Our results showed that laparoscopic colectomy with TLC with IA was similar to LAC with EA in terms of 3-year OS and DFS. IA involved exposing the ileum and colon under pneumoperitoneum in the abdominal cavity, raising concerns of increased peritoneal dissemination with IA. In the 1990s, when laparoscopic surgery for colon cancer was started, concern about port-site recurrences was widespread, but was allayed by large prospective series [12–15]. In the present study including TLC with IA for LC, only 2 patients in the EA group and 3 patients in the IA group experienced disseminated recurrence after PSM. No patients in either group experienced recurrence at the anastomosis site after PSM. Moreover, neither EA nor IA was associated with poor DFS in Cox regression analysis. No significant differences in the number of lymph nodes harvested were identified between groups. These results suggested that TLC with IA is an oncologically reasonable procedure.
In this study, the incidence of superficial SSI was significantly higher in the IA group (13%) than in the EA group (3.6%; P = 0.047). Exposing the intestinal tract in the abdominal cavity during IA procedures may result in exposure to bacteria, but the frequency of organ-space/deep SSI did not differ significantly between groups in our results (4.8% in the EA group vs. 6.0% in the IA group, P = 0.73). We showed that IA procedures did not increase the risk of dissemination, but also did not increase organ-space/deep SSI. Superficial SSI was frequently encountered at the port site through which 60-mm linear staplers were passed for side-to-side ileo-colostomy/colo-colostomy. The port through which the linear stapler was passed for anastomosis may become contaminated with stool, increasing the risk of superficial SSI. Length of postoperative hospital stay is known to be prolonged by the occurrence of SSI [16], and the IA group showed a longer hospital stay than the EA group in our study. Several reports showing that TLC with IA was favorable in terms of SSI have represented the rate of SSI as 1–4.4% [17–19], lower than our results. To prevent SSI, we have started applying additional steps, such as cleaning inside the contaminated port and administering chemical preparation with oral antibiotics the day before surgery. Since introducing such steps, we have encountered no SSIs in 13 consecutive TLCs with IA for RC in 2020 [11].
Good short-term outcomes of TLC with IA for RC have been shown in many retrospective reports [1–7]. In this study including LC, TLC with IA required a longer operation time and needed a shorter skin incision than LAC with EA. Because of the procedure dissecting the mesentery and anastomosis intracorporeally, TLC with IA took longer, but the smaller skin incision was advantageous in terms of cosmetology and postoperative pain. As another advantage, TLC with IA enables extraction site flexibility [17]. This advantage is particularly useful in natural orifice specimen extraction surgery [20] and holds promise for scarless surgery if natural orifice transluminal endoscopic surgery can be achieved.
The main potential advantages of IA lie in surgeries for obese patients and patients who have undergone polysurgery. Obese patients may have thick layers of subcutaneous fat and a shortened colonic mesentery, which could present an obstacle to EA and result in a need for longer skin incisions compared to non-obese patients. Although the length of skin incision required for EA and IA are considered similar in non-obese patients, the significantly shorter skin incision for IA in our cohort may indicate a difference in obese patients. Patients who have undergone polysurgery might also encounter difficulties with EA due to intra-abdominal adhesions, in which cases IA would prove useful. In our institution, IA was performed for patients with advanced cancers such as T4a or subtotal circumferential tumor, but if a skin incision of 8 cm or more was required for specimen removal due to bulky tumor or other-organ invasion, we ruled out the IA procedure, as the advantages of IA were considered to be neutralized. IA was also not indicated for patients with preoperative ileus symptoms because of the high risk of abdominal contamination, but we did perform IA if intestinal decompression proved effective.
Adequate proximal and distal margins are important to guarantee sufficient oncological radicality. The IA group obtained a significantly longer distal margin in this study. TLC with IA, which determined the dissection line in the abdominal cavity, can secure a wider disease-free margin compared to EA. Scatizzi et al. [4] reported similar results, with resection of a longer specimen potentially reducing the risk of residual colon ischemia.
The present study showed that none of tumor location, lymph-node metastasis, or stage III were associated with poor DFS. Two large population-based studies have reported that RCs show worse prognosis than left-sided colon cancers [21, 22], but tumor location was not a prognostic factor in our study. Similarly, lymph-node metastasis and stage III are considered to be associated with poor DFS, but again, not in our study. The benefit of adjuvant chemotherapy (AC) for stage III colon cancer has been clearly established [23, 24], and AC is recommended for patients with lymph-node metastasis; in other words, patients classified as stage III according to National Comprehensive Cancer Network guidelines [25]. The 3-year OS rate in this study including stage III cases (166 patients after PSM) was 85.7%. Our overall prognosis in this study might have been too good and the sample size too small to allow identification of significant prognostic factors.
To the best of our knowledge, two prospective study have compared TLC with IA to LAC with EA. Marco et al. [26] conducted a prospective, randomized study of 140 patients with RC, reporting earlier recovery of postoperative bowel function for TLC with IA compared to LAC with EA, but they did not meet their primary endpoint of shorter hospital stay. Similarly, Bollo et al. [27] conducted a prospective, randomized study of 140 patients with RC, and did not meet the primary endpoint of shorter hospital stay in the IA group compared to the EA group. Serra-Aracil et al. [28] are carrying out a prospective, controlled, nonrandomized study, the HEMI-D-TREND Study, in which the primary endpoint is overall morbidity and mortality for LAC with EA and TLC with IA, and open colectomy for RC. The study is ongoing and expected to finish in June 2021, and the results are eagerly awaited. No prospective studies including both RC and LC have been reported yet.
This study had some limitations, including the retrospective, single-center design. However, strengths of the study include the fact that this is the largest retrospective comparison of long-term, oncological outcomes between LAC with EA and TLC with IA, the reduction of selection bias by PSM, and the inclusion of not only RC, but also LC.
In conclusion, the present study showed that TLC with IA was an oncologically feasible procedure with long-term outcomes comparable to those of LAC with EA. A prospective, randomized trial comparing LAC with EA to TLC with IC could validate these findings.