Total neoadjuvant therapy for locally advanced rectal cancer: a three-group propensity score matched study.

PURPOSE: Total neoadjuvant therapy (TNT) has emerged as a therapeutic approach for locally advanced rectal cancer (LARC). However, the optimal chemotherapy cycles within TNT remain uncertain. This study aimed to evaluate and compare the prognostic efficacy of varying cycles of chemotherapy during TNT for LARC. METHODS: Patients diagnosed with LARC (T3-4N0M0/T1-4N1-2M0), who underwent TNT or chemoradiotherapy followed by total mesorectal excision (TME) between 2015 and 2020, were retrospective included. Patients were categorized into three groups based on their neoadjuvant strategy: CRT (long-course chemoradiotherapy), STNT (long-course CRT with one to three cycles of chemotherapy), and LTNT (long-course CRT with four or more cycles of chemotherapy). Propensity score matching (PSM) based on gender, age, body mass index, tumor distance from the anal verge, clinical T stage, clinical N stage, and mesorectal fascia status was employed to reduce confounding bias. Primary endpoints were disease-free survival (DFS) and metastasis-free survival (MFS). RESULTS: The study comprised 372 patients, with 73 patients in each group after PSM. Compared with CRT, both STNT and LTNT demonstrated improved DFS (5-year rate: 59.7% vs. 77.8% vs. 76.5%, p = 0.027) and MFS (5-year rate: 65.1% vs. 81.3% vs. 81.4%, p = 0.030). There was no difference in DFS or MFS between STNT and LTNT. These favorable outcomes were consistent among subgroups defined by tumor distance from the anal verge ≥ 5 cm, clinical T3 stage, clinical N positive status, or involved mesorectal fascia. CONCLUSION: Compared to CRT, both STNT and LTNT demonstrated improved DFS and MFS outcomes. Notably, survival outcomes were similar between STNT and LTNT, suggesting that chemotherapy cycles in TNT may not significantly impact survival.

Survival outcomes of stage I colorectal cancer: development and validation of the ACEPLY model using two prospective cohorts.

BACKGROUND: Approximately 10% of stage I colorectal cancer (CRC) patients experience unfavorable clinical outcomes after surgery. However, little is known about the subset of stage I patients who are predisposed to high risk of recurrence or death. Previous evidence was limited by small sample sizes and lack of validation. METHODS: We aimed to identify early indicators and develop a risk stratification model to inform prognosis of stage I patients by employing two large prospective cohorts. Prognostic factors for stage II tumors, including T stage, number of nodes examined, preoperative carcinoma embryonic antigen (CEA), lymphovascular invasion, perineural invasion (PNI), and tumor grade were investigated in the discovery cohort, and significant findings were further validated in the other cohort. We adopted disease-free survival (DFS) as the primary outcome for maximum statistical power and recurrence rate and overall survival (OS) as secondary outcomes. Hazard ratios (HRs) were estimated from Cox proportional hazard models, which were subsequently utilized to develop a multivariable model to predict DFS. Predictive performance was assessed in relation to discrimination, calibration and net benefit. RESULTS: A total of 728 and 413 patients were included for discovery and validation. Overall, 6.7% and 4.1% of the patients developed recurrences during follow-up. We identified consistent significant effects of PNI and higher preoperative CEA on inferior DFS in both the discovery (PNI: HR = 4.26, 95% CI: 1.70-10.67, p = 0.002; CEA: HR = 1.46, 95% CI: 1.13-1.87, p = 0.003) and the validation analysis (PNI: HR = 3.31, 95% CI: 1.01-10.89, p = 0.049; CEA: HR = 1.58, 95% CI: 1.10-2.28, p = 0.014). They were also significantly associated with recurrence rate. Age at diagnosis was a prominent determinant of OS. A prediction model on DFS using Age at diagnosis, CEA, PNI, and number of LYmph nodes examined (ACEPLY) showed significant discriminative performance (C-index: 0.69, 95% CI:0.60-0.77) in the external validation cohort. Decision curve analysis demonstrated added clinical benefit of applying the model for risk stratification. CONCLUSIONS: PNI and preoperative CEA are useful indicators for inferior survival outcomes of stage I CRC. Identification of stage I patients at high risk of recurrence is feasible using the ACEPLY model, although the predictive performance is yet to be improved.

Total neoadjuvant therapy versus chemoradiotherapy for locally advanced rectal cancer: Bayesian network meta-analysis.

BACKGROUND: Total neoadjuvant therapy is a promising treatment for locally advanced rectal cancer, utilizing either short-course radiotherapy or long-course chemoradiotherapy, but their relative efficacy remains unclear. The aim of this Bayesian network meta-analysis was to investigate clinical outcomes amongst patients receiving total neoadjuvant therapy with short-course radiotherapy or long-course chemoradiotherapy, and those receiving long-course chemoradiotherapy alone. METHODS: A systematic literature search was performed. All studies that compared at least two of these three treatments for locally advanced rectal cancer were included. The primary endpoint was the pathological complete response rate, and survival outcomes were adopted as secondary outcomes. RESULTS: Thirty cohorts were included. Compared with long-course chemoradiotherapy, both total neoadjuvant therapy with long-course chemoradiotherapy (OR 1.78, 95 per cent c.i. 1.43 to 2.26) and total neoadjuvant therapy with short-course radiotherapy (OR 1.75, 95 per cent c.i. 1.23 to 2.50) improved the pathological complete response rate. Similar benefits were observed in the sensitivity and subgroup analyses, except for short-course radiotherapy with one to two cycles of chemotherapy. No significant differences in survival outcomes were found amongst the three treatments. Long-course chemoradiotherapy with consolidation chemotherapy (HR 0.44, 95 per cent c.i. 0.20 to 0.99) exhibited higher disease-free survival than long-course chemoradiotherapy alone. CONCLUSION: Compared with long-course chemoradiotherapy, both short-course radiotherapy with greater than or equal to three cycles of chemotherapy and total neoadjuvant therapy with long-course chemoradiotherapy can improve the pathological complete response rate, and long-course chemoradiotherapy with consolidation chemotherapy may lead to a marginal benefit in disease-free survival. The pathological complete response rate and survival outcomes are similar for total neoadjuvant therapy with short-course radiotherapy or long-course chemoradiotherapy.

Closure of pelvic peritoneum with bladder peritoneum flap reconstruction after laparoscopic extralevator abdominoperineal excision: A prospective stage II study.

BACKGROUND: Extralevator abdominoperineal resection (ELAPE) has increased perineal wound complications due to the extended resection area. Closure of the pelvic peritoneum (CPP) may exclude the abdominal content from descending into the pelvic cavity and reduce the incidence of perineal complications after ELAPE. We have previously introduced bladder peritoneum flap reconstruction (BLAPER) as a novel method for patients in whom traditional CPP is not possible. The aim of the present study was to report the development and preliminary outcomes of BLAPER. METHODS: This is a prospective single-arm study at the development and exploration phase and fulfills the IDEAL framework stage II. Ultralow rectal cancer patients with rigid pelvis who underwent ELAPE with BLAPER were enrolled. Primary outcomes were intraoperative complications and postoperative complications within 1 month after surgery. RESULTS: Among 27 patients included, the overall success rate of BLAPER was 96.3% (26/27). Indocyanine green fluorescence imaging and antiadhesive barrier placement were introduced to improve the BLAPER technique. The incidence of major pelvic wound complications was 7.7%. No patient who underwent BLAPER has suffered small bowel obstruction (SBO), presence of small bowel in the retrourogenital space, or perineal hernia (PH). CONCLUSIONS: BLAPER is safe and may prevent the small bowel from descending into the retrourogenital space and subsequently developing PH and SBO without increasing the intraoperative and postoperative complications. BLAPER may serve as an option when the primary suture of the pelvic peritoneum is not feasible.

Monocyte/macrophage mediates the impact of depression on Crohn's disease.

BACKGROUND: Depression increases the risk of Crohn's disease (CD) and worsens its prognosis. Monocytes/macrophages, immune modulate cells, play vital roles in both depression and CD. OBJECTIVES: We investigated whether monocyte/macrophage could mediate the impact of depression on CD through induction of CD4 + T lymphocyte differentiation and epithelial barrier dysfunction, in addition to the alteration of their own phagocytic ability and cytokines production. METHODS: Circulating monocytes and intestinal macrophages were isolated from eligible CD patients, divided into depressed and non-depressed groups. Phagocytosis was determined using flow cytometry while in vitro cytokine production was quantified using Luminex assay and qPCR. CD4 + T cells were cocultured with monocytes, then Type 1 Helper T Lymphocytes Th1/Type 2 Helper T Lymphocytes (Th2) /Type 17 Helper T Lymphocytes (Th17)/Treg subsets were analyzed using flow cytometry and qPCR. Caco-2 monolayers simulating epithelial barrier were cocultured with macrophages, and integrity and proliferation were evaluated. Tight junction protein expression was detected using immunofluorescence and western blot. RESULTS: Decreased monocyte/macrophage phagocytosis and enhanced production of pro-inflammatory cytokines including Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6) and Interleukin-1ß (IL-1ß) were revealed in the depressed versus non-depressed CD groups. Higher proportions of Th1 and Th17 cells with a lower proportion of Treg cell were observed after cocultured with monocytes from the depressed versus non-depressed CD patients. So were the expressions of their corresponding transcription factors T-bet, Retinoic Acid Related Orphan Nuclear Receptor gamma T (RORγt) and Forkhead box protein P3 (FoxP3). Caco-2 cells cocultured with macrophages from depressed CD displayed lower Transepithelial electric resistance (TEER), reduced proliferation activity, and decreased tight junction protein expressions compared with their counterpart cocultured with macrophages from non-depressed CD. CONCLUSIONS: Monocyte/macrophage may underlie the impact of depression upon CD via decreased phagocytosis, increased pro-inflammatory cytokine production, inducing CD4 + T cell differentiation toward Th1/Th17 cells rather than Treg cell, and impairing macrophage-enhanced epithelial barrier.

The effect of BMI on long-term outcome in patients with rectal cancer and establishment of a nomogram prediction model.

BACKGROUND: The effects of body mass index (BMI) in patients with rectal cancer have been poorly studied and are still controversial. In this study, we aimed to assess the effect of BMI on the long-term outcome in patients with rectal cancer after radical surgery. MATERIALS AND METHODS: Between April 2012 and December 2020, patients who received total mesorectal excision (TME) surgery were enrolled in the study. Patients were divided into four groups according to BMI level. Kaplan-Meier survival curves with log-rank tests were used to analyze overall survival (OS), Disease-free survival (DFS), local recurrence-free survival and distant metastasis-free survival. Univariate and multivariate analyses were performed to identify the risk factors associated with the long-term outcome. Nomograms were developed to predict the OS and DFS based on independent prognostic factors. RESULTS: A total of 688 patients were included in this study. The median follow-up time was 69 months. The 5-year OS rates of the control, underweight, overweight and obese groups were 79.2%, 62.2%, 88.7% and 86.3%, respectively. The 5-year DFS rates were 74.8%, 58.2%, 80.5% and 81.4%, respectively. Overweight (HR 0.534; 95% CI 0.332-0.860, p = 0.010) was an independent protective factor for OS and DFS (HR 0.675; 95% CI 0.461-0.989, p = 0.044). Underweight was an independent risk factor for DFS (HR = 1.623; 95% CI 1.034-2.548; p = 0.035), and had a trend to be an independent risk factor for OS (HR 1.594; 95% 0.954-2.663; p = 0.075). Nomograms were established to predict the 2-year OS, 5-year OS, 2-year DFS and 5-year DFS with an area under curve (AUC) of 0.767, 0.712, 0.746 and 0.734, respectively. CONCLUSIONS: For rectal cancer patients after radical surgery, overweight was an independent protective factor for OS and DFS. Underweight was an independent risk factor for DFS and had a trend to be an independent risk factor for OS. Nomograms incorporating BMI and other prognostic factors could be helpful to predict long-term outcome.

Lymph node stain after radical resection of rectal cancer mainly increased the harvest of mini lymph node: A randomized controlled trial.

AIM: The lymph node status plays an important role in rectal cancer, which depends on adequate lymph node harvest. Lymph node stain techniques increase the lymph node harvest. The aim of this prospective study is to investigate which subgroups of lymph nodes harvested were increased mostly. METHODS: From May 2020 to May 2022, 172 stage II-III rectal cancer patients were randomized to methylene blue (MB) stained group or unstained group to retrieve the lymph nodes. Methylene blue solution was injected into the inferior mesenteric artery, we dissected lymph nodes by palpation and sight. The lymph nodes were divided into 3 groups depending on the anatomy (main lymph nodes, superior rectal and perirectal lymph nodes (SPLNs), and pericolic lymph nodes located beyond 10 cm proximal to the tumor), and 3 groups depending on the short diameter of the nodes (big: ≥ 5 mm, small: 5-2 mm, mini: ≤ 2 mm). RESULTS: The number of lymph nodes harvested with MB was significantly higher (22.0 (14.8, 32.0) vs 14.5 (11.0, 22.0); p < 0.001) without difference in positive patients or number of positive nodes. The positive rate of the big node was 3.5%, the small node was 1.9%, and the mini node was 0.2%. In the subgroup analysis, the median number of mini lymph nodes in the MB-stained group was significantly more than that of the unstained group (median (IQR): 9.0 (6.0, 14.0) vs 4.0 (2.0,6.0), p < 0.001); and the median number of SPLNs in the MB-stained group were significantly more than that of the unstained group (median (IQR): 15.0 (9.0, 19.0) vs 10.0 (6.0, 13.3), p < 0.001); these differences were existing in both patients with and without neoadjuvant treatments. CONCLUSION: Intra-arterial injection of MB can significantly increase the number of lymph nodes harvested in rectal cancers, especially those mini lymph nodes. However, methylene blue staining did not significantly increase the number of positive lymph nodes and the proportion of patients with more than 12 lymph nodes, or affect lymph node staging accuracy after radical resection of rectal cancer.

Effect of Tumor Location on Outcome After Laparoscopic Low Rectal Cancer Surgery: A Propensity Score Matching Analysis.

BACKGROUND: Dissection of the distal anterolateral aspect of the mesorectum remains a surgical challenge for low rectal cancer, posing a higher risk of residual mesorectum, which might lead to the increased incidence of local recurrence for patients with anterior wall involvement. OBJECTIVE: This study aimed to assess the effect of tumor location on outcome after laparoscopic low rectal cancer surgery. DESIGN: This is a single-center, retrospective study. SETTINGS: The study was conducted at West China Hospital in China. PATIENTS: Patients with low rectal cancer who underwent laparoscopic total mesorectal excision from 2011 to 2016 were enrolled. Patients were divided into anterior and nonanterior groups according to tumor location. Propensity score matching analysis was used to reduce the selection bias. MAIN OUTCOME MEASURES: The primary end point was local recurrence. The secondary end points included overall survival, disease-free survival, and the positive rate of circumferential resection margin. RESULTS: A total of 404 patients were included, and 176 pairs were generated by propensity score matching analysis. Multivariate analysis showed that anterior location was an independent risk factor of local recurrence (HR, 12.6; p = 0.006), overall survival (HR, 3.0; p < 0.001), and disease-free survival (HR, 2.3; p = 0.001). For patients with clinical stage II/III or T3/4, anterior location remained a prognostic factor for higher local recurrence and poorer survival. Local recurrence was rare in patients with clinical stage II/III (1.4%) or T3/4 (1.5%) tumors that were not located anteriorly. LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: Anterior location is an independent risk factor of local recurrence, overall survival, and disease-free survival for low rectal cancer. More strict and selective use of neoadjuvant therapy should be considered for patients who have clinical stage II/III or T3/4 tumors that are not located anteriorly. A larger cohort study is warranted to validate the prognostic role of anterior location for low rectal cancer. See Video Abstract at http://links.lww.com/DCR/B622. IMPACTO DE LA LOCALIZACIN DEL TUMOR EN EL RESULTADO POSTERIOR A CIRUGA LAPAROSCPICA DE CNCER DE RECTO INFERIOR UN PUNTAJE DE PROPENSIN POR ANLISIS DE CONCORDANCIA: ANTECEDENTES:La disección de la cara anterolateral distal del mesorrecto sigue siendo un desafío quirúrgico en el cáncer de recto inferior, constituyendo un alto riesgo de mesorrecto residual, que podría ocasionar una mayor incidencia de recurrencia local en pacientes con compromiso de la pared anterior.OBJETIVO:El objetivo del estudio fue evaluar el efecto de la localización del tumor en el resultado posterior a la cirugía laparoscópica de cáncer de recto inferior.DISEÑO:Estudio restrospectivo de un único centro.ÁMBITO:El estudio se realizó en el West China Hospital en China.PACIENTES:Pacientes con cáncer de recto inferior que se sometieron a excisión mesorrectal total laparoscópica entre 2011 y 2016. Los pacientes se dividieron en grupos, anterior y no anterior, según la localización del tumor. Se utilizó un puntaje de propensión por análisis de concordancia para reducir el sesgo de selección.PRINCIPALES VARIABLES EVALUADAS:El objetivo principal fue la recurrencia local. Los objetivos secundarios incluyeron la sobrevida global, la sobrevida libre de enfermedad y la tasa de positividad del margen de resección circunferencial.RESULTADOS:Se incluyeron un total de 404 pacientes y se generaron 176 pares mediante un puntaje de propensión por análisis de concordancia. El análisis multivariado mostró que la localización anterior era un factor de riesgo independiente de recidiva local (HR = 12,6, p = 0,006), sobrevida global (HR = 3,0, p <0,001) y sobrevida libre de enfermedad (HR = 2,3, p = 0,001). En pacientes con estadio clínico II /III o T3/4, la ubicación anterior continuó como un factor pronóstico para una mayor recurrencia local y una menor sobrevida. La recidiva local fue excepcional en pacientes con tumores en estadio clínico II / III (1,4%) o T3 / 4 (1,5%) que no estaban localizados hacia anterior.LIMITACIONES:Este estudio estuvo limitado por su carácter retrospectivo.CONCLUSIONES:La localización anterior es un factor de riesgo independiente de recidiva local, sobrevida global y sobrevida libre de enfermedad para el cáncer de recto inferior. Se debe considerar un uso más estricto y selectivo de la terapia neoadyuvante para pacientes en estadio clínico II / III o T3 /4 de tumores que no se localizan hacia anterior. Se justifica un estudio de cohorte más grande para validar el impacto pronóstico de una ubicación anterior del cáncer de recto inferior. Consulte Video Resumen en http://links.lww.com/DCR/B622. (Traducción-Dr. Lisbeth Alarcon-Bernes).

Establishment and validation of nomograms for predicting mesorectal lymph node staging and restaging.

BACKGROUND: Preoperative determination of lymph node (LN) status is crucial in treatment planning for rectal cancer. This study prospectively evaluated the risk factors for lymph node metastasis (LNM) at staging and restaging based on a node-by-node pairing between MRI imaging findings and histopathology and constructed nomograms to evaluate its diagnostic value. METHODS: From July 2021 to July 2022, patients with histopathologically verified rectal cancer who underwent MRI before surgery were prospectively enrolled. Histological examination of each LN status in the surgical specimens and anatomical matching with preoperative imaging. Taking histopathological results as the gold standard, federating clinical features from patients and LN imaging features on MRI-T2WI. Risk factors for LN metastasis were identified by multivariate logistic regression analysis and used to create a nomogram. The performance of the nomograms was assessed with calibration plots and bootstrapped-concordance index and validated using validation cohorts. RESULTS: A total of 500 target LNs in 120 patients were successfully matched with node-by-node comparisons. A total of 353 LNs did not receive neoadjuvant therapy and 147 LNs received neoadjuvant chemoradiotherapy (neoCRT). Characterization of LNs not receiving neoadjuvant therapy and multivariate regression showed that the short diameter, preoperative CEA level, mrT-stage, border contour, and signal intensity were associated with a high risk of LN metastasis (P < 0.05). The nomogram predicted that the area under the curve was 0.855 (95% CI, 0.794-0.916) and 0.854 (95% CI, 0.727-0.980) in the training and validation cohorts, respectively. In the neoadjuvant therapy group, short diameter, ymrT-stage, internal signal, and MRI-EMVI were associated with LN positivity (P < 0.05), and the area under the curves using the nomogram was 0.912 (95% CI, 0.856-0.968) and 0.915 (95% CI, 0.817-1.000) in two cohorts. The calibration curves demonstrate good agreement between the predicted and actual probabilities for both the training and validation cohorts. CONCLUSION: Our nomograms combined with preoperative clinical and imaging biomarkers have the potential to improve the prediction of nodal involvement, which can be used as an essential reference for preoperative N staging and restaging of rectal cancer.

Distinctive features of small vessels on the mesorectal and parietal pelvic fascia as important landmarks in guiding precise inter-fascial dissection for low rectal cancer.

BACKGROUND: The confinement of the pelvis and the complexity of pelvic fascial anatomy still pose difficulties in achieving good quality surgery for rectal cancer. We aimed to introduce small vessels on the mesorectal fascia and the parietal pelvic fascia as novel landmarks to aid in the identification of the inter-fascial dissection plane. Besides, the perioperative, survival, and functional outcomes of this surgical technique were reported. METHODS: We first described that small vessels running on the mesorectal fascia and the parietal pelvic fascia showed distinctive features, which included (1) small vessels on the parietal fascia took the same orientation as the ureter or the sympathetic and parasympathetic nerve; (2) small vessels on the mesorectal fascia were coursing cranially and medially on the anterolateral aspect, and medially and caudally on the posterolateral aspect; (3) small vessels on the mesorectal fascia became invisible at the interface between the pelvic wall and the mesorectal fascia. These features could be applied in fascial identification and separation. Then, we reported the outcomes of low rectal cancer surgery with small vessels-guided technique. RESULTS: From 2013 to 2016, a consecutive series of 310 patients with low rectal cancer underwent laparoscopic total mesorectal excision with small vessels-guided technique. The positive rate of circumferential resection margin was 3.2%, and complete mesorectal excision was achieved in 97.8% (303/310) patients. The 3-year overall survival, disease-free survival, and local recurrence rates were 89.4%, 79.7%, and 2.6%, respectively. The urinary function was considered normal in 96.8% of patients, with a moderate dysfunction in 3.2% of patients. Besides, 29.5% of male patients occurred sexual function injury. CONCLUSION: Distinctive features of small vessels on the parietal pelvic fascia and the mesorectal fascia can serve as novel and additive landmarks in guiding precise inter-fascial dissection for low rectal cancer.

Early response to upfront neoadjuvant chemotherapy (CAPOX) alone in low- and intermediate-risk rectal cancer: a single-arm phase II trial.

BACKGROUND: With local recurrence of rectal cancer continuing to decrease, distant recurrence is becoming a major concern, especially for patients with low- and intermediate-risk stage II/III rectal cancer. Therefore, a new treatment strategy is warranted for these patients. This single-arm phase II trial aimed to assess the effect of neoadjuvant chemotherapy (NCT) in low- and intermediate-risk stage II/III rectal cancer and explore candidate radiological and clinical parameters for early prediction of tumour response after two cycles of CAPOX. METHODS: Patients with mid-low stage II/III rectal cancer with low and intermediate risk were examined. The primary outcome was defined as a clinicopathological response by integrating tumour longitudinal length reduction (TLLR) on MRI into pathological tumour regression grade (TRG). After completing NCT, patients with TRG0-2 and TRG3 with a TLLR rate greater than 30 per cent were considered to be responders. Secondary outcomes included pathological complete response (pCR), adverse events and local and distant recurrence. RESULTS: This study enrolled 61 eligible patients. No patient was converted to neoadjuvant chemoradiotherapy owing to tumour progression. The clinicopathological response and pCR rates were 78.7 and 21.3 per cent respectively. After two cycles of CAPOX, TLLR, TRG on MRI, and mucosal lesion regression grade on endoscopy had potential discriminative ability (area under the curve greater than 0.7) for predicting both clinicopathological and pathological response. CONCLUSION: NCT alone achieves good tumour response rates in patients with low- and intermediate-risk stage II/III rectal cancer, and predicting tumour response to NCT is feasible at an early treatment phase. REGISTRATION NUMBER: NCT03666442 (http://www.clinicaltrials.gov).

A Modified Technique of Laparoscopic Lateral Lymph Node Dissection Combining Fascia-Oriented Dissection and Routine Upfront Distal Visceral Vessels Ligation for Mid- to Low-Lying Rectal Cancer.

INTRODUCTION: Lateral pelvic recurrence can be a cause of local failure after surgery for low rectal cancer. Lateral lymph node dissection is often performed in East Asia for patients with enlarged lateral lymph nodes or because of the presence of risk factors. However, the outcomes of the conventional lateral lymph node dissection are unsatisfactory, with a considerably high local recurrence rate for patients with positive lateral nodes. Here, we introduce a modified technique to improve lateral nodes clearance. TECHNIQUE: This modified technique has 4 key steps: 1) separation of the ureterohypogastric nerve fascia medially, 2) identification of the visceral pelvic fascia and dissection along the inferior vesical or vaginal veins down to the pelvic floor, 3) division of the distal ends of visceral vessels according to the orientation of ureterohypogastric nerve fascia and visceral pelvic fascia for better nerve preservation, and 4) en bloc dissection through a lateral approach over the surfaces of the sacral plexus and piriformis muscle to reveal the course of distal internal iliac vessels before the division of visceral veins. RESULTS: Twenty-nine patients underwent laparoscopic lateral lymph node dissection successively with no conversion. The median blood loss for each lateral procedure was 37.5 mL (range, 0-300.0 mL). Eleven lateral nodes (median; range, 1-22 lateral nodes) were harvested for each lateral side. There was no perioperative mortality, and 4 patients developed major complications (Clavien-Dindo III-IV). CONCLUSION: This modified technique characterized by the routine division of visceral vessels based on ureterohypogastric nerve fascia and visceral pelvic fascia is feasible and safe. It provides good lymph node harvest, autonomic nerve preservation, and improved bleeding control. Additional investigation is warranted to evaluate the safety, functional outcomes, and oncologic outcomes.

Indications and oncological outcomes of selective dissection for clinically suspected lateral lymph node metastasis in patients with rectal cancer based on pretreatment imaging.

BACKGROUND: The aim of this study was to identify the indications and oncological outcomes of selective lateral lymph node dissection (sLLND) in rectal cancer patients. METHODS: A retrospective study was conducted on consecutive patients with rectal cancer who had standard total mesorectal excision and sLLND at our institution. Clinicopathological characteristics and oncological outcomes were analyzed. We performed subgroup analysis and multivariate analysis based on patients with or without preoperative chemoradiotherapy to identify the related risk factors. RESULTS: A total of 77 consecutive patients with TME and sLLND were included. Twenty-two (28.6%) patients with pathological positive lateral lymph nodes metastasis (LLNM) were identified. Forty-seven (61%) patients accepted neoadjuvant chemoradiotherapy (nCRT). The pretreatment maximum short-axis diameters of LLN (≥ 8 mm) were the independent risk factors for LLNM among patients with LLN ≥ 5 mm. Lymph node metastasis were significantly higher in patients with pretreatment LLN ≥ 8 mm than in patients with LLN 5-8 mm (63% vs. 10%, p < 0.001). The receiver operating curve analysis suggested that the optimal cutoff value of LLN short-axis diameter for predicting LLNM was 8 mm. At a median follow-up of 42 months (range 6-140 months) 3 (3.9%) patients with lateral pelvic recurrence were observed. The 3-year cumulative overall survival in patients with LLNM and patients without LLNM was 76.7% and 89.8%, respectively (p = 0.01). The 3-year cumulative disease-free survival was 53.6% in patients with LLNM and 88.3% in patients without LLNM (p = 0.008). CONCLUSION: Patients with LLNM had a worse prognosis. The pretreatment maximum short-axis diameter of LLN (≥ 8 mm) should be considered as an indication for sLLND.

[Application of Automated Machine Learning Based on Radiomics Features of T2WI and RS-EPI DWI to Predict Preoperative T Staging of Rectal Cancer].

OBJECTIVE: To explore the radiomics features of T2 weighted image (T2WI) and readout-segmented echo-planar imaging (RS-EPI) plus difusion-weighted imaging (DWI), to develop an automated mahchine-learning model based on the said radiomics features, and to test the value of this model in predicting preoperative T staging of rectal cancer. METHODS: The study retrospectively reviewed 131 patients who were diagnosed with rectal cancer confirmed by the pathology results of their surgical specimens at West China Hospital of Sichuan University between October, 2017 and December, 2018. In addition, these patients had preoperative rectal MRI. Tumor regions from preoperative MRI were manually segmented by radiologists with the ITK-SNAP software from T2WI and RS-EPI DWI images. PyRadiomics was used to extract 200 features-100 from T2WI and 100 from the apparent diffusion coefficient (ADC) calculated from the RS-EPI DWI. MWMOTE and NEATER were used to resample and balance the dataset, and 13 cases of T 1-2 stage simulation cases were added. The overall dataset was divided into a training set (111 cases) and a test set (37 cases) by a ratio of 3∶1. Tree-based Pipeline Optimization Tool (TPOT) was applied on the training set to optimize model parameters and to select the most important radiomics features for modeling. Five independent T stage models were developed accordingly. Accuracy and the area under the curve ( AUC) of receiver operating characteristic (ROC) were used to pick out the optimal model, which was then applied on the training set and the original dataset to predict the T stage of rectal cancer. RESULTS: The performance of the the five T staging models recommended by automated machine learning were as follows: The accuracy for the training set ranged from 0.802 to 0.838, sensitivity, from 0.762 to 0.825, specificity, from 0.833 to 0.896, AUC, from 0.841 to 0.893, and average precision (AP) from 0.870 to 0.901. After comparison, an optimal model was picked out, with sensitivity, specificity and AUC for the training set reaching 0.810, 0.875, and 0.893, respectively. The sensitivity, specificity and AUC for the test set were 0.810, 0.813, and 0.810, respectively. The sensitivity, specificity and AUC for the original dataset were 0.810, 0.830, and 0.860, respectively. CONCLUSION: Based on the radiomics data of T2WI and RS-EPI DWI, the model established by automated machine learning showed a fairly high accuracy in predicting rectal cancer T stage.

Neoadjuvant Radiotherapy Versus Surgery Alone for Stage II/III Mid-low Rectal Cancer With or Without High-risk Factors: A Prospective Multicenter Stratified Randomized Trial.

OBJECTIVE: The aim of this study was to compare stage II/III rectal cancers with or without high-risk factors, and evaluate the effect of neoadjuvant radiotherapy (NRT) in these 2 cohorts. BACKGROUND: NRT is often used in stage II/III rectal cancers to improve local control, while not affecting overall survival. However, good-quality surgery without NRT may also achieve good local control in selected patients. METHODS: According to risk-stratification criteria and clinical staging, consecutive eligible participants of stage II/III rectal cancer were preoperatively classified into patients with (high-risk) or without (low-risk) high-risk factors. Both groups were respectively randomized to receive either short-course radiotherapy (SCRT) + total mesorectal excision (TME) or TME alone, forming the following 4 groups: high-risk patients with (HiR) or without (HiS) radiation, and low-risk patients with (LoR) or without (LoS) radiation. The primary endpoint was local recurrence. The secondary endpoints included overall survival, disease-free survival, distant recurrence, quality of surgery, and safety (NCT01437514). RESULTS: In total, 401 patients were analyzed. With a median 54 months' follow-up, low-risk patients obtained better 3-year cumulative incidence of local recurrence (2.2% vs 11.0%, P = 0.006), overall survival rate (86.9%vs 76.5%, P = 0.002), disease-free survival rate (87.0% vs 67.9%, P < 0.001), and cumulative incidence of distant recurrence (12.5% vs 29.4%, P < 0.001) than high-risk patients. With regard to 3-year cumulative incidence of local recurrence, no differences were observed between the LoR and LoS groups (1.2% vs 3.0%, P = 0.983) or the HiR and HiS groups (12.9% vs 8.9%, P = 0.483). CONCLUSIONS AND RELEVANCE: Stratification of stage II/III rectal cancers according to risk factors to more precise subclassifications may result in noteworthy differences in survivals and local pelvic control. An extremely low cumulative incidence of local recurrence and survivals in low-risk patients can be achieved with upfront good quality of surgery alone. This trial, owing to the insufficient power, could not prove the noninferiority of surgery alone, but suggest a discriminative use of NRT according to clinical risk stratification in stage II/III rectal cancer.

The effect of pericolic lymph nodes metastasis beyond 10 cm proximal to the tumor on patients with rectal cancer.

BACKGROUND: This study aims to determine the real incidence of pericolic lymph nodes metastasis beyond 10 cm proximal to the tumor (pPCN) and its prognostic significance in rectal cancer patients. METHODS: Consecutive patients with rectal cancer underwent curative resection between 2015 and 2017 were included. Margin distance was marked and measured in vivo and lymph nodes were harvested on fresh specimens. Clinicopathological characteristics and oncological outcomes (3-year overall survival (OS) and disease-free survival (DFS)) were analyzed between patients with pPCN and patients without pPCN (nPCN). RESULTS: There were 298 patients in the nPCN group and 14 patients (4.5%) in pPCN group. Baseline characteristics were balanced except more patients received preoperative or postoperative chemoradiotherapy in pPCN group. Preoperative more advanced cTNM stage (log-rank p = 0.005) and intraoperative more pericolic lymph nodes beyond 10 cm proximal to the tumor (PCNs) (log-rank p = 0.002) were independent risk factors for pPCN. The maximum short-axis diameter of mesenteric lymph nodes ≥8 mm was also contributed to predicting the pPCN. pPCN was an independent prognostic indicator and associated with worse 3-year OS (66% vs 91%, Cox p = 0.033) and DFS (58% vs 92%, Cox p = 0.012). CONCLUSION: The incidence of pPCN was higher than expected. Patients with high-risk factors (cTNM stage III or more PCNs) might get benefits from an extended proximal bowel resection to avoid residual positive PCNs.

Oxaliplatin versus mitomycin C in HIPEC for peritoneal metastasis from colorectal cancer: a systematic review and meta-analysis of comparative studies.

BACKGROUND: Hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) following cytoreductive surgery (CRS) has been applied for peritoneal metastasis (PM) from colorectal cancer (CRC). This study aimed to compare oxaliplatin (OX) with mitomycin C (MMC) in HIPEC for PM from CRC in surgical and survival outcomes. METHODS: A systematic literature search was performed in PubMed and Ovid databases for studies comparing OX with MMC in HIPEC for PM from CRC. The last search was performed on June 21, 2020. RESULTS: Eleven articles published between 2006 and 2020 with 2091 patients were included. When compared with MMC group, the OX group showed significantly higher rate of major complications (P = 0.006, OR = 1.57, 95% CI [1.14, 2.16], I2 = 0%). Besides, no significant difference was observed between the two groups for survival outcomes, regardless of 3-year overall survival (P = 0.98, OR = 1.00, 95% CI [0.83, 1.22], I2 = 0%), 3-year disease-free survival (P = 0.98, OR = 1.00, 95% CI [0.83, 1.22], I2 = 0%), or 5-year overall survival (P = 0.91, OR = 1.01, 95% CI [0.81, 1.26], I2 = 0%). CONCLUSION: OX and MMC could achieve comparable survival in HIPEC for PM from CRC. However, in consideration of the high incidence of major complication in OX group, MMC might be the safer one in clinical routines.

Ligating the rectum with cable tie facilitates rectum transection in laparoscopic anterior resection of rectal cancer.

PURPOSE: Proper transection of the distal rectum is important for reconstruction of bowel continuity in rectal cancer surgery. In this study, we introduced a modified technique for ligation of the distal rectum, and investigated its safety and efficiency to facilitate the rectum transection. METHODS: After complete mobilization and transection of the mesorectum, a cable tie was carefully positioned distal to the tumor, followed by washout and transecting the rectum with a linear stapler. From September 2017 to June 2018, consecutive 67 mid-low rectal cancer patients with laparoscopic anterior resection underwent this technique. Clinical data of these patients, including number of firings, pathological and operative variables, and postoperative outcomes, were compared with those of 132 consecutive patients who underwent traditional surgery from January 2016 to August 2017. RESULTS: Compared with the traditional method, cable tie ligation significantly reduced the number of firings (1.1 ± 0.32 vs. 1.3 ± 0.52, p < 0.001). A very high ratio of one firing transection of rectum was observed in the cable tie group (94.0% vs. 68.9%, p < 0.001), even in patients with tumor at or below the peritoneal reflection (90.2% vs. 54.4%, p < 0.001), in male patients (95.5% vs. 65.8%, p < 0.001), and in obese patients (93.8% vs. 64.9%, p = 0.005). The mean distal margin was longer in the cable tie group (3.19 ± 1.77 cm vs. 2.54 ± 1.36 cm, p = 0.005), with no positive distal margin observed. The operation time, quality of mesorectum, and morbidity between two groups were comparable. Two leaks (3.0%) in the cable tie group were observed, similar to 3.8% in the control. CONCLUSIONS: Ligation of the rectum with a cable tie reduces the number of cartridges, and increases the rate of one stapler firing for rectal transection, even in those difficult cases like male, overweight, and low rectal cancer patients. It is also useful for occlusion of the rectum before washout. It is safe, feasible, and worthwhile for popularization. TRIAL REGISTRATION: Registered at ClinicalTrial.gov, number NCT03570684.

First-line cetuximab versus bevacizumab for RAS and BRAF wild-type metastatic colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: A first-line biologic treatment for metastatic colorectal cancer (mCRC) is still controversial. We, therefore, performed a meta-analysis to determine the efficacy of first-line cetuximab versus bevacizumab for RAS and BRAF wild-type mCRC. METHODS: In March 2018, an electronic search of the following biomedical databases was performed: PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov and Web of Knowledge. Randomized controlled trials (RCTs) and prospective or observational cohort studies (OCSs) were included. Subgroup analyses of all RCTs were performed in all outcomes. All statistical analyses were performed using RevMan software 5.3. RESULTS: Two RCTs and three OCSs, involving a total 2576 patients, were included. The meta-analysis reported that cetuximab was associated with a longer overall survival (OS) [HR 0.89, 95% CI (0.81-0.98); p = 0.02], a higher ORR [RR 1.11, 95% CI (1.03-1.19); p = 0.006], higher complete response [RR 3.21, 95% CI (1.27-8.12); p = 0.01] and a greater median depth of response than bevacizumab. However, no significant difference was observed between cetuximab and bevacizumab groups for PFS, DCR, partial response, progressive disease, curative intent metastasectomy, EORR and incidence of grade 3 or higher adverse events. In the subgroup meta-analyses of the RCTs, inconsistent results compared to the main analysis, however, were found, in the ORR, DCR and curative intent metastasectomy. CONCLUSIONS: The current evidence indicates that compared to bevacizumab treatment, cetuximab provides a clinically relevant effect in first-line treatment against mCRC, at the cost of having lower stable disease.

A Novel Laparoscopic Technique With a Bladder Peritoneum Flap Closure for Pelvic Cavity for Patients With Rigid Pelvic Peritoneum After Neoadjuvant Radiotherapy in Laparoscopic Extralevator Abdominoperineal Excision.

BACKGROUND: In laparoscopic extralevator abdominoperineal excision, reconstruction of the pelvic peritoneum helps to prevent the small intestine from adhering to pelvic wall tissues, thus avoiding small-bowel obstruction and perineal complications. However, there are difficulties in pelvic peritoneum closure if the patient has received preoperative radiotherapy and has a rigid pelvis. We report a novel laparoscopic method for pelvic peritoneum reconstruction using the bladder peritoneum flap in laparoscopic extralevator abdominoperineal excision after neoadjuvant radiotherapy. TECHNIQUE: After transection of the rectum, if the patient had a rigid pelvis, we chose to perform the novel technique for the pelvic peritoneum closure in a 3-step approach. The flap has an arch shape with the bottom at the anterior wall of the pelvic cavity entrance. The height of the arched flap is equal to the distance from the bladder to the sacral promontory. The peritoneum was incised with electrocautery at the planned level and peeled off the bladder. The bladder peritoneum flap was then rotated to cover the entrance of the pelvic cavity and sutured to the brim of the pelvis. RESULTS: Acceptable postoperative short-term and long-term outcomes (5- to 22-month follow-ups) were achieved in 3 patients who underwent bladder peritoneum flap closure. CONCLUSIONS: The bladder peritoneum flap appears to be safe and feasible for intracorporeal closure of the pelvic cavity in laparoscopic extralevator abdominoperineal excision after neoadjuvant radiotherapy. The procedure provides a novel option for patients with severe fibrosis of the pelvis when another peritoneum reconstruction method is not feasible.