Application of NOSES Combined with ERAS in the Treatment of Rectal Cancer

Background: In recent years, Natural Orice Specimen Extraction Surgery (NOSES) has been developed rapidly, and the feasibility and advantages of Enhance Recovery after Surgery (ERAS) also have been recognized in colorectal cancer. How about combining NOSES with ERAS? In this article, we are trying to answer this question. Methods: The 120 cases of rectal cancer patients who met the inclusion criteria from January 2018 to December 2019 were divided into three groups using the random number table method: traditional care control group (laparoscopic assisted surgery + traditional care), ERAS control group (laparoscopic adjuvant surgery + ERAS) and experimental group (NOSE + ERAS), 40 cases in each group, randomized controlled study was performed. Results: There were no signicant differences in surgical time, bleeding volume, number of detected lymph nodes, incidence of venous thrombosis in the lower extremities, anastomotic leakage, and abdominal infection among the three groups (P> 0.05). The total complication rate, incidence of incision-related complications, incidence of pulmonary and urinary tract infections, and postoperative pain NRS score in the NOSES+ERAS group cases were signicantly lower than those in the other two control groups. Patients in the NOSES + ERAS group had higher satisfaction rates and shorter postoperative hospital stay than those in the other two control groups. The feeding time and exhaust time after surgery in NOSES+ERAS group and ERAS control group were earlier than those in traditional care control group. The above differences are statistically signicant (P <0.05). Conclusion: The NOSES radical resection of rectal cancer under the guidance of ERAS achieved more minimally invasive cosmetic and functional, individualized treatment effect in laparoscopic surgery. There is a greater advantage that ERAS combined with the NOSES radical resection of rectal cancer which is worthy of popularization and with good application prospect.


Background
In recent years, with the advancement of economic, culture and medicine, patients' demands for quality of life and cosmetic effects after surgery have been increasing. Natural Ori ce Specimen Extraction Surgery (NOSES) has been developed rapidly in the world; at the same time, the feasibility and advantages of Enhance Recovery after Surgery (ERAS) in colorectal cancer have been recognized by numerous scholars. How about combining NOSES with ERAS? In this article, we are trying to answer this question, and it is reported as follows:

General Information
The 120 cases of rectal cancer patients who met the inclusion criteria from January 2018 to December 2019 in the Central Hospital of Shaoyang were divided into three groups using the random number table method: traditional care control group (laparoscopic assisted surgery + traditional care), ERAS control group (laparoscopic assisted surgery + ERAS) and experimental group (NOSE surgery + ERAS), 40 cases in each group. All patients were clearly diagnosed with upper or middle rectal cancer, the distance from the tumor site to the dentate line is greater than 5 cm, tumor invasion depth T1-T3, and tumor circumference diameter < 5 cm; and patients with poor cardiopulmonary function, distant metastases, neoadjuvant chemoradiotherapy, or prophylactic stoma were excluded.

Surgical Method
All patients underwent D 3 lymph node dissection, proximal mesentery and distal rectal cut off under laparoscopy abide by TME (or TSME) principles. In the laparoscopic assisted surgery group, a 5-8 cm abdominal incision was needed to remove the tumor specimen and to connect the sigmoid to rectum by end-to-end anastomosis. In the NOSES group, there was no auxiliary incision, depending on the location of the tumor and the length of the sigmoid mesentery, NOSES II or IV was adopted to remove the specimen from the rectum as showed in the following gure.
Perioperative treatment plans ERAS treatment plan Strengthen pre-operative education and communication, and introduce the ERAS measures and treatment plans to the patients in detail; Regular diet as usual after admission, fasting 12 hours before surgery and oral mannitol catharsis cleans the intestines, and drink 300 ml of carbohydrates 2 hours before surgery; no gastric tube and no enema before operation; urinary catheter was indwelled after anesthesia and remove in 24 hours after operation; transabdominal fascia block anesthesia combined with general anesthesia; Restricted infusion during the operation, vasoactive drugs should be used to maintain blood pressure when blood pressure is lowered; warmed liquid and insulation blankets should be used to keep warm during the operation; postoperative rehydration should be limited within 2000 ml/day, and the amount of infusion should be gradually reduced as oral consumption increases; start drinking water 6 hours after surgery, start a full ow diet on the rst day after surgery, and start eating semi-liquid food after venting the anus, but anastomotic leak must be ruled out; remove the pelvic drainage tube 3-5 days after operation according to the in ammatory index and the amount and color of the drainage tube; Postoperative intravenous analgesia, nonsteroidal analgesics if necessary; began to walk out of bed on the rst day after surgery, and so on.
Traditional care plan General education after admission; intestinal preparation started 3 days before surgery, mannitol was used for diarrhea one day before surgery, and enema was cleaned in the morning on the day of surgery; fasting was performed 12 hours before surgery, and water was absent 8 hours before surgery; nasogastric tubes and catheters were done in the ward; general anesthesia is used for anesthesia, and uid rehydration is adopted when the blood pressure is low after anesthesia; there is no thermal insulation during the operation, The volume of uid replacement is greater than 2000 ml/d after surgery; remove the abdominal drainage7 days after operation; remove the stomach tube and drink water after venting anus, take a full liquid food the next day after exhausting, and a semi-liquid food after defecation; use morphine and dulidine to relieve pain; Voluntary out of bed activities for recovery.

Evaluation methods
Ceftriaxone was used to prevent infection for all patients during the perioperative period. The drainage tube ascites was cultured on the rst day after operation. The data of surgical conditions (e.g. the operation time, incision length, blood loss, number of lymph node dissections), postoperative complications (e.g. the incidence of postoperative pulmonary infection, urinary tract infection, abdominal infection, anastomotic leakage, venous thrombosis of the lower limbs, and incision-related complications), and patient recovery (e.g. postoperative pain score, recovery time, exhaust time, postoperative hospitalization days, and patient satisfaction) from the three groups was compared and analyzed.
NRS pain grade score (digital scoring method) was used to grade the patients' postoperative incision pain: 0 for no pain; 1 to 3 for mild pain; 4 to 6 for moderate pain; 7 to 10 for severe pain. Patients can be discharged when they meet the following conditions: can enter a semi-liquid diet, have smooth defecation, can move freely, do not require intravenous infusion treatment, and oral pain medication can effectively relieve pain Statistical analysis SPSS 19.0 software was used for statistical analysis. The measurement data was expressed by (`x ± s). The measurement data were analyzed by single factor analysis of variance and SNK-q test, and the count data by χ 2 test. P < 0.05, the difference is statistically signi cant.

Surgical conditions
The operation of all patients were successfully completed without major bleeding and anesthesia complications. General information (age, gender, comorbidities, clinical stage, etc.) of the three groups was not statistically different. The incision length of the NOSES + ERAS group was signi cantly shorter than that of the two control groups, and the difference was statistically signi cant (F = 23.798, P < 0.01).There were no signi cant differences in surgical time, bleeding volume, and number of detected lymph nodes among the three groups (F = 1.604, 1.835, 2.351 respectively, all P > 0.05). The detailed data were showed in Table 1. Table 1 Data of surgical conditions (`x ± s,n 1 = n 2 = n 3 =40)

Groups
Surgical time ( hernia, etc.), lower extremity venous thrombosis, pulmonary infection, abdominal infection, anastomotic leakage, were observed and recorded. The incidence of total complications in NOSES + ERAS group was signi cantly lower than that in the two control groups (7.5% VS 17.5% VS 57.5%, χ 2 = 9.46, P < 0.01), and the rate of total complications in ERAS control group was also signi cantly lower than that in the traditional control group (17.5% VS 55%, χ 2 = 11.86, P < 0.01); the incidence of incision-related complications in the NOSES + ERAS group was signi cantly lower than that in the two control groups (0% VS 10% VS12 .5%, χ 2 = 9.83, P < 0.01); the incidence of pulmonary infection and urinary tract infection in patients in the NOSES + ERAS group and the ERAS group control group was signi cantly lower than that in the traditional control group (0% VS 0% VS 10% and 0% VS 0% VS 25%, χ 2 = 6.83,16.97 respectively, P 0.05 and P 0.01); There were no statistically signi cant differences in the incidence of lower extremity venous thrombosis, anastomosis leaks and abdominal infections among the three groups (χ 2 = 1.43, 0.45, 0.87 respectively, all P > 0.05). The detailed data as shown in table 2.

Postoperative Recovery
Postoperative pain NRS score, postoperative feeding time, exhaust time, postoperative hospitalization time, and patient satisfaction were statistically analyzed. Postoperative pain NRS score in the NOSES + ERAS group were signi cantly lower than those in the two control groups (4.5 VS 5.6 VS 7.6 respectively, F = 5.62, P < 0.01), and the NRS score in the ERAS control group was also signi cantly lower than the traditional control group (5.6 VS 7.6, q = 3.52, P < 0.05). The postoperative feeding time and exhaust time of the NOSES + ERAS group and the ERAS control group were earlier than those of the traditional control group (1.2 VS 1.3 VS 2.8 and 2.0 VS 2.1 VS 2.9, F = 4.37, 3.57 respectively, P < 0.01 and P < 0.05), and there was no signi cant difference between the NOSES + ERAS group and the ERAS control group (q = 2.74, P > 0.05). The postoperative hospital stay time of the NOSES + ERAS group was signi cantly shorter than that of the two control groups (6.2 VS 7.3 VS 9.1, F = 3.46, P < 0.05), and the time of the ERAS control group was also signi cantly shorter than that of traditional control group (7.3 VS 9.1, q = 3.54, P < 0.05). Patient satisfaction in the NOSES + ERAS group was signi cantly higher than that in the two control group (95% VS 85% VS 70%, χ 2 = 6.86, P < 0.05), and the ERAS control group also had higher satisfaction than the traditional control group (85% VS 70%, χ 2 = 6.43, P < 0.05). As shown in Table 3.

Discussion
With the advancement of economic and medicine, patients' demands for quality of life and cosmetic effects after surgery are increasing. At the same time, higher requirements and challenges have been put forward to surgeons.
In the past 20 years, from traditional open surgery to conventional laparoscopic surgery to NOSES surgery, surgery has been developed rapidly. NOSES surgery uses conventional laparoscopic surgical instruments and familiar surgical paths to complete the radical resection of the tumor under laparoscopy, and then removes the specimen through the natural port and completes the digestive tract reconstruction [1] . There are only a few small puncture holes in the abdomen, without assistance incisions, and overcoming NOTES surgical instruments and technical obstacles, to obtain good cosmetic and minimally invasive results, and to maximize the bene ts of conventional laparoscopic platforms. At present, it is believed that the NOSES radical resection of rectal cancer is mainly applicable to tumors with a depth of no more than T 3 .
Transanal specimens require a maximum peripheral diameter of less than 5 cm, and transvaginal specimens require a maximum peripheral diameter of less than 5-7cm. At the same time, we should fully grasp the operation speci cations of specimen collection, and strictly abide by the principles of aseptic operation and no tumor [1,2] . According to the location of the rectal tumor and the way of removing the specimen, rectal NOSES surgery is currently divided into ve types of surgery: , , , , and [1,4] . Because the anastomosis position of type I is very low, prophylactic colostomy is often required, and type III / V type requires a vaginal incision, which causes some patients and their families to be unacceptable. Transanal specimens are not restricted by gender, so they have become the most widely used method for specimen collection.
At present, the NOSES operation in our center is mainly type and type . In this study, compared with patients with traditional laparoscopy (traditional nursing control group and ERAS control group), NOSES surgery does not affect the radical dissection of the tumor, and does not increase the risk of surgery time, bleeding, abdominal infection and anastomotic leakage, but it has obvious advantages in terms of postoperative pain, incision infection, and postoperative hospital stay. It not only achieves a radical resection of the tumor, but also greatly reduces the patient's trauma, postoperative wound pain, and stress response is reduced, and then to promote the patient's postoperative recovery.
On the other hand, with the long-term clinical observation of specialists and the introduction of evidence-based medicine theory, the feasibility and superiority of the application of the ERAS concept in colorectal cancer have been recognized by many scholars in recent years. Studies show that ERAS can reduce postoperative complications and the risk of death, reduce hospitalization costs and length of stay, improve patient compliance and satisfaction, and thus obtain good treatment results. [4][5][6][7] In addition, Gustafsson and their team's studies have shown that ERAS can not only achieve satisfactory short-term effects, but also signi cantly improve the 5-year survival rate of patients with colorectal cancer after surgery, and the higher the compliance with the ERAS program, the more obvious the effect [8] . In this study, postoperative complications such as lung infection and urinary tract infection in patients treated with ERAS were signi cantly lower than those in the traditional care group. At the same time, the incidence of postoperative anastomotic leakage was not increased, indicating that the application of ERAS is safe. The postoperative pain of patients treated with ERAS was signi cantly lower than that of the traditional care group, at the same time, patients with ERAS intervention had faster recovery, shorter hospital stays, and higher satisfaction, indicating that ERAS is more effective in promoting postoperative rehabilitation of patients with rectal cancer.
NOSE surgery and ERAS are mutually reinforcing. In this study, the patients in the NOSE + ERAS group were not signi cantly different from the traditional nursing control group and the ERAS control group in terms of surgical time, bleeding volume, degree of tumor resection (number of lymph node dissection), postoperative abdominal infection, and anastomotic leakage, which indicates that NOSE combined with ERAS does not affect the radicalness of the tumor and does not increase the risk of postoperative abdominal infections and anastomotic leakage. At the same time, patients in the NOSE + ERAS group were signi cantly better than the other two control groups in terms of postoperative pain score, postoperative hospital stays, and patient satisfaction, further indicating that NOSE surgery combined with ERAS treatment is more superior in the eld of postoperative rehabilitation. NOSE surgery makes full use of the advantages of laparoscopic clear vision and convenient operation. At the same time, removing specimens from natural channels, NOSES is less invasive than traditional laparoscopic surgery, and can reduce incision infection, postoperative incision pain, reduce complications, thereby enable patients to get out of bed early, promote intestinal peristalsis of patients, and promote rapid recovery after surgery.
In summary, in the ERAS treatment plan for patients with rectal cancer, choosing the appropriate case for NOSES minimally invasive surgery will greatly reduce the incidence of postoperative complications and accelerate the recovery of patients. NOSE minimally invasive surgery conforms to the basic concept of ERAS, and is also a fundamental need for ERAS, the perfect combination of the two is worthy of clinical promotion and will bene t more patients. However, in the exploration process of NOSES combined with the ERAS, the indications should be fully evaluated and selected.
Regardless of the ERAS treatment or the resected specimen removed through the natural ori ce, the safety, tumor-free principle and sterility principle need to be fully considered.

Conclusion
This study revealed that the NOSES radical resection of rectal cancer under the guidance of ERAS achieved more minimally invasive cosmetic and functional, individualized treatment effect in laparoscopic surgery. There is a greater advantage that ERAS combined with the NOSES radical resection of rectal cancer which is worthy of popularization and with good application prospect.
Abbreviations NOSES: natural ori ce specimen extraction surgery; ERAS: enhanced recovery after surgery; TME: total mesorectal excision; TSME: tumor-speci c mesorectal excision; NRS: numerical rating scale; NOTES: nature ori ce transluminal endoscopic surgery. Figure 1 D3 lymph node dissection under laparoscope, Disconnect the distal end of the tumor, Cut the stump of the rectum and disinfect it, Place the protective sleeve through the main operation hole and pull it out through the anus, and then insert the Stapler anvil into the abdominal cavity through the sleeve, Cut the sigmoid approximately 10cm from the proximal end of the tumor and sterilize it, The Stapler anvil is insert into the proximal sigmoid and xed in a suture, Remove the disconnected specimen through the anal protective sleeve, Pull out the uncut rectum and tumor through the anal sleeve, Resect the tumor and insert the sigmoid xed with a Stapler anvil into the abdomen, The rectal stump is cut off and closed again, The rectum-sigmoid anastomosis is completed through the anus, There is no incision in the abdomen after surgery. The steps of NOSES-operation are:

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