Advances in tumor regression patterns and safe distance of distal resection margin after neoadjuvant therapy for rectal cancer / 中华胃肠外科杂志

Neoadjuvant therapy has been widely applied in the treatment of rectal cancer, which can shrink tumor size, lower tumor staging and improve the prognosis. It has been the standard preoperative treatment for patients with locally advanced rectal cancer. The efficacy of neoadjuvant therapy for rectal cancer patients varies between individuals, and the results of tumor regression are obviously different. Some patients with good tumor regression even achieve pathological complete response (pCR). Tumor regression is of great significance for the selection of surgical regimes and the determination of distal resection margin. However, few studies focus on tumor regression patterns. Controversies on the safe distance of distal resection margin after neoadjuvant treatment still exist. Therefore, based on the current research progress, this review summarized the main tumor regression patterns after neoadjuvant therapy for rectal cancer, and classified them into three types: tumor shrinkage, tumor fragmentation, and mucin pool formation. And macroscopic regression and microscopic regression of tumors were compared to describe the phenomenon of non-synchronous regression. Then, the safety of non-surgical treatment for patients with clinical complete response (cCR) was analyzed to elaborate the necessity of surgical treatment. Finally, the review studied the safe surgical resection range to explore the safe distance of distal resection margin.

Cross-sectional study of low anterior resection syndrome in patients who have survived more than 5 years after sphincter-preserving surgery for rectal cancer / 中华胃肠外科杂志

Objective: In this study, we aimed to investigate the prevalence of low anterior resection syndrome (LARS) in patients who had survived for more than 5 years after sphincter-preserving surgery for rectal cancer and to analyze its relationship with postoperative time. Methods: This was a single-center, retrospective, cross-sectional study. The study cohort comprised patients who had survived for at least 5 years (60 months) after undergoing sphincter- preserving radical resection of pathologically diagnosed rectal adenocarcinoma within 15 cm of the anal verge in the Department of Gastrointestinal Surgery, Peking University People's Hospital from January 2005 to May 2016. Patients who had undergone local resection, had permanent stomas, recurrent intestinal infection, local recurrence, history of previous anorectal surgery, or long- term preoperative defecation disorders were excluded. A LARS questionnaire was administered by telephone interview, points being allocated for incontinence for flatus (0-7 points), incontinence for liquid stools (0-3 points), frequency of bowel movements (0-5 points), clustering of stools (0-11 points), and urgency (0-16 points). The patients were allocated to three groups based on these scores: no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30-42 points). The prevalence of LARS and major LARS in patients who had survived more than 5 years after surgery, correlation between postoperative time and LARS score, and whether postoperative time was a risk factor for major LARS and LARS symptoms were analyzed. Results: The median follow-up time of the 160 patients who completed the telephone interview was 97 (60-193) months; 81 (50.6%) of them had LARS, comprising 34 (21.3%) with minor LARS and 47 (29.4%) with major LARS. Spearman correlation analysis showed no significant correlation between LARS score and postoperative time (correlation coefficient α=-0.016, P=0.832). Multivariate analysis identified anastomotic height (RR=0.850, P=0.022) and radiotherapy (RR=5.760, P<0.001) as independent risk factors for major LARS; whereas the postoperative time was not a significant risk factor (RR=1.003, P=0.598). The postoperative time was also not associated with LARS score rank and frequency of bowel movements, clustering, or urgency (P>0.05). However, the rates of incontinence for flatus (3/31, P=0.003) and incontinence for liquid stools (8/31, P=0.005) were lower in patients who had survived more than 10 years after surgery. Conclusions: Patients with rectal cancer who have survived more than 5 years after sphincter-preserving surgery still have a high prevalence of LARS. We found no evidence of major LARS symptoms resolving over time.

Surgical skills and precautions of pelvic exenteration combined with pelvic wall resection / 中华胃肠外科杂志

The treatment of locally advanced rectal cancer (LARC) or locally recurrent rectal cancer (LRRC) has been a difficulty and challenge in the field of advanced rectal cancer, while pelvic exenteration (PE), as an important way to potentially achieve radical treatment of LARC and LRRC, has been shown to significantly improve the long-term prognosis of patients. The implementation of PE surgery requires precise assessment of the extent of invasion of LARC or LRRC and adequate preoperative preparation through multidisciplinary consultation before surgery. The lateral pelvis involves numerous tissues, blood vessels, and nerves, and resection is most difficult, and the ureteral and Marcille triangle approaches are recommended; while the supine transabdominal approach combined with intraoperative change to the prone jacket position facilitates adequate exposure of the surgical field and enables precise overall resection of the bony pelvis and pelvic floor muscle groups invaded by the tumor. Empty pelvic syndrome has always been an major problem to be solved during PE. The application of extracellular matrix biological mesh to reconstruct pelvic floor defects and isolate the abdominopelvic cavity is expected to reduce postoperative pelvic floor related complications. Reconstruction of the urinary system and important vessels after PE is essential, and the selection of appropriate reconstruction methods helps to improve the patient's postoperative quality of life, while more new methods are also being continuously explored.

Classification system of radical surgery for rectal cancer based on membrane anatomy / 中华胃肠外科杂志

Because the classification system of radical surgery for rectal cancer has not been established, it is impossible to select the appropriate surgical method according to the clinical stage of the tumor. In this paper, we explained the theory of " four fasciae and three spaces " of pelvic membrane anatomy and then combined this theory with the membrane anatomical basis of Querleu-Morrow classification for radical cervical cancer resection. Based on this theory and the membrane anatomy of Querleu-Morrow classification of radical cervical cancer resection, we proposed a new classification system of radical rectal cancer surgery based on membrane anatomy according to the lateral lymph node dissection range of the rectum. This system classifies the surgery into four types (ABCD) and defines corresponding subtypes based on whether the autonomic nerve was preserved. Among them, type A surgery is total mesorectal excision (TME) with urogenital fascia preservation, type B surgery is classical TME, type C surgery is extended TME, and type D surgery is lateral extended resection. This classification system unifies the anatomical terminology of the pelvic membrane, validates the feasibility of using the " four fasciae and three fascial spaces " theory to classify rectal cancer surgery, and lays the theoretical foundation for the future development of a unified and standardized classification of radical pelvic tumor surgery.

Meta-analysis comparing long-term outcomes of intersphincteric resection versus abdominoperineal resection for low rectal cancer / 中华胃肠外科杂志

Objective: To compare the long-term outcomes of intersphincteric (trans-internal and external) sphincter resection (ISR) and abdominoperineal proctocolectomy (APR) for low-grade rectal cancer. Methods: We used a meta-analytic approach to compare these procedures . Published reports comparing ISR and APR for low rectal cancer in Pubmed, Medline, EMBASE and Cochrane, China Knowledge Network (CNKI), China Biomedical Literature Database, and Vipers databases between January 2005 and January 2023 were searched and those meeting the eligibility criteria were selected for extraction of data for analysis. Inclusion criteria were as follows: (1) all reports comparing ISR and APR for low rectal cancer before January 2023; and (2) prospective randomized controlled studies or well-designed cohort studies. Exclusion criteria were as follows: (1) full text not available; (2) duplicate publications, missing primary outcome indicators, and unknown data; and (3) invalid statistical analysis. Results: Sixteen studies with 2498 patients were included in this study. Compared with the APR group, patients in the ISR group were relatively younger (weighted mean difference [WMD]=-1.82, 95%CI=-2.94 to -0.70, P=0.01), had tumors farther from the anal verge (WMD=0.43, 95%CI=0.18 to 0.67, P<0.01), and lower pathological T-stage (T3-4 stage: OR=0.54, 95%CI=0.36 to 0.81, P<0.01). In contrast, there were no statistically significant differences between the two groups in gender (P=0.78), body mass index (P=0.77), or pathological N stage (P=0.09). Compared with the APR group, patients in the ISR group had a lower rate of postoperative complications (OR=0.77, 95%CI=0.60 to 0.99, P=0.04), shorter hospital stay (WMD=-4.30, 95%CI=-7.07 to -1.53, P<0.01), higher 5-year overall survival (HR=0.54, 95%CI=0.33 to 0.88, P=0.01), and higher 5-year disease-free survival (HR=0.65, 95%CI=0.47 to 0.90, P<0.01). Five-year locoregional failure (HR=0.66, 95%CI=0.40 to 1.10, P=0.11) and time to surgery (WMD=-9.71, 95%CI=-41.89 to 22.47, P=0.55) did not differ significantly between the two groups. Conclusion: ISR is a safe and effective alternative to APR for early-stage low-grade rectal cancer.

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.

Network meta-analysis comparing the clinical outcomes and safety of robotic, laparoscopic, and transanal total rectal mesenteric resection for rectal cancer / 中华胃肠外科杂志

Objective: To methodically assess the clinical effectiveness and safety of robot-assisted total rectal mesenteric resection (RTME), laparoscopic-assisted total rectal mesenteric resection (laTME), and transanal total rectal mesenteric resection (taTME). Methods: A computer search was conducted on PubMed, Embase, Cochrane Library, and Ovid databases to identify English-language reports published between January 2017 and January 2022 that compared the clinical efficacy of the three surgical procedures of RTME, laTME, and taTME. The quality of the studies was evaluated using the NOS and JADAD scales for retrospective cohort studies and randomized controlled trials, respectively. Direct meta-analysis and reticulated meta-analysis were performed using Review Manager software and R software, respectively. Results: Twenty-nine publications comprising 8,339 patients with rectal cancer were ultimately included. The direct meta-analysis indicated that the length of hospital stay was longer after RTME than after taTME, whereas according to the reticulated meta-analysis the length of hospital stay was shorter after taTME than after laTME (MD=-0.86, 95%CI: -1.70 to -0.096, P=0.036). Moreover, the incidence of anastomotic leak was lower after taTME than after RTME (OR=0.60, 95%CI: 0.39 to 0.91, P=0.018). The incidence of intestinal obstruction was also lower after taTME than after RTME (OR=0.55, 95%CI: 0.31 to 0.94, P=0.037). All of these differences were statistically significant (all P<0.05). There were no statistically significant differences between the three surgical procedures regarding the number of lymph nodes cleared, length of the inferior rectal margin, or rate of positive circumferential margins (all P>0.05). An inconsistency test using nodal analysis revealed no statistically significant differences between the results of direct and indirect comparisons of the six outcome indicators (all P>0.05). Furthermore, we detected no significant overall inconsistency between direct and indirect evidence. Conclusion: taTME has advantages over RTME and laTME, in terms of radical and surgical short-term outcomes in patients with rectal cancer.

Short-course radiotherapy combined with CAPOX and PD-1 inhibitor for the total neoadjuvant therapy of locally advanced rectal cancer: the preliminary single-center findings of a prospective, multicentre, randomized phase II trial (TORCH) / 中华胃肠外科杂志

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.

Diagnosis of advanced disease in cases of colorectal cancer in a developing country

Objectives Colorectal cancer (CRC) is the second leading cause of cancer death in the world, with survival correlated with the extension of the disease at diagnosis. In many low-/middle-income countries, the incidence of CRC is increasing rapidly, while decreasing rates are observed in high-income countries. We evaluated the anatomopathological profile of 390 patients diagnosed with CRC who underwent surgical resection, over a six-year period, in the state of Paraíba, northeastern Brazil. Results Adenocarcinomas accounted for 98% of the cases of primary colorectal tumors, and 53.8% occurred in female patients. The average age of the sample was 63.5 years, with 81.8% of individuals older than 50 years of age and 6.4% under 40 years of age. The most frequent location was the distal colon; pT3 status was found in 71% of patients, and pT4 status, in 14.4%. Angiolymphatic and lymph-node involvements were found in 48.7% and 46.9% of the cases respectively. Distant metastasis was observed in 9.2% of the patients. Advanced disease was diagnosed in almost half of the patients (48.1%). The women in the sample had poorly-differentiated adenocarcinomas (p=0.043). Patients under 60 years of age had a higher rate of lymph-node metastasis (p=0.044). Tumor budding was present in 27.2% of the cases, and it was associated with the female gender, themucinous histological type, and the depth of invasion (pT3 and pT4). Conclusions We conclude that the diagnosis of advanced disease in CRC is still a reality, with a high occurrence of aggressive prognostic factors, which results in a worse prognosis. (AU)

Predictive value of MRI pelvic measurements for "difficult pelvis" during total mesorectal excision / 中华胃肠外科杂志

Objective: Total mesorectal resection (TME) is difficult to perform for rectal cancer patients with anatomical confines of the pelvis or thick mesorectal fat. This study aimed to evaluate the ability of pelvic dimensions to predict the difficulty of TME, and establish a nomogram for predicting its difficulty. Methods: The inclusion criteria for this retrospective study were as follows: (1) tumor within 15 cm of the anal verge; (2) rectal cancer confirmed by preoperative pathological examination; (3) adequate preoperative MRI data; (4) depth of tumor invasion T1-4a; and (5) grade of surgical difficulty available. Patients who had undergone non-TME surgery were excluded. A total of 88 patients with rectal cancer who underwent TME between March 2019 and November 2021 were eligible for this study. The system for scaling difficulty was as follows: Grade I, easy procedure, no difficulties; Grade II, difficult procedure, but no impact on specimen quality (complete TME); Grade III, difficult procedure, with a slight impact on specimen quality (near-complete TME); Grade IV: very difficult procedure, with remarkable impact on specimen quality (incomplete TME). We classified Grades I-II as no surgical difficulty and grades III-IV as surgical difficulty. Pelvic parameters included pelvic inlet length, anteroposterior length of the mid-pelvis, pelvic outlet length, pubic tubercle height, sacral length, sacral depth, distance from the pubis to the pelvic floor, anterior pelvic depth, interspinous distance, and inter-tuberosity distance. Univariate and multivariate logistic regression analyses were performed to identify the factors associated with the difficulty of TME, and a nomogram predicting the difficulty of the procedure was established. Results: The study cohort comprised 88 patients, 30 (34.1%) of whom were classified as having undergone difficult procedures and 58 (65.9%) non-difficult procedures. The median age was 64 years (56-70), 51 patients were male and 64 received neoadjuvant therapy. The median pelvic inlet length, anteroposterior length of the mid-pelvis, pelvic outlet length, pubic tubercle height, sacral length, sacral depth, distance from the pubis to the pelvic floor, anterior pelvic depth, interspinous distance, and inter-tuberosity distance were 12.0 cm, 11.0 cm, 8.6 cm, 4.9 cm, 12.6 cm, 3.7 cm, 3.0 cm, 13.3 cm, 10.2 cm, and 12.2 cm, respectively. Multivariable analyses showed that preoperative chemoradiotherapy (OR=4.97,95% CI: 1.25-19.71, P=0.023), distance between the tumor and the anal verge (OR=1.31, 95% CI: 1.02-1.67, P=0.035) and pubic tubercle height (OR=3.36, 95% CI: 1.56-7.25, P=0.002) were associated with surgical difficulty. We then built and validated a predictive nomogram based on the above three variables (AUC = 0.795, 95%CI: 0.696-0.895). Conclusion: Our research demonstrated that our system for scaling surgical difficulty of TME is useful and practical. Preoperative chemoradiotherapy, distance between tumor and anal verge, and pubic tubercle height are risk factors for surgical difficulty. These data may aid surgeons in planning appropriate surgical procedures.

Standardization in performing regional lymph node dissection for rectum and sigmoid colon cancer / 中华胃肠外科杂志

Tumor spreading through the lymphatic drainage is an important metastatic pathway for rectum and sigmoid colon carcinoma. Regional lymph node dissection, as an important part of radical resection of colorectal cancer, is the main way for patients with colorectal cancer to achieve radical resection and acquire tumor-free survival. The regional lymph nodes of sigmoid cancer include paracolic lymph nodes, intermediate lymph nodes, and central lymph nodes locating at the root of blood vessel, and radical surgery should include lymph node dissection at the above three stations. The lymphatic pathways of metastasis for rectal cancer include longitudinal metastasis within the mesorectum and lateral metastasis beyond the mesorectum. The standard surgical method of rectal cancer is total mesorectal excision (TME) at present, and the resection range includes the metastatic lymph nodes within the mesorectum through the longitudinal pathway. However, there are many different opinions about lateral lymph node dissection(LLND) aiming at the metastatic lymph nodes locating at the lateral space of rectum. The range of lymph node dissection for rectum and sigmoid cancer is a vital factor that determines the prognosis of patients. Insufficient range of dissection can lead to residual metastatic lymph nodes and have serious impacts on the prognosis of patients. Excessive range of dissection can result in greater surgical trauma, prolonged operation time, more blood loss, and higher rate of complication without oncological benefits. Individualizating the appropriate resection range of rectum and sigmoid colon cancer on the basis of standardization and according to the clinical stage and invasion range of tumor demonstrates great significance of ensuring the radical operation, reducing trauma, promoting rehabilitation, protecting the function and improving the prognosis.

Safety and prognosis analysis of transanal total mesorectal excision versus laparoscopic mesorectal excision for mid-low rectal cancer / 中华胃肠外科杂志

Objective: To compare the short-term and long-term outcomes between transanal total mesorectal excision (taTME) and laparoscopic total mesorectal excision (laTME) for mid-to-low rectal cancer and to evaluate the learning curve of taTME. Methods: This study was a retrospective cohort study. Firstly, consecutive patients undergoing total mesorectal excision who were registered in the prospective established database of Division of Colorectal Diseases, Department of General Surgery, Peking Union Medical College Hospital during July 2014 to June 2020 were recruited. The enrolled patients were divided into taTME and laTME group. The demographic data, clinical characteristics, neoadjuvant treatment, intraoperative and postoperative complications, pathological results and follow-up data were extracted from the database. The primary endpoint was the incidence of anastomotic leakage and the secondary endpoints included the 3-year disease-free survival (DFS) and the 3-year local recurrence rate. Independent t-test for comparison between groups of normally distributed measures; skewed measures were expressed as M (range). Categorical variables were expressed as examples (%) and the χ(2) or Fisher exact probability was used for comparison between groups. When comparing the incidence of anastomotic leakage, 5 variables including sex, BMI, clinical stage evaluated by MRI, distance from tumor to anal margin evaluated by MRI, and whether receiving neoadjuvant treatment were balanced by propensity score matching (PSM) to adjust confounders. Kaplan-Meier curve and Log-rank test were used to compare the DFS of two groups. Cox proportional hazard model was used to analyze and determine the independent risk factors affecting the DFS of patients with mid-low rectal cancer. Secondly, the data of consecutive patients undergoing taTME performed by the same surgical team (the trananal procedures were performed by the same main surgeon) from February 2017 to March 2021 were separately extracted and analyzed. The multidimensional cumulative sum (CUSUM) control chart was used to draw the learning curve of taTME. The outcomes of 'mature' taTME cases through learning curve were compared with laTME cases and the independent risk factors of DFS of 'mature' cases were also analyzed. Results: Two hundred and forty-three patients were eventually enrolled, including 182 undergoing laTME and 61 undergoing taTME. After PSM, both fifty-two patients were in laTME group and taTME group respectively, and patients of these two groups had comparable characteristics in sex, age, BMI, clinical tumor stage, distance from tumor to anal margin by MRI, mesorectal fasciae (MRF) and extramural vascular invasion (EMVI) by MRI and proportion of receiving neoadjuvant treatment. After PSM, as compared to laTME group, taTME group showed significantly longer operation time [(198.4±58.3) min vs. (147.9±47.3) min, t=-4.321, P<0.001], higher ratio of blood loss >100 ml during surgery [17.3% (9/52) vs. 0, P=0.003], higher incidence of anastomotic leakage [26.9% (14/52) vs. 3.8% (2/52), χ(2)=10.636, P=0.001] and higher morbidity of overall postoperative complications [55.8%(29/52) vs. 19.2% (10/52), χ(2)=14.810, P<0.001]. Total harvested lymph nodes and circumferential resection margin involvement were comparable between two groups (both P>0.05). The median follow-up for the whole group was 24 (1 to 72) months, with 4 cases lost, giving a follow-up rate of 98.4% (239/243). The laTME group had significantly better 3-year DFS than taTME group (83.9% vs. 73.0%, P=0.019), while the 3-year local recurrence rate was similar in two groups (1.7% vs. 3.6%, P=0.420). Multivariate analysis showed that and taTME surgery (HR=3.202, 95%CI: 1.592-6.441, P=0.001) the postoperative pathological staging of UICC stage II (HR=13.862, 95%CI:1.810-106.150, P=0.011), stage III (HR=8.705, 95%CI: 1.104-68.670, P=0.040) were independent risk factors for 3-year DFS. Analysis of taTME learning curve revealed that surgeons would cross over the learning stage after performing 28 cases. To compare the two groups excluding the cases within the learning stage, there was no significant difference between two groups after PSM no matter in the incidence of anastomotic leakage [taTME: 6.7%(1/15); laTME: 5.3% (2/38), P=1.000] or overall complications [taTME: 33.3%(5/15), laTME: 26.3%(10/38), P=0.737]. The taTME was still an independent risk factor of 3-year DFS only analyzing patients crossing over the learning stage (HR=5.351, 95%CI:1.666-17.192, P=0.005), and whether crossing over the learning stage was not the independent risk factor of 3-year DFS for mid-low rectal cancer patients undergoing taTME (HR=0.954, 95%CI:0.227-4.017, P=0.949). Conclusions: Compared with conventional laTME, taTME may increase the risk of anastomotic leakage and compromise the oncological outcomes. Performing taTME within the learning stage may significantly increase the risk of postoperative anastomotic leakage.

Robotic surgery in rectal cancer* / Cirurgia robótica no cancro do reto

Abstract Rectal cancer is an important cause of morbidity and mortality worldwide. The most effective and curative treatment is surgery, and the standard procedure is total mesorectal excision, initially performed by open surgery and posteriorly by minimally invasive techniques. Robotic surgery is an emerging technology that is expected to overcome the limitations of the laparoscopic approach. It has several advantages, including a stable camera platform with high definition three-dimensional image, flexible instrumentswith seven degrees of freedom, a third arm for fixed retraction, fine motion scaling, excellent dexterity, ambidextrous capability, elimination of physiological tremors and better ergonomics, that facilitate a steady and precise tissue dissection. The main technical disadvantages are the loss of tactile sensation and tensile feedback and the complex installation process. The aim of the present study is to review the importance and benefits of robotic surgery in rectal cancer, particularly in comparison with the laparoscopic approach. Intraoperative estimated blood loss, short and long-term outcomes as well as pathological outcomes were similar between robotic and laparoscopic surgery. The operative time is usually longer in robotic surgery and the high costs are still itsmajor drawback. Robotic surgery for rectal cancer demonstrated lower conversion rate to open surgery and benefits in urinary and sexual functions and has been established as a safe and feasible technique.

Resumo O cancro do reto é uma importante causa de morbidade e mortalidade em todo o mundo. O único tratamento curativo e mais eficaz é a cirurgia, sendo que o procedimento padrão é a excisão total do mesoreto, inicialmente realizada por cirurgia aberta e mais tarde por técnicas minimamente invasivas. A cirurgia robótica é uma tecnologia emergente que pretende ultrapassar as limitações da laparoscopia. As vantagens incluem plataforma de câmera estável, imagem tridimensional com alta definição, instrumentos flexíveis com sete graus de liberdade, terceiro braço para retração fixa, movimentos finos, excelente destreza, ambidestria, eliminação do tremor fisiológico e maior conforto ergonômico, que facilitam uma disseção firme e precisa dos tecidos. As principais desvantagens técnicas são a perda da sensação táctil e feedback tensional e o complexo processo de instalação. O objetivo deste estudo é fazer uma revisão bibliográfica da importância e dos benefícios da cirurgia robótica no cancro do reto, particularmente em comparação coma cirurgia laparoscópica. A perda estimada de sangue intraoperatória, os outcomes a curto e longo-prazo e os outcomes patológicos foram equivalentes entre a cirurgia robótica e laparoscópica. O tempo operatório é geralmente mais longo na cirurgia robótica e os elevados custos são a sua principal desvantagem. A cirurgia robótica no cancro do reto demonstrou menor taxa de conversão para cirurgia aberta e benefícios nas funções urinária e sexual e está estabelecida como uma técnica segura e viável.

Establishment and clinical application value of an automatic diagnosis platform for rectal cancer T-staging based on a deep neural network / 中华医学杂志(英文版)

BACKGROUND@#Colorectal cancer is harmful to the patient's life. The treatment of patients is determined by accurate preoperative staging. Magnetic resonance imaging (MRI) played an important role in the preoperative examination of patients with rectal cancer, and artificial intelligence (AI) in the learning of images made significant achievements in recent years. Introducing AI into MRI recognition, a stable platform for image recognition and judgment can be established in a short period. This study aimed to establish an automatic diagnostic platform for predicting preoperative T staging of rectal cancer through a deep neural network.@*METHODS@#A total of 183 rectal cancer patients' data were collected retrospectively as research objects. Faster region-based convolutional neural networks (Faster R-CNN) were used to build the platform. And the platform was evaluated according to the receiver operating characteristic (ROC) curve.@*RESULTS@#An automatic diagnosis platform for T staging of rectal cancer was established through the study of MRI. The areas under the ROC curve (AUC) were 0.99 in the horizontal plane, 0.97 in the sagittal plane, and 0.98 in the coronal plane. In the horizontal plane, the AUC of T1 stage was 1, AUC of T2 stage was 1, AUC of T3 stage was 1, AUC of T4 stage was 1. In the coronal plane, AUC of T1 stage was 0.96, AUC of T2 stage was 0.97, AUC of T3 stage was 0.97, AUC of T4 stage was 0.97. In the sagittal plane, AUC of T1 stage was 0.95, AUC of T2 stage was 0.99, AUC of T3 stage was 0.96, and AUC of T4 stage was 1.00.@*CONCLUSION@#Faster R-CNN AI might be an effective and objective method to build the platform for predicting rectal cancer T-staging.@*TRIAL REGISTRATION@#chictr.org.cn: ChiCTR1900023575; http://www.chictr.org.cn/showproj.aspx?proj=39665.

Impact of neoadjuvant chemoradiotherapy on the local recurrence and distant metastasis pattern of locally advanced rectal cancer: a propensity score-matched analysis / 中华医学杂志(英文版)

BACKGROUND@#Previous studies have demonstrated different predominant sites of distant metastasis between patients with and without neoadjuvant chemoradiotherapy (NCRT). This study aimed to explore whether NCRT could influence the metastasis pattern of rectal cancer through a propensity score-matched analysis.@*METHODS@#In total, 1296 patients with NCRT or post-operative chemoradiotherapy (PCRT) were enrolled in this study between January 2008 and December 2015. Propensity score matching was used to correct for differences in baseline characteristics between the two groups. After propensity score matching, the metastasis pattern, including metastasis sites and timing, was compared and analyzed.@*RESULTS@#After propensity score matching, there were 408 patients in the PCRT group and 245 patients in the NCRT group. NCRT significantly reduced local recurrence (4.1% vs. 10.3%, P = 0.004), but not distant metastases (28.2% vs. 27.9%, P = 0.924) compared with PCRT. In both the NCRT and PCRT groups, the most common metastasis site was the lung, followed by the liver. The NCRT group developed local recurrence and distant metastases later than the PCRT group (median time: 29.2 [18.8, 52.0] months vs. 18.7 [13.3, 30.0] months, Z = -2.342, P = 0.019; and 21.2 [12.2, 33.8] vs. 16.4 [9.3, 27.9] months, Z = -1.765, P = 0.035, respectively). The distant metastases occurred mainly in the 2nd year after surgery in both the PCRT group (39/114, 34.2%) and NCRT group (21/69, 30.4%). However, 20.3% (14/69) of the distant metastases appeared in the 3rd year in the NCRT group, while this number was only 13.2% (15/114) in the PCRT group.@*CONCLUSIONS@#The predominant site of distant metastases was the lung, followed by the liver, for both the NCRT group and PCRT group. NCRT did not influence the predominant site of distant metastases, but the NCRT group developed local recurrence and distant metastases later than the PCRT group. The follow-up strategy for patients with NCRT should be adjusted and a longer intensive follow-up is needed.

Sobrevida de pacientes com câncer colorretal em um Cancer Center / Survival of patients with colorectal cancer in a cancer center

ABSTRACT BACKGROUND: Hospital-based studies recently have shown increases in colorectal cancer survival, and better survival for women, young people, and patients diagnosed at an early disease stage. OBJECTIVE: To describe the overall survival and analyze the prognostic factors of patients treated for colorectal cancer at an oncology center. METHODS: The analysis included patients diagnosed with colon and rectal adenocarcinoma between 2000 and 2013 and identified in the Hospital Cancer Registry at A.C.Camargo Cancer Center. Overall 5-year survival was estimated using the Kaplan-Meier method, and prognostic factors were evaluated in a Cox regression model. Hazard ratios (HR) are reported with 95% confidence intervals (CI). RESULTS: Of 2,279 colorectal cancer cases analyzed, 58.4% were in the colon. The 5-year overall survival rate for colorectal cancer patients was 63.5% (65.6% and 60.6% for colonic and rectal malignancies, respectively). The risk of death was elevated for patients in the 50-74-year (HR=1.24, 95%CI =1.02-1.51) and ≥75-year (HR=3.02, 95%CI =2.42-3.78) age groups, for patients with rectal cancer (HR=1.37, 95%CI =1.11-1.69) and for those whose treatment was started >60 days after diagnosis (HR=1.22, 95%CI =1.04-1.43). The risk decreased for patients diagnosed in recent time periods (2005-2009 HR=0.76, 95%CI =0.63-0.91; 2010-2013 HR=0.69, 95%CI =0.57-0.83). CONCLUSION: Better survival of patients with colorectal cancer improves with early stage and started treatment within 60 days of diagnosis. Age over 70 years old was an independent factor predictive of a poor prognosis. The overall survival increased to all patients treated in the period 2000-2004 to 2010-2013.

RESUMO CONTEXTO: Estudos hospitalares recentes têm demonstrado aumento da sobrevida do câncer colorretal e melhor sobrevida para mulheres, jovens e pacientes diagnosticados em estágio precoce da doença. OBJETIVO: Descrever a sobrevida global e analisar os fatores prognósticos de pacientes tratados para câncer colorretal em um centro de oncologia. MÉTODOS: Foram incluídos pacientes com diagnóstico de adenocarcinoma de cólon e reto entre 2000 e 2013, identificados no Registro Hospitalar de Câncer do A.C.Camargo Cancer Center. A sobrevida global aos 5 anos foi estimada pelo método de Kaplan-Meier e os fatores prognósticos foram avaliados pelo modelo de Cox. As razões de risco (HR) são relatadas com intervalos de confiança (IC) de 95%. RESULTADOS: Dos 2.279 casos de câncer colorretal analisados, 58,4% eram de cólon. A taxa de sobrevida global aos 5 anos para pacientes com câncer colorretal foi de 63,5% (65,6% e 60,6% para câncer de cólon e retal, respectivamente). O risco de óbito foi elevado para pacientes na faixa etária de 50-74 anos (HR=1,24; IC95% =1,02-1,51) e ≥75 anos (HR=3,02; IC95% =2,42-3,78), para pacientes com câncer retal (HR=1,37; IC95% =1,11-1,69) e para aqueles cujo tratamento foi iniciado >60 dias após o diagnóstico (HR=1,22; IC95% =1,04-1,43). O risco diminuiu para pacientes diagnosticados em períodos recentes (2005-2009 HR=0,76; IC95% =0,63-0,91; 2010-2013 HR=0,69; IC95% =0,57-0,83). CONCLUSÃO: A sobrevida dos pacientes com câncer colorretal é maior naqueles em estágio inicial e com início do tratamento antes dos 60 dias.. Idade acima de 70 anos foi fator independente preditivo de mau prognóstico. A sobrevida global aumentou para todos os pacientes tratados no período de 2000-2004 a 2010-2013.

Adjuvant chemotherapy in locally advanced rectal cancer: deciding on the optimal strategy

ABSTRACT Background: Neoadjuvant therapy, followed by surgery, reduces the risk of local relapse in rectal cancer, but approximately 30% will relapse with distant metastases, highlighting the importance of adjuvant chemotherapy (aCT). Objective: The objective of the study was to study two regimens of adjuvant treatment in patients with locally advanced rectal cancer and analyze their efficacy and toxicity. Methods: Between January 2009 and December 2016, 193 patients with Stage II-III rectal cancer who had received neoadjuvant therapy were included by consecutive non-probability sampling. The decision to administer aCT, as well as the specific regimen, was at the discretion of the medical oncologist. Disease-free survival (DFS) and overall survival (OS) were calculated. Results: The mean DFS was 84.85 (95% confidence interval [CI]: 79-90) months in 164 patients receiving aCT, compared to 57.71 (95% CI: 40-74) months in 29 who did not receive aCT (p < 0.001). Then, mean OS was 92.7 (95% CI: 88-97) months and 66.18 (95% CI 51-81) months, respectively (p < 0.001). DFS was 83.6 (95% CI: 76-91) months in 74 patients receiving adjuvant 5-fluorouracil (5-FU), and 82.9 (95% CI: 75-90) months in 90 receiving 5-FU plus oxaliplatin (p = 0.49). OS was 87 (95% CI: 80-94) versus 93.65 (95% CI: 88-99) months, respectively (p = 0.76). The multivariate analysis identified aCT hazard ratio (HR) 0.30 (95% CI: 0.1-0.46), perineural invasion HR 3.36 (95% CI: 1.7-6.5), and pathological complete response HR 0.10 (95% CI; 0.01-0.75) as independent markers of DFS. Conclusions: In our study, aCT was associated with longer DFS and OS. 5-FU plus oxaliplatin showed greater toxicity with no added benefit in DFS or OS.

Tumor Budding en cáncer rectal. Relación entre la densidad de los brotes tumorales y otros factores pronósticos / Budding tumor in rectal cancer. Relationship between tumor outbreak density and other prognostic factors

Introducción: El budding tumor (BT) es la presencia de células tumorales aisladas o en pequeños grupos situadas en el frente de invasión del tumor. Su hallazgo en alto grado es un factor de mal pronóstico independiente del cáncer colorrectal. El objetivo de este trabajo es determinar si el grado de BT está asociado con otros factores pronósticos del cáncer rectal. Material y métodos: Se incluyen las resecciones oncológicas de recto en el período 2013-2017. Los casos se agruparon según la densidad en la formación de los BT en 3 grupos, los de grado bajo, intermedio y alto. Se utilizó como valor estadístico el cálculo del odds ratio (OR). Resultados: Se analizaron las piezas de resección de 27 pacientes (15 mujeres y 12 hombres) con una media de edad de 68,4 años (40-86). Se calculó el OR para invasión ganglionar, vascular y recidiva en función del grado de budding tumoral. Discusión: Se observó una tendencia a la presencia de factores histológicos de mal pronóstico en relación al budding de alto grado, si bien el bajo número de casos no permitió demostrarlo en este estudio. Conclusiones: El análisis del grado de tumor budding es reproducible y podría ayudar a identificar pacientes con cáncer rectal de peor pronóstico. (AU)

Introduction: Tumor budding (BT) is defined as isolated or small groups of neoplastic cells located at the invasive front of the tumor. High-grade BT is a poor prognostic factor in colorectal cancer. Objective: To determine if the degree of BT is associated with other prognostic factors in rectal cancer. Materials and methods: Rectal oncological resections during the 2013-2017 period were included. Cases were stratified according to the density in the formation of BT in 3 groups: low, intermediate and high. The calculation of the odds ratio (OR) was used as a statistical value. Results: The resection specimens of 27 patients (15 women and 12 men) with a mean age of 68.4 years (40-86) were analyzed. OR for node metastases, vascular invasion and relapse was calculated according to tumor budding grade. Discussion: High-grade tumor budding seems to associate with the presence of poor prognostic factors. However, it was not possible to demonstrate it because of the small sample size. Conclusions: Tumor budding is a reproducible marker and could help to identify rectal cancer patients with a worse prognosis. (AU)

Tumores ano-rectales del músculo liso / Smooth muscle ano-rectal tumors

Introducción: Los tumores ano-rectales del musculo liso son raros, la relación respecto de los de recto es de 0.1%, presentándose con un rango entre 40-70 años. El objetivo es analizar una serie de pacientes, el tratamiento empleado y actualización bibliográfica. Material y Método: Sobre una base de datos retrospectiva entre enero de 1983 y diciembre de 2018, sobre 421 pacientes operados por cáncer recto-anal, fueron extraídos 6 que correspondieron a tumores del musculo liso. Resultados: Correspondieron al sexo femenino 4, con edades entre 49 y 75 años (57.5 años); 4 de localización rectal, de ellos 3 fueron leiomiosarcoma, y 2 anales (leiomioma). En 2 se obtuvo diagnostico preoperatorio de certeza por punción mediante Tru-Cut. De 3 pacientes con leiomiosarcoma, a 2 se les realizo cirugía radical y al restante biopsia. Los 2 resecados recidivaron a los 6 meses y al año. Los 3 fallecieron entre los 2 y 16 meses por progresión de la enfermedad. La paciente con diagnóstico de leiomioma rectal, operada mediante cirugía radical, se encuentra sin recidiva a 18 meses. Los 2 pacientes resecados localmente por leiomioma de ano, presentaron en el postoperatorio absceso y fistula extraesfinteriana, uno de ellos con incontinencia severa. Ambos fueron re-operados y se encuentran asintomáticos, libres de recidiva a los 36 y 60 meses. Discusión: Los tumores del músculo liso ano-rectal son infrecuentes y presentan síntomas inespecíficos. La biopsia preoperatoria es imperiosa a fin de establecer una adecuada estrategia quirúrgica. Los malignos tienen alto índice de recidiva y mortalidad. (AU)

Introduction: Smooth muscle ano-rectal tumors are rare; the relation with respect to the rectum is 0.1%, in a patient's age range between 40-70 years. The objective is the analysis of a series of patients, the treatment used and bibliographic update. Material and method: On a retrospective, database between January 1983 and December 2018. About 421 patients operated for rectum-anal cancer, of which 6 corresponded to smooth muscle tumors. Results: Four were female, with ages between 49 and 75 years (57.5 years average); 4 were of rectal location, of which 3 were leiomyosarcoma, and 2 anal (leiomyoma). In two, a preoperative diagnosis of certainty was obtained by Tru-Cut. Two out of 3 patients with leiomyosarcoma, underwent radical surgery and the remaining one a biopsy. The two resected relapsed at 6 months and at one year. All 3 died between 2 and 16 months due to disease progression. The patient diagnosed with rectal leiomyoma, operated by radical surgery, is without recurrence at 18 months. The 2 patients resected locally for anus leiomyoma showed abscess and extrasphincteric fistula in the postoperative period, one of them with severe incontinence. Both were re-operated and are asymptomatic, free of recurrence at 36 and 60 months. Discussion: Ano-rectal smooth muscle tumors are uncommon and have nonspecific symptoms. Preoperative biopsy is imperative in order to establish an appropriate surgical strategy. Malignant tumors have a high rate of recurrence and mortality. (AU)

Opciones terapéuticas en el cáncer de recto inferior. Actualización / Therapeutic options in lower rectal cancer. Upgrade

Motiva esta presentación el hecho que desde el Relato "Opciones terapéuticas del Cáncer de Recto Inferior" en el año 2008 han pasado 10 años y por supuesto aparecieron algunos progresos y cambios. Se conoce gran heterogeneidad genética debido que puede desarrollarse por diferentes vías. Nuevos fármacos han aparecido para lograr terapia eficiente. La clasificación clínica TNM fue actualizada en el año 2018. Los métodos de diagnóstico siguen teniendo vigencia. La resección local endoanal se presenta como una conducta factible con resultados favorables debido al progreso instrumental. Combinado con R/T y Q mostró excelentes resultados ("Watch and Wait"). La escisión total de mesorecto sigue ocupando un lugar importante. En la amputación abdomino perineal debemos incluir la resección de ambos músculos elevadores del ano. La cirugía laparoscópica ocupa cada vez más lugar siendo tan segura como la convencional. Se adjuntan los algoritmos terapéuticos. Continuarán las investigaciones para mejorar los resultados. (AU)

The aim of this presentation is to update the one written in 2008 "Low rectal cancer therapeutic options" since some progress and changes have appeared after ten years. Great genetic heterogeneity is known because it can develop in different pathways. New drugs have appeared to achieve efficient therapy. The TNM clinical classification was updated in 2018. The diagnosis methods are still in effect. Endoanal local resection is presented as feasible behavior with favorable results due to instrumental progress. Combined with R/T and Ch showed excellent results (Watch and Wait). The total mesorectal continues to occupy an important place. The resection of both elevator muscles of anus must be included in the abdominoperineal amputation. Laparoscopic surgery is increasingly in place, being as safe as the conventional. Therapeutic algorithms are attached. Research will continue to improve results. (AU)