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As science and technology have advanced, surgical techniques have become increasingly sophisticated. A revolution was triggered by the appearance of new electrical and optical instruments, shifting the field of surgery in the direction of "minimally invasive" and "noninvasive" procedures. Natural orifice specimen extraction surgery has emerged as a rising star in the field of minimally invasive surgery. It has increased rapidly, and it has become a hot topic in recent years. Natural orifice specimen extraction surgery has shown advantages in alleviating postoperative pain, improving bowel movements, providing a cosmetic effect, and improving psychological state without adversely affecting cancer outcomes. Different approaches have been classified and summarized for natural orifice specimen extraction surgery based on the procedure for specimen extraction and the location of the tumor, and natural orifice specimen extraction surgery can be used in resection all parts of the colorectum. The international natural orifice specimen extraction surgery consensus and monograph have also been published to improve the standardization of the application of this technique. Additional steps need to be taken to standardize natural orifice specimen extraction surgery, such as conducting large-scale randomized controlled trials, establishing a training system, and developing specific tools. Still, the natural orifice specimen extraction surgery procedure continues to follow the development of minimally invasive surgery and may be one of the future treatment options.

Because of its significant advantage of fast postoperative recovery, natural orifice specimen extraction surgery (NOSES) has attracted increasing attention worldwide. However, the NOSES in gastric cancer (GC) treatment still needs more clinical practice, especially for the rare anatomical anomaly. Situs inversus totalis (SIT) is a rare autosomal recessive anatomical anomaly with an incidence ranging between 1/8,000 and 1/25,000 births. We present a video of transvaginal specimen extraction following totally laparoscopic D2 distal gastrectomy performed in a 59-year-old woman known to have SIT. Preoperative investigations revealed that the patient had early GC at the antrum. A gastroscopy report from the local hospital showed signet-ring cell carcinoma. The preoperative computed tomography scan revealed irregular thickening of the gastric wall at the junction of the greater curvature and antrum without metastasis to the lymph nodes. In total, laparoscopic D2 distal gastrectomy was performed with transvaginal specimen extraction. Billroth II with Braun anastomosis was performed for reconstruction. The length of the operation was 240 min without intraoperative complications and with minimal blood loss of 50 ml. The patient was uneventfully discharged on postoperative Day 7. The final pathology confirmed signet-ring cell carcinoma confined to the mucosal muscle without metastasis in 16 lymph nodes. Transvaginal specimen extraction following totally laparoscopic D2 distal gastrectomy can be safely performed in patients with SIT and has similar surgical outcomes to usual laparoscopic gastrectomy.

Objective To compare the short-term efficacy indicators of laparoscopic technique and open surgery in patients with rectal cancer surgery, and to further evaluate the safety and efficacy of laparoscopic rectal cancer surgery. Methods This study adopted a prospective multicenter, open-label, non-randomized concurrent control method to analyze patients who received rectal cancer surgery from 10 colorectal tumor centers across the country from January 2017 to December 2018. The two groups of patients received laparoscopic-assisted surgery and conventional open surgery respectively. All surgeons were selected according to relevant standards and participated in the two groups of operations at the same time. Comprehensive evaluation and analysis of the operation and postoperative recovery, postoperative pathological results, survival information, postoperative related functional scores and other indicators. Results In the open surgery group, the proportion of tumors with a maximum diameter of more than 5 cm was higher (χ2 = 0.089, P = 0.018), and the proportion of T4 was higher (χ2 = 0.478, P P P P P = 0.105), but the incidence of incision infection was lower in the laparoscopy group (χ2 = 0.19, P P = 0.170). Multivariate analysis suggested that intraoperative blood loss, T stage, N stage, nerve invasion, and postoperative sepsis were independent prognostic factors for disease-free survival. Wexner score, IPSS score and LARS score were not statistically different between the two groups. Conclusion The pathological results and short-term outcomes of laparoscopic surgery for rectal cancer are comparable to those of conventional open surgery, and laparoscopic surgery is safe and feasible for rectal cancer patients.

Introduction This study aimed to compare the short-term and survival outcomes in laparoscopic low rectal cancer surgery with three different specimen extraction techniques, and whether it affects loop ileostomy closure. Materials and methods A consecutive series of patients with low rectal cancer who underwent laparoscopic low anterior resection plus protective loop ileostomy (LAR-PLI) were enrolled. Three main techniques, namely specimen extraction through auxiliary incision (EXAI), specimen extraction through stoma incision (EXSI), and specimen eversion and extra-abdominal resection (EVER), were employed. The postoperative short-term and survival outcomes of the three techniques and the impact on loop ileostomy closure were compared. Results In all, 254 patients were enrolled in this study: 104 (40.9%) in the EXAI group, 104 (40.9%) in the EXSI group, and 46 (18.1%) in the EVER group. For primary surgery, EXAI group had significantly longer operative time (P Conclusions Our single-center results found that in LAR-PLI surgery for low rectal cancer, the short-term outcomes of specimen extraction through the stoma incision or anus were better than that through the auxiliary incision, but the 3-year LRFS was no statistically different.

Colorectal cancer (CRC) is the second most common cause of cancer-related death among both men and women worldwide and the third most common cancer overall. About 20% of patients diagnosed with CRC were discovered to have distant metastatic lesions, the majority of which were located in the liver. For the optimum treatment of CRC patients with hepatic metastases, interventional radiologists, medical oncologists, and surgeons must all collaborate. The surgical excision of the primary tumor is an important part of CRC treatment since it has been found to be curative in cases of CRC with minimal metastases. However, given the evidence to date was gathered from retrospective data, there is still controversy over the effectiveness of primary tumor resection (PTR) in improving the median overall survival (OS) and quality of life. Patients who have hepatic metastases make up a very tiny fraction of those who are candidates for resection. With a focus on the PTR, this minireview attempted to review the current advancements in the treatment options for hepatic colorectal metastatic illness. This evaluation also included information on PTR’s risks when performed on individuals with stage IV CRC.

Background The diagnostic criteria and effect of persistent descending mesocolon (PDM) on sigmoid and rectal cancers (SRCs) remain controversial. This study aims to clarify PDM patients' radiological features and short-term surgical results. Method From January 2020 to December 2021, radiological imaging data from 845 consecutive patients were retrospectively analyzed using multiplanar reconstruction (MRP) and maximum intensity projection (MIP). PDM is defined as the condition wherein the right margin of the descending colon is located medially to the left renal hilum; this is usually proved intraoperatively. The anatomical features and surgical results of PDM patients were compared with those of non-PDM patients. Results The frequency of PDM was 3.8%. The lengths from the inferior mesenteric artery (IMA) to the inferior mesenteric vein (1.6 vs. 2.5 cm, p＜0.001), IMA to marginal artery arch (2.7 vs. 8.4 cm, p＜0.001), and IMA to the colon (3.5 vs. 9.8 cm, p＜0.001) were significantly shorter in the PDM group than those in the non-PDM group. The conversion to open surgery (12.5% vs. 1.2%, p=0.001), operative time (207.5 vs. 156 min, p=0.001), intraoperative blood loss (p＜0.001), marginal arch injury (15.6% vs. 1.1%, p＜0.001), splenic flexure free (21.9% vs. 3.3%, p＜0.001), and Hartmann procedure (15.6% vs. 0.1%, p＜0.001) were significantly higher in the PDM group. Moreover, PDM was an independent risk factor for prolonged operative time (OR=3.205, p=0.004) and anastomotic failure (OR=7.601, p=0.003). Conclusion PDM was an independent risk factor for prolonged operative time and anastomotic failure in SRC surgery. Preoperative radiological evaluation using MRP and MIP can help surgeons better handle this rare congenital variant.

Background There are different surgical strategies that can treat synchronous colorectal cancer (SCRC) involving separate segments, namely extensive resection (EXT) and left hemicolon-sparing resection (LHS). We aim to comparatively analyze short-term surgical results, bowel function, and long-term oncological outcomes between SCRC patients treated with the two different surgical strategies. Methods One hundred thirty-eight patients with SCRC lesions located in the right hemicolon and rectum or sigmoid colon were collected at the Cancer Hospital, Chinese Academy of Medical Sciences, and the Peking University First Hospital from January 2010 to August 2021 and divided into EXT group (n = 35) and LHS group (n = 103), depending on their surgical strategies. These two groups of patients were compared for postoperative complications, bowel function, the incidence of metachronous cancers, and prognosis. Results The operative time for the LHS group was markedly shorter compared with the EXT group (268.6 vs. 316.9 min, P = 0.015). The post-surgery incidences of total Clavien-Dindo grade ≥ II complications and anastomotic leakage (AL) were 8.7 vs. 11.4% (P = 0.892) and 4.9 vs. 5.7% (P = 1.000) for the LHS and EXT groups, respectively. The mean number of daily bowel movements was significantly lower for the LHS group than for the EXT group (1.3 vs. 3.8, P P = 0.037). No metachronous cancer was found in the residual left colon during the 51-month (median duration) follow-up period. The overall and disease-free survival rates at 5 years were 78.8% and 77.5% for the LHS group and 81.7% and 78.6% for the EXT group (P = 0.565, P = 0.712), respectively. Multivariate analysis further confirmed N stage, but not surgical strategy, as the risk factor that independently affected the patients’ survival. Conclusions LHS appears to be a more appropriate surgical strategy for SCRC involving separate segments because it exhibited shorter operative time, no increase in the risk of AL and metachronous cancer, and no adverse long-term survival outcomes. More importantly, it could better retain bowel function and tended to reduce the severity of LARS and therefore improve the post-surgery life quality of SCRC patients.

With its great advantages of fast post-operative recovery, natural orifice specimen extraction surgery (NOSES) has attracted increasingly attention worldwide. However, the NOSES in gastric cancer (GC) treatment still needs more clinical practice, especially for the rare anatomical anomaly. Situs inversus totalis (SIT) is a rare autosomal recessive anatomical anomaly with an incidence ranging between 1/8,000 and 1/25,000 births. We present a video of transvaginal specimen extraction following totally laparoscopic D2 distal gastrectomy performed in a 59-year-old female known to have SIT. Preoperative investigations revealed that the patient had early gastric cancer at the antrum. A gastroscopy report from the local hospital showed signet-ring cell carcinoma. The preoperative computed tomography scan revealed irregular thickening of the gastric wall at the junction of the greater curvature and antrum without metastasis to the lymph nodes. In total, laparoscopic D2 distal gastrectomy was performed with transvaginal specimen extraction. Billroth II with Braun anastomosis was performed for reconstruction. The length of the operation was 240 min without intraoperative complications and minimal blood loss of 50 ml. The patient was uneventfully discharged on postoperative Day 7. The final pathology confirmed signet-ring cell carcinoma confined to the mucosal muscle without metastasis in 16 lymph nodes. Transvaginal specimen extraction following totally laparoscopic D2 distal gastrectomy can be safely performed in patients with SIT and has similar surgical outcomes as usual laparoscopic gastrectomy.

Figure S1: Distribution of CAG repeat length in different centers. Table S1: Clinical and pathological characteristics of patients. Table S2: Comparison of CAG repeat length. Table S3: Comparison of AR expression. Table S4: relationship of CAG repeat length and AR expression in CRC patients.

Although somatic alterations in CAG repeats in the androgen receptor (AR) gene have been suggested to predispose to colorectal cancer, less is known about AR in colorectal cancer carcinogenesis. Because of lack of relevant analysis on CAG repeat length and AR expression in colorectal cancer, we aimed to investigate the prognostic value of polymorphic CAG and protein expression of the AR gene in patients with colorectal cancer. A case–control study was carried out on 550 patients with colorectal cancer and 540 healthy controls to investigate whether polymorphic CAG within the AR gene is linked to increased risk for colorectal cancer. Polymorphic CAG and AR expression were analyzed to clarify their relationship with clinicopathologic and prognostic factors in patients with colorectal cancer. The study showed that the AR gene in patients with colorectal cancer had a longer CAG repeat sequence than those in the control group, as well as increased risk for colorectal cancer among females (P = 0.013), males (P = 0.002), and total colorectal cancer population (P < 0.001), respectively. AR expression exhibited a significant difference in long CAG repeat sequence among males (P < 0.001), females (P < 0.001), and total colorectal cancer study population (P < 0.001). Both long CAG repeat sequence and negative AR expression were associated with a short 5-year overall survival (OS) rate in colorectal cancer. Long CAG repeat sequences and the absence of AR expression were closely related to the development of colorectal cancer. Both long CAG and decreased AR expression were correlated with the poor 5-year OS in patients with colorectal cancer. Mol Cancer Ther; 14(4); 1066–74. ©2015 AACR.

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PurposeTotal laparoscopic anterior resection (tLAR) has been gradually applied in the treatment of rectal cancer (RC). This study aims to develop a scoring system to predict the surgical difficulty of tLAR.MethodsRC patients treated with tLAR were collected. The blood loss and duration of excision (BLADE) scoring system was built to assess the surgical difficulty by using restricted cubic spline regression. Multivariate logistic regression was used to evaluate the effect of the BLADE score on postoperative complications. The random forest (RF) algorithm was used to establish a preoperative predictive model for the BLADE score.ResultsA total of 1,994 RC patients were randomly selected for the training set and the test set, and 325 RC patients were identified as the external validation set. The BLADE score, which was built based on the thresholds of blood loss (60 ml) and duration of surgical excision (165 min), was the most important risk factor for postoperative complications. The areas under the curve of the predictive RF model were 0.786 in the training set, 0.640 in the test set, and 0.665 in the external validation set.ConclusionThis preoperative predictive model for the BLADE score presents clinical feasibility and reliability in identifying the candidates to receive tLAR and in making surgical plans for RC patients.

PurposeRecently, totally laparoscopic ileostomy reversal (TLAP) has received increasing attention and exhibited promising short-term outcomes. The aim of this study was to detail the learning process of the TLAP technique.MethodsBased on our initial experience with TLAP from 2018, a total of 65 TLAP cases were enrolled. Demographics and perioperative parameters were assessed using cumulative sum (CUSUM), moving average, and risk-adjusted CUSUM (RA-CUSUM) analyses.ResultsThe overall mean operative time (OT) was 94 min and the median postoperative hospitalization period was 4 days, and there was an estimated 10.77% incidence rate of perioperative complications. Three unique phases of the learning curve were derived from CUSUM analysis, and the mean OT of phase I (1–24 cases) was 108.5 min, that of phase II (25–39 cases) was 92 min, and that of phase III (40–65 cases) was 80 min, respectively. There was no significant difference in perioperative complications between these 3 phases. Similarly, moving average analysis indicated that the operation time was reduced significantly after the 20th case and reached a steady state after the 36th case. Furthermore, complication-based CUSUM and RA-CUSUM analyses indicated an acceptable range of complication rates during the whole learning period.ConclusionOur data demonstrated 3 distinct phases of the learning curve of TLAP. For an experienced surgeon, surgical competence in TLAP can be grasped at around 25 cases with satisfactory short-term outcomes.

Tears of the medial collateral ligament of the knee are common and often managed non-operatively [1]. Grade 3 tears that fail to heal are often treated with surgical repair through an open incision on the medial aspect of the knee. Many other ligament injuries of the knee are now managed with arthroscopic surgery. This has not yet been described for medial collateral ligament injuries of the knee. We describe a new arthroscopically assisted technique for MCL repair after grade III injury which avoids some of these complications.

BackgroundRecently, totally laparoscopic (TLAP) surgery has suggested its potential on ileostomy reversal. This study aimed to compare the short-term outcomes between TLAP and traditional open ileostomy reversal.Patients and methodsFrom September 2016 to September 2021, 107 eligible patients underwent TLAP (n = 48) or open (n = 59) loop ileostomy reversal were retrospectively enrolled. Surgical parameters, postoperative recovery and complications were identified and compared between TLAP technique vs. open surgery.ResultsThe operation time and estimated blood loss showed no obvious difference between TLAP and open group. However, TLAP reversal significantly decreased the incision length (4.5cm vs. 6cm, P P P = 0.004) and shorter postoperative stay (5 days vs. 7 days, P = 0.007). More importantly, postoperative complications were significantly reduced after TLAP reversal (3 cases vs. 10 cases, P = 0.026). Further logistic regression analyses also indicated the TLAP technique was associated with lower incidence of complications (OR=3.316, CI, 1.118–9.835; P = 0.031).ConclusionsTLAP surgery is competitive in promoting postoperative recovery as well as reducing complications compared to the traditional open ileostomy reversal.

Background Colorectal cancer (CRC) is a common malignant cancer with a poor prognosis. Liver metastasis is the dominant cause of death in CRC patients, and it often involves changes in various gene expression profiling. This study proposed to construct and validate a risk model based on differentially expressed genes between primary and liver metastatic tumors from CRC for prognostic prediction. Methods Transcriptomic and clinical data of CRC were downloaded from The Cancer Genome Atlas database (TCGA) and Gene Expression Omnibus database (GEO). Identification and screening of candidate differentially expressed genes (DEGs) between liver metastatic tissues and corresponding primary tumors were conducted by R package “limma” and univariate Cox analysis in the GSE50760 and TCGA cohort. Last, absolute shrinkage and selection operator (LASSO) Cox regression was carried out to shrink DEGs and develop the risk model. CRC patients from the GSE161158 cohort were utilized for validation. Functional enrichment, CIBERSORT algorithm, and ESTIMATE algorithm for further analysis. Results An 8-gene signature risk model, including HPD, C8G, CDO1, FGL1, SLC2A2, ALDOB, SPINK4, and ITLN1, was developed and classified the CRC patients from TCGA and GEO cohorts into high and low-risk groups. The high-risk group has a worse prognosis compared with the low-risk group. The model was verified as an independent indicator for prognosis. Moreover, tumor immune infiltration analyses demonstrated that monocytes (P = 0.006), macrophage M0 (P

Yuchen Zhong,1,2 Tianyi Ma,1 Tianyu Qiao,1 Hanqing Hu,1 Zhengliang Li,1 Kangjia Luo,1 Yuliuming Wang,1 Qingchao Tang,1 Guiyu Wang,1,2 Rui Huang,1 Xishan Wang3 1Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150080, People’s Republic of China; 2Department of Colorectal Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, 310002, People’s Republic of China; 3Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Cancer, Beijing, 100021, People’s Republic of ChinaCorrespondence: Guiyu Wang; Rui HuangDepartment of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150080, People’s Republic of ChinaTel/Fax +86-19558225177; +86-15204620800Email guiyWang@163.com; huangrui2019@163.comObjective: To investigate the relationship between circulating tumor cells (CTCs) and their subpopulations and colorectal cancer (CRC). To explore the application of CTCs’ numbers and positive rates in the diagnosis and treatment of CRC, and to assess the effect of surgery on CTCs numbers and positivity.Methods: We identified CTCs using the CanPatrol technique after enrollment. Peripheral blood samples were collected from 74 CRC patients before anti-tumor treatment. CTCs can be divided into the following three phenotypes: epithelial CTCs (E-CTCs) (EpCAM+, Vimentin-), mesenchymal CTCs (M-CTCs) (EpCAM-, Vimentin+), and mixed CTCs (E/M-CTCs) (EpCAM+, Vimentin+). CTCs and the proportion of subtypes were statistically compared with clinicopathological characteristics.Results: The positive rate of M-CTCs was significantly higher in patients with tumor size ≥ 5 cm (85.7% vs 49.1%, P = 0.004) and carcinoembryonic antigen (CEA) > 5 ng/mL (83.3% vs 51.0% p = 0.024). Moreover, the T stage (T1 0, T2 33.3%, T3 59.4%, T4 100%, p < 0.0005) and TNM stage (stage I 11.8%, stage II 79.2%, stage III 64.3%, stage IV 100%, p < 0.0005) were correlated with the positive rate of M-CTCs. We also found that the proportion of M-CTCs was correlated with the T stage (p < 0.0005) and TNM stage (p=0.0200), but not with the N stage (p=0.6889). In survival analysis, M-CTCs > 1 were found associated with worse disease-free survival (p=0.007). After treatment, the number and proportion of CTCs and M-CTCs were significantly reduced.Conclusion: The positive rate of M-CTCs was associated with tumor size, T stage, TNM stage, vascular invasion, and CEA. As the disease progressed, the proportion of M-CTCs gradually increased, and the survival performance was worse in patients with a high positive rate of M-CTCs.Keywords: circulating tumor cells, colorectal cancer, surgery, EMT

Whether natural orifice specimen extraction surgery (NOSES) could provide beneficial effects in treating elderly patients is still under debate. The aim of the study was to compare the clinical outcomes of transanal NOSES with conventional laparoscopic-assisted resection (LA) in elderly colorectal cancer (CRC) patients. A retrospective analysis from the Second Affiliated Hospital of Harbin Medical University between 2013 and 2017 was performed. Outcomes related to surgery, body image, quality of life, anal function and long-term survival were compared between the two groups with the propensity-score matching (PSM) method. After PSM, 78 patients were successfully compared. Patients with NOSES had faster gastrointestinal function recovery (P = 0.028), less postoperative complications (P = 0.025), lower pain scores on days 1, 3 and 5 after surgery (P

Introduction: The aim of this study was to compare whether laparoscopic low rectal cancer surgery with three different specimen extraction methods affects loop ileostomy closure. Materials and methods: A consecutive series of patients with low rectal cancer who underwent laparoscopic low anterior resection plus protective loop ileostomy (LAR-PLI) were enrolled. Three main techniques, namely specimen extraction through auxiliary incision (EXAI), specimen extraction through stoma incision (EXSI), and specimen eversion and extra-abdominal resection (EVER), were employed. The postoperative outcomes of the three techniques and the impact on loop ileostomy closure were compared. Results: In all, 254 patients were enrolled in this study: 104 (40.9%) in the EXAI group, 104 (40.9%) in the EXSI group, and 46 (18.1%) in the EVER group. For primary surgery, EXAI group had significantly longer operative time (PConclusions: All three techniques of LAR-PLI for low rectal cancer were safe and feasible, but specimen extraction via EXAI had no advantages in terms of early postoperative recovery and loop ileostomy closure.

BackgroundLymphangiomatosis is an extremely rare disease with potential soft tissue, bone, and spleen involvement, which can be characterized by lymphangioma. Only a few cases of colon and mesenteric lymphangiomatosis have been reported. We report a case presenting with fatigue, periumbilical pain, and intermittent bloody stools. This patient underwent a series of examinations. Exploratory laparoscopy, in particular, yielded very valuable images and videos for this disease, which can provide evidence for the diagnosis of this disease.Case summaryThe current patient had fatigue, periumbilical pain, and intermittent bloody stools. Colonoscopy indicated numerous variable-sized hyaline cysts in the colon. Submucosal puncture was performed during colonoscopy. The patient was readmitted to the hospital due to periumbilical pain. B-ultrasound and abdominal CT showed multiple hypoechoic nodules in the mesenteric area. Exploratory laparoscopy was performed, and histopathology revealed that D2-40 was positive. Based on auxiliary examination and laparoscopic biopsy, surgeons and pathologists reached the diagnosis of mesenteric lymphangiomatosis.ConclusionClinicians need to comprehensively improve their knowledge of lymphangiomatosis, and the combination of clinical symptoms, histological characteristics, and colonoscopy biopsy findings should be considered to improve lymphangiomatosis diagnosis, thereby reducing misdiagnosis.Core tipColon and mesenteric lymphangiomatosis is an extremely uncommon benign condition of unknown etiology and pathogenesis in adult patients. We report a case of mesenteric lymphangiomatosis in a 37-year-old woman who presented with fatigue, periumbilical pain, and intermittent bloody stools, as well as lesions in the kidney, spleen, and bones. This case provides new insights into the diagnosis and treatment of this disease.

Background Distant metastasis (DM) is an important prognostic factor and determines the following treatments in patients with colorectal cancer (CRC). The purpose of this study was to construct prediction models for DM in patients with CRC based on machine learning. Methods CRC patients between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were identified. Prediction models for DM were developed by applying four machine-learning methods including eXtreme Gradient Boost (XGB), decision tree (DT), random forest (RF), and support vector machine (SVM). The performance of models was quantitatively assessed by receiver operating characteristics (ROC) curve, calibration curve and decision curve analysis (DCA) curve. The SHapley Additive exPlanation (SHAP) method was used for visualization analysis to better explain the results of the machine learning models. Results A total of 51788 patients were identified in the SEER database. ROC curves exhibited excellent accuracy of machine learning models. Calibration curves for the probability of DM showed good agreement between model prediction and actual observation in both the training and validation cohorts. The DCA demonstrated that each machine learning model can provide net benefits with treat-none and treat-all strategies. In the SHAP summary plot of the RF and XGB models, carcinoembryonic antigen (CEA), N stage, T stage and tumor deposits were identified as the most important risk factors for DM. Conclusion The XGB and RF were ideal machine learning models and showed that CEA, N stage, T stage and tumor deposits were the most important DM-related risk factors.

BackgroundRadiation therapy (RT) is a standard treatment for the local control of primary pelvic cancers (PPC), yet the risk of second corpus uteri cancer (SCUC) in PPC patients undergoing RT is still controversial. This study investigated the impact of RT on the risk of SCUC and assessed the survival outcome.MethodsWe queried nine cancer registries for PPC cases in the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence of SCUC was analyzed using Cox regression and Fine–Gray competing risk regression analysis. The Poisson regression analysis was employed to assess the standardized incidence ratios (SIRs) and radiation-attributed risk (RR) for SCUC. We evaluated the overall survival of patients with SCUC using the Kaplan–Meier method.ResultsReceiving radiotherapy was strongly associated with a higher risk of developing SCUC for PPC patients in Fine–Gray competing risk regression (No-RT vs. RT: adjusted HR = 1.77; 95% CI, 1.40–2.28; p < 0.001). The incidence of SCUC in PPC patients who received RT was higher than in the US general population (SIR, 1.66; 95% CI, 1.41–1.93; p < 0.05), but the incidence of SCUC in patients who did not receive RT was lower than with the US general population (SIR, 0.68; 95% CI, 0.61–0.75; p < 0.05). The dynamic SIR and RR for SCUC decreased with decreasing age at PPC diagnosis and decreased with time progress. In terms of overall survival, 10-year survival rates with SCUC after No-RT (NRT) and SCUC after RT were 45.9% and 25.9% (HR = 1.82; 95% CI, 1.46–2.29; p < 0.001), respectively.ConclusionRadiotherapy for primary pelvic cancers is associated with a higher risk of developing SCUC than patients unexposed to radiotherapy. We suggest that patients with pelvic RT, especially young patients, should receive long-term monitoring for the risk of developing SCUC.

Background: The type 2 mannose receptor C (MRC2) is involved in tumor biological processes and plays a new role in the remodeling of the extracellular matrix turnover. Previous studies have demonstrated MRC2 expression profiling and prognostic relevance in some tumor types. However, the clinical and immunotherapeutic value of MRC2 in pan-cancers remains controversial. Our study aimed to evaluate MRC2 expression pattern, clinical characteristics and prognostic significance in 33 cancers, explore the relationship between MRC2 and immune-related characteristics, and assess the prediction of MRC2 for the immunotherapeutic response.Methods: Transcriptional and clinical data of 33 cancers were downloaded from The Cancer Genome Atlas database (TCGA) database and two independent immunotherapeutic cohorts were obtained from GSE67501 and the IMvigor210 study. Next, patients stratified by MRC2 expression levels were displayed by Kaplan-Meier plot to compare prognosis-related indexes. Meanwhile, immune infiltrates of different cancers were estimated by tumor immune estimation resources (TIMER) and CIBERSORT. The ESTIMATE algorithm was used to estimate the immune and stromal scores in tumor tissues. MRC2 expression and immunological modulators, including immune inhibitors, immune stimulators, and MHC molecules, were screened through the TISIDB portal. Gene-set enrichment analysis analyses were performed to explore the underlying biological process of MRC2 across different cancers. The immunotherapeutic response prediction was performed in two independent cohorts (GSE78220: metastatic melanoma with pembrolizumab treatment and IMvigor210: advanced urothelial cancer with atezolizumab intervention).Results: MRC2 is expressed differently in many cancers and has been shown to have potential prognostic predicting significance. MRC2 was significantly associated with immune cell infiltration, immune modulators, and immunotherapeutic markers. Notably, the immunotherapeutic response group was associated with lower MRC2 expression in metastatic melanoma and advanced urothelial carcinoma cohort.Conclusion: This study demonstrated that MRC2 could be a prognostic indicator for certain cancer and is critical for tumor immune microenvironments. MRC2 expression level may influence and predict immune checkpoint blockade response as a potential indicator.

BackgroundRecent data based on large databases show that bowel preparation (BP) is associated with improved outcomes in patients undergoing elective colorectal surgery. However, it remains unclear whether BP in elective colectomies would lead to similar results in patients with diverticulitis. The purpose of this study was to investigate whether bowel preparation affected the surgical site infections (SSI) and anastomotic leakage (AL) in patients with diverticulitis undergoing elective colectomies.Study designWe identified 16,380 diverticulitis patients who underwent elective colectomies from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) colectomy targeted database (2012–2017). Multivariate logistic regression models were employed to investigate the impact of different bowel preparation strategies on postoperative complications, including SSI and AL.ResultsIn the identified population, a total of 2524 patients (15.4%) received no preparation (NP), 4715 (28.8%) mechanical bowel preparation (MBP) alone, 739 (4.5%) antibiotic bowel preparation (ABP) alone, and 8402 (51.3%) MBP + ABP. Compared to NP, patients who received any type of bowel preparations showed a significantly decreased risk of SSI and AL after adjustment for potential confounders (SSI:MBP[OR = 0.82, 95%CI: 0.70–0.96],ABP[0.69, 95%CI: 0.52–0.92]; AL:MBP[OR = 0.66, 95%CI: 0.51–0.86],ABP[0.56, 95%CI: 0.34–0.93]), where the combination type of MBP + ABP had the strongest effect (SSI:OR = 0.58, 95%CI:0.50–0.67; AL:OR = 0.46, 95%CI:0.36–0.59). The significantly decreased risk of 30-day mortality was observed in the bowel preparation of MBP + ABP only (OR = 0.32, 95%CI: 0.13–0.79). After the further stratification by surgery procedures, patients who received MBP + ABP showed consistently lower risk for both SSI and AL when undergoing open and laparoscopic surgeries (Open:SSI[OR = 0.51, 95%CI: 0.37–0.69],AL[OR = 0.47, 95%CI: 0.25–0.91]; Laparoscopic:SSI[OR = 0.58, 95%CI: 0.47–0.72, AL[OR = 0.49, 95%CI: 0.35–0.68]).ConclusionsMBP + ABP for diverticulitis patients undergoing elective open or laparoscopic colectomies was associated with decreased risk of SSI, AL, and 30-day mortality. Benefits of MBP + ABP for diverticulitis patients underwent robotic surgeries warrant further investigation.

Background and purpose Comprehensive geriatric assessment (CGA) is a diagnostic method to assess the physical and mental health status of older patients. The purpose of this study was to assess the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for intermediate or locally advanced rectal cancer in older people who were classified as “fit” by CGA. The interim analysis focusing on safety was reported here as the first part of this trial. Methods and materials This is a single arm, multicenter, phase II trial. The eligible patients for this study were aged 70 years or above that fulfilled the standard of intermediate or locally advanced risk category, and met the standard of fit (SIOG1) evaluated by CGA. All patients received preCRT (50 Gy) with Raltitrexed (3 mg/m2 on d1 and d22). Qualitative and quantitative variables were described using descriptive statistics. The surgery adherence predicting was analyzed by multivariate logistic regression. Results Thirty-nine fit patients were enrolled. All patients except one finished radiotherapy without dose reduction. Thirty-two patients finished the prescribed Raltitrexed therapy as scheduled. A serious toxicity was observed in 12 patients (30.8%), and only six patients (15.4%) experienced non-hematological side effects. Conclusion Overall, our results showed that preCRT was feasible and safe in older patients with rectal cancer who were evaluated as fit based on CGA, supporting the use of CGA to tailor oncological treatment and predict the tolerance of a specific therapy. Completing this trial as planned would provide further valuable insights.

Tianyi Ma,1 Tianyu Qiao,1 Ziming Yuan,1 Guiyu Wang,1 Rui Huang,1 Meng Wang,1 Hanqing Hu,1 Yihao Zhu,1 Xiaoming Zou,2 Xishan Wang1,3 1Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China; 2Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China; 3Department of Colorectal Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, People’s Republic of ChinaCorrespondence: Xiaoming Zou; Xishan Wang Email zou4930@163.com; wxshan1208@126.comBackground: The identification of cancer-associated long noncoding RNAs and the investigation of their molecular and biological functions are important for understanding the molecular biology and progression of cancer. JAKMIP2-AS1 has not been reported in the literature, especially in the context of colorectal cancer. The aim of the present study was to examine the expression pattern of JAKMIP2-AS1 in colorectal cancer (CRC) and evaluate its biological role and clinical significance in tumor progression.Methods: JAKMIP2-AS1 expression was analyzed in 56 CRC tissues and nine CRC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Overexpression and RNA interference (RNAi) approaches were used to investigate the biological functions of JAKMIP2-AS1. The effect of JAKMIP2-AS1 on proliferation was evaluated by CCK-8, colony formation, and EdU assays. Subcutaneous injection of cells was used to study proliferation in BALB/c nude male mice. Proliferation-related protein levels were examined by immunohistochemical analysis. Differences between groups were tested for significance using Student’s t-test (two-tailed).Results: JAKMIP2-AS1 was highly expressed in both CRC samples and cell lines compared with the corresponding normal counterparts. The upregulation of JAKMIP2-AS1 expression promoted the proliferation of colorectal cancer cells. Moreover, patients with high levels of JAKMIP2-AS1 expression had a relatively poor prognosis. Inhibition of JAKMIP2-AS1 by RNAi decreased the proliferation of CRC cells in vitro and impeded cell growth in vivo. Ki-67 and PCNA levels were affected by JAKMIP2-AS1 knockdown or overexpression in vivo.Conclusion: Our findings indicate that JAKMIP2-AS1 is significantly upregulated in CRC tissues and regulates CRC cell proliferation. Thus, JAKMIP2-AS1 may represent a new marker of poor prognosis and is a potential therapeutic target for CRC intervention.Keywords: colorectal cancer, long noncoding RNA, proliferation, prognosis

Purpose This study performed an analysis of clinicopathological characteristics, surgical treatment strategy and survival for CRC patients with LM between China and the U.S. Methods The CRC patients with simultaneous LM were identified from the Surveillance, Epidemiology, and End Results (SEER) registry and the Chinese National Cancer Center (CNCC) database from 2010 to 2017. We assessed 3-year cancer specific survival (CSS) according to surgical treatment strategy and time period. Results Differences in patient age, gender, primary tumor location, tumor grade, tumor histology, tumor stage were observed between the U.S. and China. Compared to the U.S., a larger proportion of patients in China underwent both primary site resection (PSR) and hepatic resection (HR) (35.1% vs 15.6%, P

BackgroundRadiation therapy (RT) is a crucial modality for the local control of pelvic cancer (PC), but the effect of pelvic RT on the development of secondary malignancy is still unclear. This study aimed to identify the relationship between radiation therapy received for the treatment of primary PC and subsequent secondary bladder cancer (SBC).MethodsThe Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for PC. Fine-gray competing risk regression and Cox regression analyses were employed to assess the cumulative incidence of SBC. Poisson regression and multiple primary standardized incidence ratios (SIR) were used to evaluate the radiotherapy-associated risk for patients receiving RT. Subgroup analyses of patients stratified by latency time since PC diagnosis, calendar year of PC diagnosis stage, and age at PC diagnosis were also performed. Overall survival (OS) was compared among different treatment groups with SBC by Kaplan–Meier analysis.ResultsA total of 318,165 observations showed that the primary cancers were located in pelvic cavity, 256,313 patients did not receive radiation therapy (NRT), 51,347 patients who underwent external beam radiation therapy (EBRT), and 10,505 patients receiving a combination of EBRT and brachytherapy (EBRT–BRT) who developed SBC. Receiving two types of radiotherapy was strongly consistent with a higher risk of developing SBC for PC patients in Fine-Gray competing risk regression (NRT vs. EBRT, adjusted HR= 1.71, 95% CI: 1.54-1.90, PConclusionRadiotherapy for primary PC was associated with higher risks of developing SBC than patients unexposed to radiotherapy. Different pelvic RT treatment modalities had different effects on the risk of SBC.

Laparoscopic surgery has become the standard surgical approach for the treatment of colon cancer. However, the surgical procedure for right colectomy is not standardized. Selection between laparoscopy-assisted right colectomy (LARC) with extracorporeal anastomosis and totally laparoscopic procedures with intracorporeal anastomosis is still a hot topic. The aim of this study was to compare the short-term outcomes of totally laparoscopic right colectomy (TLRC) and LARC in the treatment of right colon cancer. This was a retrospective and single-center study conducted between January 2016 and December 2019 featuring 120 TLRC patients and 180 LARC patients following the principles of the CME. We then collated and analyzed the clinicopathological characteristics, operative characteristics, and short-term outcomes. The baseline characteristics were balanced between two groups. TLRC was associated with a significantly lower estimated blood loss (p

Colorectal cancer is the third leading cancer in the world in terms of incidence and mortality. The role of differentially expressed Claudin14 (CLDN14) in CRC has not been reported. We observed that CLDN14 was associated with the progression of CRC. Our functional studies have shown that CLDN14 promoted the proliferation of CRC cells. In addition, and CLDN14 also increased the migration and invasion of CRC cells. In vivo experiments also showed that CLDN14 promoted the growth of colorectal cancer via the PI3K/AKT/mTOR. In summary, our research suggests that CLDN14 promotes the progression of colorectal cancer. Our findings may provide new strategies for clinical management and patient prognosis of CRC.

Background: Microsatellite instability (MSI) is a prognostic biomarker used to guide medication selection in multiple cancers, such as colorectal cancer. Traditional PCR with capillary electrophoresis and next-generation sequencing using paired tumor tissue and leukocyte samples are the main approaches for MSI detection due to their high sensitivity and specificity. Currently, patient tissue samples are obtained through puncture or surgery, which causes injury and risk of concurrent disease, further illustrating the need for MSI detection by liquid biopsy. Methods: We propose an analytic method using paired plasma/leukocyte samples and MSI detection using next-generation sequencing technology. Based on the theoretical progress of oncogenesis, we hypothesized that the microsatellite site length in plasma equals the combination of the distribution of tumor tissue and leukocytes. Thus, we defined a window-judgement method to identify whether biomarkers were stable. Results: Compared to traditional PCR as the standard, we evaluated three methods in 20 samples (MSI-H:3/MSS:17): peak shifting method using tissue vs. leukocytes, peak shifting method using plasma vs. leukocytes, and our method using plasma vs. leukocytes. Compared to traditional PCR, we observed a sensitivity of 100%, 0%, and 100%, and a specificity of 100.00%, 94.12%, and 88.24%, respectively. Conclusion: Our method has the advantage of possibly detecting MSI in a liquid biopsy and provides a novel direction for future studies to increase the specificity of the method.

BACKGROUND Conventional clinical guidelines recommend that at least 12 lymph nodes should be removed during radical rectal cancer surgery to achieve accurate staging. The current application of neoadjuvant therapy has changed the number of lymph node dissection. AIM To investigate factors affecting the number of lymph nodes dissected after neoadjuvant chemoradiotherapy in locally advanced rectal cancer and to evaluate the relationship of the total number of retrieved lymph nodes (TLN) with disease-free survival (DFS) and overall survival (OS). METHODS A total of 231 patients with locally advanced rectal cancer from 2015 to 2017 were included in this study. According to the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) classification system and the NCCN guidelines for rectal cancer, the patients were divided into two groups: group A (TLN ≥ 12, n = 177) and group B (TLN < 12, n = 54). Factors influencing lymph node retrieval were analyzed by univariate and binary logistic regression analysis. DFS and OS were evaluated by Kaplan-Meier curves and Cox regression models. RESULTS The median number of lymph nodes dissected was 18 (range, 12-45) in group A and 8 (range, 2-11) in group B. The lymph node ratio (number of positive lymph nodes/total number of lymph nodes) (P = 0.039) and the interval between neoadjuvant therapy and radical surgery (P = 0.002) were independent factors of the TLN. However,TLN was not associated with sex, age, ASA score, clinical T or N stage, pathological T stage, tumor response grade (Dworak), downstaging, pathological complete response, radiotherapy dose, preoperative concurrent chemotherapy regimen, tumor distance from anal verge, multivisceral resection, preoperative carcinoembryonic antigen level, perineural invasion, intravascular tumor embolus or degree of differentiation. The pathological T stage (P < 0.001) and TLN (P < 0.001) were independent factors of DFS, and pathological T stage (P = 0.011) and perineural invasion (P = 0.002) were independent factors of OS. In addition, the risk of distant recurrence was greater for TLN < 12 (P = 0.009). CONCLUSION A shorter interval to surgery after neoadjuvant chemoradiotherapy for rectal cancer under indications may cause increased number of lymph nodes harvested. Tumor shrinkage and more extensive lymph node retrieval may lead to a more favorable prognosis.

Although PD-1/PD-L1 immunotherapy has been used successfully in treating many cancers, metastatic colorectal cancer (CRC) patients are not as responsive. B7-H3 is a promising target for immunotherapy and we found it to have the highest expression among B7-CD28 family members in CRC. Thus, the aim of the present study was to investigate B7-H3 expression in a large CRC cohort. B7-H3, B7-H4, and PD-L1 protein levels and differential lymphocyte infiltration were evaluated in tissue microarrays from 805 primary tumors and matched metastases. The relationships between immune markers, patient characteristics, and survival outcomes were determined. B7-H3 (50.9%) was detected in more primary tumors than B7-H4 (29.1%) or PD-L1 (29.2%), and elevated B7-H3 expression was associated with advanced overall stage. Co-expression of B7-H3 only with B7-H4 or PD-L1 was infrequent in primary tumors (6.3%, 5.7%, respectively). Moreover, B7-H3 in primary tumors was positively correlated with their respective expression at metastatic sites (ρ = 0.631; p

Purpose The molecular mechanism of perineural invasion (PNI) in stage II colorectal cancer (CRC) remains not to be defined clearly. This study aims to identify the genomic aberrations related to PNI in stage II CRC. Patients and Methods Using array-based comparative genomic hybridization (array-CGH), primary tumor tissues and paracancerous normal tissues of stage II CRC with PNI and without PNI were analyzed. We identified genomic aberrations by using Genomic Workbench and MD-SeeGH and validated the aberrations of selected genes by real-time polymerase chain reaction (PCR). Gene ontology (GO) and pathway analysis were performed to determine the most likely biological effects of these genes. Results The most frequent gains in stage II CRC were at 7q11.21-q11.22, 8p11.21, 8p12-p11.23, 8q11.1-q11.22, 13q12.13-q12.2, and 20q11.21-q11.23 and the most frequent losses were at 17p13.1-p12, 8p23.2, and 118q11.2-q23. Four high-level amplifications at 8p11.23-p11.22, 18q21.1, 19q11-q12, and 20q11.21-q13.32 and homozygous deletions at 20p12.1 were discovered in Stage II CRC. Gains at 7q11.21-q22.1, 16p11.2, 17q23.3-q25.3, 19p13.3-p12, and 20p13-p11.1, and losses at 11q11-q12.1, 11p15.5-p15.1, 18p11.21, and 18q21.1-q23 were more commonly found in patients with PNI by frequency plot comparison together with detailed genomic analysis. It is also observed that gains at 8q11.1-q24.3, 9q13-q34.3, and 13q12.3-q13.1, and losses at 8p23.3-p12, 17p13.3-p11.2, and 21q22.12 occurred more frequently in patients without PNI. Further validation showed that the expression of FLT1, FBXW7, FGFR1, SLC20A2 and SERPINI1 was significantly up-regulated in the NPNI group compared to the PNI group. GO and pathway analysis revealed some genes enriched in specific pathways. Conclusion These involved genomic changes in the PNI of stage II CRC may be useful to reveal the mechanisms underlying PNI and provide candidate biomarkers.

Objective This study aims to develop feasible nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of the local advanced rectal cancer (LARC) patients who were treated with neoadjuvant chemoradiotherapy (nCRT) and operation. Methods A total of 243 LARC patients undergoing nCRT followed by total mesorectal excision (TME) were enrolled. Preoperative clinical features and postoperative pathological characteristics were collected. A Cox regression analysis was performed, and Cox-based nomograms were developed to predict the OS and CSS. We assessed the predictive performance of the nomogram with concordance index and calibration plots. Results A total of 243 patients were included with a median follow-up period of 46 months (range from 9 to 86 months). Cox regression analysis showed that low BMI (BMI < 18.5, HR= 21.739, P < 0.05), high level of preoperative CA19-9 (HR = 3.369, P = 0.036), high ypStage (HR = 19.768, P < 0.001), positive neural invasion (HR = 4.218, P = 0.026) and no adjuvant chemotherapy (HR = 5.495, P < 0.001) were independent predictors of poor OS. Age ≥70 (HR = 2.284, P

The aim of this study was to evaluate the safety of natural orifice specimen extraction surgery (NOSES) and to compare the short- and long-term outcomes of three techniques of NOSES for rectal cancer (RC).A consecutive series of RC patients in stage I-III who underwent laparoscopic NOSES were enrolled. Three main techniques of NOSES included specimen eversion and extra-abdominal resection (EVER), specimen extraction and extra-abdominal resection (EXER) and intra-abdominal resection and specimen extraction (IREX). The postoperative complications, 5-year disease free survival (DFS), 5-year local recurrence rate (LRR) and 5-year distant metastasis rate (DMR) were compared in three techniques.268 RC patients met inclusion criteria, including 83 patients treated with EVER, 75 patients treated with EXER and 110 patients treated with IREX. Tumor location was the most critical factor associated with technique selection, with P 0.001. Postoperative complication rate was 12.3% for all patients, and it was 18.1% for EVER, 13.3% for EXER and 7.3% for IREX. There were no significant differences for anastomotic leakage, anastomotic bleeding and intraabdominal abscess among three technique groups, with P 0.05. For long-term outcomes, the 5-year DFS, 5-year LRR and 5-year DMR were 85.03%, 4.22% and 11.00% for all patients. Patients in advanced tumor stage have worse long-term survival compared with patients in early stage, but no significant survival differences were observed among three technique groups.Three techniques of NOSES for RC had acceptable short- and long-term outcomes, and tumor location was a determinant of technique selection.

Reversal of loop ileostomy after colorectal surgery in obese patients can be challenging and total laparoscopic (TLAP) approach may be beneficial. This study aims to compare short-term outcomes of TLAP and open approaches in obese patients undergoing loop ileostomy reversal after laparoscopic-assisted colorectal surgery. A retrospective review was performed for consecutive patients who underwent laparoscopic-assisted colorectal surgery previously and underwent loop ileostomy reversal between January 2017 and April 2020. TLAP and open cases performed in obese patients were identified and compared for the following outcomes: baseline characteristics, operative outcomes, postoperative recovery, and postoperative complications. TLAP or open-loop ileostomy reversal was performed on 30 and 34 patients, respectively. TLAP approach was associated with a similar operation time and blood loss compared with an open approach (P 0.05). The median length of incision for stoma removal was significantly shorter in the TLAP group than in the open group (6.5 cm vs. 8.5 cm; P 0.05), and a lower incidence of incisional infection was also noted in the TLAP group (6.7% vs. 26.5%; P 0.05). The groups were comparable as regards the time to ground activities and length of hospitalization (P 0.05), but the time to first flatus was decreased (2.0 vs. 3.0 days; P 0.05). This retrospective study demonstrated that TLAP loop ileostomy reversal may have a satisfactory short-term outcome for obese patients after laparoscopic-assisted colorectal surgery, with a shorter incisional length and a lower incidence of incisional infection as well as an earlier time to first flatus.

P21-activated kinase 1 (PAK1), a serine/threonine protein kinase which functions downstream of RAC and CDC42 GTPase, is activated by a variety of stimuli, including RAS and other growth signaling factors. The extracellular signal kinase (ERK) and protein kinase B (AKT) signal pathways have been implicated in the pathogenesis of cancers. Whether PAK1 is sensitive to KRAS mutation signals and plays a role through ERK and AKT signaling pathways in NSCLC needs to be studied. The expression of PAK1, ERK and AKT was detected in both lung cancer cell lines and clinical samples. PAK1 RNA interference and specific inhibitor of PAK1(IPA-3) were applied to lung cancer cell lines and mouse xenograft tumors. Cell growth was measured by MTT and colony formation assays. Cell migration and invasion were detected by wound healing and transwell assays. RAS mutation was detected by Taqman probe method. Correlation between KRAS, PAK1, ERK and AKT activities was analyzed in lung cancer patients. PAK1 was highly expressed not only in RAS mutant but also in RAS wild-type lung cancer cells. Using specific inhibitor of PAK1, IPA-3 and PAK1 RNA interference, cell proliferation, migration and invasion of lung cancer cells were reduced significantly, accompanied by decreased activities of ERK and AKT. Dual inhibition of ERK and AKT suppressed these cellular processes to levels comparable to those achieved by reduction in PAK1 expression. In NSCLC patients, PAK1 was not correlated with KRAS mutation but was significantly positively correlated with pERK and pAKT. PAK1 played roles in NSCLC proliferation and invasion via ERK and AKT signaling and suggested a therapeutic target for NSCLC.

With recent advances in laparoscopic-surgery techniques and neoadjuvant therapy options, there have been improvements in sphincter-preservation outcomes in patients with low rectal cancer [1–3]. However, several issues remain controversial, such as the incidence of anastomotic leakage, the local recurrence rate, and anal-function outcome [4–5]. Moreover, prophylactic stoma at the end of sphincter-preserving surgery is necessary to prevent anastomotic leakage, especially in patients undergoing neoadjuvant chemoradiotherapy [7]. To avoid prophylactic colostomy and decrease excessive expense, we developed a new method of overlapped end-to-end anastomosis for treating low rectal cancer—a technique referred to as ‘oversleeve anastomosis.’

Objective The aim of our study was to analyze the factors affecting lymph node metastasis (LNM) and the prognosis of colorectal neuroendocrine tumors (NETs). Patients and Methods A retrospective analysis was conducted to collect the clinical data of 135 patients with colorectal NETs from January 2000 to December 2018, including clinical manifestations, pathological results, treatment methods, etc. Follow-up was regularly performed to observe the recurrence and metastasis of tumors and to identify the clinical and pathological features of colorectal NETs, risk factors for LNM and survival outcomes. Results Among 135 patients, there were 57 (42.2) patients with LNM, and the independent risk factors for LNM in the multivariable analyses were tumor diameter ≥2 cm (P= 0.040) and tumor grade G3 (P=0.001). Patients were followed up for 1 to 190 months, and of the 133 patients who were successfully followed up, the 5-year OS was 71.7%, and the 5-year PFS was 69.0%. The multivariate analysis for survival outcomes showed that age ≥65 years (P=0.002/

BACKGROUND Natural orifice specimen extraction (NOSE) surgery has been widely implemented in colorectal cancer surgery due to its good short-term efficacy. However, anastomotic leakage (AL) is a serious postoperative complication in colorectal cancer, and the risk factors for this complication after NOSE surgery have rarely been investigated. The aim of this study was to explore the predictive factors for AL after laparoscopic resection with transrectal NOSE for rectal cancer and sigmoid colon cancer. METHODS A total of 208 patients who underwent total laparoscopic resection with transrectal NOSE for rectal cancer and sigmoid colon cancer from January 2014 to June 2019 were systematically reviewed. Univariate and multivariate analyses were performed to identify the relevant risk factors. RESULTS The rate of AL was 10.1% (21 of 208 patients). The univariate analyses showed that male sex (85.7% vs 57.8%, P = .013), the distance from the anal verge (10.5 vs 14.5 cm, P = .011), and a duration of operation ≥140 min (71.4% vs 29.4%, P