Are the width, length, depth, and area of submucosal invasion predictive of lymph node metastasis in pT1 colorectal cancer?

PURPOSE: Submucosa-limited (pathological T1, pT1) colorectal cancers (CRCs) pose a continuing challenge in the choice of treatment options, which range from local excision to radical surgery. The aim of this study was to evaluate the morphometric and morphologic risk factors associated with regional lymph node metastasis (LNM) in pT1 CRC. METHODS: We performed a histological review of patients who underwent oncological resection between 2016 and 2022. Tumor grade, budding, poorly differentiated clusters (PDCs), cancer gland rupture, lymphovascular invasion (LVI), and presence of deep submucosal invasion (DSI), as well as width, length, total area, and area of DSI, were evaluated as potential risk factors for LNM. RESULTS: A total of 264 cases of colon and rectal carcinomas with invasion into the submucosal layer (pT1) were identified. LNM was found in 46 of the 264 cases (17.4%). All morphometric parameters, as well as DSI (P=0.330), showed no significant association with LNM. High grade adenocarcinoma (P=0.050), budding (P=0.056), and PDCs (P<0.001) were associated with LNM. In the multivariate analysis, LVI presence remained the only significant independent risk factor (odds ratio, 15.7; 95% confidence interval, 8.5-94.9; P<0.001). CONCLUSION: The DSI of T1 CRC, as well as other morphometric parameters of submucosal tumor spread, held no predictive value in terms of LNM. LVI was the only independent risk factor of LNM.

Total neoadjuvant therapy in rectal cancer: a network meta-analysis of randomized trials.

PURPOSE: To assess the efficacy of total neoadjuvant therapy (TNT) for rectal carcinoma in comparison with conventional chemoradiotherapy (CRT). METHODS: A systematic review was performed according to the PRISMA guidelines. A Bayesian network meta-analysis was done using NetMetaXL and WinBUGS. This study was registered in PROSPERO on March 3, 2022 (No. CRD-42022307867). RESULTS: Outcomes of 2,719 patients from 10 randomized trials between 2010 and 2022 were selected. Of these 1,191 (44%) had conventional long-course CRT (50-54 Gy) and capecitabine, 506 (18%) had induction chemotherapy followed by CRT (50-54 Gy) and capecitabine (iTNT), 230 (9%) had long-course CRT (50-54 Gy) followed by consolidation chemotherapy (cTNT), and 792 (29%) undergone modified short-course radiotherapy (25 Gy) with subsequent chemotherapy (mTNT). Total pathologic complete response (pCR) was 20% in the iTNT group, 21% in the mTNT group, 22% in the cTNT group, and 12% in the CRT group. Statistically significant difference in pCR rates was detected when comparing iTNT with CRT (odds ratio [OR], 1.76; 95% credible interval [CrI], 1.06-2.8), mTNT with CRT (OR, 1.90; 95% CrI, 1.25-2.74), and cTNT with CRT groups (OR, 2.54; 95% CrI, 1.26-5.08). No differences were found in R0 resection rates. No significant difference was found in long-term outcomes. CONCLUSION: The early administration of systemic chemotherapy in the TNT regimen has improved short-term outcomes, though long-term results are underreported. Randomized trials with survival as the endpoint are necessary to evaluate the possible advantages of TNT modes.

Does transanal endoscopic microsurgery affect rectal function?

PURPOSE: Transanal endoscopic microsurgery (TEM) is the most standardized method for the local excision of rectal neoplasms. Unfortunately, local excisions of rectal lesions by means of TEM are not completely free from undesirable functional sequela. This study was performed to evaluate the risk factors of major loss of function after TEM. METHODS: Eighty-nine patients underwent TEM between 2019 and 2020. Anorectal manometry was performed before the surgery and 3, 6, and 12 months after the surgery. The quality of life (QoL) was assessed using the Fecal Incontinence Quality of Life scale. RESULTS: The major decrease in QoL was observed in women in 3 months after the surgery in terms of lifestyle and frustration domains (3.6 and 3.64 points, respectively). In 3 months after the surgery, there was a significant decrease in resting pressure both in male and female patients (P=0.01). This difference remained significant 6 months after the surgery (P=0.01). In 12 months after the surgery, resting pressure returned to the preoperative level in most patients (P=0.50). A significant decrease in manometric parameters appeared when the surgery time is more than 55 minutes (P=0.05), the tumor localization is lower than 3 cm from the anus (P=0.03), and the tumor size is over 3 cm (P=0.001). CONCLUSION: The most significant risk factors for the development of functional disorders after TEM are surgery time of >55 minutes, tumor localization at <3 cm from the anal verge, and tumor size of >3 cm.

Intraoperative fluorescence angiography as an independent factor of anastomotic leakage and a nomogram for predicting leak for colorectal anastomoses.

PURPOSE: Colorectal anastomotic leakage (AL) is a life-threatening complication, which increases morbidity, hospital stay and cost of treatment. The aim of this study is to identify risk factors, including intraoperative indocyanine green fluorescence angiography (ICG FA), associated with the leak of stapled colorectal anastomosis. METHODS: Four hundred twenty-nine consecutive patients underwent surgery between 2017 and 2019 for benign (n=10, 2.3%) or malignant (n=419, 97.7%) and rectal (n=349, 81.4%) or distal sigmoid (n=80, 18.6%) lesions with double-stapling technique reconstruction were included into retrospective study. Univariate analysis and multivariate logistic regression of the tumor-, patient- and treatment-related risk factors of AL was performed. RESULTS: An AL developed in 52 patients (12.1%). In multivariate analysis following variables were independently associated with AL; male sex (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.9-7.7; P<0.01), anastomosis at ≤6.5 cm from anal verge (OR, 3.1; 95% CI, 1.3-7.5; P=0.01), and age of ≤62.5 years (OR, 2.1; 95% CI, 1.1-4.1; P=0.03). ICG FA was found as independent factor reducing colorectal AL rate (OR, 0.4; 95% CI, 0.2-0.8; P=0.02). A nomogram with high discriminative ability (concordance index, 0.81) was created. CONCLUSION: ICG FA is a modifiable surgery-related risk factor associated with a decrease of colorectal AL rate. A suggested nomogram, which takes into consideration ICG FA, might be helpful to identify the individual risk of AL.

Evaluation of Colon-Specific Plasma Nanovesicles as New Markers of Colorectal Cancer.

PURPOSE: Developing new and efficient approaches for the early diagnosis of colorectal cancer (CRC) is an important issue. Circulating extracellular nanovesicles (ENVs) present a promising class of cancer markers. Cells of well-differentiated adenocarcinomas retain the molecular characteristics of colon epithelial cells, and the ENVs secreted by these cells may have colon-specific surface markers. We hypothesize that an increase in the number of ENVs carrying colon-specific markers could serve as a diagnostic criterion for colorectal cancer. EXPERIMENTAL DESIGN: Potential colon-specific markers were selected based on tissue-specific expression profile and cell surface membrane localization data. Plasma was collected from CRC patients (n = 48) and healthy donors (n = 50). The total population of ENVs was isolated with a two-phase polymer system. ENVs derived from colon epithelium cells were isolated using immune-beads with antibodies to colon-specific markers prior to labelling with antibodies against exosomal tetraspanins (CD63 and CD9) and quantification by flow cytometry. RESULTS: The number of ENVs positive for single colon cancer markers was found to be significantly higher in the plasma of CRC patients compared with healthy donors. The efficacy of detection depends on the method of ENV labelling. The diagnostic efficacy was estimated by ROC analysis (the AUC varied between 0.71 and 0.79). The multiplexed isolation of colon-derived ENVs using immune-beads decorated with antibodies against five markers allowed for a further increase in the diagnostic potency of the method (AUC = 0.82). CONCLUSIONS: ENVs derived from colon epithelium may serve as markers of differentiated CRC (adenocarcinomas). The composition of ligands used for capturing colon-derived ENVs and their method of labelling are critical for the efficacy of this proposed diagnostic approach.

Transanal reinforcement of low rectal anastomosis versus protective ileostomy after total mesorectal excision for rectal cancer. Preliminary results of a randomized clinical trial.

AIM: The study aimed to show if transanal reinforcement of the suture line can prevent anastomotic leakage (AL) after rectal cancer surgery, thus avoiding the need for a covering ileostomy. METHODS: This is a prospective, multicentre, parallel-arm randomized controlled equivalence trial. After standard total mesorectal excision, patients with anastomotic line at 1-3 cm from the dentate line were randomized to have transanal suture reinforcement (TAR group) or protective ileostomy (PI group). RESULTS: Twenty-nine patients had PI, 25 had TAR. The two groups were comparable both for baseline characteristics and intra-operative aspects. Clinically evident AL occurred in four (16%) and five (17.24%) patients of the TAR and PI group, respectively, resulting in a difference of -1.20% (90% CI -17.93, 15.45), while subclinical AL at proctography was absent in 15 (65.22%) and 13 (50%) patients of the TAR and PI groups, respectively, resulting in a difference of 15% (90% CI -7.74 to 38.17). CONCLUSION: Preliminary data suggest that transanal reinforcement of the suture line performed in rectal cancer patients with suture line at 1-3 cm from the dentate line carries a similar (even if not equivalent) AL rate to covering ileostomy, suggesting that a covering ileostomy could be avoided in this selected group of patients. This indication needs to be addressed with future larger trials (clinicaltrials.gov ID number NCT02279771).

Impact of oral antibiotic prophylaxis on surgical site infection after rectal surgery: results of randomized trial.

AIM: To evaluate the impact of oral antibiotic prophylaxis on surgical site infection (SSI) rate after rectal surgery. METHODS: It was a single-center 1:1 randomized controlled open parallel trial (registration number NCT03436719). The patients undergoing rectal resection for benign and malignant tumors were assigned randomly to two groups: the oral plus intravenous (IV) antibiotic prophylaxis (AP) and the IV antibiotic prophylaxis only. The primary endpoint was the overall rate of SSI. RESULTS: Between November 2017 and December 2018, 116 (male-55, the mean age-64 years) patients were enrolled into the trial. Of them, 57 had oral erythromycin 500 mg + metronidazole 500 mg a day before surgery and 1,000 mg of cephalosporin IV 30-90 min before operation. In the other group, 59 patients had the same IV antibiotics only. The incidence of SSIs was 22% (13/59) and 3.5% (2/57) correspondingly (р = 0.002). The statistically significant difference was detected for superficial SSI 0 (0%) vs. 5 (8.5%) (p = 0.03) and organ/space SSI 2 (3.5%) vs. 9 (15.3%) (p = 0.03), respectively. A multivariate analysis of risk factors of SSI identified two independent ones: bacterial contamination of the pelvic cavity ≥ 105 CFU at the end of surgery OR 17.9, 95% CI 2.1-150.0 (p = 0.008) and oral antimicrobial prophylaxis OR 0.2, 95% CI 0.03-0.8 (p = 0.02). CONCLUSION: Oral-parenteral AP significantly reduced the risk of SSI following elective rectal surgery. Bacterial contamination of the pelvic cavity ≥ 105 CFU at the end of surgery and oral antimicrobial prophylaxis were independent risk factors of SSI.

Intraoperative use of fluorescence with indocyanine green reduces anastomotic leak rates in rectal cancer surgery: an individual participant data analysis.

BACKGROUND: Fluorescence imaging by means of Indocyanine green (ICG) has been applied to intraoperatively determine the perfusion of the anastomosis. The purpose of this Individual Participant Database meta-analysis was to assess the effectiveness in decreasing the incidence of anastomotic leak (AL) after rectal cancer surgery. METHODS: We searched PubMed, Embase, Cochrane Library and ClinicalTrial.gov, EU Clinical Trials and ISRCTN registries on September 1st, 2019. We considered eligible those studies comparing the assessment of anastomotic perfusion during rectal cancer surgery by intraoperative use of ICG fluorescence compared with standard practice. We defined as primary outcome the incidence of AL at 30 days after surgery. The studies were assessed for quality by means of the ROBINS-I and the Cochrane risk tools. We calculated odds ratios (ORs) using the Individual patient data analysis, restricted to rectal lesions, according to original treatment allocation. RESULTS: The review of the literature and international registries produced 15 published studies and 5 ongoing trials, for 9 of which the authors accepted to share individual participant data. 314 patients from two randomized trials, 452 from three prospective series and 564 from 4 non-randomized studies were included. Fluorescence imaging significantly reduced the incidence of AL (OR 0.341; 95% CI 0.220-0.530; p < 0.001), independent of age, gender, BMI, tumour and anastomotic distance from the anal verge and neoadjuvant therapy. Also, overall morbidity and reintervention rate were positively influenced by the use of ICG. CONCLUSIONS: The incidence of AL may be reduced when ICG fluorescence imaging is used to assess the perfusion of a colorectal anastomosis. Limitations relate to the consistent number of non-randomized studies included and their heterogeneity in defining and assessing AL. Ongoing large randomized studies will help to determine the exact role of routine ICG fluorescence imaging may decrease the incidence of AL in surgery for rectal cancer.

Risk factors and inflammatory predictors for Anastomotic Leakage following Total Mesorectal Excision with defunctioning stoma.

BACKGROUND: This study aims to examine the factors involved in anastomotic leak (AL) following low anterior resection and total mesorectal excision (LAR-TME) and to determine the usefulness of early measurement of the inflammatory biomarkers C-Reactive Protein (CRP) and Procalcitonin (PCT). METHODS: One hundred patients undergoing LAR-TME with a proximal diverting stoma were analyzed between 2013 and 2016. Postoperative CRP and PCT levels were measured on the 3rd and the 6th postoperative days. RESULTS: There were 11 clinical leaks with a negative impact in univariate analysis on AL of male gender, larger and stenotic tumours, intraoperative blood loss > 200 mL, the need for perioperative blood transfusion, postoperative anaemia and an operating time exceeding 180 minutes. On multivariate analysis, only perioperative blood transfusion was an independent AL risk factor. Recorded CRP was higher in AL patients when compared with non-AL cases on both the 3rd postoperative day (152.4 mg/L vs. 93 mg/L, respectively; P < 0.0001) and the 6th postoperative day (130.5 mg/L vs. 68.2 mg/L; P < 0.0001). The PCT levels also significantly differed between AL and non-AL cases on the 3rd postoperative day (0.5 ng/mL vs. 0.2 ng/mL, respectively; P < 0.0001) and the 6th postoperative day (1.16 ng/mL vs. 0.1 ng/mL, respectively; P < 0.0001). Both CRP and PCT showed high negative predictive values (NPV) for the diagnosis of an AL on both postoperative days. CONCLUSION: Following low restorative proctectomy, the high NPV of CRP and PCT measurements for the diagnosis of anastomotic leaks may assist decision-making for early hospital discharge.