Comparison of effectiveness and safety of Da Vinci robot’s “3 + 1” and “4 + 1” modes of treatment for colorectal cancer

To compare the effectiveness of the Da Vinci Surgical Robot System (DSRS) “3 + 1” and “4 + 1” models for colorectal cancer (CRC). A total of 107 patients with CRC admitted to our hospital from February 2021 to May 2022 were selected for the retrospective analysis. Of these, 57 patients underwent the DSRS “4 + 1” model (control group), while the rest 50 underwent the DSRS “3 + 1” model (research group). The operation time, intraoperative bleeding, number of lymph nodes detected, time of first postoperative urinary catheter removal, time of first feeding, time of first venting and hospitalization were compared between the two groups. The changes of white blood cell (WBC) and C-reactive protein (CRP) levels before and after surgery were detected, and patients’ adverse effects and treatment costs between surgery and hospital discharge were counted. The Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS) were used to assess the psychological state of the patients. There was no difference in operative time, intraoperative bleeding, and number of lymph nodes detected between both groups (P > 0.05), while time to first postoperative urinary catheter removal, time to first feeding, time to first venting, length of stay (LOS), postoperative inflammatory factor levels, incidence of adverse events, and treatment costs were all lower in the research group than in the control group (P < 0.05). SAS and SDS scores decreased after treatment in both groups, but the decrease was more obvious in the research group (P < 0.05). Both DSRS “4 + 1” and “3 + 1” modes have better treatment effects for CRC. However, the “3 + 1” mode has higher safety and lower treatment cost, which can significantly improve the postoperative recovery process of patients and is more worthy to be promoted in clinical practice.


Introduction
Colorectal cancer (CRC) is one of the most common malignant tumors in the world, threatening the lives of more than 3 million patients [1].According to statistics, there have been more than 1.8 million new CRC patients worldwide in 2018, of which even more about 800,000-900,000 patients died [2].CRC is mostly seen in the middle-aged and elderly population over 40 years of age, but the incidence has shown a younger trend, with CRC diagnosed in those under 30 years of age becoming more common [3].In addition, as a malignant tumor with high infiltration and metastasis capacity, CRC has a high risk of involving surrounding tissues and distant metastasis, and such patients usually have a prognostic mortality rate of more than 80% [4].In clinical practice, the treatment of CRC is still based on surgery or (and) combined with chemotherapy (or radiotherapy), which is still ideal for early stage tumors, but complete clearance of the lesion is usually no longer possible for those with advanced tumors [5].Therefore, improving the early diagnosis of CRC and finding more effective treatment modalities is considered a clinical breakthrough in safeguarding the prognosis of CRC patients [6].
With the development of modern technology and medical level, more and more high-tech products are put into the clinical medical services.Among them, the Da Vinci Surgical Robot System (DSRS) is an advanced robotic platform, whose design concept is to perform complex surgery using a minimally invasive method [7].Currently, DSRS has been approved for a variety of procedures in general surgery, thoracic surgery, urology, obstetrics and gynecology, head and neck surgery, and cardiac surgery in adults and children, with remarkable results [8,9].Compared with traditional surgery, DSRS has following advantages, including more accurate surgery, less trauma, reduced workload of surgeons and improved surgical outcomes [10].Currently, the use of DSRS is more common in countries, such as Northern Europe, where the level of medical care is more developed [11].In China, the application of DSRS is still limited due to the lack of sufficient DSRS experience and related references.In the face of this situation, summarizing the operational experience of DSRS as soon as possible and realizing the universal use of DSRS may provide important help to improve the treatment effect of CRC in the future.
At present, we have achieved remarkable results in DSRS in the surgical treatment of CRC and have accumulated enough cases.The difference in the effectiveness of DSRS "4 + 1" mode (traditional 5-hole method) and "3 + 1" (4-hole method) in treating CRC will be compared, with the aim of providing a reliable reference for the future clinical use of DSRS.

Patient data
A total of 107 patients with CRC admitted to our hospital from February 2021 to May 2022 were selected for the retrospective analysis.Of these, 57 patients underwent the DSRS "4 + 1" model (control group), while the rest 50 underwent the DSRS "3 + 1" model (research group).The study was conducted in strict compliance with the Declaration of Helsinki, and all study subjects signed an informed consent form.

Inclusion and exclusion criteria
Inclusion criteria: pathology biopsy confirming the diagnosis of CRC; indications for DSRS surgery were met [12]; the pathological staging was all stages I-II; all patients did not receive neoadjuvant chemotherapy; American Society of Anesthesiologists (ASA) grades II-III; patients all underwent radical resection, which is performed from the inside out, complete tumor resection; no continuous postoperative analgesia; aged 18-70 years.Exclusion criteria: DSRS surgery in transit to open surgery; a previous history of abdominal surgery; combined with severe cardiopulmonary dysfunction; abnormal coagulation function; combined with other oncological diseases.

Surgery methods
All procedures are performed by the same surgical team at our hospital.Preoperative pulmonary and bowel function exercises were performed, and a catheter was left in place.The organs were intubated with general anesthesia, and the appropriate position was selected according to the surgical site.The surgical procedure was performed in strict compliance with the Chinese Expert Consensus on Robotic Colorectal Cancer Surgery (2020 version) [13], and the Trocar placement is shown in Table 1, Figs. 1 and 2.

Blood sample collection and testing
Fasting peripheral blood was drawn from patients before (T0), on the 1st (T1), 3rd (T1) and 5th (T3) days after surgery, respectively.The levels of white blood cells (WBC) and C-reactive protein (CRP), indicators of inflammation, were measured using a fully automated hematology analyzer.

Scoring criteria
Patients' psychology was assessed before and after treatment (at discharge) using the Self-Assessment Scale for Anxiety (SAS) and the Self-Rating Scale for Depression (SDS) [14].SAS and SDS have 20 questions, respectively, and the score × 1.25 obtains the standard score, higher standard score indicating the more severe negative emotion of anxiety and depression.

Outcome measures
Clinical baseline data: age, gender, and surgical component, etc. (2) Surgery: the operation time, intraoperative bleeding, and number of lymph nodes detected in both groups were counted.(3) Postoperative condition: the time of first removal of urinary catheter, first feeding, first venting and hospitalization of patients were counted.(4) Inflammation: changes in WBC and CRP levels before and after surgery.( 5) Safety: patients' adverse reactions between surgery and discharge were counted, all adverse reactions are classified according to Clavien-Dindo.Class I: medical management that interferes with normal postoperative recovery (e.g., analgesics, diuretics, antipyretics, etc.) but does not require pharmacologic, surgical, endoscopic, or radiologic interventions.Grade II: medications or interventions requiring other than Grade I (e.g., blood transfusions, parenteral and parenteral nutritional support, etc.).Grade III: requires surgical, radiologic, or endoscopic intervention.( 6) Economic effect: the cost of robotic consumables for patients and the total cost of hospitalization were counted.(7) Mentality: results of SAS and SDS scores before and after treatment.

Statistical methods
Statistical analysis was performed using SPSS 22.0 software.The counting data such as gender and pathological stage were expressed as (%) and compared through the chi-square test.The measurement data such as age and operation time were expressed as ( ± s) and compared via the independent samples t test.Paired t tests were used for pre-and posttreatment comparisons, and ANOVA with LSD intra-group tests were used for comparisons between multiple groups.A difference of statistical significance was indicated at P < 0.05.

Comparison of clinical baseline data
First, to ensure the accuracy of the experimental results, we first compared the clinical baseline data of both groups of patients included in the study.In addition, the comparative results manifested no statistically remarkable differences in age, gender composition, and surgical site between groups (P > 0.05), confirming that both groups were comparable (Table 2).

Comparison of surgical situations
The operative time, intraoperative bleeding, and number of lymph nodes detected were (228.90 ± 40.20) min,  bleeding, and number of lymph nodes detected were not statistically remarkable when comparing both groups (P > 0.05) (Fig. 3).

Comparison of postoperative conditions
The time of first urinary catheter removal, first feeding, first venting and hospitalization after surgery in the research group were (2.90 ± 1.07) days, (4.26 ± 1.03) days, (3.48 ± 1.03) days and (9.38 ± 3.06) days, respectively.The time to first postoperative urinary catheter removal, first feeding, first venting, and hospitalization in the control group were longer (P < 0.05) (Fig. 4).

Comparison of changes in inflammation
At T0 and T3, no differences were seen between both groups in WBC and CRP levels (P > 0.05), while at T1 and T2, the two levels were lower in the research group than in the control group (P < 0.05).Inflammatory factor levels were dramatically higher in both groups at T1 compared to T0 and continued to decrease at T2 and 3 but were still higher than T0 (P < 0.05) (Fig. 5).

Safety comparison
After surgery, adverse effects such as intestinal obstruction, intra-abdominal bleeding, and delayed gastric emptying were observed in both groups, belonging to Clavien-Dindo classifications I-III.There was no statistically significant difference in the number of Clavien-Dindo grades I and III between the two groups (P > 0.05).However, the number of   Clavien-Dindo grade III was less in the research group than in the control group (P < 0.05) (Table 3).

Comparison of economic effects
The cost of robot consumables in the research group was (13,578.16 ± 1286.04) yuan, which was lower than the control group (17,374.25 ± 1703.24) yuan (P < 0.05).In addition, the total cost of hospitalization was also lower in the research group than in the control group (P < 0.05) (Fig. 6).

Comparison of mentality
Before treatment, there was no statistically obvious difference between the SAS and SDS scores of both groups (P > 0.05).While after treatment, the scores of both groups were dramatically lower than before treatment.Among them, the SAS and SDS scores of the research group were (33.06 ± 12.61) and (29.72 ± 7.72), respectively, which were lower than those of the control group (P < 0.05) (Fig. 7).

Discussion
The incidence of CRC, one of the most common malignancies, has been increasing in recent years [15].In addition, due to the insidious nature of early CRC, most patients have progressed to the intermediate and advanced stages by the time of diagnosis, and the prognosis is generally unsatisfactory [16].DSRS was first used in CRC surgery in 2001, after more than 20 years of progress and development [17].Compared with the traditional procedure, DSRS's break through the limitations of the human hand and have a more stable robotic arm to improve accuracy while reducing surgical trauma [18].Although the superiority of DSRS over conventional open or laparoscopic surgery has been repeatedly mentioned in previous studies [19][20][21], comparisons of the clinical outcomes of different modalities of DSRS are still rare.Therefore, this study compares the "4 + 1" and "3 + 1" modes of DSRS, which is an important reference for further clinical mastery of DSRS.
In this study, we found no difference in operative time, intraoperative bleeding, and lymph node detection between the DSRS "4 + 1" mode and the "3 + 1" mode, indicating that there was no marked difference between the two modes of implementation, and that the reduction of one operating arm was equally effective in clearing the lymph nodes of CRC.However, in the comparison of postoperative conditions, we found that the recovery time of patients in the research group was dramatically shorter than that of the control group, which indicates that the DSRS "3 + 1" model can more effectively promote the postoperative recovery of CRC patients.In a study on DSRS, we found that in the "4 + 1" mode, arm 3 was mostly placed near the subcostal arch of the anterior axillary line in the right quadrant of the rib cage [22].The high distribution of nerves in this region and the long intraoperative lifting of the abdominal wall by the 3rd arm will greatly stimulate the occurrence of postoperative pain and stress injury in patients.Compared with this, the "3 + 1" mode reduces the puncture hole in the abdominal wall, avoids the mechanical damage caused by lifting, traction, and compression of the No. 3 arm, reduces the tissue damage caused by mechanical invasion, and greatly improves the comfort and safety of surgery [23].In addition, when we compared the levels of inflammatory factors between the two groups, we also saw that the inflammation levels in the research group were low on postoperative T1 and T2, which could initially validate our point.Furthermore, in a previous study, we also found that Piazza et al. indicated that patients recovered better with the DSRS "3 + 1" model of cystectomy, which is also consistent with our view [24].Subsequently, we also found that the incidence of adverse reactions was lower in the research group than in the control group, further suggesting that the DSRS "3 + 1" model is safer.The reason for this may also be related to our assumption that the DSRS "3 + 1" mode reduces intraoperative mechanical injuries and damages to the intra-abdominal environment.In addition, the relief of postoperative pain in patients of the research group reduced the negative stimulation of the gastrointestinal tract and maintained the stability of normal immune metabolism of the body, thereby reducing the occurrence of adverse reactions [25].Besides, we found that treatment costs were lower in the research group, suggesting that the DSRS "3 + 1" model has a higher economic impact.Studies have shown that although DSRS has better clinical outcomes than laparoscopic surgery, and the high cost of treatment has caused some patients to refuse DSRS treatment due to financial difficulties [26].By changing to the "3 + 1" mode, the cost of consumables for the robot was reduced by about 3,500 RMB.If the operation mode can be further optimized and the use of the surgical arm can be reduced, it may create a higher economic effect for patients, thus achieving the universal use of DSRS.It is well-known that the pain and expensive treatment caused by tumor diseases will inevitably cause severe negative emotions, such as anxiety, fear, resistance in patients [27].In addition, this may not only affect patients' postoperative recovery, but also is not conducive to cultivating the sense of trust and dependence on the health care provider [28].In this study, the postoperative psychology of patients in the research group also manifested a more obvious improvement than that of the control group, which indicates the importance of the DSRS "3 + 1" model in enhancing patients' treatment experience.The reason for this may be due to the excellent treatment results of DSRS and the reduced cost of treatment for patients, once again validating the above inference.
Nevertheless, due to the short experimental period, we were not able to assess the impact of the two surgical modalities on the prognosis of patients for the time being.Because this paper is a retrospective analysis, there may be a bias in the results.This all requires us to conduct better and comprehensive experiments to verify the analysis as soon as possible.Later, we will conduct a more detailed experimental analysis on the application of DSRS in the clinical practice to provide a more reliable reference.
In conclusion, compared with the DSRS "4 + 1" model, the DSRS "3 + 1" model is safer and less expensive for treating CRC, and has higher clinical applicability.We believe that the use of the DSRS "3 + 1" modality can provide more reliable prognosis for CRC patients in the future.

Fig. 3 Fig. 4 Fig. 5
Fig. 3 Comparison of surgical situations.A Comparison of surgery times.B Comparison of intraoperative bleeding.C Comparison of number of lymph node detection

Fig. 6 Fig. 7
Fig. 6 Comparison of economic effects.A Comparison of robotic consumables costs between both groups.B Comparison of total hospitalization costs between both groups.*P < 0.05

Table 3
Adverse effects after surgery in both groups