Total Mesorectal Excision with or without Lateral Pelvic Lymph Node Dissection in Rectal Cancer

Results Incidence of local recurrence was slightly higher in Group A (8.7%) than in Group B (4.3%) but was not statistically significant. There was no statistical significance between both groups regarding distant metastasis (8.7% in Group A and 13% in Group B). Urinary and sexual dysfunctions were higher in Group B (26.1%) compared to those in Group A (21.7%) but were not statistically significant. The incidence of lateral pelvic lymph node metastasis was 30.4%. Also, intraoperative blood loss was higher and operative time was longer in Group B which was statistically significant (P value <0.001). Conclusion Our conclusion was that prophylactic addition of LPLD to TME was not associated with a statistically significant decrease in the risk of local recurrence or distant metastasis in patients with rectal cancer, although it was numerically better. LPLD is associated with longer operative time and higher intraoperative blood loss.


Introduction
Colorectal cancer is the third leading cause of death round the world with a rising incidence [1].Patients presenting with lower rectal cancer where the lower margin is at or below the peritoneal refection may develop metastases to lateral pelvic lymph nodes which are outside the surgical feld of TME.A retrospective multicenter study in Japan reported that the incidence of lateral pelvic lymph node metastasis in patients with T3 or T4 lower rectal cancer was 18.1% [2].
Two pathways are involved in lymphatic drainage of the middle and lower rectum.Te superior lymphatic drainage system runs along the inferior mesenteric artery and lateral lymphatic drainage runs along the internal iliac artery [3][4][5].
Te diferent approaches to LPLD between the East and West originate from the concept that lateral pelvic nodes are considered regional according to Japanese literature while the Western world, according to the AJCC guidelines (AJCC 8 th edition), confrms pelvic lateral lymph node stations as remote stations.Japanese surgeons suggest performing TME with bilateral pelvic lymphadenectomy without neoadjuvant treatment, as they expect that the risk of intrapelvic recurrence decreases by 50% [4,6].

Aim of Work
Te primary objective of this study was to compare the incidence of local recurrence in patients who underwent TME with or without LPLN dissection in extraperitoneal rectal cancer.Te secondary objective of this study was to compare the incidence of distant metastasis, intraoperative time, intraoperative blood loss, and urinary/sexual dysfunction between both groups.

Study Type.
Tis was an observational study.

Study
Settings.Tis study was carried out from June 2020 to November 2021, and follow-up was completed in February 2023 on patients with rectal cancer of both genders and from all age groups presenting with extraperitoneal mid-and low-rectal cancer (T3 and T4) presenting to the colorectal general surgery department, Cairo University hospitals.

Inclusion Criteria and Exclusion
Criteria.Patients from both sexes and all age groups diagnosed with extraperitoneal rectal cancer (T3 and T4) who are candidates for neoadjuvant chemoradiation were included in the study.Figure 1 shows the exclusion criteria plus patients who were recruited and then excluded from the study.

Preoperative Preparations.
Ninety-two patients scheduled for surgery for rectal cancer were evaluated for the study.Te patients were randomized using the closed envelope technique into two equal groups, each with 46 patients: Group (A) received preoperative neoadjuvant chemoradiation and TME was done Group (B) received no neoadjuvant chemoradiation and TME with LPLN dissection was done Informed written consent was obtained from all individuals that participated in the study.
Group (A) was considered the control group from which the results of Group (B) were compared.Both groups were compared regarding demographic features and regarding comorbidities.Postoperative chemoradiation was administered in all cases according to the examined pathological specimen after resection.
Patients were assessed preoperatively by proper history taking and full clinical and digital rectal examination, colonoscopy, biopsy, MRI pelvis for locoregional staging, and CT for chest, abdomen, and pelvis to detect distant metastasis.

Preoperative Neoadjuvant Regimen.
Neoadjuvant therapy involved 28 fractions totaling 50.4 Gy (45 Gy to the entire pelvis and 5.4 Gy to the tumor) over 5 weeks.Tis was supplemented with fuorouracil (5-FU) infusions at weeks one and fve.Surgery was performed 6-8 weeks after the last chemoradiation session.
3.6.Surgical Procedure.Group A: patients who received preoperative neoadjuvant chemoradiation; TME was done.Group B: In addition to TME, the lateral pelvic lymph nodes in fatty and connective tissues were dissected after TME (Figure 2).All surgeries in both groups were done laparoscopically.Diversion loop ileostomy was done on all patients in whom bowel continuity was restored after completing postoperative adjuvant therapy.

3.7.
Postoperative Follow-Up.Patients were referred to receive adjuvant chemoradiotherapy according to the stage and were followed up for 18 months to detect local recurrence.Follow-up is done monthly during a routine outpatient visit by clinical examination.MRI pelvis and CT chest and abdomen and pelvis are done every six months.Colonoscopy is done annually.
Both groups were compared regarding operative time, estimated intraoperative blood loss, incidence of local recurrence, incidence of distant metastasis (recurrence), histopathological examination of the surgical specimen, and urogenital complications (sexual and urinary dysfunctions).Urinary and sexual dysfunctions are assessed clinically during the follow-up visits, mainly erection, retrograde ejaculation, and urine retention or difculty in micturition.
Te manuscript was developed according to the STROBE checklist [7].

Statistical Analysis.
Data were coded and entered using the Statistical Package for the Social Sciences (SPSS) version 28 (IBM Corp., Armonk, NY, USA).Data were summarized using mean, standard deviation, minimum, and maximum in quantitative data and frequency (count) and relative frequency (percentage) for categorical data.Comparisons between quantitative variables were done using the nonparametric Kruskal-Wallis and Mann-Whitney tests.For comparing categorical data, a chi-square (χ 2 ) test was performed.Te exact  2 International Journal of Surgical Oncology test was used instead when the expected frequency is less than 5. Correlations between quantitative variables were done using the Spearman correlation coefcient.P values less than 0.05 were considered statistically signifcant.

Results
Patients were compared on the following aspects.

Patients' Demographics.
Table 1 shows the diference between both groups regarding demographic features including age and gender.Tere was no statistically signifcant diference between both groups regarding demographic features.

Comorbidities and ASA.
Table 2 shows the distribution of diabetes mellitus, hypertension, and ASA grade between both groups; there was no statistically signifcant diference in all aspects.

Tumor Location.
Table 3 shows the diference between both groups regarding tumor location.Tere was no statistical diference between either groups (P value � 0.225).

Pathological Type.
Table 3 shows the diference between both groups regarding pathological types of tumors between both groups.Tere was no statistical diference between either groups (P value � 1).

Operative Time and Estimated Blood
Loss.Table 4 shows the comparison between both groups regarding intraoperative blood time and estimated blood loss.Group B, who was subjected to a pelvic lymphadenectomy, showed more blood loss and operative time which was statistically signifcant (P value <0.001).

Local
Recurrence and Distant Metastasis.Te incidence of local recurrence was 8.7% in Group A and 4.3% in Group B (pelvic lymphadenectomy).Metastasis was in 4 patients in Group A (8.7%) and 6 patients in Group B (13.0%).However, there was no statistically signifcant diference between the 2 groups in both parameters.Tis is shown in Table 5.
All our patients have free distal, proximal, and circumferential margins which help compare local recurrence and distant metastasis rates.

Urinary and Sexual Dysfunctions and Postoperative
Complications.We did not experience any mortality or major postoperative complications such as leakage (as all patients were diverted) or wound dehiscence.As for urinary and sexual dysfunctions, they occurred in 12 patients in Group B (26.1%) compared to 10 patients (21.7%) in Group A. Tis was statistically insignifcant (P value � 0.730).

Mesorectal Lymph Nodes.
Tere was no statistically signifcant diference between either groups in the number of retrieved and positive mesorectal lymph node.Tis is shown in Table 6.

Lateral Pelvic Lymph Nodes in Group B.
Te number of patients with a positive pelvic lymph node was 14 (30.4%).Te mean number of retrieved pelvic lymph node in Group B was 12.04 ± 3.48 with a minimum of 2 and a maximum of 18 lymph nodes retrieved, while the mean of positive pelvic lymph node was (0.39 ± 0.14).
Regarding local recurrence, it occurred in 4 out of 18 patients with mucinous adenocarcinoma (22.2%) and in 2 out of 74 patients with nonmucinous adenocarcinoma (2.7%).Te P value was 0.093; however, this was statistically insignifcant.

Discussion
From the results of our study, LPLD showed no superiority over the routine neoadjuvant followed by TME strategy regarding distant metastasis, local recurrence, or number of retrieved lymph nodes but was also not associated by more urogenital consequences.
Regarding operative time, Hajibandeh et al. reported that TME with LPLD resulted in longer operative time (P < 0.00001) [8].Also, Cribb et al. in 2021 reported that signifcantly longer operative times were observed in patients who underwent LPLD (P � 0.008) [9].In our study, operative time was greater in group B (LPLD) with significant diference.
Regarding estimated intraoperative blood loss, several studies reported more intraoperative blood loss in the lateral pelvic lymphadenectomy group and the diference was International Journal of Surgical Oncology signifcant [9,10].In our study, operative time was greater in Group B (LPLD) which was also statistically signifcant.
As for local recurrence, Anania et al. in 2020 reported that the incidence of the overall local recurrence was not statistically diferent between the lateral pelvic lymph node dissection group and the nonlateral pelvic lymph node dissection group [4,8].Also, Ma et al. reported that there were no signifcant diferences observed between both groups regarding local recurrence (P � 0.077) [11,12].Tamura et al. reported a slight increase in local recurrence in TME without lateral pelvic lymphadenectomy compared to lateral pelvic lymphadenectomy, but it was not statistically signifcant.(21.4% vs. 14.8%,P � 0.833) [13].However, Fujita et al. in 2017 reported there was a statistical signifcance in the local recurrence rate in the TME with LPLN dissection (7.4%) compared to (12.6%) in TME alone groups (P � 0.024) [2].In our results, the incidence of local recurrence was 8.7% in Group A in and 4.3% in Group B (LPLD).Our results slightly favor lateral pelvic lymph node dissection, but there is no statistical signifcance.
Regarding distant metastasis, several studies reported that there was no statistically signifcant diference in metastasis between the dissection group and the nonlateral pelvic lymph node dissection group [4,8,11,12].However, Fahy et al. reported that the rate of metastasis was lower in  [14].In our study, metastasis was seen in 4 patients in Group A (8.7%) while 6 patients in Group B (13%), there is no statistical signifcance in metastasis in both groups (P value � 1).Regarding genitourinary complications, Wang et al. in 2020 reported that no statistically signifcant diference was observed regarding urinary complication (P � 0.3) between patients who underwent LPLN dissection and those who did not, but with a higher possibility of sexual dysfunction [15].Hajibandeh et al. reported that patients who underwent LPLN dissection had an increasing risk of urinary dysfunction (P < 0.00001) and sexual dysfunction (P � 0.002) [8].Anania et al. reported that the incidence of urinary dysfunction was signifcantly higher in the LPLN dissection patients group (37%) compared to the non-LPLN dissection patients' group (24.4%), while the incidence of sexual dysfunction was similar between both groups [4].Also, Saito et al. in 2016 reported the incidences of sexual dysfunction in patients who underwent TME alone and TME with LPLN dissection were 68% and 79% (P � 0.37) [16].On the other side, Maeda et al. reported that only minor disturbances of bladder function were reported in 15% of patients who underwent LPLN dissection compared to only 25% of the nonpelvic lymph node dissection group, while regarding sexual dysfunction, the percentage was 27% in the LPLN dissection group compared to 20% in the other group who had partial or total impotency after surgery [17].Also, Ito et al. demonstrated that urinary function would not be worse in cases where autonomic nerves were surgically preserved, even if LPLN dissection was performed for lower rectal cancer [18].Our study revealed an increase in urinary and sexual dysfunction in Group B compared to Group A, but with no statistical signifcance between both groups.
Tere are a lot of variations in the incidence of lateral LN afection among the literature.Kobayashi et al. reported in their study in 2009 that the lateral pelvic LN involvement was 14.9%, while Ueno and his colleagues in 2005 reported that 17.9% had lateral pelvic lymph node metastasis [19,20].However, in 2021, Wang et al., in their study, reported much more patients with lateral pelvic LN disease reaching about 62.5% [21].Lastly, Dev et al. in 2018 reported that the incidence of lateral pelvic LN metastasis in lower rectal cancer was 26.5% [22].In our study, the incidence of lateral pelvic lymph node involvement was 30.4%.
Regarding the relation between recurrence and pathological type, Park et al. in 2015 reported that locoregional recurrence in colorectal cancers was 17.2% in the mucinous adenocarcinoma group and 13.7% in the nonmucinous adenocarcinoma group (P � 0.451).Distant metastasis was 75.9% in the mucinous adenocarcinoma group and 81.1% in the nonmucinous adenocarcinoma group (P � 0.329); these were statistically insignifcant [23].Numata et al. in 2012 reported that local recurrence in rectal cases and peritoneal dissemination were more frequently observed in patients with mucinous histology [24].In our current study, there was no statistically signifcant diference between the mucinous and nonmucinous types regarding local recurrence, but there was a signifcant diference in distant metastasis in the mucinous adenocarcinoma type.
Lastly, whether you go for LPLN dissection or not, the most important issue for rectal cancer is to do total TME and to achieve clear distal, proximal, and circumferential surgical margins which can be achieved either by open, laparoscopic, robotic, or transanal surgery (TaTME) [25,26].

Conclusion
Our conclusion was that prophylactic addition of LPLD in patients who do not have radiologically lateral LN afection to TME was not associated with a statistically signifcant decrease in the risk of local recurrence or distant metastasis in patients with rectal cancer.LPLD is associated with longer operative time and higher intraoperative blood loss.

Limitations of Study.
A relatively small number of patients were included in the study.A larger number of patients are needed to assess and compare recurrence rates between both groups who underwent LPLD and those who did not in rectal cancer and to assess sexual and urinary dysfunctions.Also, a longer period of follow-up is needed to detect long-term outcomes and complications.

Table 3 :
Tumor location distribution and pathological type distribution.

Table 4 :
Operative time distribution and estimated blood loss distribution.

Table 5 :
Local recurrence distribution and distant metastasis distribution.