Abstract
Background:
Natural orifice specimen extraction surgery (NOSES) is currently widely used in left-sided colorectal cancer. Some clinical comparative studies have been conducted, providing evidence of its safety and oncological benefits. However, these studies are typically characterized by small sample sizes and short postoperative follow-up periods. Consequently, in this research, the authors adopt the propensity score matching method to undertake a large-scale retrospective comparative study on NOSES colectomy for left-sided colorectal cancer, with the goal of further augmenting the body of evidence-based medical support for NOSES.
Methods:
This retrospective study involved patients who underwent NOSES colectomy and conventional laparoscopic (CL) colectomy for left-sided colorectal cancer between January 2014 and April 2021. In the NOSES group, specimens were extracted through the anus with the help of a Cai tube (homemade invention: ZL201410168748.2). The patients were matched at a ratio of 1:1 according to age, sex, BMI, tumor diameter, tumor location (descending and splenic flexure colon/ sigmoid colon/ middle and upper rectum), tumor height from anal verge, ASA grade, previous abdominal surgery, clinical pathologic stage, preoperative CEA. After matching, 132 patients in the NOSES group and 132 patients in the CL group were eligible for analysis.
Results:
Compared with CL group, NOSES group was associated with decreased postoperative maximum pain score (2.6±0.7 vs. 4.7±1.7, P=0.000), less additional analgesia required (6.8 vs. 34.8%, P=0.000), faster time to passage of flatus (2.3±0.6 days vs. 3.3±0.7 days, P=0.000), less wound infection (0.0 vs. 6.1%, P=0.007), and longer operative time (212.5±45.8 min vs. 178.0±43.4 min, P=0.000). No significant differences were observed in estimated blood loss, time to resume regular diet, postoperative hospital stay, conversion to open surgery or conventional minilaparotomy, total morbidity, readmission, mortality, pathologic outcomes, and Wexner incontinence score between groups. After a median follow-up of 63.0 months, the 5-year overall survival rates were 88.3 versus 85.0% (P=0.487), disease-free survival rates were 82.9 versus 83.6% (P=0.824), and the local recurrence rates were 4.4 versus 4.0% (P=0.667) in the NOSES and CL groups, respectively.
Conclusions:
This study suggests that NOSES colectomy using a Cai tube for left-sided colorectal cancer is a safe and feasible option with better cosmetic results, less pain, faster recovery of gastrointestinal function, and comparable long-term clinical and oncologic outcomes to CL colectomy.
Keywords: Cai tube, left-sided colorectal cancer, long-term oncological outcomes, natural orifice specimen extraction surgery, propensity score matching
Introduction
Highlights
In this retrospective control study, propensity score matching was used to reduce potential bias in baseline data. After matching, 132 patients in the Natural orifice specimen extraction surgery (NOSES) group and 132 patients in the conventional laparoscopic (CL) group were eligible for analysis.
Compared with the CL group, the NOSES group was associated with a decreased postoperative maximum pain score, less additional analgesia required, a faster time to passage of the flatus, and less wound infection.
After a median follow-up of 63.0 months, 5-year oncological outcomes (5-year overall survival, disease-free survival, local recurrence) in the NOSES group were similar to those in the CL group.
To the best of our knowledge, our study is the most extensive retrospective controlled study with the longest follow-up in NOSES colectomy for left-sided colorectal cancer.
In 1993, Franklin first reported laparoscopic-assisted natural orifice specimen extraction surgery (NOSES) surgery in colorectal cancer1. Proven by established studies, NOSES outperforms conventional laparoscopic (CL) colectomy in cosmetic results, shorter hospital stays, and less postoperative pain, making it an appealing, minimally invasive surgery for colorectal cancer2–6. Despite challenges in specimen removal for left-sided colorectal cancer, a homemade auxiliary incision-free tube (Cai tube, patent number: ZL201410168748.2) has been utilized to facilitate extraction through the anus7–11. Since 2014, we have successfully applied Cai tube in NOSES for descending colon cancer and gastric cancer7,9. In 2015, we initiated the first randomized controlled study on NOSES for left-sided colorectal cancer10. Moreover, in 2016, we were the first to use the propensity score matching (PSM) method to study retrospective cases of NOSES radical surgery for colorectal cancer8. To date, we have performed nearly 350 cases radical NOSES surgeries for gastrointestinal tumors11.
With its minimally invasive advantages, NOSES is being increasingly utilized in laparoscopic-assisted radical surgery for colorectal cancer12,13. While there are existing studies on NOSES, our utilization of the Cai tube and the focus on left-sided colorectal cancer with long-term follow-up introduces a new dimension to the field. This emphasis on a specific type of cancer, combined with our unique methodology, seeks to address a significant gap in the literature and offers a fresh perspective on NOSES. At present, the majority of available data is derived from small sample controlled studies4–6,10,14–20, or from large-sample controlled studies that encompass all types of colorectal cancer21. There are also large-sample multicenter single-arm studies22, as well as several high-quality evidence-based medical meta-analyses23–27. Together, these form a favorable foundation for implementing NOSES. However, a significant gap exists: there have been no large-sample, long-term follow-up clinical controlled studies that exclusively focus on left-sided colorectal cancer. This omission is notable, especially given that the radical resection of left-sided colorectal cancer is the most commonly performed, well-established, and standard procedure within the NOSES repertoire, particularly in terms of surgical scope and specimen removal. Consequently, we selected left-sided colorectal cancer as our study object to delve deeper into the clinical value of NOSES. To the best of our knowledge, our study is the most extensive retrospective controlled study with the longest follow-up in this domain. We employed PSM to reduce potential biases from baseline data.
Methods
Patients
As part of routine clinical practice, patients were informed about the advantages and disadvantages of both NOSES and CL colectomy. After understanding these, they voluntarily selected their surgical method. For this retrospective study, we later analyzed the data without directly involving patients’ choices during the research phase.
The inclusion criteria were: (1) patient age between 18 and 75 years; (2) preoperative diagnosis of left-sided colorectal cancer confirmed by colonoscopy with biopsy. Exclusion criteria included: (1) a BMI >30 kg/m2; (2) tumor maximum transverse diameter >4.5 cm on thoracoabdominal computed tomography scans (large tumors are challenging to extract through the Cai tube or anus); (3) contraindications for laparoscopic surgery; (4) anal strictures; (5) local infiltration and distant metastasis; (6) postoperative recurrence or multiple primary colorectal cancers; (7) severe intestinal obstruction (presented with intense pain, vomiting, an inability to pass gas or stool, abdominal distension, and potentially life-threatening complications), perforation, or bleeding requiring emergency surgery; (8) chronic opioid use; (9) incomplete clinical and pathological data; and (10) patients underwent chemoradiotherapy before surgery.
PSM was used to analysis perioperative and long-term clinical outcomes of the two groups. The matching covariates were as follows: age, sex, BMI, tumor diameter, tumor location (descending and splenic flexure colon/ sigmoid colon/ middle and upper rectum), tumor height from anal verge, ASA grade, previous abdominal surgery, clinical pathologic stage, and preoperative CEA.
We analyzed data from 629 patients who underwent laparoscopic surgery for left-sided colorectal cancer between January 2014 and April 2021 at our center. Of these, 40 patients were excluded due to various reasons, as detailed in Figure 1. Ultimately, 132 patients undergoing NOSES colectomy were matched 1:1 using PSM with 132 patients receiving CL colectomy. The groups were compared on factors such as operative time, estimated blood loss, conversion to open surgery or conventional minilaparotomy, postoperative maximum pain score, additional analgesia required, time to passage of flatus, postoperative hospital stay, morbidity, mortality within 30 days of surgery, harvested lymph nodes, proximal margin, distal margin, histological differentiation, and pathologic stage. The postoperative maximum pain score was the most severe pain score from day 1 to day 5 after surgery, which was assessed twice daily using a visual analog score28. The pathologic stage was categorized as per the American Joint Committee on Cancer (AJCC) 8th edition. Following the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology, it is advised for all patients diagnosed with AJCC stage III or high-risk AJCC stage II cancers to undergo adjuvant chemotherapy. This treatment regimen includes either Folfox or Xelox administered intravenously over 12 cycles, or orally taking Capecitabine (2 g/day) for a duration of 6 months29. Postoperative complications were graded according to the Clavien–Dindo classification30.
Figure 1.
Flow diagram of the patient allocation process. CL, conventional laparoscopy; NOSES, natural orifice specimen extraction.
This work has been reported in line with the strengthening the reporting of cohort, cross-sectional and case–control studies in surgery (STROCSS) criteria31.
Cai tube
The Cai tube is a homemade, incision-free device for specimen extraction through natural orifices (Fig. 2)9. It consists of a guide tube, an outer tube, a rear cover, and a hole cover. The outer tube, the key component in specimen exteriorization, measures 4.0 cm in diameter and comes in lengths of either 28 cm or 33 cm. The guide tube, with its rounded, blunt head, is housed inside the outer tube, and its purpose is to guide the outer tube into the abdominal cavity without harming the intestinal wall. The rear cover, fitting over the end of the outer tube, is specifically used for extracting specimens, playing a key role in maintaining pneumoperitoneum during this phase. In contrast, the hole cover is primarily employed during the passage of surgical instruments, ensuring the maintenance of pneumoperitoneum throughout the instrument exchange.
Figure 2.
Structure graph of Cai tube, a homemade auxiliary incision-free tube. (A) The assembled Cai Tube. (B) Guide tube. (C) Outer tube. (D) Rear cover. (E) Hole cover9.
Surgical techniques
Both groups underwent radical surgery following the total mesenteric resection principle. The key difference was that the NOSES group used Cai tube for specimen removal, as previously described7–11. Here, we outline the extraction steps succinctly.
The rectum was dissected 5 cm from the tumor’s distal lower margin, with 3 cm ligated using a vascularized line and secured with titanium forceps. The perineal surgeon inserted the Cai tube through the anus to the bare rectum wall, while the abdominal surgeon performed a small colotomy near the Cai tube margin (Fig. 3A). A circular stapling device anvil was passed through the Cai tube from the perineal surgeon to the abdominal surgeon (Fig. 3B).
Figure 3.
Surgical illustrations showing the application of Cai tube assisting extraction of specimens from the natural orifice in NOSES colectomy. (A) The guide tube and outer tube of Cai tube were inserted through the anus into the exposed rectum wall. (B) A circular stapling device anvil was passed into the abdominal cavity through Cai tube. (C, D) The anvil was placed in the proximal colon and then secured with two Hemolocks. (E) Smaller specimen was directly extracted via Cai tube. (F) Larger specimen was first placed into an unclosed specimen bag before being passed through Cai tube.
A subsequent proximal colon dissection was executed 10 cm from the tumor’s upper edge, ligation occurred at 7 cm, and another small colotomy was performed at 8 cm proximal to the tumor’s upper edge, with the anvil placed in the proximal colon. The anvil was then secured with two Hemolocks (Fig. 3C, D).
Smaller specimens were transferred directly through the Cai tube (Fig. 3E). For larger specimens, a specimen bag was used along with a Cai tube (Fig. 3F). An unclosed specimen bag was passed through the Cai tube, with the specimen placed within it. The specimen was then clamped into the Cai tube, the specimen bag was tightened and tied, and finally, the entire specimen was slowly removed by the perineal surgeon.
Patient follow-up
The follow-up protocol was based on the NCCN guidelines for colorectal cancer. This entailed scheduling routine follow-up visits at 1 month postoperation, then every 3 months for the first 2 years, followed by every 6 months for up to 5 years. The carcinoembryonic antigen evaluations, and imaging procedures including chest, abdominopelvic, and brain CT were conducted in accordance with these time intervals. A colonoscopy was performed 1 year after surgery. Overall survival (OS) was measured from the surgery date to the date of death or the final follow-up. Disease-free survival (DFS) was defined as the period from surgery to recurrence or death, whichever came first. Local recurrence (LR) was defined as any suspected or diagnosed recurrence of the abdomen or pelvis. Anorectal function was assessed by the Wexner fecal incontinence scoring system before surgery and at 6 months and 12 months after surgery32,33.
Statistical analysis
Given the retrospective nature of our cohort study and to ensure comparability between groups concerning potential confounding variables, we adopted the PSM method. The propensity scores were calculated using logistic regression, incorporating the aforementioned 10 covariates. Patients were then matched in a 1:1 ratio using a caliper width, akin to the methods mentioned in the referenced literature5,15,16,20. Before and after matching, baseline demographic, and clinical characteristics were presented using appropriate descriptive statistics. Continuous variables were expressed as mean±SD and assessed using the t-test, while categorical variables were analyzed using the χ2 or Fisher’s exact test. Recurrence and survival rates were evaluated using the Kaplan–Meier method and compared with the log-rank test. All statistical analyses were executed using SPSS (version 26.0). A P-value <0.05 was considered statistically significant34.
Results
Screening and inclusion process for PSM
In our retrospective analysis, we considered a broad range of patients but needed to ensure a fair comparison between the NOSES and CL colectomy groups. Hence, specific inclusion and exclusion criteria were employed. Initially, 629 patients were considered from January 2014 to April 2021, but 40 were excluded based on predefined criteria including BMI, tumor size, presence of metastasis, emergency surgery needs, and data completeness. Following this, out of the remaining 589 patients, only those who precisely met our criteria (155 from the NOSES group and 391 from the CL group) were considered for PSM. (Fig. 1) These criteria were meticulously designed to eliminate any potential confounders in our analysis. Prior to matching, there were notable disparities between the NOSES and CL groups in baseline variables such as tumor diameter, tumor height from the anal verge, and ASA grade. Other covariates did not show significant differences prematching. After matching, the two groups (each containing 132 patients) were well balanced in terms of all selected covariates, ensuring a robust comparison of perioperative and long-term clinical outcomes (Table 1).
Table 1.
Comparison of baseline data between NOSES group and CL group before and after propensity score matching.
| Before PSM | After PSM | |||||
|---|---|---|---|---|---|---|
| NOSES (n=155) | CL (n=391) | P | NOSES (n=132) | CL (n=132) | P | |
| Age (years) | 61.6±10.1 | 61.5±11.8 | 0.959 | 61.8±10.3 | 60.6±12.6 | 0.421 |
| Sex (%) | 0.631 | 0.901 | ||||
| Male | 88 (56.8) | 231 (59.1) | 77 (58.3) | 75 (56.8) | ||
| Female | 67 (43.2) | 160 (40.9) | 55 (41.7) | 57 (43.2) | ||
| BMI (kg/m2) | 22.7±3.4 | 22.5±3.3 | 0.465 | 22.8±3.6 | 22.2±2.5 | 0.125 |
| Tumor diameter (cm) | 3.5±1.0 | 3.7±1.0 | 0.042 | 3.6±1.0 | 3.6±1.1 | 0.809 |
| Tumor location (%) | 0.332 | 0.431 | ||||
| Descending and splenic flexure colon | 14 (9.0) | 27 (6.9) | 10 (7.6) | 7 (5.3) | ||
| Sigmoid colon | 65 (41.9) | 146 (37.3) | 52 (39.4) | 62 (47.0) | ||
| Middle and upper rectum | 76 (49.0) | 218 (55.8) | 70 (53.0) | 63 (47.7) | ||
| Tumor height from anal verge (cm) | 18.7±10.1 | 16.2±9.0 | 0.006 | 17.3±8.9 | 18.5±10.5 | 0.313 |
| ASA grade (%) | 0.000 | 0.093 | ||||
| I | 3 (1.9) | 78 (19.9) | 3 (2.3) | 7 (5.3) | ||
| II | 136 (87.7) | 277 (70.8) | 117 (88.6) | 104 (78.8) | ||
| III | 16 (10.3) | 35 (9.0) | 12 (9.1) | 21 (15.9) | ||
| Previous abdominal surgery (%) | 0.102 | 1.000 | ||||
| Presence | 33 (21.3) | 60 (15.3) | 25 (18.9) | 25 (18.9) | ||
| Absence | 122 (78.7) | 331 (84.7) | 107 (81.1) | 107 (81.1) | ||
| cTNM stage (%) | 0.137 | 0.782 | ||||
| I | 41 (26.5) | 75 (19.2) | 30 (22.7) | 32 (24.2) | ||
| II | 53 (34.2) | 160 (40.9) | 47 (35.6) | 51 (38.6) | ||
| III | 61 (39.4) | 156 (39.9) | 55 (41.7) | 49 (37.1) | ||
| Preoperative CEA | 5.6±11.4 | 7.4±11.8 | 0.102 | 5.9±12.3 | 5.7±7.6 | 0.906 |
Results in the table are presented as mean±SD or numbers (%).
ASA, American Society of Anesthesiologists; CEA, carcinoembryonic antigen; CL, conventional laparoscopy; cTNM, clinical TNM stage; NOSES, natural orifice specimen extraction; PSM, propensity score matching.
Intraoperative and perioperative outcomes
The operation time was longer in the NOSES group (212.5±45.8 min vs. 178.0±43.4 min, P=0.000). There were no significant differences in estimated blood loss between the two groups (P=0.419). There was no conversion to open surgery or conventional minilaparotomy in either group. Compared with those who underwent CL colectomy, patients who underwent NOSES colectomy showed a decreased postoperative maximum pain score (2.6±0.7 vs. 4.7±1.7, P=0.000) and required less additional analgesia (6.8 vs. 34.8%, P=0.000). NOSES group showed a faster time to passage of the flatus (2.3±0.6 days vs. 3.3±0.7 days, P=0.000). There were no significant differences in time to resume a regular diet between the two groups (P=0.388). Postoperative hospital stay did not significantly differ between the two groups (13.7±7.0 days vs. 14.0±4.8 days, P=0.721). The two groups showed similar rates of total morbidity (7.6 vs. 9.8%, P=0.663). The total morbidity (7.6 vs. 9.8%, P=0.663) and grade of morbidity (P=0.154) were comparable between the two groups. However, the rate of wound infection in the CL group was higher than that in the NOSES group (6.1 vs. 0.0%, P=0.007). NO significant differences were found in readmission within 30 days of surgery between the two groups (P=1.000). No mortality within 30 days after surgery was revealed in either of the two groups. Wexner incontinence scores were comparable between the two groups before surgery and at 6 months and 12 months after surgery. The median follow-up was 63.0 months (Table 2). The scarring on the abdominal wall was less noticeable 5 years after the NOSES colectomy (Fig. 4).
Table 2.
Intraoperative and perioperative outcomes in NOSES group and CL group.
| NOSES (n=132) | CL (n=132) | P | |
|---|---|---|---|
| Operative time (min) | 212.5±45.8 | 178.0±43.4 | 0.000 |
| Estimated blood loss (ml) | 44.7±16.9 | 42.9±19.6 | 0.419 |
| Conversion (%) | 1.000 | ||
| To open surgery | 1 (0.8) | 3 (2.3) | |
| To conventional minilaparotomy | 2 (1.5) | – | |
| Postoperative maximum pain score | 2.6±0.7 | 4.7±1.7 | 0.000 |
| Additional analgesia required (%) | 9 (6.8) | 46 (34.8) | 0.000 |
| Time to passage of flatus (days) | 2.3±0.6 | 3.3±0.7 | 0.000 |
| Time to resume regular diet (days) | 4.0±0.1 | 4.1±0.1 | 0.388 |
| Postoperative hospital stay (days) | 13.7±7.0 | 14.0±4.8 | 0.721 |
| Total morbidity (%) | 10 (7.6) | 13 (9.8) | 0.663 |
| Anastomotic leak (%) | 2 (1.5) | 1 (0.8) | 1.000 |
| Stenosis (%) | 1 (0.8) | 0 (0.0) | 1.000 |
| Anastomotic bleeding (%) | 3 (2.3) | 2 (1.5) | 1.000 |
| Wound infection (%) | 0 (0.0) | 8 (6.1) | 0.007 |
| Intra-abdominal abscess (%) | 3 (2.3) | 1 (0.8) | 0.622 |
| Ileus (%) | 1 (0.8) | 1 (0.8) | 1.000 |
| Grade of morbidity (%) | 0.154 | ||
| Dindo I–II | 8 (6.1) | 13 (9.8) | |
| Dindo III–IV | 2 (1.5) | 0 (0.0) | |
| Readmission within 30 days of surgery (%) | 4 (3.0) | 3 (2.3) | 1.000 |
| Mortality within 30 days of surgery (%) | 0 | 0 | 1.000 |
| Wexner incontinence score before surgery | 4.9±1.4 | 5.0±1.4 | 0.825 |
| Wexner incontinence score at 6 months after surgery | 3.5±1.2 | 3.3±1.1 | 0.372 |
| Wexner incontinence score at 12 months after surgery | 1.5±0.5 | 1.5±0.6 | 0.396 |
Results in the table are presented as mean±SD or numbers (%).
CL, conventional laparoscopy; NOSES Natural Orifice Specimen Extraction.
Figure 4.
Appearances of abdominal wall after 5 years of NOSES colectomy.
Pathologic and oncologic outcomes
The number of harvested lymph nodes were similar between the two groups (15.8±6.8 vs. 14.6±6.8, P=0.1157). Neither the proximal margin (8.7±1.2 cm vs. 8.4±2.8 cm, P=0.591) no distal margin (4.6±3.0 cm vs. 5.0±3.4 cm, P=0.278) had a significant difference between the two groups. The majority of postoperative histological differentiation was moderate in both groups and also balanced among groups (P=0.350). pTNM stage were also comparable between the NOSES and CL groups (P=0.622). The difference in the percentage of patients who underwent adjuvant chemotherapy was not statistically significant, with 28.8% in NOSES compared to 27.3% in the CL (P=0.893) (Table 3).
Table 3.
Pathologic and oncologic outcomes in NOSES group and CL group.
| NOSES (n=132) | CL (n=132) | P | |
|---|---|---|---|
| Harvested lymph nodes | 15.8±6.8 | 14.6±6.8 | 0.157 |
| Proximal margin (cm) | 8.7±1.2 | 8.4±2.8 | 0.591 |
| Distal margin (cm) | 4.6±3.0 | 5.0±3.4 | 0.278 |
| Histological differentiation (%) | 0.350 | ||
| Well | 2 (1.5) | 6 (4.5) | |
| Moderately | 126 (95.5) | 121 (91.7) | |
| Poorly | 4 (3.0) | 5 (3.8) | |
| pTNM stage | |||
| T (%) | 0.064 | ||
| Tis | 2 (1.5) | 9 (6.8) | |
| T1 | 11 (8.3) | 12 (9.1) | |
| T2 | 24 (18.2) | 14 (10.6) | |
| T3 | 95 (72.0) | 97 (73.5) | |
| N (%) | 0.622 | ||
| N0 | 84 (63.6) | 87 (65.9) | |
| N1 | 30 (22.7) | 24 (18.2) | |
| N2 | 18 (13.6) | 21 (15.9) | |
| Adjuvant postoperative chemotherapy | 38 (28.8) | 36 (27.3) | 0.893 |
Results in the table are presented as mean±SD or numbers (%).
CL, conventional laparoscopy; NOSES, Natural Orifice Specimen Extraction; pTNM, pathological TNM stage.
The 5-year OS rates in the NOSES group were comparable to that in CL group [82.9 vs. 83.6%, (P=0.824)]. The two groups did not significantly differ with regard to 5-year DFS rates [88.3 vs. 85.0%, (P=0.487)]. For the 5-year LR rates, the two groups were also similar [4.4 vs. 4.0%, (P=0.667)] (Fig. 5).
Figure 5.
Comparisons of long-term outcomes between the NOSES and CL groups. (A) The 5-year disease-free survival rates postoperatively were 82.9% versus 83.6% (P=0.824) in NOSES and CL groups, respectively. (B) The 5-year overall survival rates postoperatively were 88.3 versus 85.0% (P=0.487) in NOSES and CL groups, respectively. (C) The 5-year local recurrence rates postoperatively were 4.4 versus 4.0% (P=0.667) in NOSES and CL groups, respectively.
Discussion
After a decade of focused research and dedicated surgical practice, NOSES colectomy for colorectal cancer has been substantiated as safe and feasible as CL colectomy by numerous studies20,21,26,35,36. However, there remains a dearth of comprehensive data comparing the long-term survival outcomes between NOSES and CL colectomy procedures in the treatment of left-sided colorectal cancer. With years of experience performing NOSES colectomy, our center gathered and analyzed clinical data from left-sided colorectal cancer patients who underwent laparoscopic surgery between January 2014 and April 2021. Perioperative clinical and long-term oncological outcomes were assessed using PSM to eliminate bias in baseline data from retrospective controlled studies.
The allure of minimally invasive surgery lies in its ability to improve esthetics and mitigate postoperative pain. Compared to CL colectomy, NOSES, by eliminating the need for a 5 cm abdominal auxiliary incision, offers superior cosmetic outcomes6,20,37. A recent randomized controlled trial by Zhu et al.4 indicated that postoperative day 1 and 3 visual analog score scores were lowest in the NOSES group. Using PSM for analysis, Tang et al.21 found significantly reduced postoperative pain and less analgesic in patients undergoing NOSES. Echoing these findings, our study noted a decreased postoperative maximum pain score and less additional analgesia required in the NOSES.
In our study, we found that NOSES and CL had similar rates of postoperative complications such as anastomotic leak, stenosis, bleeding, intra-abdominal abscess, and ileus. However, the NOSES group had a lower incidence of wound infection. These findings are in agreement with some high-quality clinical studies6,15. Despite this, the NOSES group took longer, potentially due to the steep learning curve and challenges associated with full laparoscopic operations. Previous studies also demonstrated a longer operation time for NOSES15–17. In our study, the NOSES group showed faster gastrointestinal recovery, marked by a quicker first flatus, compared to the CL group. Prior studies also favor NOSES due to its reduced abdominal trauma and pain, leading to less additional analgesia, quicker postsurgery mobility, and faster intestinal function recovery21,35,37. Even though specimens were extracted anally, postoperative anal function recovery was satisfactory. We utilized the Wexner incontinence score to assess anal sphincter function before and postsurgery. Consistent with previous studies, there was no significant disparity in Wexner incontinence scores15,20,21. This outcome can be attributed to stringent tumor size control during NOSES patient selection, and the protective role of the Cai tube during specimen extraction, safeguarding the anal sphincter, and rectal mucosa10. While previous studies have touched upon NOSES, our methodological approach, particularly with the introduction and application of the Cai tube, stands as a significant innovation in the domain. We believe this tailored approach provides insights that can be instrumental in further refining NOSES procedures in the future.
NOSES is often controversial as a new approach because specimens are removed from the anus. Some have raised concerns about the oncological safety of NOSES. However, consistent with previous findings, our long-term follow-up found that the NOSES group had the same survival outcomes and oncological safety as the CL group6,16,18,37. Our research also found that comparable pathlogical outcomes in the two groups. This promising result stems from the crucial process of adequate specimen protection and the tumor-free technique during surgery, as described in our previous study10. While long-term survival outcomes align with our findings, past studies have limitations due to small5,18,20,37, diverse sample sizes, and covering various cancers21. To address this, we undertook a larger, more focused study on radical resection of left-sided colorectal cancer.
NOSES’ potential risk for abdominal infection during manipulation continue remains another stir debate. A large, recent retrospective study comparing the inflammatory response between the NOSES and CL groups for colorectal cancer (172 individuals per group) found a more prominent early systemic inflammatory response in the NOSES group. Yet, strictly adhering to NOSES asepsis principles prevented increased infection-related complications38. Other researches also indicated that NOSES did not increase the incidence of infectious morbidity when stringent and cautious protective measures were employed37,39. In our previous prospective randomized trial, results from the NOSES and CL groups all revealed that no bacteria and peritoneal tumor-shedding cells were found in the peritoneal lavage fluids, and no postoperative intraperitoneal infection complications were found10. Similar to previous researches, our current study showed no significant difference in the incidence of postoperative abdominal infection complications and local recurrence between the two groups. This is mainly due to the following measures. Firstly, the precise coordination of an experienced laparoscopic colorectal cancer surgical team; moreover, adequate intestinal preparation and strict control of the risk of intestinal fluid leakage during the operation.
An essential aspect of our study concerns the patient selection criteria for NOSES colectomy. When comparing NOSES to traditional CL colectomy, certain specific patient populations and clinical situations can pose challenges for the implementation of NOSES. Firstly, obese patients with a BMI exceeding 30 kg/m2 may face difficulties in extracting tumor specimens through the Cai tube or anus due to excessive visceral fat and the size of the tumor. Additionally, tumors with a maximum transverse diameter greater than 4.5 cm were excluded, as their extraction through the Cai tube or anus might be problematic. Lastly, patients with anal strictures were not considered, indicating the necessity of an intact anal sphincter for a successful NOSES procedure10.
A critical aspect of the NOSES technique that warrants discussion is the choice of natural orifice for specimen extraction. While our study predominantly focused on extraction through the anus, the NOSES technique also facilitates specimen retrieval from the vagina in age-appropriate women. This dual approach, employing both the rectum and vagina as extraction sites, enhances the versatility of the procedure, accommodating various clinical scenarios3,9,40,41. However, our study emphasizes the uniformity of the NOSES surgical procedure. As such, we have defined specific inclusion criteria: the resection of the left colon and the extraction of specimens from the rectum. This was done with the intention of achieving consistency in our research results. Vaginal extraction, although possible, is limited due to ethical concerns related to opening the posterior fornix. Additionally, vaginal extraction might influence the overall interpretation of our experimental results.
There are several limitations in our study. First, this study was a single-center retrospective controlled study. Second, the sample size of the study is still not large enough. Third, the study did not follow-up for long enough. Fourth, the NOSES technique presents certain patient selection challenges, particularly for obese individuals or those with larger tumors. And there remain concerns about the potential for damage to the colorectal mucosa and anal sphincter, as well as questions about the oncological safety and the potential risk of abdominal infection associated with this technique.
Conclusions
In selected cases, using a Cai tube for NOSES colectomy in left-sided colorectal cancer appears to be safe and potentially superior to conventional laparoscopy, with improved cosmetic results, lower postoperative pain scores, fewer additional analgesic needs, and quicker gastrointestinal function recovery. The long-term oncological outcomes are also comparable. However, this study’s limitations include its retrospective, single-center nature. To fully assess long-term oncological results, larger, multicenter randomized controlled trials are necessary to account for confounding factors.
Ethical approval
There is no potential conflict of interest. The study received approval from the Institutional Review Board at Zhongshan Hospital Xiamen University. The reference number is (2015.005).
Consent
This is a retrospective study, and the data were collected as part of routine clinical care. Due to the retrospective nature of the study, no new informed consent was required for the data collection. However, for the publication of potentially identifiable patient information and accompanying images in this manuscript, written informed consent was obtained from the patient or their guardian. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.
Sources of funding
This work was supported by National Natural Science Foundation of China (NO. 81871979), Natural Science Foundation of Fujian Province (NO. 2021J02056), and the Medical and Health Sciences Foundation of Xiamen (NOS. 3502Z20199171 and 3502Z20204002).
Author contribution
S.-Z.X.: conceptualization, methodology, software, data curation, writing – original draft, writing – review and editing, validation, and investigation; Z.-F.W.: conceptualization, methodology, data curation, writing – original draft, writing – review and editing, software, validation, and investigation; Z.-J.D.: software, data curation, writing – review and editing, validation; S.-F.Z.: methodology, software, data curation, writing – review and editing, validation; S.-B.Y.: software, data curation, writing – review and editing, and validation; F.Y.: formal analysis, methodology, software, and validation; G.-Y.L.: formal analysis, methodology, software, and validation; J.-C.C.: conceptualization, methodology, formal analysis, software, data curation, writing – original draft, writing – review and editing, validation, investigation, and supervision.
Conflicts of interest disclosure
Dr Jian-Chun Cai has a patent for Cai tube (homemade invention: ZL201410168748.2) but no other related conflicts of interest or financial ties to disclose. Drs Shu-Zhen Xu, Zhen-Fa Wang, Zhi-Jie Ding, Shi-Feng Zhang, Si-Bo Yuan, Feng Yan, and Guo-Yan Li have no conflicts of interest or financial ties to disclose.
Research registration unique identifying number (UIN)
Registration number: ChiCTR-OOR-15007060 (http://www.chictr.org.cn/).
Guarantor
Shu-Zhen Xu, Zhen-Fa Wang, and Jian-Chun Cai are the guarantors.
Data availability statement
The research data are available at electronic medical record system of Zhongshan Hospital Xiamen University. We guarantee that all patient information and data will be protected in privacy.
Provenance and peer review
Not commissioned, externally peer-reviewed.
Acknowledgements
Assistance with the study: none.
Footnotes
Shu-Zhen Xu and Zhen-Fa Wang contributed equally to this work.
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Published online 17 January 2024
Contributor Information
Shu-Zhen Xu, Email: 547813513@qq.com.
Zhen-Fa Wang, Email: 13806062519@139.com.
Zhi-Jie Ding, Email: zhijieding@sina.com.
Shi-Feng Zhang, Email: cnfj@xmu.edu.cn.
Si-Bo Yuan, Email: yuansb8627860592@sina.cn.
Feng Yan, Email: yanfeng@xmzsh.com.
Guo-Yan Liu, Email: liuguoyan@163.com.
Jian-Chun Cai, Email: jianchunfh2@sina.com.
References
- 1. Franklin ME, Jr, Ramos R, Rosenthal D, et al. Laparoscopic colonic procedures. World J Surg 1993;17:51–56. [DOI] [PubMed] [Google Scholar]
- 2. Wolthuis AM, Fieuws S, Van Den Bosch A, et al. Randomized clinical trial of laparoscopic colectomy with or without natural-orifice specimen extraction. Br J Surg 2015;102:630–637. [DOI] [PubMed] [Google Scholar]
- 3. Li XW, Wang CY, Zhang JJ, et al. Short-term efficacy of transvaginal specimen extraction for right colon cancer based on propensity score matching: a retrospective cohort study. Int J Surg 2019;72:102–108. [DOI] [PubMed] [Google Scholar]
- 4. Zhu Z, Wang KJ, Orangio GR, et al. Clinical efficacy and quality of life after transrectal natural orifice specimen extraction for the treatment of middle and upper rectal cancer. J Gastrointest Oncol 2020;11:260–268. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Chang SC, Lee TH, Chen YC, et al. Natural orifice versus conventional mini-laparotomy for specimen extraction after reduced-port laparoscopic surgery for colorectal cancer: propensity score-matched comparative study. Surg Endosc 2022;36:155–166. [DOI] [PubMed] [Google Scholar]
- 6. Zhang M, Hu X, Guan X, et al. Surgical outcomes and sexual function after laparoscopic colon cancer surgery with transvaginal versus conventional specimen extraction: a retrospective propensity score matched cohort study. Int J Surg 2022;104:106787. [DOI] [PubMed] [Google Scholar]
- 7. Cai JC, Hong XY. Laparoscopic-assisted natural orifice specimen extraction radical descending colectomy using a Cai Tube. World J Surg 2016;40:2803–2807. [DOI] [PubMed] [Google Scholar]
- 8. Xu SZ, Ding ZJ, Zhang SF, et al. [Propensity score matching-based analysis of short-term outcomes of Laparoscopic-assisted Natural Orifice Specimen Extraction for left colorectal cancer radical resection]. Zhonghua Yi Xue Za Zhi 2016;96:1578–1581. [DOI] [PubMed] [Google Scholar]
- 9. Xu SZ, Cai JC. Laparoscopic-assisted natural orifice specimen extraction gastrectomy using an auxiliary incision-free tube for gastric cancer. J Surg Res 2022;270:31–38. [DOI] [PubMed] [Google Scholar]
- 10. Xu SZ, Ding ZJ, Zhang SF, et al. Clinical outcomes of laparoscopic-assisted natural orifice specimen extraction colectomy using a Cai tube for left-sided colon cancer: a prospective randomized trial. Surg Endosc 2023;37:749–758. [DOI] [PubMed] [Google Scholar]
- 11. Zhuang YF, Xu SZ, Wang ZF, et al. [Specimen extraction through natural orifices with Cai tubes in gastrointestinal surgery: a single-institute series of 234 cases]. Zhonghua Wei Chang Wai Ke Za Zhi 2023;26:357–364. [DOI] [PubMed] [Google Scholar]
- 12. Park JS, Choi GS, Kim HJ, et al. Natural orifice specimen extraction versus conventional laparoscopically assisted right hemicolectomy. Br J Surg 2011;98:710–715. [DOI] [PubMed] [Google Scholar]
- 13. Denost Q, Adam JP, Pontallier A, et al. Laparoscopic total mesorectal excision with coloanal anastomosis for rectal cancer. Ann Surg 2015;261:138–143. [DOI] [PubMed] [Google Scholar]
- 14. Leung AL, Cheung HY, Fok BK, et al. Prospective randomized trial of hybrid NOTES colectomy versus conventional laparoscopic colectomy for left-sided colonic tumors. World J Surg 2013;37:2678–2682. [DOI] [PubMed] [Google Scholar]
- 15. Park JS, Kang H, Park SY, et al. Long-term outcomes after Natural Orifice Specimen Extraction versus conventional laparoscopy-assisted surgery for rectal cancer: a matched case-control study. Ann Surg Treat Res 2018;94:26–35. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Chang SC, Chen HC, Chen YC, et al. Long-term oncologic outcomes of laparoscopic anterior resections for cancer with natural orifice versus conventional specimen extraction: a case-control study. Dis Colon Rectum 2020;63:1071–1079. [DOI] [PubMed] [Google Scholar]
- 17. Zhou ZQ, Wang K, Du T, et al. Transrectal Natural Orifice Specimen Extraction (NOSE) with oncological safety: a prospective and randomized trial. J Surg Res 2020;254:16–22. [DOI] [PubMed] [Google Scholar]
- 18. Kong FB, Deng QM, Deng HQ, et al. Propensity score-matched comparison between totally laparoscopic right hemicolectomy with transcolonic natural orifice specimen extraction and conventional laparoscopic surgery with mini-laparotomy in the treatment of ascending colon cancer (with video). Gastrointest Endosc 2021;94:642–650. [DOI] [PubMed] [Google Scholar]
- 19. Bu J, Li N, He S, et al. Effect of laparoscopic surgery for colorectal cancer with N. O. S. E. on recovery and prognosis of patients. Minim Invasive Ther Allied Technol 2022;31:230–237. [DOI] [PubMed] [Google Scholar]
- 20. Houqiong J, Ziwen W, Chonghan Z, et al. Comparison of transabdominal wall specimen retrieval and natural orifice specimen extraction robotic surgery in the outcome of colorectal cancer treatment. Front Surg 2023;10:1092128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Tang Q, Zhu Y, Xiong H. Natural orifice specimen extraction surgery versus conventional laparoscopic-assisted resection in the treatment of colorectal cancer: a propensity-score matching study. Cancer Manag Res 2021;13:2247–2257. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Guan X, Hu X, Jiang Z, et al. Short-term and oncological outcomes of natural orifice specimen extraction surgery (NOSES) for colorectal cancer in China: a national database study of 5055 patients. Sci Bulletin 2022;67:1331–1334. [DOI] [PubMed] [Google Scholar]
- 23. Ma B, Huang XZ, Gao P, et al. Laparoscopic resection with natural orifice specimen extraction versus conventional laparoscopy for colorectal disease: a meta-analysis. Int J Colorectal Dis 2015;30:1479–1488. [DOI] [PubMed] [Google Scholar]
- 24. Chin YH, Decruz GM, Ng CH, et al. Colorectal resection via natural orifice specimen extraction versus conventional laparoscopic extraction: a meta-analysis with meta-regression. Tech Coloproctol 2021;25:35–48. [DOI] [PubMed] [Google Scholar]
- 25. Lin J, Lin S, Chen Z, et al. Meta-analysis of natural orifice specimen extraction versus conventional laparoscopy for colorectal cancer. Langenbeck’s Arch Surg 2021;406:283–299. [DOI] [PubMed] [Google Scholar]
- 26. Wang S, Tang J, Sun W, et al. The natural orifice specimen extraction surgery compared with conventional laparoscopy for colorectal cancer: a meta-analysis of efficacy and long-term oncological outcomes. Int J Surg 2022;97:106196. [DOI] [PubMed] [Google Scholar]
- 27. Zhou Z, Chen L, Liu J, et al. Laparoscopic natural orifice specimen extraction surgery versus conventional surgery in colorectal cancer: a meta-analysis of randomized controlled trials. Gastroenterol Res Pract 2022;2022:6661651. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Bousquet PJ, Combescure C, Klossek JM, et al. Change in visual analog scale score in a pragmatic randomized cluster trial of allergic rhinitis. J Allergy Clin Immunol 2009;123:1349–1354. [DOI] [PubMed] [Google Scholar]
- 29. National Comprehensive Cancer Network Colon cancer (Version 1 2020). Accessed 12 January 2020. https://www.nccn.org/professionals/physician_gls/default.aspx
- 30. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205–213. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Mathew G, Agha R, Group ftS . STROCSS 2021: strengthening the reporting of cohort, cross-sectional and case-control studies in surgery. Int J Surg 2021;96:106165. [DOI] [PubMed] [Google Scholar]
- 32. Jorge JM, Wexner SD. Etiology and management of fecal incontinence. Dis Colon Rectum 1993;36:77–97. [DOI] [PubMed] [Google Scholar]
- 33. Wexner SD. Further validation of the Wexner Incontinence Score: a note of appreciation and gratitude. Surgery 2021;170:53–54. [DOI] [PubMed] [Google Scholar]
- 34. Austin PC. Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat 2011;10:150–161. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Seow-En I, Chen LR, Li YX, et al. Outcomes after natural orifice extraction vs conventional specimen extraction surgery for colorectal cancer: a propensity score-matched analysis. World J Clin Oncol 2022;13:789–801. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. Xu S, Liu K, Chen X, et al. The safety and efficacy of laparoscopic surgery versus laparoscopic NOSE for sigmoid and rectal cancer. Surg Endosc 2022;36:222–235. [DOI] [PubMed] [Google Scholar]
- 37. Zhou S, Wang X, Zhao C, et al. Comparison of short-term and survival outcomes for transanal natural orifice specimen extraction with conventional mini-laparotomy after laparoscopic anterior resection for colorectal cancer. Cancer Manag Res 2019;11:5939–5948. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38. Zhou S, Wang X, Zhao C, et al. Can transanal natural orifice specimen extraction after laparoscopic anterior resection for colorectal cancer reduce the inflammatory response? J Gastroenterol Hepatol 2020;35:1016–1022. [DOI] [PubMed] [Google Scholar]
- 39. Costantino FA, Diana M, Wall J, et al. Prospective evaluation of peritoneal fluid contamination following transabdominal vs. transanal specimen extraction in laparoscopic left-sided colorectal resections. Surg Endosc 2012;26:1495–1500. [DOI] [PubMed] [Google Scholar]
- 40. Wu L, Zhao Q, Yang F, et al. Transvaginal natural orifice specimen extraction surgery for 3D laparoscopic radical cystectomy: a cohort study. J Cancer Res Ther 2023;19:892–897. [DOI] [PubMed] [Google Scholar]
- 41. Nishimura A, Kawahara M, Kawachi Y, et al. Totally laparoscopic resection of right-sided colon cancer using transvaginal specimen extraction with a 10-mm-long abdominal incision. Tech Coloproctol 2022;26:755–760. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The research data are available at electronic medical record system of Zhongshan Hospital Xiamen University. We guarantee that all patient information and data will be protected in privacy.