eIF3i promotes colorectal cancer cell survival via augmenting PHGDH translation.

Translational regulation is one of the decisive steps in gene expression, and its dysregulation is closely related to tumorigenesis. Eukaryotic translation initiation factor 3 subunit i (eIF3i) promotes tumor growth by selectively regulating gene translation, but the underlying mechanisms are largely unknown. Here, we show that eIF3i is significantly increased in colorectal cancer (CRC) and reinforces the proliferation of CRC cells. Using ribosome profiling and proteomics analysis, several genes regulated by eIF3i at the translation level were identified, including D-3-phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in the de novo serine synthesis pathway that participates in metabolic reprogramming of tumor cells. PHGDH knockdown significantly represses CRC cell proliferation and partially attenuates the excessive growth induced by eIF3i overexpression. Mechanistically, METTL3-mediated N6-methyladenosine modification on PHGDH mRNA promotes its binding with eIF3i, ultimately leading to a higher translational rate. In addition, knocking down eIF3i and PHGDH impedes tumor growth in vivo. Collectively, this study not only uncovered a novel regulatory mechanism for PHGDH translation but also demonstrated that eIF3i is a critical metabolic regulator in human cancer.

Comparison of laparoscopic lateral lymph node dissection for rectal cancer with and without routine resection of the visceral branches of internal iliac artery.

PURPOSE: This study aimed to explore the safety and feasibility of the modified lateral lymph node dissection (LLND) with routine resection of the visceral branches of internal iliac vessels (IIVs) for mid-low-lying rectal cancer. MATERIALS AND METHOD: Consecutive patients undergoing LLND for rectal cancer were divided into the routine visceral branches of the IIVs resection group (RVR group) and the NRVR group (without routine resection). The main outcomes were postoperative complications and the number of lateral lymph nodes harvested. RESULTS: From 2012 to 2021, a total of 75 and 57 patients were included in the RVR and NRVR group, respectively. The operative time was reduced in the RVR group (p = 0.020). No significant difference was observed between the two groups for the incidence of total, major, or minor postoperative complications. Pathologically confirmed LLNM were 24 (32%) patients in the RVR group and 12 (21.1%) in the NRVR group (p = 0.162). The number of lateral lymph nodes harvested had no significant difference between two groups (11 vs. 12, p = 0.329). CONCLUSION: LLND with routine resection of visceral branches of IIVs is safe and feasible, which brings no major complication or long-term urinary disorder.

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.

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.

The same parastomal hernia repairs rate in the different approaches to colostomy.

PURPOSE: This study aimed to compare the parastomal hernia repairs rate in the different approaches to colostomy and investigate the risk factors for parastomal hernia formation in patients with permanent colostomies. METHODS: Consecutive rectal cancer patients who underwent abdominoperineal resection from June 2014 to July 2020 in West China Hospital were divided into two groups according to their surgical approach for permanent colostomies. The impact of different approaches to colostomy on parastomal hernia repairs was determined by comparing a group of patients receiving an extraperitoneal route to colostomy with a group receiving transperitoneal. Potential variables were evaluated first with univariate and then multivariate analyses to identify the risk factors for the formation of parastomal hernia. RESULTS: Two hundred two subjects in the transperitoneal group and 103 in the extraperitoneal group attended the follow-up visit with a median follow-up period of 33 (25th-75th percentiles, 17-46) months. Clinically and radiologically detectable parastomal hernias were present in 76 of 202 (37.6%) and 14 of 103 (13.6%) subjects in the transperitoneal and extraperitoneal groups during the follow-up period (p＜0.01). Besides, 10 of 76 (13.1%) subjects in the transperitoneal group and 2 of 14 (14.3%) subjects in the extraperitoneal group underwent a parastomal hernia operation during the follow-up (p = 0.82). In addition, the transperitoneal approach of colostomy (p = 0.002), older age (p＜0.001), and higher body mass index (p = 0.013) were identified as independent risk factors for the occurrence of parastomal hernia. CONCLUSIONS: Extraperitoneal colostomy decreased the detectable parastomal hernias but did not reduce the surgical repair rate of parastomal hernias.

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.

Methylene blue can increase the number of lymph nodes harvested in colorectal cancer: a meta-analysis.

AIM: The lymph node (LN) status plays an important role in colorectal cancer (CRC), which depends on adequate LN harvest. In some studies, methylene blue has been used to increase the number of LNs harvested in vitro. The purpose was to evaluate the effect of methylene blue staining on LN harvest during radical resection of CRC. METHODS: The Cochrane Library, MEDLINE, Embase, PubMed, and Web of Science were searched from the dates of inception until 15 October 2022. Studies were included if they were randomized controlled trials or nonrandomized controlled trials for radical resection of rectal cancer according to the principle of total mesorectal excision that compared the use of methylene blue with blank control in LN harvest. The primary outcomes were the number of LNs harvested and the incidence of fewer than 12 LNs harvested. RESULT: Of 328 articles found, a meta-analysis was conducted of 15 studies (2 randomized controlled trials and 13 non-randomized controlled trials) composed of 3104 patients. Meta-analysis showed that methylene blue could not only significantly increase the number of LNs harvested in CRC specimens (stained group 28.23 vs unstained group 16.15; weighted mean difference 12.08; 95% CI, 8.03-16.12; p < 0.001; I2 = 95%), but also reduce the incidence of fewer than 12 LNs harvested (methylene blue-stained group 7.91% vs unstained group 30.90%; OR 0.12; 95% CI, 0.05-0.26; p < 0.001; I2 = 78%). CONCLUSION: Methylene blue can increase the number of LNs harvested in CRC, reduce the incidence of fewer than 12 LNs harvested, and ensure the accuracy of LN staging.

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.

Frailty index is useful for predicting postoperative morbidity in older patients undergoing gastrointestinal surgery: a prospective cohort study.

BACKGROUND: Many assessment tools have been used to identify frail surgical patients. This study was designed to explore the prediction value of the frailty index (FI) for postoperative morbidity in older patients undergoing elective gastrointestinal surgery. METHODS: Between January 2019 and September 2020, we conducted a prospective study in our hospital, and patients aged over 65 years were enrolled. The FI assessment was conducted by two specialist nurses based on the 38-item scale, and patients were considered frail if the FI score was ≥ 0.25. The primary outcome was 30-day postoperative morbidity. Univariable and multivariable analyses were used to find the risk factors related to postoperative morbidity. RESULTS: A total of 246 consecutive patients were enrolled, for whom the median age was 72.0 [interquartile range (IQR): 67.0-77.0] years old, and 175 (71.1%) were male. Of these, 47 (19.1%) were frail. Patients with frailty were associated with older age (p < 0.001), higher American Society of Anesthesiologists (ASA) grade (p = 0.006), lower body mass index (p = 0.001), lower albumin (p = 0.003) and haemoglobin (p < 0.001) levels, increased blood loss (p = 0.034), increased risk of postoperative morbidity (p < 0.001), increased median length of stay (p = 0.017), and increased median postoperative hospital stay (p = 0.003). Multivariable analysis revealed that ASA grade [odds ratio (OR): 2.59, 95% confidence interval (CI) 1.19-5.64, p = 0.016], FI score (OR 7.68, 95% CI 3.19-18.48, p < 0.001) and surgical complexity (OR 22.83, 95% CI 5.46-95.51, p < 0.001) were independent predictors of 30-day postoperative morbidity. However, for patients with major surgery, FI score was the only independent predictor (OR 8.67, 95% CI 3.23-23.25, p < 0.001). CONCLUSION: Frailty was associated with adverse perioperative outcomes, and the 38-item FI scale was a useful frailty screening tool for older patients undergoing elective gastrointestinal surgery. For patients with major surgery, frailty was a more reliable predictor of postoperative 30-day morbidity than age and ASA grade.

A potential target for liver cancer management, lysophosphatidic acid receptor 6 (LPAR6), is transcriptionally up-regulated by the NCOA3 coactivator.

Lysophosphatidic acid receptor 6 (LPAR6) is a G protein-coupled receptor that plays critical roles in cellular morphology and hair growth. Although LPAR6 overexpression is also critical for cancer cell proliferation, its role in liver cancer tumorigenesis and the underlying mechanism are poorly understood. Here, using liver cancer and matched paracancerous tissues, as well as functional assays including cell proliferation, quantitative real-time PCR, RNA-Seq, and ChIP assays, we report that LPAR6 expression is controlled by a mechanism whereby hepatocyte growth factor (HGF) suppresses liver cancer growth. We show that high LPAR6 expression promotes cell proliferation in liver cancer. More importantly, we find that LPAR6 is transcriptionally down-regulated by HGF treatment and that its transcriptional suppression depends on nuclear receptor coactivator 3 (NCOA3). We note that enrichment of NCOA3, which has histone acetyltransferase activity, is associated with histone 3 Lys-27 acetylation (H3K27ac) at the LPAR6 locus in response to HGF treatment, indicating that NCOA3 transcriptionally regulates LPAR6 through the HGF signaling cascade. Moreover, depletion of either LPAR6 or NCOA3 significantly inhibited tumor cell growth in vitro and in vivo (in mouse tumor xenograft assays), similar to the effect of the HGF treatment. Collectively, our findings indicate an epigenetic link between LPAR6 and HGF signaling in liver cancer cells, and suggest that LPAR6 can serve as a biomarker and new strategy for therapeutic interventions for managing liver cancer.

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.

Single-incision versus conventional multiport laparoscopic surgery for colorectal cancer: a meta-analysis of randomized controlled trials and propensity-score matched studies.

PURPOSE: To compare single-incision laparoscopic surgery (SILS) and multiport laparoscopic surgery (MLS) for colorectal cancer in terms of short- and long-term outcomes. METHODS: A systematic literature search was performed in PubMed, Web of Science, and Embase. Randomized controlled trials (RCTs) and propensity-score matched (PSM) studies comparing SILS and MLS for colorectal cancer were enrolled. Outcomes of interests included intraoperative, postoperative, pathological, and survival outcomes. RESULTS: Sixteen studies (6 RCTs and 10 PSM studies) published between 2012 and 2020 with a total of 2425 patients were enrolled. Compared with MLS, SILS was associated with less postoperative pain at postoperative day (POD) 1 (P = 0.02, MWD = -0.73, 95%CI: -1.37, -0.09) and POD2 (P < 0.001, MWD= -1.10, 95%CI: -1.45, -0.74) and shorter length of total incision length (P < 0.001, MWD = -3.31, 95%CI: -3.95, -2.67). No differences were observed in terms of operative time, blood loss, intraoperative and postoperative complications, incision hernia, and pathological or survival outcomes between SILS and MLS. Subgroup analysis for right-sided colon cancer, sigmoid colon cancer, and rectosigmoid colon cancer showed that the SILS group was only associated with less postoperative pain and shorter total incision length. The surgical and pathological outcomes were comparable between SILS and MLS. CONCLUSIONS: SILS is a beneficial alternative to MLS in select colorectal cancer patients, especially for right-sided colon cancer, sigmoid colon cancer, and rectosigmoid cancer, with better cosmetic effects and less postoperative pain. Simultaneously, SILS does not compromise intraoperative and postoperative complications, surgical quality, or long-term outcomes.

Diagnosis and treatment of obturator hernia: retrospective analysis of 86 clinical cases at a single institution.

BACKGROUND: To explore the clinical characteristics, diagnosis and treatment of obturator hernia. METHODS: Eighty-six patients who were diagnosed as obturator hernia by abdominal CT in the Department of Gastrointestinal Surgery of our hospital between 2009 and 2019 were enrolled in this study. Patient characteristics, surgical method, postoperative complications and mortalities were retrospectively reviewed. RESULTS: Thirty days mortality rate of 5.5% and 46.1% were observed in surgery group and non-surgery group, respectively. Surgery was performed as an emergency procedure in 59 cases and elective procedure in 14 cases depending on different hernia contents, intestinal necrosis and signs of peritonitis. In the emergency surgery group, segmental intestinal resection with anastomosis was performed in 24 patients (24/59, 40.7%). There were 4 deaths (4/59, 6.8%) in this group, all of which occurred in patients undergoing SI resections. In contrast, no bowel resection, postoperative complications, or death occurred in the elective surgery group. 3-year recurrence rates of 5.1% (3/59) and 7.1% (1/14) were observed in the emergency surgery and the elective surgery group, respectively. CONCLUSIONS: CT examination plays an important role in improving the diagnostic rate of obturator hernia. Timely surgical treatment is the key to improve the efficacy of obturator hernia and prevent the deterioration of the condition. In addition, intestinal resection and postoperative complications may be the important factors leading to postoperative death.

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.

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.

miR-203 inhibits cell proliferation and ERK pathway in prostate cancer by targeting IRS-1.

INTRODUCTION: Prostate cancer (PCa) is one of the most common types of cancer in men. In the course of the development and progression of this disease, abnormal expression of miR-203 is usually accompanied. However, its role in prostate tumorigenesis and the underlying mechanism are poorly understood. METHODS: Dual luciferase reporter gene analysis was used to detect miR-203 binding site in insulin receptor substrates 1 (IRS-1). Cell proliferation was assessed by MTT assay in PCa cells with either IRS-1 knockdown or miR-203 overexpression. IRS-1 and other proteins expression in PCa cells was assessed by Western Blot. RESULTS: we found that the insulin receptor substrates 1 (IRS-1) is a novel target of miR-203 in PCa and miR-203 can specifically bind to the 3'UTR region of the IRS-1 thus suppresses its expression. Moreover, we demonstrate that miR-203 functions as a tumor suppressor by directly targeting IRS-1 to inhibit cell proliferation and migration which results in PCa cell cycle arrest. Importantly, miR-203 overexpression blocks ERK signalling pathway by down-regulating IRS-1 expression. CONCLUSIONS: Our results show a novel link between miR-203 and IRS-1, and reveal the importance of strict control of IRS - 1 by miR-203 in the progression of PCa, suggesting miR-203 may act as a promising target for the diagnosis and treatment of advanced PCa.

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.

Low-residual diet versus clear-liquid diet for bowel preparation before colonoscopy: meta-analysis and trial sequential analysis of randomized controlled trials.

BACKGROUND AND AIMS: The aim of this study was to compare a low-residual diet (LRD) with a clear-liquid diet (CLD) for bowel preparation before colonoscopy. METHODS: A systematic literature search was performed in PubMed, Ovid, and Cochrane databases for randomized clinical trials comparing LRD with CLD for bowel preparation before colonoscopy. The last search was performed on September 20, 2019. The primary outcome was adequate bowel preparation. The outcomes were compared using systematic review with meta-analysis and trial sequential analysis (TSA). RESULTS: Twenty randomized controlled trials published between 2005 and 2019 with 4323 participants were included. LRD was comparable with CLD for adequate bowel preparation (P = .79; odds ratio [OR], 0.96; 95% confidence interval [CI], 0.72-1.29). The detection rates for polyps (P = .68; OR, 1.04; 95% CI, 0.86-1.27) or adenomas (P = .78; OR, 1.03; 95% CI, 0.86-1.23) were similar between the groups. There were significantly fewer advents in individuals in the LRD group: nausea (P = .02; OR, 0.72; 95% CI, 0.56-0.94), vomiting (P = .04; OR, 0.61; 95% CI, 0.38-0.98), hunger (P < .001; OR, 0.36; 95% CI, 0.24-0.53), and headache (P = .02; OR ,0.64; 95% CI, 0.44-0.93). In addition, significantly more individuals in the LRD group found it easy to complete the diet (P = .01; OR, 1.86; 95% CI, 1.15-3.00) and showed willingness to repeat it (P = .005; OR, 2.23; 95% CI, 1.28-3.89). TSA demonstrated that the cumulative Z curve crossed both the traditional boundary and the trial sequential monitoring boundary for adequate bowel preparation. CONCLUSION: The present study demonstrated that LRD was comparable with CLD in the quality of bowel preparation before colonoscopy. More clinical trials are needed to confirm other outcomes.

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.