration group, 28 in threeport laparoscopic exploration and 44 patients in the fiveport anatomical laparoscopic exploration group.
The hospital stay of patients who only received exploration was significantly shortened in the laparoscopy group versus those patients who had exploratory laparotomy. There was no differences between Group II and Group III (p=0.318). There were significant differences between Group I and Group II (p=0.001) and there was significant differences between Group I and Group III (p<0.001) (Figure 2). No perioperative complications were associated with the laparoscopic procedure. The hole implant was found in one patient  from Group III 36 days later. The operating time was less in the laparoscopy Group II and Group III than in Group I (p<0.001). These numbers not statistically carry significant in Group II and Group III (p=0.167). As regards the accuracy of peritoneum implantation rate, there are no differences in the three group (p=0.57). With regards to the accuracy resection rate, there are significant differences in these three groups (p=0.022) with the highest in Group III (97.7%) and the lowest in Group II (78.6%)( Table 2).
There was one false positive ( Figure 3) and no false negatives in the five-port anatomical laparoscopic exploration group. No pancreas invasion were missed in Group I and Group III. Six patients were not resected because of the extension of the tumor into the pancreas in Group II.

Discussion
Surgical resection remain the curative treatment for patients with gastric cancer. However, the majority of patients in China present with advanced gastric adenocarcinoma, and many are first found to be incurable or unresectable. Ruling out unresectable cancers from an unnecessary ''open'' exploration and ruling out resectable patients from patients suspected of having borderline resection is very important. CT and EUS are not sensitive enough to detect the small metastatic intra-abdominal deposits typical of gastric adenocarcinoma, specially to identify patient who can be resectable (Burbidge et al., 2013). It is precisely this group of patients that would benefit from five-port anatomical laparoscopic exploration. It is well-known that exploratory laparotomy to confirm of unresectability in advanced gastric cancer has its disadvantages (Yamagata et al.,2012).In our study we showed that laparoscopy was very sensitive in detecting metastasis. Prior to the introduction of laparoscopic exploration, the rate of unnecessary laparotomy in our institution was high due to improper staging. Furthermore, with the current approach of neoadjuvant treatment for advanced stage diseases, the introduction of laparoscopy would lead to a quicker referral of patients to oncology treatment (Yano et al., 2000;Shimizu et al. 2010;Cardona et al., 2013). Although laparoscopy in patients with gastric cancer has been practiced for many years, the overall number of patients in each reported series is small (Mahadevan et al., 2010). It is reported that simple laparoscopic exploration is useful for confirmation of unresectability for advanced gastric cancer (Burke et al., 1997). But in our study we found three-port simple laparoscopy had low accuracy resection rate, which was different from results of other studies, probably the reason is that three-port simple laparoscopy only three trocar. The liver, diaphragm, serosal surfaces, peritoneum, omentum, bowel, mesentery, and pelvic organs can be inspected clearly. But the lesser sac is a blind spot (Burbidge et al., 2013), because it is difficult to direct access to the lesser sac in three-port laparoscopy (D'Ugo et al., 1997), thus it can't inspect the posterior wall and pancreas invasion (Burke et al.,1997;Mahadevan et al.,2010;Cardona et al.,2013). There was no Differences between Group II and Group III (p=0.318). There were Significant Differences between Group I and Group II (p=0.001). There was Significant Differences between Group I and Group III (p<0.001)

Figure 3. There was One False Positive Case in Five-Port Anatomical Laparoscopic Exploration Group.
Implantation of Pelvic Organs Serosal Surfaces was Confirmed in Operation (Black Arrow), but Pathology Confirmed that they were Blood Fluke Eggs Only five-port anatomical laparoscopy can scissor gastrocolic ligament to penetrate the lesser sac (Brennan et al., 2005). Then inspect the posterior wall and pancreas invasion. Five-port anatomical laparoscopic exploration has a place in the management of patients with gastric cancer by preventing unnecessary laparotomy and better selecting patients for neoadjuvant treatment. We found there were no significant differences of the complication rate and length of hospital stay in the three-port laparoscopy exploration group and five-port anatomical laparoscopy exploration group. In contrast to laparotomy exploration group, five-port anatomical laparoscopic exploration group had fewer days of hospital stay. Up to now, to predict lymph node positivity still remains a challenge during laparotomy.
In conclusion, five-port anatomical laparoscopic exploration could reduce the rate of unnecessary laparotomy in advanced-stage gastric cancer patients. Five-port anatomical laparoscopic exploration was superior to three-port laparoscopic exploration and laparotomy exploration. Our results supported the use of five-port anatomical laparoscopy as the standard of care in evaluating patients with advanced gastric cancer. However important issues remain unsolved, our study was a retrospective study, and the number of patients required for statistical power was not adequately included. Thus a controlled, randomized comparison would provide valuable information to help guide clinical management of advanced gastric cancer patients.