The impact of laparoscopic, open, extended right, and left colectomy on clinical outcomes of splenic flexure colon cancer: A meta-analysis

Background:

Surgical intervention is the recommended line for the management of colon cancer. The aim of this study was to evaluate the impact of different surgical techniques (laparoscopic, open, extended right, and left colectomy) on clinical outcomes such as mortality, postoperative complications, operation and hospitalization time, and oncological factors.

Methods:

A total of 15 studies have been included in the current study. The outcomes of these studies were analyzed using a random-effect model and it was used to calculate the mean difference with 95% confidence intervals to quantify the impact of open, laparoscopic, extended right, and left colectomy. Inclusion criteria included studies in which subjects undergo splenic flexure colon cancer surgery with 2 comparable different surgical techniques.

Results:

Laparoscopic splenic flexure colon cancer surgery showed a significant beneficial impact on the length of hospital stay (P < .001), the volume of blood loss during surgery (P < .001), postoperative complications (P < .001), and time to an oral diet (P < .001). On the other hand, there was no significance regarding anastomotic leakage, infection of the surgical site, and operation time. Regarding the comparison between extended right colectomy (ERC) and lift colectomy (LC), analysis findings showed a significant (P = .001) higher efficacy of ERC in harvested number of lymph nodes compared with LC. On the other hand, there was no significant difference for the rest of the parameters. The neoadjuvant therapy as an influencing factor on postoperative outcome showed a beneficial impact regarding the overall survival rate.

Conclusion:

Laparoscopic splenic flexure colon cancer surgery showed a significant beneficial impact compared with open surgery as proved by clinical outcomes. On the other hand, ERC and LC resulted in similar findings except for harvested lymph nodes, results were in favor of ERC.

1. Introduction

Splenic flexure adenocarcinomas make up just 2% to 8% of all colorectal cancers that are surgically treated, but they have a particularly dismal survival rate because of the high likelihood of presenting with an obstruction, at a more advanced stage, and with lymphatic invasion.^[1–3]

Surgical resection of splenic flexure carcinomas (SFCs) can be difficult depending on several criteria such as tumor stage, precise location, presenting pattern, and patient characteristics.^[4–7] In a nutshell, extended right colectomy (ERC) and left colectomy are the 2 most common surgical methods advocated for the permanent removal of SFCs lift colectomy (LC). Left hemicolectomy (LH) or left segmental colectomy describes the latter operation.^[6] To guarantee the removal of all mesocolic lymph nodes along the superior mesenteric artery, extensive resections of SFCs have been advocated, such as ERC with or without splenectomy and distal pancreatectomy.^[2] To prevent needless excision of the middle colic artery, alternative, more conservative procedures like LH or left segmental colectomy have been promoted.^[8,9] Which of these 2 methods to choose is still up for debate.^[6,7,10]

Laparoscopic surgery for colorectal cancer has been shown to be safe and effective in multiple randomized clinical trials.^[11–14] No substantial difference in long-term survival has been found between laparoscopic and open surgery, but it does provide less pain, quicker recovery of bowel movements, and a shorter hospital stay. The use of laparoscopic surgery for the treatment of colorectal cancer is on the rise and is rapidly replacing more invasive procedures at most high-throughput facilities. Even so, most laparoscopic surgery studies have neglected to include patients with splenic flexure colon cancer. Among all colorectal malignancies, this area has a relatively low prevalence, and laparoscopic abilities for dissecting main lymph nodes with moving colon are technically hard. When compared to open surgery, laparoscopic procedures have a lower success rate and a higher risk of intraoperative and postoperative complications.

Using neoadjuvant therapy for patients undergoing colectomy showed a clinical impact on the safety and efficacy as shown by several studies.^[15–18]

The aim of the study was to evaluate the impact of different surgical techniques on clinical outcomes such as mortality, postoperative complications, operation and hospitalization time, and oncological factors.

2. Methods

2.1. Study design

The current meta-analysis was included in the epidemiological statement and followed a predetermined study design. For data collection and analysis, numerous databases, including OVID, Cochrane Library, Embase, PubMed, and Google Scholar, were consulted.

2.2. Data pooling

Clinical studies assessing the outcomes related to different surgical procedures for the management of splenic flexure colon cancer. No matter the language, only human-related research was included. No limitations were placed on the sample size of each study. We did not include reviews, editorials, or letters to the editor because they do not provide a measurement of association. Figure 1 depicts the scientific method in its entirety.

Figure 1.

Schematic diagram of the study procedure.

2.3. Eligibility and inclusion criteria

In this summary, we analyzed the outcomes related to different surgical procedures for the management of splenic flexure colon cancer to draw conclusions and make recommendations.

In the sensitivity analysis, only publications were considered that compared the outcomes related to different surgical procedures for the management of splenic flexure colon cancer such as operation time, hospitalization time, mortality, postoperative complication, an astrological leakage, reoperation R0 resection, blood loss, and the number of harvested lymph nodes.

For a study to be considered for inclusion in the meta-analysis, it must satisfy the following inclusion criteria: The study was either retrospective, prospective, or cohort studies. The target intervention population consisted of subjects with splenic flexure colon cancer undergoing surgery whether open or laparoscopic and with ERC or LC. In addition, the intervention regimen of the included studies was based on comparing the incidence of operative, postoperative, and oncological outcomes.

The exclusion criteria were studies that other surgical techniques not related to open or laparoscopic surgeries and studies that are not based on the comparison between different surgical procedures. In addition, review articles, letters, books, and book chapters were also excluded from the current study.

2.4. Identification

In accordance with the PICOS principle, the following protocol of search tactics was established and outlined: P (population) colon cancer; I (intervention/exposure): surgery; C (comparison): operation time, hospitalization time, R0 resection, blood loss, complications, mortality, and an astrological leakage.; S (design of the study): prospective studies.

We did a comprehensive search of the databases PubMed, OVID, Cochrane Library, Embase, and Google Scholar through October 2022 using the keywords and phrases as indicated in Table 1 (Search techniques for different databases). There was a review of the study elements such as paper titles besides abstracts of all the recruited articles that had been compiled into a reference management program, as well as any research that did not establish a connection between probiotic use and the outcomes. The 2 authors acted as reviewers for the identification of suitable studies.

Table 1.

Search strategy for each database.

Database	Search strategy
Pubmed	#1 “colon cancer” [MeSH terms] OR “laparoscopy” [all fields] #2 “colectomy” [MeSH terms] OR “open surgery” [all fields] #3 #1 AND #2
OVID	#1 “ Colon cancer” [all fields] OR “ laparoscopy “[all fields] #2 “ colectomy” [all fields] OR “ open surgery “[all fields] #3 #1 AND #2
Google scholar	#1 “Colon cancer” OR “laparoscopy” #2 “colectomy” OR “open surgery” #3 #1 AND #2
Embase	“Colon cancer/exp OR laparoscopy” #2 ‘‘colectomy”/exp OR “open surgery” #3 #1 AND #2
Cochrane library	(Colon cancer): ti, ab, kw (laparoscopy): ti, ab, kw (word variations have been Searched) #2 (“colectomy”): ti, ab, kw OR (open surgery): ti, ab, kw (word variations have been searched) #3 #1 AND #2

exp = exploded indexing term, ti, ab, kw = terms in either title or abstract or keyword fields.

2.5. Screening

According to the following criteria, data were reduced to include: study and subject-related features in a standard format; the sir name of the first author; the period of the study the year of publication; the country of the study; and the design of the study; the population type recruited in the studies; the total number of subjects; qualitative and quantitative evaluation method, demographic data; clinical and treatment characteristics; information source; outcome; the population type recruited in the studies; the total number of subjects; qualitative and quantitative evaluation method, demographic data; clinical. Each study was analyzed for bias, and the chosen studies methodological quality was appraised by 2 blinded authors.

2.6. Statistical analysis

All findings from recruited trials were analyzed and the mean difference besides the 95% confidence interval was estimated using a random-effects model in the current study. The log odds ratio was used as the primary statistic to assess study results. To statistically examine the data and make a scientific conclusion, a random model was implemented during the analysis. It was the constrained maximum-likelihood estimator that was used to measure the level of variety. We also examined the heterogeneity of included trials by performing the Q test and the I² statistic. If heterogeneity is discovered (tau2 > 0), a prediction interval for the true values is also provided. The significance and lack thereof of a study and its associated results were assessed by studentized residuals and Cook’s distances. Analysis of data was carried out using Jamovi 2.3 software (https://www.jamovi.org/).^[19]

3. Results

After screening and identification of all suspected articles, a total of fifteen studies were incorporated into the current analysis (Table 2).

Table 2.

Characteristics of included studies.

Study	Year	1st group	2nd group	Total	Intervention type
Degiuli et al[20]	2020	100	314	414	ERC vs LC
Arévalo et al[21]	2018	59	60	119	ERC vs LC
De’Angelis et al[6]	2016	27	27	54	ERC vs LC
Garavante et al[10]	2016	64	34	98	ERC vs LC
Odermatt et al[7]	2014	38	30	68	ERC vs LC
Rega et al[22]	2019	22	24	46	ERC vs LC
De’Angelis et al[23]	2020	134	131	265	ERC vs LC
Han et al[24]	2010	55	35	90	Open vs labaroscopic
Nakashima et al[25]	2011	22	33	55	Open vs labaroscopic
Okuda et al[26]	2016	34	61	95	Open vs labaroscopic
Kim et al[27]	2017	18	33	51	Open vs labaroscopic
Beghdadi et al[28]	2021	64	64	128	Open vs labaroscopic
Chi et al[29]	2018	62	62	124	Open vs labaroscopic
Pedrazzani et al[30]	2021	130	130	260	Open vs labaroscopic

ERC = extended right colectomy, LC = left colectomy.

3.1. Open versus laparoscopic surgery

The postoperative complication for subjects undergoing open compared with those undergoing laparoscopic surgery had been evaluated using the random model by recruiting findings from 8 studies. Analysis findings showed a significant (P < .001) lower occurrence regarding postoperative complication for the laparoscopic surgery group compared with open, mean difference (MD) = 0.60 confidence interval (CI) 95%, [0.27, 0.93] as shown in Figure 2A. No risk of publication bias was detected using both rank correlation and regression tests, P = .27 and P = .46 respectively.

Figure 2.

Analysis of postoperative complications, (A) anastomotic leakage, (B) infection of the surgical site, (C) time to oral diet, (D) length of hospital stay, (E) operation time, (F) and blood loss, and (G) for both open and laparoscopic surgery.

The anastomotic leakage for subjects undergoing open compared with those undergoing laparoscopic surgery had been evaluated using the random model by recruiting findings from 6 studies. Analysis findings showed a nonsignificant (P = .15) difference regarding Anastomotic leakage for the laparoscopic surgery compared with open, MD = 0.54 CI 95%, [0.20, 1.27] as shown in Figure 2B. No risk of publication bias was detected using both rank correlation and regression tests, P = .17 and P = .22, respectively.

The infection of the surgical site for subjects undergoing open compared with those undergoing laparoscopic surgery had been evaluated using the random model by recruiting findings from 6 studies. Analysis findings showed a nonsignificant (P = .17) difference regarding the infection of the surgical site for the laparoscopic surgery compared with open, MD = 0.59 CI 95%, [−0.25, 1.34] as shown in Figure 2C. No risk of publication bias was detected using both rank correlation and regression tests, P = .99 and P = .54, respectively.

The time to oral diet for subjects undergoing open compared with those undergoing laparoscopic surgery had been evaluated using the random model by recruiting findings from 6 studies. Analysis findings showed a significantly (P < .001) shorter time to oral diet for the laparoscopic surgery group compared with open, MD = 0.82 CI 95%, [0.42, 1.23] as shown in Figure 2D. No risk of publication bias was detected using both rank correlation and regression tests, P = .56 and P = .58 respectively.

The length of hospital stays for subjects undergoing open compared with those undergoing laparoscopic surgery had been evaluated using the random model by recruiting findings from 7 studies. Analysis findings showed a significantly (P < .001) shorter length of hospital stay for the laparoscopic surgery group compared with open, MD = 0.82 CI 95%, [0.40, 1.24], as shown in Figure 2E. No risk of publication bias was detected using both rank correlation and regression tests, P = .24 and P = .12, respectively.

The operation time for subjects undergoing open compared with those undergoing laparoscopic surgery had been evaluated using the random model by recruiting findings from 6 studies. Analysis findings showed a nonsignificant (P = .054) difference regarding the operation time for the laparoscopic surgery compared with open, MD = −1.44 CI 95%, [−2.91, 0.03] as shown in Figure 2F. No risk of publication bias was detected using both rank correlation and regression tests, P = .17 and P = .27, respectively.

The blood loss volume for subjects undergoing open compared with those undergoing laparoscopic surgery had been evaluated using the random model by recruiting findings from 5 studies. Analysis findings showed a significantly (P < .001) lower blood loss for the laparoscopic surgery group compared with open, MD = 1.34 CI 95%, [0.55, 2.12], as shown in Figure 2G. No risk of publication bias was detected using both rank correlation and regression tests, P = .82 and P = .92, respectively.

3.2. Extended right colectomy versus left colectomy

The number of lymph nodes harvested for subjects undergoing ERC compared with those undergoing LC had been evaluated using the random model by recruiting findings from 6 studies. Analysis findings showed a significantly (P = .001) higher efficacy of ERC in harvested number of lymph nodes compared with LC, MD = 0.37 CI 95%, [0.17, 0.57], as shown in Figure 3A. No risk of publication bias was detected using both rank correlation and regression tests, P = 1 and P = .79, respectively.

Figure 3.

Analysis of the number of lymph nodes harvested, (A) operation time (B) hospitalization time, (C) R0 resection, (D) anastomotic leakage, (E) reoperation, (F) mortality, (G) and postoperative complication, and (H) for subjects undergoing ERC compared with those undergoing LC. ERC = extended right colectomy, LC = left colectomy.

The operation time for subjects undergoing ERC compared with those undergoing LC had been evaluated using the random model by recruiting findings from 5 studies. Analysis findings showed a nonsignificant (P = .59) difference regarding operation time between ERC and LC, MD = 0.12 CI 95%, [−0.31, 0.54] as shown in Figure 3B. No risk of publication bias was detected using both rank correlation and regression tests, P = .82 and P = .42, respectively.

The hospitalization time for subjects undergoing ERC compared with those undergoing LC had been evaluated using the random model by recruiting findings from 4 studies. Analysis findings showed a nonsignificant (P = .88) difference regarding hospitalization time between ERC and LC, MD = 0.02 CI 95%, [−0.21, 0.25], as shown in Figure 3C. No risk of publication bias was detected using both rank correlation and regression tests, P = .75 and P = .09, respectively.

The R0 resection (If no gross or microscopic tumor remains in the initial tumor bed after a resection) for subjects undergoing ERC compared with those undergoing LC had been evaluated using the random model by recruiting findings from 5 studies. Analysis findings showed a nonsignificant (P = .52) difference regarding R0 resection between ERC and LC, MD = 0.52 CI 95%, [−1.07, 2.10], as shown in Figure 3D. No risk of publication bias was detected using both rank correlation and regression tests, P = .48 and P = .40, respectively.

The anastomotic leakage for subjects undergoing ERC compared with those undergoing LC had been evaluated using the random model by recruiting findings from 7 studies. Analysis findings showed a nonsignificant (P = .68) difference regarding anastomotic leakage between ERC and LC, MD = 0.14 CI 95%, [−0.53, 0.81], as shown in Figure 3E. No risk of publication bias was detected using both rank correlation and regression tests, P = .99 and P = .46, respectively.

The reoperation for subjects undergoing ERC compared with those undergoing LC had been evaluated using the random model by recruiting findings from 7 studies. Analysis findings showed a nonsignificant (P = .74) difference regarding reoperation between ERC and LC, MD = 0.12 CI 95%, [−0.58, 0.82], as shown in Figure 3E. No risk of publication bias was detected using both rank correlation and regression tests, P = .82 and P = .98, respectively.

The mortality rate for subjects undergoing ERC compared with those undergoing LC had been evaluated using the random model by recruiting findings from 6 studies. Analysis findings showed a nonsignificant (P = .26) difference regarding mortality rate between ERC and LC, MD = 0.65 CI 95%, [−0.49, 1.80], as shown in Figure 3G. No risk of publication bias was detected using both rank correlation and regression tests, P = .47 and P = .53, respectively.

The postoperative complication for subjects undergoing ERC compared with those undergoing LC had been evaluated using the random model by recruiting findings from 7 studies. Analysis findings showed a nonsignificant (P = .62) difference regarding postoperative complication between ERC and LC, MD = 0.09 CI 95%, [−0.28, 0.47], as shown in Figure 3H. No risk of publication bias was detected using both rank correlation and regression tests, P = .99 and P = .37, respectively.

Neoadjuvant therapy as a factor that could influence the outcomes of surgery showed a beneficial impact on the overall survival rate postoperative as shown by 4 studies (Table 3). Due to the limited number of studies, subgroup analyses, and meta-regressions were unable to investigate differences in outcomes by neoadjuvant regimen. The majority of the included studies were not randomized; only 1 study was a randomized clinical trial.

Table 3.

Role of neoadjuvant therapy on clinical outcomes after surgery.

Study	Year	Design	Number of patients	Findings
Agbamu et al[16]	2012	Randomized clinical trial	150	Tolerable toxicity and perioperative morbidity can be expected from preoperative chemotherapy for radiologically staged, locally advanced, operable primary colon cancer.
Dehal et al[15]	2018	Retrospective cohort	27.575	Patients with clinical T4b colon cancer may have an increased chance of survival if they have neoadjuvant chemotherapy treatment.
Krishnamurty et al[18]	2018	Retrospective cohort	131	Neoadjuvant therapy is safe and is linked to greater downstaging in locally advanced T4 colon cancer. There was a tendency for the NRT group to have a better local recurrence and margin-negative resections, although this was not statistically significant.
Hawkins et al[17]	2019	Retrospective cohort	15.207	The use of neoadjuvant therapy for clinical T4 disease may be associated with higher rates of R0 resection and enhanced overall survival.

4. Discussion

A total of 1867 subjects from different countries were recruited for the current analysis through the inclusion of 15 clinical studies.

The laparoscopic splenic flexure colon cancer surgery was shown to have a significant beneficial impact on the length of hospital stay (P < .001), the volume of blood loss during surgery (P < .001), postoperative complications (P < .001), and time to an oral diet (P < .001). On the other hand, there was no significant difference in operation time, anastomotic leakage, or infection at the surgical site. When compared to LC, extended right colectomy (ERC) had a significantly (P = .001) higher efficacy in terms of the number of lymph nodes that were removed during the procedure than LC did. This was determined by the outcomes of the analysis. On the other hand, there was not a significant difference between the 2 groups for the rest of the parameters, including operation time, R0 resection, reoperation rate, anastomotic leakage, mortality rate, inpatient time, and postoperative complications.

About 5% of all colorectal tumors are found in the splenic flexure.^[8,31] Males account for a disproportionate share of those affected, the average age at diagnosis is lower, and obstruction is a more frequent presenting symptom.^[8] Laparoscopic surgery for splenic flexure colon cancer is rarely studied because of its rarity and the high level of technical ability required for the procedure. Both the LCA and the left branch of the main colic artery^[32] send blood to the splenic flexure colon. For this reason, lymphadenectomy and identification of these 2 vessels at their origin are required for total radical surgery. The hazards of performing such an operation near vital organs like the pancreatic and duodenum are high, though. In addition, tension-free anastomosis and an adequate resection margin necessitate full mobilization of the splenic flexure colon, which is challenging due to the splenic flexure’s elevated anatomical position and omental adhesion. Jamali et al^[33] found that splenic flexure mobilization is the most challenging treatment for even the most seasoned laparoscopic colorectal surgeons. In a multivariate analysis of left colon resection, Akiyoshi et al^[34] found that splenic flexure mobilization was the most influential factor in extending the length of the operation, increasing the number of intraoperative problems, and increasing the volume of predicted blood loss. These factors explain why colon cancer in the splenic flexure has been left out of large-scale randomized therapeutic trials. Only 2 studies have been published on this topic, and both focus on the short-term safety of laparoscopic surgery^[9,35] and the comparison of short-term results between laparoscopic splenic flexure colon cancer surgery and open surgery.^[25] Laparoscopic versus open surgery for this lesion has not been compared for long-term survival rates.

Carcinomas of the splenic flexure present a technical challenge because of the difficulty in achieving complete tumor removal with appropriate margins and lymph node retrieval. Anatomical variables linked to the blood flow to this section of the colon, which have been shown to widely differ between people, are mostly to blame for this challenge.^[32,33] Blood supply to the splenic flexure is typically provided by tributaries of the inferior mesenteric artery, according to a landmark study conducted by Griffiths in 1956. However, in about 11% of patients, this supply may be provided by the superior mesenteric artery by the left branches of the middle colic artery.^[32] Lymph node metastases from SFCs are most commonly found along the paracolic arcade and the left colic artery; however, some evidence suggests that they may also be present near the origin of the middle colic artery and the superior mesenteric artery.^[8,36] These results suggest that extended colonic resections (ERCs) are warranted in the surgical treatment of SFCs in order to remove all potentially implicated lymph nodes that would be inaccessible with a more conservative technique (i.e., LC). However, there is scant evidence that metastatic nodes exist in the branches of the superior mesenteric artery, and recent literature has suggested the existence of novel metastatic routes for carcinomas of the transverse colon and both flexures, including the intrapancreatic lymph node region and the gastroepiploic arcade.^[37] In spite of the issues, the surgical therapy of regional lymph nodes may be improper or inadequate if diverse anatomies are not taken into account. This places a risk on the oncologic outcomes of the surgical treatment, which could be life-threatening. The use of lymph node road mapping with blue sentinel and/or a radiocolloid has been proposed for the assessment of the true lymphatic drainages of SFCs, and these procedures may allow for the avoidance of unnecessary resections of the middle colic artery or the inferior mesenteric artery. On the other hand, the use of these methods has not yet reached a widespread level of implementation, most likely as a result of the difficulty associated with the intraoperative identification of the sentinel node and the high level of radioactivity at the injection site.^[38–40] It is possible that the employment of a magnetic nanoparticle tracer to perform sentinel lymph node mapping could provide an option that is both promising and valuable to existing procedures.^[41] However, the safety, application, and accuracy of this technique in the process of deciding which type of surgical resection should be done for SFCs still need to be researched. This technique is used in the process of determining which sort of surgical resection should be used.

5. Conclusion

Clinical results demonstrated that laparoscopic splenic flexure colon cancer surgery had a significantly more favorable impact than open surgery did on the patient’s condition. On the other hand, ERC and LC both produced comparable results, with the exception of the harvested lymph nodes, where ERC produced better results. However, further multicenter future studies are still needed.

Author contributions

Conceptualization: Hefei Cheng.

Data curation: Ziqi Sui, Minjian Zhou, Lianlei Yang.

Methodology: Hefei Cheng, Minjian Zhou, Lianlei Yang.

Software: Hefei Cheng.

Validation: Ziqi Sui.

Writing – original draft: Ziqi Sui, Minjian Zhou, Lianlei Yang.

Writing – review & editing: Ziqi Sui.