Clinical application and standardized implementation of intersphincteric resection / 中华胃肠外科杂志

Intersphincteric resection (ISR) is the ultimate sphincter-preserving surgical technique for low rectal cancer. To promote the standardized implementation of ISR, this review discusses the important issues regarding the clinical application of ISR with reference to the latest Chinese expert consensus on ISR. In terms of ISR-related pelvic anatomy of the rectum/anal canal, hiatal ligament is not identical with the anococcygeal ligament. At the level where the rectourethralis muscle continuously extends to the posteroinferior area of the membranous urethra from the rectum, the neurovascular bundle is identified between the posterior edge of rectourethralis muscle and the anterior edge of the longitudinal muscle of the rectum. This knowledge is crucial to detect the anterior dissection plane during ISR at the levator hiatus level. The indication criteria for ISR included: (1) stage I early low rectal cancer; (2) stage II-III low rectal cancer undergoing neoadjuvant treatment, and supra-anal tumors and juxta-anal tumors of stage ycT3NxM0, or intra-anal tumors of stage ycT2NxM0. However, signet ring cell carcinoma, mucinous adenocarcinoma and undifferentiated carcinoma should be contraindicated to ISR. For locally advanced low rectal cancer (especially anteriorly located tumor), neoadjuvant treatment should be carried out in a standardized manner. However, it should be recognized that neoadjuvant chemoradiotherapy was a risk factor for poor anal function after ISR. For surgical approaches for ISR, including transanal, transabdominal, and transanal transabdominal approaches, the choice should be based on oncological safety and functional consequences. While ensuring the negative margin, maximal preservation of rectal walls and anal canal contributs to better postoperative anorectal function. Careful attention must be paid to complications regarding ISR, with special focus on the anastomotic complications. The incidence of low anterior resection syndrome (LARS) was higher than 40%. However, this issue is often neglected by clinicians. Thus, management and rehabilitation strategies for LARS with longer follow-ups were required.

Anatomical and histological investigation of the area anterior to the anorectum passing through the levator hiatus / 中华胃肠外科杂志

Objective: To document the anatomical structure of the area anterior to the anorectum passing through the levator hiatus between the levator ani slings bilaterally. Methods: Three male hemipelvises were examined at the Laboratory of Clinical Applied Anatomy, Fujian Medical University. (1) The anatomical assessment was performed in three ways; namely, by abdominal followed by perineal dissection, by examining serial cross-sections, and by examining median sagittal sections. (2) The series was stained with hematoxylin and eosin to enable identification of nerves, vessels, and smooth and striated muscles. Results: (1) It was found that the rectourethralis muscle is closest to the deep transverse perineal muscle where the longitudinal muscle of the rectum extends into the posteroinferior area of the membranous urethra. The communicating branches of the neurovascular bundle (NVB) were identified at the posterior edge of the rectourethralis muscle on both sides. The rectum was found to be fixed to the membranous urethra through the rectourethral muscle, contributing to the anorectal angle of the anterior rectal wall. (2) Serial cross-sections from the anal to the oral side were examined. At the level of the external anal sphincter, the longitudinal muscle of the rectum was found to extend caudally and divide into two muscle bundles on the oral side of the external anal sphincter. One of these muscle bundles angled dorsally and caudally, forming the conjoined longitudinal muscle, which was found to insert into the intersphincteric space (between the internal and external anal sphincters). The other muscle bundle angled ventrally and caudally, filling the gap between the external anal sphincter and the bulbocavernosus muscle, forming the perineal body. At the level of the superficial transverse perineal muscle, this small muscle bundle headed laterally and intertwined with the longitudinal muscle in the region of the perineal body. At the level of the rectourethralis and deep transverse perineal muscle, the external urethral sphincter was found to occupy an almost completely circular space along the membranous part of the urethra. The dorsal part of the external urethral sphincter was found to be thin at the point of attachment of the rectourethralis muscle, the ventral part of the longitudinal muscle of the rectum. We identified a venous plexus from the NVB located close to the oral and ventral side of the deep transverse perineal muscle. Many vascular branches from the NVB were found to be penetrating the longitudinal muscle and the ventral part of rectourethralis muscle at the level of the apex of the prostate. The rectourethral muscle was wrapped ventrally around the membranous urethra and apex of the prostate. The boundary between the longitudinal muscle and prostate gradually became more distinct, being located at the anterior end of the transabdominal dissection plane. (3) Histological examination showed that the dorsal part of the external urethral sphincter (striated muscle) is thin adjacent to the striated muscle fibers from the deep transverse perineal muscle and the NVB dorsally and close by. The rectourethral muscle was found to fill the space created by the internal anal sphincter, deep transverse perineal muscle, and both levator ani muscles. Many tortuous vessels and tiny nerve fibers from the NVB were identified penetrating the muscle fibers of the deep transverse perineal and rectourethral muscles. The structure of the superficial transverse perineal muscle was typical of striated muscle. These findings were reconstructed three-dimensionally. Conclusions: In intersphincteric resection or abdominoperineal resection for very low rectal cancer, the anterior dissection plane behind Denonvilliers' fascia disappears at the level of the apex of the prostate. The prostate and both NVBs should be used as landmarks during transanal dissection of the non-surgical plane. The rectourethralis muscle should be divided near the rectum side unless tumor involvement is suspected. The superficial and deep transverse perineal muscles, as well as their supplied vessels and nerve fibers from the NVB. In addition, the cutting direction should be adjusted according to the anorectal angle to minimize urethral injury.

Anatomical classification of and laparoscopic surgery for left-sided colorectal cancer with persistent descending mesocolon / 中华胃肠外科杂志

Objective: To investigate anatomical morphology and classification of persistent descending mesocolon (PDM) in patients with left-sided colorectal cancer, as well as the safety of laparoscopic radical surgery for these patients. Methods: This is a descriptive study of case series. Relevant clinical data of 995 patients with left colon and rectal cancer who had undergone radical surgery in Fujian Medical University Union Hospital from July 2021 to September 2022 were extracted from the colorectal surgery database of our institution and retrospectively analyzed. Twenty-four (2.4%) were identified as PDM and their imaging data and intra-operative videos were reviewed. We determined the distribution and morphology of the descending colon and mesocolon, and evaluated the feasibility and complications of laparoscopic surgery. We classified PDM according to its anatomical characteristics as follows: Type 0: PDM combined with malrotation of the midgut or persistent ascending mesocolon; Type 1: unfixed mesocolon at the junction between transverse and descending colon; Type 2: PDM with descending colon shifted medially (Type 2A) or to the right side (Type 2B) of the abdominal aorta at the level of the origin of the inferior mesentery artery (IMA); and Type 3: the mesocolon of the descending-sigmoid junction unfixed and the descending colon shifted medially and caudally to the origin of IMA. Results: The diagnosis of PDM was determined based on preoperative imaging findings in 9 of the 24 patients (37.5%) with left-sided colorectal cancer, while the remaining diagnoses were made during intraoperative assessment. Among 24 patients, 22 were male and 2 were female. The mean age was (63±9) years. We classified PDM as follows: Type 0 accounted for 4.2% (1/24); Type 1 for 8.3% (2/24); Types 2A and 2B for 37.5% (9/24) and 25.0% (6/24), respectively; and Type 3 accounted for 25.0% (6/24). All patients with PDM had adhesions of the mesocolon that required adhesiolysis. Additionally, 20 (83.3%) of them had adhesions between the mesentery of the ileum and colon. Twelve patients (50.0%) required mobilization of the splenic flexure. The inferior mesenteric artery branches had a common trunk in 14 patients (58.3%). Twenty-four patients underwent D3 surgery without conversion to laparotomy; the origin of the IMA being preserved in 22 (91.7%) of them. Proximal colon ischemia occurred intraoperatively in two patients (8.3%) who had undergone high ligation at the origin of the IMA. One of these patients had a juxta-anal low rectal cancer and underwent intersphincteric abdominoperineal resection because of poor preoperative anal function. Laparoscopic subtotal colectomy was considered necessary for the other patient. The duration of surgery was (260±100) minutes and the median estimated blood loss was 50 (20-200) mL. The median number of No. 253 lymph nodes harvested was 3 (0-20), and one patient (4.2%) had No.253 nodal metastases. The median postoperative hospital stay was 8 (4-23) days, and the incidence of complications 16.7% (4/24). There were no instances of postoperative colon ischemia or necrosis observed. One patient (4.2%) with stage IIA rectal cancer developed Grade B (Clavien-Dindo III) anastomotic leak and underwent elective ileostomy. The other complications were Grade I-II. Conclusions: PDM is frequently associated with mesenteric adhesions. Our proposed classification can assist surgeons in identifying the descending colon and mesocolon during adhesion lysis in laparoscopic surgery. It is crucial to protect the colorectal blood supply at the resection margin to minimize the need for unplanned extended colectomy, the Hartmann procedure, or permanent stomas.

Delayed gastric emptying after surgery for transverse colon cancer: diagnosis, management and prevention / 中华胃肠外科杂志

Delayed gastric emptying is a syndrome of gastric motility disorder with slow gastric emptying as the main sign, provided that mechanical factors such as intestinal obstruction and anastomotic stricture are excluded. The incidence of delayed gastric emptying after colon cancer surgery is 1.4%, mainly after transverse colon cancer surgery. Most of the studies on delayed gastric emptying are case reports, lacking systematic studies. The diagnoses and treatments can be draw on the experience of delayed gastric emptying after pancreatic surgery. Our retrospective study indicated that the incidence of delayed gastric emptying after surgery for transverse colon cancer was 4.0%, higher than that for other colon cancer. Patients who underwent gastrocolic ligament lymph node dissection were at higher risk than those who did not (3.6% vs. 0.8%). Gastrocolic ligament lymph node dissection and stress are causative factors for delayed gastric emptying after surgery for transverse colon cancer. We add the gastrografin test upon the diagnostic criteria of the International Study Group for Pancreatic Surgery, which is simple and practical. Nasogastric tube decompression, enteral nutrition combined with parenteral nutrition, glucocorticoids, and prokinetic agents can cure most patients with postoperative delayed gastric emptying. All the patients with postoperative delayed gastric emptying were cured in our studies. Strict indications for gastrocolic ligament lymph node dissection (patients with cT3-4 and cN+) may decrease the occurrence of delayed gastric emptying after surgery for transverse colon cancer.

Anatomical observation and clinical significance of the prostatic part of neurovascular bundle in total mesorectal excision / 中华胃肠外科杂志

Objective: To observe the anatomical architecture of the prostatic part of the neurovascular bundle (NVB) in total mesorectal excision (TME). Methods: A descriptive cohort study and an anatomical observation study were carried out. A total of 38 male patients with rectal cancer who underwent TME in the Department of Colorectal Surgery at the affiliated Union hospital of Fujian Medical University between November 2013 and March 2015 were included. A total of 4 hemipelvis were examined at the Laboratory of Clinical Applied Anatomy, Fujian Medical University. The following outcomes were observed: 1) the clinical significance of bleeding of the prostatic part of NVB: surgical videos were reviewed and the incidence of bleeding was recorded. The urogenital function was assessed using the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF) score. The correlation between prostatic part bleeding and postoperative urogenital function was evaluated. 2) anatomical observation: the vessels, nerve fibers, as well as their surrounding fatty tissue from the prostatic part were treated as a whole, namely, the fat pad of the prostatic part. The anatomical architecture of the prostatic part in the surgical videos was reviewed and interpreted with the cadaveric findings. Categorical variables were compared between groups using a Fisher exact probability. while continuous variables with skewed distribution were compared between groups using the Mann-Whiteny U test. Results: The median age of the included 38 patients was 57 years (range, 31-75), and the median tumor distance to the anal verge was 6 cm (range, 1-8). Of them, a total number of 21 (55.3%) patients had bleeding of the prostatic part of NVB (bleeding group), while the rest had not (17 cases, 44.7%, non-bleeding group). 1) the clinical significance of bleeding of the prostatic part of NVB. The urinary function significantly decreased in patients in the bleeding group according to IPSS score after the 3rd month and the 6rd month of the surgery [7 (0-16) vs. 2 (0-3), Z=-1.787, P=0.088; 2 (0-15) vs. 0 (0-2), Z=-2.270, P=0.028]. There was no difference regarding the IPSS score between the two groups after 1 year of the surgery (P>0.05). With a total of 23 patients with normal preoperative sexual activity included, 87.5% (7/8) of patients in the non-bleeding group can expect to return to their preoperative baseline, this incidence was significantly higher than that of only 40% (6/15) in the bleeding group (P=0.029). 2) anatomical observation: for cadaveric observation, the prostatic part of NVB was located in the narrow triangular space composed of anterolateral walls of the rectum, the posterolateral surface of the prostate and the medial surface of the levator ani musculature. The tiny vascular branches and nerve fibers from the prostatic part were hard to identify. The cavernosal nerves cannot reliably be distinguished from the neural supply to the prostate, rectum and levator ani. In the cross-section of levels of prostatic base and mid-prostate in cadaveric hemipelvis specimens, the boundary of the prostatic part fat pad was partly overlapped and merged with the boundary of the mesorectum. Intraoperative observation showed that the areas of overlap referred to the rectal branches from the prostatic part piercing the proper fascia to supply the mesorectum, which carried the largest tension and high risk of bleeding during circumferential dissection toward the perirectal plane. The ultrasonic scalpel was required to pre-coagulate the rectal branches at the point close to the proper fascia of the rectum to prevent bleeding. In the cross-section of the prostatic apex level, the prostatic part approached ventrally and its boundary was away from the boundary of the mesorectum. Conclusions: NVB prostatic part injury is one of the causes of urogenital dysfunction after TME. The nerve fibers from the prostatic part were tiny, and its functional zones cannot be distinguished during operation. Therein, the fat pad of the prostatic part should be protected as a whole. Understanding the morphology of the fat pad of the prostatic part provides invaluable surgical guidance to dissect this critical area. When dissecting around the anterolateral rectal wall, appropriate anti-traction tension should be maintained and the rectal branches from the prostatic part should be coagulated with an ultrasonic scalpel to prevent bleeding.

Prognostic value of gastroepiploic lymph node metastasis in transverse colon cancer / 中华消化外科杂志

Objective:To investigate the prognostic value of gastroepiploic lymph node (GLN) metastasis in transverse colon cancer.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 371 patients with transverse colon cancer who were admitted to Fujian Medical University Union Hospital from November 2010 to November 2017 were collected. There were 202 males and 169 females, aged from 21 to 92 years, with a median age of 58 years. Patients were performed complete mesocolic excision combined with GLN dissection by one group of surgeons. Of the 371 patients with transverse colon cancer, 15 cases had positive GLN metastasis (GLN+), and 356 cases had negative GLN metastasis (GLN-). Observation indicators: (1) the propensity score matching conditions and comparison of baseline data between GLN- patients and GLN+patients with transverse colon cancer after propensity score matching; (2) follow-up and survival of GLN- patients and GLN+patients with transverse colon cancer; (3) influencing factors for prognosis of patients with transverse colon cancer. Patients were followed up by outpatient examination or telephone interview to detect tumor metastasis and survival. Follow-up was conducted once every 3 months within postoperative 2 years, once every 6 months within postoperative 2-5 years and once a year thereafter up to January 2020. The propensity score matching was conducted by 1∶4 matching using the nearest neighbor method. Measurement data with skewed distribution were described as M (range), and comparison between groups was analyzed using the rank sum test. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to calculate survival rates and draw survival curves, and Log-rank test was used for survival analysis. Univariate and multivariate analyses were performed using the COX proportional hazard regression model. The variables with P<0.10 in the univariate analysis were included for multivariate analysis. Results:(1) The propensity score matching conditions and comparison of baseline data between GLN- patients and GLN+ patients with transverse colon cancer after propensity score matching: 55 of 371 patients had successful matching, including 44 GLN- patients and 11 GLN+ patients. Before propensity score matching, the age, cases in stage 0 or stage 1 of M staging, preoperative carcinoembryonic antigen were 60 years(range, 24-92 years), 328, 22, 4.1 μg/L(range, 0.2-343.7 μg/L) for GLN- patients, respectively, versus 67 years(range, 21-79 years), 11, 4, 5.0 μg/L(range, 0.7-952.4 μg/L) for GLN+ patients, showing significant differences in the above indicators between the two groups ( Z=-1.440, χ2=9.031, Z=-2.086, P<0.05). After propensity score matching, the above indicators were 58 years(range, 45-67 years), 40, 4, 4.0 μg/L(range, 2.0-10.0 μg/L) for GLN- patients, respectively, versus 67 years(range, 59-71 years), 9, 2, 5.0 μg/L(range, 8.0-19.0 μg/L) for GLN+ patients, showing no significant difference between the two groups ( Z=-1.580, χ2=0.105, Z=-0.821, P>0.05). (2) Follow-up and survival of GLN- patients and GLN+ patients with transverse colon cancer: GLN- patients and GLN+ patients with transverse colon cancer were followed-up for 12-92 months and 1-70 months, with a median time of 53 months and 30 months respectively. Three cases of GLN- patients and 2 cases of GLN+patients had postoperative liver metastasis, respectively, showing no significant difference between the two groups ( χ2 =0.344, P>0.05). One case of GLN- patients and 3 cases of GLN+ patients had heterochronous lung metastasis, respectively, showing a significant difference between the two groups ( χ2 =4.870, P<0.05). The 5-year disease progression-free survival rates were 82.3% and 33.9% for GLN- patients and GLN+ patients, respectively, showing a significant difference between the two groups ( χ2 =13.366, P<0.05). (3) Influencing factors for prognosis of patients with transverse colon cancer: results of univariate analysis showed that pT staging, pN staging, M staging and GLN metastasis were related factors for prognosis of patients with transverse colon cancer ( hazard ratio=1.599, 5.107, 4.511, 6.273, 95% confidence interval as 0.467-5.471, 1.867-13.971, 1.385-14.694, 2.052-19.176, P<0.05). Results of multivariate analysis showed that pN staging, M staging and GLN metastasis were independent influencing factors for prognosis of patients with transverse colon cancer ( hazard ratio=6.399, 6.163, 4.024, 95% confidence interval as 2.028-20.189, 1.666-22.800, 1.177-13.752, P<0.05). Conclusion:For the patients with transverse colon cancer, GLN metastasis is associated with high postoperative heterochronous lung metastasis rate and poor prognosis. GLN metastasis is an independent prognostic factor for patients with transverse colon cancer.

Chylous ascites has a higher incidence after robotic surgery and is associated with poor recurrence-free survival after rectal cancer surgery / 中华医学杂志(英文版)

BACKGROUND@#Postoperative chylous ascites is an infrequent condition after colorectal surgery and is easily treatable. However, its effect on the long-term oncological prognosis is not well established. This study aimed to investigate the short-term and long-term impact of chylous ascites treated with neoadjuvant therapy followed by rectal cancer surgery and to evaluate the incidence of chylous ascites after different surgical approaches.@*METHODS@#A total of 898 locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy followed by surgery between January 2010 and December 2018 were included. The clinicopathological data and outcomes of the patients with chylous ascites were compared with those of the patients without chylous ascites. The primary endpoint was recurrence-free survival (RFS). To balance baseline confounders between groups, propensity score matching (PSM) was performed for each patient with a logistic regression model.@*RESULTS@#Chylous ascites was detected in 3.8% (34/898) of the patients. The incidence of chylous ascites was highest after robotic surgery (6.9%, 6/86), followed by laparoscopic surgery (4.2%, 26/618) and open surgery (1.0%, 2/192, P = 0.021). The patients with chylous ascites had a significantly higher number of lymph nodes harvested (15.6 vs. 12.8, P = 0.009) and a 3-day longer postoperative hospital stay (P = 0.017). The 5-year RFS rate was 64.5% in the chylous ascites group, which was significantly lower than the rate in the no chylous ascites group (79.9%; P = 0.007). The results remained unchanged after PSM was performed. The chylous ascites group showed a nonsignificant trend towards a higher peritoneal metastasis risk (5.9% vs. 1.6%, P = 0.120). Univariate analysis and multivariate analysis confirmed chylous ascites (hazard ratio= 3.038, P < 0.001) as an independent negative prognostic factor for RFS.@*CONCLUSIONS@#Considering the higher incidence of chylous ascites after laparoscopic and robotic surgery and its adverse prognosis, we recommend sufficient coagulation of the lymphatic tissue near the vessel origins, especially during minimally invasive surgery.

Intraoperative anatomical observation of mesentery morphology of colonic splenic flexure / 中华胃肠外科杂志

Objective: At present, surgeons do not know enough about the mesenteric morphology of the colonic splenic flexure, resulting in many problems in the complete mesenteric resection of cancer around the splenic flexure. In this study, the morphology of the mesentery during the mobilization of the colonic splenic flexure was continuously observed in vivo, and from the embryological point of view, the unique mesenteric morphology of the colonic splenic flexure was reconstructed in three dimensions to help surgeons further understand the mesangial structure of the region. Methods: A total of 9 patients with left colon cancer who underwent laparoscopic radical resection with splenic flexure mobilization by the same group of surgeons in Union Hospital of Fujian Medical University from January 2018 to June 2019 were enrolled. The splenic flexure was mobilized using a "three-way approach" strategy based on a middle-lateral approach. During the process of splenic flexure mobilization, the morphology of the transverse mesocolon and descending mesocolon were observed and reconstructed from the embryological point of view. The lower margin of the pancreas was set as the axis, and 4 pictures for each patient (section 1-section 4) were taken during middle-lateral mobilization. Results: The median operation time of the splenic flexure mobilization procedure was 31 (12-55) minutes, and the median bleeding volume was 5 (2-30) ml. One patient suffered from lower splenic vessel injury during the operation and the bleeding was stopped successfully after hemostasis with an ultrasound scalpel. The transverse mesocolon root was observed in all 9 (100%) patients, locating under pancreas, whose inner side was more obvious and tough, and the structure gradually disappeared in the tail of the pancreatic body, replaced by smooth inter-transitional mesocolon and dorsal lobes of the descending colon. The mesenteric morphology of the splenic flexure was reconstructed by intraoperative observation. The transverse mesocolon was continuous with a fan-shaped descending mesocolon. During the embryonic stage, the medial part (section 1-section 2) of the transverse mesocolon and the descending mesocolon were pulled and folded by the superior mesenteric artery (SMA). Then, the transverse mesocolon root was formed by compression of the pancreas on the folding area of the transverse mesocolon and the descending mesocolon. The lateral side of the transverse mesocolon root (section 3-section 4) was distant from the mechanical traction of the SMA, and the corresponding folding area was not compressed by the tail of the pancreas. The posterior mesangial lobe of the transverse mesocolon and the descending mesocolon were continuous with each other, forming a smooth lobe. This smooth lobe laid flat on the corresponding membrane bed composed of the tail of pancreas, Gerota's fascia and inferior pole of the spleen. Conclusions: From an embryological point of view, this study reconstructs the mesenteric morphology of the splenic flexure and proposes a transverse mesocolon root structure that can be observed consistently intraopertively. Cutting the transverse mesocolon root at the level of Gerota's fascia can ensure the complete resection of the mesentery of the transverse colon.

Significance of the intact of the fascia propria in protection of pelvic plexus during total mesorectal excision / 中华胃肠外科杂志

Total mesorectal excision (TME) is the gold standard of surgical treatment for mid and low rectal cancer. It aims to improve the oncological outcomes as well as preserve anal sphincter, sexual and urinary function. Compared with sympathetic nerve injury alone, pelvic plexus and neurovascular bundle (NVB) injury has significant effect on postoperative sexual dysfunction, especially erectile function. Since the lateral surgical plane of TME is narrow and densely packed, dissecting outside the plane causes pelvic plexus injury, while dissecting inside it results in residual mesorectum. In this commentary, we review the research progress of lateral fascial anatomy of TME, and describe the anatomical characteristics of rectosacral fascia based on our previous research results. The prehypogastric fascia acts as a "fascia barrier" when dissecting the lateral space constantly from posterior to anterior. In addition, the pelvic plexus fuses with the prehypogastric fascia which is considered as the outer side layer of rectosacral fascia laterally. Thus, the rectosacral fascia should be dissected at the level of S4 vertebral body posterior to the rectum in an arc shape and then enter the superior-levator space. Before dissecting the lateral spaces, the anterior space of the rectum should be dissected first. After an "U" shape cutting of the Denonvilliers' fascia, the lateral space should be dissected from anterior to posterior. Finally, the lateral attachment of rectosacral fascia is transected to ensure the integrity of the mesorectum without damaging the pelvic plexus.

Robotic versus laparoscopic total mesorectal excision with partial preservation of Denonvilliers fascia: a comparative study of short-term efficacy and urinary and erectile function / 中华胃肠外科杂志

Objective: Postoperative sexual and urinary dysfunctions are common in rectal cancer patients. This study was conducted to compare the short-term efficacy and the impact of surgery on urinary and erectile functions between laparoscopy and robotic-assisted total mesorectal excision (TME) with partial preservation of Denonvilliers fascia. Methods: A retrospective cohort study was carried out. Clinical data of 276 patients with low rectal cancer who underwent TME with partial preservation of Denonvilliers fascia in our department between January 2016 and March 2019, including 143 in robotic group and 133 in laparoscopic group, were analyzed. All the patients were positioned by rigid rectoscope, and the distance between the tumor and the anal verge was ≤7 cm. The urinary and erectile functions were followed up at postoperative 12-month and evaluated by IPSS score (0-7 points as mild symptoms, 8-19 points as moderate symptoms, 20-35 points as severe symptoms; the excellent rate was defined as the rate of mild symptoms) and IIEF-5 score (score ≥ 22 as no dysfunction, 12-21 as mild, 8-11 as moderate, and 5-7 as severe) respectively. Results: There were no significant differences in operation ways between the two groups (P>0.05). The operation time of the robotic group was longer than that of the laparoscopic group [(312.5±75.4) minutes vs. (273.9±65.6) minutes, t=4.514, P<0.001]. However, in patients with higher body mass index (BMI ≥25 kg/m(2)), there was no significant difference in operation time between the two groups [(309.3±78.5) minutes vs. (276.1±75.3) minutes, t=1.751, P=0.085]. The time to postoperative flatus [(1.3±0.4) days vs. (1.5±1.0) days, t=-2.037, P=0.046], defecation [1 (1-5) days vs. 1 (1-12) days, Z=-2.209, P=0.008] and liquid diet [(1.0±0.1) days vs. (1.2±0.1) days, t=3.195, P=0.002] in the robotic group were all shorter than those in the laparoscopic group. While postoperative length of hospital stay in the robotic group was longer than that in the laparoscopic group [(8.5±5.5) days vs. (7.2±3.3) days, t=2.419, P=0.016]. There were no significant differences between the two groups in intraoperative blood loss, conversion rate, morbidity of postoperative complications, positive rate of distal resection margin, positive rate of circumferential resection margin, and the number of resected lymph nodes (all P>0.05). At postoperative 12 months, none of the robotic group nor the laparoscopic group had severe urinary dysfunction, and the overall excellent rate of urinary function reached 97.6% (83/85) and 98.4% (61/62) respectively. The rate of normal and mild erectile dysfunction in the robotic group and the laparoscopic group were 92.2% (47/51) and 92.6% (38/41) respectively (P>0.05). There was no significant difference between the two groups was found regarding the urinary and erectile function (both P>0.05). Conclusions: Compared with laparoscopic, the robotic TME with partial preservation of Denonvilliers fascia has no significant differences in surgical safety and short-term efficacy. They have similar advantages in the protection of urinary and erectile function. Meanwhile the robotic surgery presents faster postoperative recovery of gastrointestinal function.

Anatomical observation of the left parietal peritoneum and its clinical significance in left retro-mesocolic space dissection / 中华胃肠外科杂志

Objective: To investigate the anatomic characteristics of the left parietal peritoneum and its surgical implementation while dissecting in left retro-mesocolic space. Methods: A descriptive case series research methods was used. (1) surgical videos of 35 patients who underwent laparoscopic radical resection (complete mobilization of splenic flexure) of colorectal cancer in Union Hospital of Fujian Medical University between January 2018 and December 2018 were reviewed; (2) four specimens after radical resection of rectal cancer performing in June 2020 were prospectively enrolled and reviewed; (3) five specimens of left parietal peritoneum from 5 cadaveric abdomen (3 males and 2 females) were enrolled and reviewed as well; Tissues of 3 unseparated regions, namely the root of the inferior mesenteric artery (IMA), the medial region and the lateral region (including kidney tissue), from above the 5 cadaveric abdominal specimens were selected to perform Masson staining and histopathological examination. Results: (1) Surgical video observation: "Staggered layer phenomenon" and typical left parietal peritoneum was found in 77.1% (27/35) of patients when the left retro-mesocolic space was separated from the lateral and central approaches. The left parietal peritoneum presented as a rigid fascia barrier between the lateral and central approaches, which was a translucent dense connective tissue fascia. After the splenic flexure were completely mobilized, the left parietal peritoneum stump continued to the cephalic side. (2) Observation of 4 surgical specimens: The dorsal side of the left mesocolon specimen was studied, and the left parietal peritoneum stump edge was identified. The outside of the stump edge was the left hemicolon dorsal layer, which was continuously downward to the rectal fascia propria. (3) Cadaveric abdominal specimens: The left retro-mesocolic space was separated through lateral and central approaches, and the rigid fascia barrier, essentially the left parietal peritoneum and Gerota fascia, was encountered. Cross-section view showed that the left parietal peritoneum could be further detached from the dorsal layer of the left mesocolon from the outside, but could not be further detached from the inside out. (4) Histological examination: There was no obvious fascia structure in the IMA root region, while outside the IMA root region, the left bundle of inferior mesenteric plexus penetrating Gerota fascia was observed. There were 4 layers of fascias in the medial region, including the ventral layer of the left mesocolon, the dorsal layer of the left mesocolon, left parietal peritoneum and Gerota fascia. Small vessels were observed between the dorsal layer of the left mesocolon and the left parietal peritoneum. In lateral region, renal tissue and renal fascia were observed. Three layers of fascia structures were observed clearly under high power field, including the dorsal layer of the left mesocolon, left parietal peritoneum, and Gerota fascia. Conclusions: The left parietal peritoneum is the anatomical basis of the "staggered layer phenomenon" from the lateral or central approaches during the separation of left retro-mesocolic space. The small vessels in the dissection plane are the anatomical basis of intraoperative microbleeding, which need pre-coagulation. The central part of Gerota fascia is penetrated by the branches of the inferior mesenteric plexus, which results in a relatively dense surgical plane. Thus, during the dissection through the central approach, it is easy to involve in wrong surgical plane by deeper dissection.

Anatomical observation of the right retroperitoneal fascia and its clinical significance in complete mesocolic excision for right colon cancer / 中华胃肠外科杂志

Objective: To investigate the anatomic characteristics of the right retroperitoneal fascia and its surgical implementation while performing complete mesocolic excision (CME) for right colon cancer. Methods: A descriptive study was carried out. (1) Clinicopathological data and surgical videos of 17 non-consecutive patients undergoing laparoscopic right hemicolectomy (extended right hemicolectomy) with CME for right colon cancer at Department of Colorectal Surgery of Union Hospital, Fujian Medical University between January 2020 and October 2020 were retrospectively collected. The construction of right retroperitoneal fascia was observed from caudal dorsal direction and caudal ventral direction. (2) Three postoperative specimens from 3 cases undergoing laparoscopic right hemicolectomy with CME for right colon cancer in June 2020 were prospectively included to observe anatomy and examine histology. (3) Five abdominal cadaver specimens from the Department of Anatomy of Fujian Medical University were enrolled, including 3 males and 2 females. Anatomical observation and histological studies were performed from the cranial approach and the caudal dorsal approach. Masson staining was used to examine the histology. Results: (1) Surgical video observation: The typical structure of right retroperitoneal fascia could be observed in all the 17 patients. The fascia was a rigid barrier between the posterior space of the ascending colon and the anterior pancreaticoduodenal space behind the transverse colon. The right retroperitoneal fascia should be sharply cut to communicate between the two spaces to avoid entering the right mesocolon by mistake. The severed ventral stump of the right retroperitoneal fascia ran along the dorsal side of the right hemicolon to the lateral side, and the dorsal stump covered the level of the duodenum caudally, and continued to move downward, covering the surface of Gerota's fascia. (2) Observation of 3 surgical specimens: The dorsal side of the right mesocolon was smooth and intact, which could be anchored in the corresponding area of the lateral edge of the duodenum. The ventral stump of the right retroperitoneal fascia could be seen, which attached to the dorsal side of the right mesocolon semi-circularly. Masson staining observation: The ventral stump of the right retroperitoneal fascia ran cephalad, fused with the dorsal side of the right mesocolon tightly and curled. The caudal side of confluence and the dorsal side of the right mesocolon presented a bilobed structure. (3) Anatomy of 5 cadaveric specimens: The right retroperitoneal fascia was a thin fascia structure, which was a rigid barrier between the anterior pancreaticoduodenal space behind the transverse colon and the posterior space of the ascending colon. The ventral stump of the right retroperitoneal fascia (including the dorsal side of the right mesocolon), the dorsal stump of the right retroperitoneal fascia (including part of the duodenal wall) and the dorsal side of the right mesocolon were retrieved for histological examination. The ventral stump of the right retroperitoneal fascia fused with the dorsal side of the right mesocolon by the cephalic side, and the dorsal side of the right hemi-mesocolon on the fusion level by caudal side gradually separated into a double-layer loose fascial structure. The dorsal stump of the right retroperitoneal fascia covered the surface of the duodenum level, moved on from the ventral side to the surface of the prerenal fascia, and continued to the caudal side. Conclusions: The right retroperitoneal fascia is a rigid barrier between the anterior pancreaticoduodenal space behind the transverse colon and the posterior space of the ascending colon. The Toldt fascia formed by fusion with the dorsal lobe of the right colon travels to the edge of the descending and horizontal part of the duodenum and separates again. The right retroperitoneal fascia is attached to the edge of the duodenum, reversing and running on the surface of the prerenal fascia, while the dorsal lobe of the right colon runs in front of the pancreas and duodenum, and shifts to the pancreaticoduodenal fascia. During the operation, this fascia should be identified and cut to penetrate the anterior pancreaticoduodenal space behind the transverse colon and the posterior ascending colon space, which helps to ensure the integrity of the dorsal side of the right hemi-mesocolon.

Controversies and prospects of rectum preserving surgery after neoadjuvant therapy for rectal cancer / 中华消化外科杂志

There are three goals of the treatments for rectal cancer, including risk reduction of local recurrence in the pelvic cavity through treatment to the most extent (better down to less than 5%), reduction of acute or chronic complications as soon as possible, and preservation of good sphincter function as well as life quality. As a new concept, rectum preserving surgery following neoadjuvant therapy, remains controversial in its implementation process. There are controversies in the selection criteria, regimens of neoadjuvant therapy, therapy procedures, complications, and evaluation of oncological prognosis and life quality. The authors discuss the above issues in this article based on literatures and our own practical experience, in order to provide references for the promotion of rectum preserving surgery.

Identification of gene biomarkers to predict responses to neoadjuvant chemoradiotherapy in patients with rectal cancer and pathways enrichment analysis / 中华胃肠外科杂志

Objective@#To screen out the potential gene biomarkers to predict responses to neoadjuvant chemoradiotherapy (CRT) in patients with rectal cancer and to explore the main downstream pathways of resistance.@*Methods@#The gene expression profiles (GSE35452) of locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy from 46 specimens (24 responders, TRG 0/1, and 22 non-responders, TRG 2/3) were downloaded from the GEO database. The differentially expressed genes were identified to screen out the potential biomarkers by use of the GCBI platform. GO and KEGG pathways enrichment analysis were performed to integrate enrichment results of differentially expressed genes. Signal-signal interaction network was constructed and analyzed to screen out potential main downstream pathways.@*Results@#A total of 1079 differentially expressed genes were screened, including 657 up-regulated and 422 down-regulated ones. Among these genes, REG4 had the maximum fold change value of -6.029 491. In GO term, these differentially expressed genes were mainly enriched in molecule metabolic process, cell cycle, DNA-dependent transcription, signal transduction and apoptotic process. The KEGG pathways enrichment analysis showed that the differentially expressed genes were enriched in 65 KEGG pathways, including metabolic pathways, cell cycle and metabolism pathways. Signal-signal interaction network analysis showed that MAPK signaling pathway and cell cycle pathway might play a determinant role in the development of neoadjuvant chemoradiotherapy resistance. Further analysis showed that CDKN1B, CDKN2A, RBL1, TFDP1, CCND2, CCNE2, CDC6 and CDK6 in cell cycle might induce chemoradiotherapy resistance by blocking G1/S phase cell cycle arrest, decreasing the apoptosis of tumor cells and increasing S phase ratio of chemoradiotherapy resistance.@*Conclusion@#G1/S phase cell cycle arrest blocking plays an important role in the development of chemoradiotherapy resistance in patients with rectal cancer. Moreover, the key genes, such as REG4, may be useful in predicting responses to neoadjuvant chemoradiotherapy.

Effects of the number of harvested lymph nodes in neoadjuvant chemoradiotherapy combined with surgery on prognosis of middle-low rectal cancer / 中华消化外科杂志

Objective To investigate the effects of the number of harvested lymph nodes in neoadjuvant chemoradiotherapy (nCRT) combined with surgery on prognosis of middle-low rectal cancer.Methods The retrospective case-control study was conducted.The clinicopathological data of 373 patients with middle-low rectal cancer who underwent nCRT combined with surgery in the Fujian Medical University Union Hospital from January 2009 to December 2013 were collected.There were 241 males and 132 females,aged from 26 to 81 years,with the age of (55 ± 11) years.Observation indicators:(1) treatment situations;(2) follow-up and survival;(3)influencing factors for the number of harvested lymph nodes;(4) prognostic analysis of the different number of harvested lymph nodes as cut-off for grouping;(5) stratified analysis.Follow-up using telephone interview and outpatient examination was performed to detect postoperative survival of patients once every three months within postoperative 2 years and once every 6 months during the postoperative third year up to March 2016.The endpoint of follow-up was tumor recurrence,retastasis or death.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was done using the independent sample t test.Measurement data with skewed distribution were represented as M (range),and comparison between groups was done using the Kruska1-Wallis H test.Count data was described as absolute numbers.Univariate and multivariate analyses were done by the multiple linear regression model.Survival rate was calculated by the Kaplan-Meier method,and Logrank test was used for survival analysis.Results (l) Treatment situations:373 patients underwent nCRT combined with surgery,including 329 combined with sphincter-sparing rectal resection and 44 combined with abdominoperineal rectal resection.The number of harvested lymph nodes was 12 ± 6 in 373 patients.There were 185 patients with the number of harvested lymph nodes ＜ 12 and 188 with the number of harvested lymph nodes ≥ 12.(2) Follow-up and survival:373 patients were followed up for 5-77 months,with a median follow-up time of 43 months.During the follow-up,the 1-,3-,5-year disease-free survival rates were respectively 90.4％,76.3％,and 67.5％ in the 373 patients.(3) Influencing factors for the number of harvested lymph nodes:univariate analysis showed that distance between the tumor and anal verge,tumor diameter,tumor pathological N staging,and regression grade of rectal cancer were associated factors for the number of harvested lymph nodes (t =3.156,2.992,x2=8.183,10.839,P＜0.05).Multivariate analysis showed that distance between the tumor and anal verge,regression grade of rectal cancer,and tumor pathological N staging were independent factors for the number of harvested lymph nodes (t=3.308,2.690,2.584,95％ confidence interval:0.808-3.180,0.446-2.873,0.332-2.448,P＜0.05).(4) Prognostic analysis of the different number of harvested lymph nodes as cut-off for grouping:with the number of harvested lymph nodes of 6,7,8,9,10,11,12,13,14,15,and 16 as cut-off for grouping,there was no significant difference in the 3-year disease-free survival rate,cumulative local recurrence rate,and cumulative distant metastasis rate between ＜6 group and ≥6 group,between ＜7 group and ≥7 group,between＜8 group and ≥8 group,between ＜9 group and ≥9 group,between ＜10 group and ≥ 10 group,between ＜11 group and ≥ll group,between ＜12 group and ≥12 group,between ＜13 group and ≥13 group,between ＜ 14 group and ≥ 14 group,between ＜ 15 group and ≥ 15 group,between ＜ 16 group and ≥ 16 group,respectively (P＞0.05).(5) Stratified analysis:with the number of harvested lymph nodes of 7,8,9,and 10 as cut-off for grouping in 45 of 373 patients with Ⅱ-Ⅲ regression grade of rectal cancer and negative lymph nodes (NO staging),there was no significant difference in the 3-year disease-free survival rate between ＜7 group and ≥ 7group,between ＜8 group and ≥8 group,between ＜9 group and ≥9 group,between＜10 group and ≥ 10 group,respetively (x2 =3.946,5.346,6.375,4.297,P＜0.05).Conclusions The number of lymph nodes as 12 is not the independent factor for prognosis of patients with middle-low rectal cancer after nCRT combined with surgery.The number of harvested lymph nodes as 7 to 10 is the important factor for evaluating the prognosis of middle-low rectal cancer patients with Ⅱ-Ⅲ regression grade of rectal cancer and negative lymph nodes after nCRT combined with surgery.

Membrane anatomy: motivation to promote precise laparoscopic and robot colorectal surgery / 中华胃肠外科杂志

During the past 20 years, the development of minimally invasive surgery had developed through three stages: organ excision, radical organ excision centered on arteries and functional radical organ excision based on membrane anatomy.While high-definition laparoscopy was gaining more popularity, surgeons gradually observed the fascial spaces and fascial structures which could not be recognized by naked eye during open surgery. With the development of membrane anatomical architecture, we discovered several fascial spaces and fascial structures that had never been recognized before. Inspired with the anatomical concept, proposed by Professor Gong Jianping, we systematically observed and expounded the laparoscopic radical surgery for colorectal cancer based on membrane anatomy, and explored the fascial anatomy structure and fascial space during operations for right semicolon, left semicolon and rectum through the high-definition visualization of the endoscope and robot in combination with clinical practice. Meanwhile, the membrane anatomy theory was systematically studied through repeated surgical operations and verified through practice. The fascial anatomy structures, such as "space between small intestine and ascending mesentery", "transverse mesocolon radix" and "terminal line of total mesorectal excision" were proposed. This theory can promote the stable development of "microbleeding" or "no blood" minimally invasive colorectal surgery.

Efficacy analysis of radiotherapy combined with surgery for locally advanced rectal mucinous adenocarcinoma: a retrospective study based on data of Surveillance, Epidemiology, and End results population / 中华胃肠外科杂志

OBJECTIVE@#To explore the efficacy of radiotherapy combined with surgery for locally advanced rectal mucinous adenocarcinoma.@*METHODS@#Clinical data of patients with locally advanced rectal mucinous adenocarcinoma (T3-4 and/or N+) diagnosed by postoperative pathology from 1992 to 2013 were retrieved from the US Surveillance, Epidemiology, and End Results (SEER) database. Patients with local excision only, tumor biopsy or combined organ excision and incomplete follow-up information were excluded. All the enrolled patients were divided into three groups according to different treatments, including surgery alone (SA) group, preoperative radiotherapy combined with surgery (RT+S) group and surgery combined with postoperative radiotherapy (S+RT) group. The extracted data included basic data of patients and tumor, treatment status, and follow-up results. The χ² test was used to compare the count data. Kaplan-Meier method was used to draw the survival curve and calculate the survival rate. The survival was analyzed and compared by Log-rank test. The R language 2.8.1 was used to match the patients as 1:1 pairing through the propensity score matching (PSM). The matching variables included gender, age at diagnosis, year at diagnosis, ethnicity, degree of tissue differentiation, TNM stage, depth of invasion, making the baseline data of subgroups comparable. The Cox proportional hazard model was used for multivariate analysis of prognostic factors.@*RESULTS@#A total of 2 149 patients with locally advanced rectal mucinous adenocarcinoma were enrolled in the study, including 1 255 males (58.4%) and 894 females (41.6%). There were 706 patients (32.9%) in the SA group, 772 patients (35.9%) in the RT+S group and 671 patients (31.2%) in the S+RT group. In SA, RT+S and S+RT groups, the median overall survival time was 39, 85, and 74 months respectively; the 5-year overall survival (OS) rate was 38.7%, 56.5%, and 55.2% respectively; the median cancer-specific survival (CSS) time was 86, 127, and 111 months respectively, and the 5-year CSS rate was 53.7%, 62.2% and 60.7% respectively. In comparison among the 3 groups, the 5-year OS rate and CSS rate in the SA group were significantly lower than those in the RT+S group and S+RT group (all P<0.001); the 5-year OS rate and CSS rate between RT+S group and S+RT group were not significantly different (P=0.166 and 0.392,respectively). After the baseline data of subgroups were corrected through PSM, the 5-year OS rate and CSS rate in the SA group (n=375) were significantly lower than those in the RT+S group (n=375)(OS:40.1% vs. 54.5%, P<0.001; CSS:54.3% vs. 63.3%, P=0.023). The 5-year OS rate and CSS rate in the SA group (n=403) were also lower than those in the S+RT group (n=403) (OS:37.4% vs. 54.7%,P<0.001;CSS:51.6% vs. 61.0%,P=0.031). The 5-year OS rate and CSS rate between RT+S group (n=363) and S+RT group (n=363) were not significantly different (OS:51.7% vs. 55.5%, P=0.789; CSS:57.7% vs. 60.5%, P=0.484). Cox multivariate analysis showed that radiotherapy (HR=0.845, 95%CI: 0.790 to 0.903, P=0.001) was an independent prognostic factor for OS of locally advanced rectal mucinous adenocarcinoma; radiotherapy (HR=0.907, 95% CI: 0.835 to 0.985, P=0.021) was also an independent prognostic factor affecting CSS in patients with locally advanced rectal mucinous adenocarcinoma.@*CONCLUSION@#As compared with surgery alone, surgery combined with preoperative or postoperative radiotherapy is beneficial to the long-term survival of patients with locally advanced rectal mucinous adenocarcinoma.

Anastomotic leakage after rectal cancer surgery: classification and management / 中华胃肠外科杂志

Many studies have focused on the identification of risk factors and prevention of anastomotic leakage following rectal cancer surgery. However, there is little knowledge regarding classification and management of anastomotic leakage in clinic. Herein, we reviewed and summarized the classification and management of anastomotic leakage after rectal cancer surgery. The relevant treatments of anastomotic leakage should be chosen based on patient's manifestation, including general and local reactions, anatomical location, and nature of the leakage (contained or free, controlled or uncontrolled leakage) . 1) Surgery is imperative for anastomotic leakage with acute general peritonitis and sepsis. 2) Circumscribed peritonitis and the pelvic abscess can be managed conservatively with complete drainage. During the conservative management, diverting stoma, minimally invasive techniques of seal or repair should be implemented at an appropriate time, if necessary. 3) Subclinical leakage seldom requires surgical intervention promptly. 4) For persistent anastomotic leakage after diverting stoma, we should consider whether chronic presacral abscess, epithelialized sinus, fistula or local recurrence of cancer is present. With regard to definitive salvage surgery, reconstruction of the coloanal anastomosis or permanent stoma is usually required under these circumstances. 5) Complicated fistula often necessitates surgical repair with advancement tissue flap or tissue interposition under the condition of diversion. Reconstructing the coloanal anastomosis is the alternative management, whereas other treatments are invalid, including ultra-low anterior resection, intersphincteric resection, proctectomy with colon pull-through, and primary or staged coloanal anastomosis. 6) During the surgical repair of recto-vaginal fistula and recto-urinary fistula, colorectal surgeons may require the cooperation of gynecologists, urologists, and orthopedists. 7) For anastomotic leakage with local recurrence of cancer after conservative management, diverting stoma should be performed promptly to facilitate the subsequent chemoradiotherapy. Surgeons should pay more attention to systemic knowledge and understanding of the classification and management of anastomotic leakage following rectal cancer surgery. Accordingly, we can follow the principles of management, individualize the treatments, apply the concepts of damage control and minimally invasive surgery, and enhance the recovery of anastomotic leakage. Prevention remains more important than remedies. To prevent the occurrence of permanent injuries, not only early diagnoses and treatments should be performed, but also the timing of cancer treatments is warranted for anastomotic leakage.

Whether the transanal total mesorectal excision can achieve a real total mesorectal excision / 中华消化外科杂志

The total mesorectal excision (TME) developed by Heald in 1982,is the present gold standard treatment of middle and low rectal cancer.However,traditional transabdominal TME remains a technically demanding procedure in patients with a narrow pelvis,bulky tumors,or obesity.To overcome the technical difficulties associated with transabdominal rectal dissection,transanal total mesorectal excision (TaTME) has recently been introduced.However,can TaTME achieve comparable outcomes in comparison with transabdominal TME? Is the distal margin of the mesorectum sufficient? Where is the sign of distal margin of mesorectum? Can the circumferential margin (CRM) and specimen quality be guaranteed? The aim of this comment was to discuss whether the TaTME can achieve a real TME from the following aspects:the principles of transabdominal TME,current published TaTME clinical trials,and the anorectal and pelvic anatomy.

A six-gene model using an artificial neural network to predict regional lymph node metastasis after neo-adjuvant chemoradiotherapy for locally advanced rectal cancer / 中华消化外科杂志

Objective To screen out the potential gene to predict regional lymph node metastasis after neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC) and develop a 6-gene model using an artificial neural network (ANN).Methods The gene expression profiles (GSE46862) of locally advanced rectal cancer undergoing preoperative chemoradiotherapy from 64 specimens (21 with ypN-and 43 with ypN+) were downloaded from the gene expression omnibus (GEO) database.The differentially expressed genes were identified to screen out the potential biomarkers through the Gene-Cloud of Biotechnology Information (GCBI) platform.The top 6 genes were screened out for building model.An ANN model was trained and validated using the SPSS Modeler software.The study samples were allocated randomly into the training sample group and testing sample group with a 7∶3 ratio.The training samples and testing samples were respectively used for building an ANN model and independent back-substitution test.Observation indicators:(1) screening results of differentially expressed genes;(2) analysis results of ANN model.The receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to evaluate the predictive abilities of ANN and each biomarker.Results (1) Screening results of differentially expressed genes:A total of 50 genes were screened.Six top genes included IL6,AKR1B1,AREG,SELE,ROBO1 and CD274.(2) Analysis results of ANN model:Six top genes were selected to construct a three-layer ANN model with a 7-5-2 structure.The IL6 made the greatest effect on the ANN model,followed by ROBO1,AKR1B1,AREG,CD274 and SELE.The AUC was 0.929.The sensitivity and specificity of ANN model were 96.7％ and 85.7％,and accuracy of training samples was 93.2％.In the independent back-substitution test,sensitivity and specificity were 92.3％ and 85.7％,and accuracy of testing samples was 90.0％.Conclusion The prediction ANN model based on multiple molecular markers (IL6,ROBO1,AKR1B1,AREG,CD274 and SELE) for regional lymph node metastases in LARC patients after CRT would be beneficial in selecting potential candidates for rectum-preserving surgery following CRT for LARC.