Robotic natural orifice specimen extraction surgery versus robotic transabdominal specimen extraction surgery for early-stage rectal cancer: a multicenter propensity score-matched analysis (in China).

BACKGROUND: Despite the global increase in the adoption of robotic natural orifice specimen extraction surgery (R-NOSES), its advantages over robotic transabdominal specimen extraction surgery (R-TSES) for treating early-stage rectal cancer remain debated. There is scant nationwide, multicenter studies comparing the surgical quality and short-term outcomes between R-NOSES and R-TSES for this condition. OBJECTIVE: This retrospective cohort study was conducted nationally across multiple centers to compare the surgical quality and short-term outcomes between R-NOSES and R-TSES in early-stage rectal cancer. DESIGN: Multicenter retrospective cohort trial. SETTING: Eight experienced surgeons from 8 high-volume Chinese colorectal cancer treatment centers. PATIENTS: The study included 1086 patients who underwent R-NOSES or R-TSES from October 2015 to November 2023 at the 8 centers. Inclusion criteria were: (1) histologically confirmed rectal adenocarcinoma; (2) robotic total mesorectal excision; (3) postoperative pathological staging of TisN0M0 or T1-2N0M0; (4) availability of complete surgical and postoperative follow-up data. Patients were matched 1:1 in the R-NOSES and R-TSES groups using the propensity score matching (PSM) technique. RESULTS: After PSM, 318 matched pairs with well-balanced patient characteristics were identified. The operation time for the R-NOSES group was significantly longer than that for the R-TSES group [140 min (125-170 min) vs. 140 min (120-160 min), P = 0.032]. Conversely, the times to first flatus and initial oral intake in the R-NOSES group were significantly shorter than those in the R-TSES group [48 h (41-56 h) vs. 48 h (44-62 h), P = 0.049 and 77 h (72-94 h) vs. 82 h (72-96 h), P = 0.008], respectively. Additionally, the length of postoperative hospital stay was shorter in the R-NOSES group compared with the R-TSES group [7 day (7-9 day) vs. 8 day (7-9 day), P = 0.005]. The overall postoperative complication rates were similar between the groups (10.7% in the R-NOSES group vs. 11.9% in the R-TSES group, P = 0.617). However, the R-NOSES group had a lower incidence of wound complications compared to the R-TSES group (0.0% vs. 2.2%, P = 0.015). Regarding surgical stress response, the R-NOSES group showed superior outcomes. Additionally, patients in the R-NOSES group required fewer additional analgesics on postoperative days 1, 3, and 5 and reported lower pain scores compared to the R-TSES group. The body image scale (BIS) and cosmetic scale (CS) scores were also significantly higher in the R-NOSES group. Furthermore, the R-NOSES group demonstrated significantly better outcomes in functional dimensions such as physical, role, emotional, social, and cognitive functioning, and in symptoms like fatigue and pain, when compared to the R-TSES group. LIMITATIONS: It is imperative to ensure the safe and standardized implementation of R-NOSES through the establishment of a uniform training protocol. CONCLUSIONS: These results affirm that R-NOSES is a safe and effective treatment for early-stage rectal cancer when meticulously executed by skilled surgeons.

Robot-assisted laparoscopic combined with endoscopic partial gastrectomy (RALE-PG) for the treatment of gastric gastrointestinal stromal tumors in challenging anatomical locations: single-center experience.

Background: Gastric gastrointestinal stromal tumors in challenging anatomical locations are difficult to remove. Methods: This study retrospectively analyzed the clinical data of 12 patients with gastric GISTs in challenging anatomical locations who underwent robot-assisted laparoscopic combined with endoscopic partial gastrectomy (RALE-PG) and manual suturing of the gastric wall. Results: This study included 12 patients with a mean age of 56.8 ± 9.8 years and a mean BMI of 23.9 ± 1.9 kg/m2. Tumors were located in the GEJ (n = 3), lesser curvature (n = 3), posterior gastric wall (n = 3) and antrum (n = 3). The cardia and pylorus were successfully preserved in all patients regardless of the tumor location. The mean tumor size was 4.5 ± 1.4 cm. The mitotic-count/50 mm2 was less than 5 in all patients (100%). There was no intraoperative tumor rupture (0%) and no conversion to open surgery (0%). The median operation time was 122 (97-240) min, and the median blood loss volume was 10 (5-30) ml. The median postoperative VAS score was 2 (2-4). The median time to first flatus was 2 (2-3) days. The median time to first fluid intake was 2 (2-3) days. The median time to first ambulation after the operation was 3 (2-4) days. No cases of anastomotic stenosis or leakage were found. The median time to drain removal for 6 patients was 5 (4-7) days. The median time to nasogastric tube removal for all patients was 2 (1-5) days. The median postoperative hospital stay was 5 (4-8) days. One patient (female/41 year) developed moderate anemia (Clavien-Dindo grade II complication). There was no unplanned readmission within 30 days after the operation. The median distance from the tumor to the resection margin was 1 (1-2) cm. R0 resection was achieved in all patients. The median follow-up period was 19 (10-25) months, and all patients survived with no recurrence or metastasis. Conclusions: RALE-PG is a safe, feasible and advantageous technique for treating GISTs in challenging anatomical locations. It can be used to accurately remove the tumor while preserving gastric function to the greatest extent, but long-term oncologic outcomes need to be evaluated in a study with a larger sample size and longer follow-up period.

Correlation Analysis Between Tumor Deposit and Clinicopathologic Characteristics and Prognosis of Gastric Cancer: A Multicenter Retrospective Study.

BACKGROUND: The mechanism underlying the formation of gastric tumor deposits (TDs) is unclear. We aimed to explore the risk factors for the formation and prognostic value of TDs. METHODS: This retrospective analysis included 781 locally advanced gastric cancer (LAGC) patients from four medical institutions in China, from June 2014 to June 2018. The risk factors for TD formation and prognostic value were determined through univariate and multivariate analyses. RESULTS: Univariate analysis revealed that TD positivity was closely related to tumor diameter, Borrmann classification, differentiation degree, pT stage, pN stage, pTNM stage, and nerve and vascular invasion (p < 0.05). Multivariate logistic regression revealed that tumor diameter ≥ 5 cm (odds ratio [OR] 1.836, 95% confidence interval [CI] 1.165-2.894, p = 0.009) and vascular invasion (OR 2.152, 95% CI 1.349-3.433, p = 0.001) were independent risk factors for TD positivity. Multivariate Cox analysis revealed that TD positivity (OR 1.533, 95% CI 1.101-2.134, p = 0.011), tumor diameter ≥ 5 cm (OR 1.831, 95% CI 1.319-2.541, p < 0.001), pT4a stage (OR 1.652, 95% CI 1.144-2.386, p = 0.007), and vascular invasion (OR 1.458, 95% CI 1.059-2.008, p = 0.021) were independent risk factors for GC prognosis. The 5-year overall and disease-free survival of the TD-positive group showed significant effects among patients in the pT4a and pN3b stages (p < 0.05). CONCLUSIONS: TDs are closely related to tumor diameter and vascular invasion in LAGC patients, and TD positivity is an independent prognostic factor for LAGC patients, especially those at pT4a and pN3b stages.

DR6 Augments Colorectal Cancer Cell Growth, Invasion, and Stemness by Activating AKT/NF-κB Pathway.

This study aims to elucidate the role and mechanisms of Death Receptor 6 (DR6), a member of the tumor necrosis factor receptor superfamily, in the malignant progression of colorectal cancer (CRC). The association of DR6 expression levels and CRC patient survival was examined using the CRC cohort data from GEPIA database. The functional role of DR6 in CRC cells was investigated by performing loss-of-function and gain-of-function experiments based on CCK-8 proliferation assay, transwell migration and invasion assay, and sphere-forming assays. Xenograft model of CRC cells in nude mouse was established to evaluate the impact of DR6 knockdown on CRC tumorigenesis. Elevated expression of DR6 was correlated with an unfavorable prognosis in CRC patients. In vitro functional assays demonstrated that silencing DR6 considerably suppressed the proliferation, migration, invasion, and stemness of CRC cells, whereas its overexpression showed an opposite effect. DR6 knockdown also attenuated tumor formation of CRC cells in the nude mice. Mechanistically, silencing DR6 reduced the phosphorylation of AKT and NF-κB in CRC cells, and the treatment with an AKT activator (SC79) abrogated the inhibitory effects of DR6 knockdown on the malignant features of CRC cells. Our data suggest that DR6 contributes to the malignant progression of CRC by activating AKT/NF-κB pathway, indicating its clinical potential as a prognostic marker and therapeutic target for CRC.

Activin A/ACVR2A axis inhibits epithelial-to-mesenchymal transition in colon cancer by activating SMAD2.

Colorectal cancer is one of the most common malignancies worldwide. Liver metastasis is the major direct cause of colorectal cancer-related deaths. Although radical resection is the most effective treatment for colorectal cancer liver metastasis, several patients are not eligible for surgery. Therefore, there is a need to develop novel treatments based on the understanding of the biological mechanisms underlying liver metastasis in colorectal cancer. This study demonstrated that activin A/ACVR2A inhibits colon cancer cell migration and invasion, as well as suppresses the epithelial-to-mesenchymal transition of mouse colon cancer cells. This finding has been further validated in animal experiments. Mechanistic studies revealed that activin A binds to Smad2 (instead of Smad3) and activates its transcription. Analysis of the paired clinical samples further confirmed that the expression levels of ACVR2A and SMAD2 were the highest in adjacent healthy tissues, followed by primary colon cancer tissues and liver metastasis tissues, suggesting that ACVR2A downregulation may promote colon cancer metastasis. Bioinformatics analysis and clinical studies demonstrated that ACVR2A downregulation was significantly associated with liver metastasis and poor disease-free and progression-free survival of patients with colon cancer. These results suggest that the activin A/ACVR2A axis promotes colon cancer metastasis by selectively activating SMAD2. Thus, targeting ACVR2A is a potential novel therapeutic strategy to prevent colon cancer metastasis.

Prognostic model construction and validation of esophageal cancer cellular senescence-related genes and correlation with immune infiltration.

Introduction: Cellular senescence is a cellular response to stress, including the activation of oncogenes, and is characterized by irreversible proliferation arrest. Restricted studies have provided a relationship between cellular senescence and immunotherapy for esophageal cancer. Methods: In the present study, we obtained clinical sample of colon cancer from the TCGA database and cellular senescence-related genes from MSigDB and Genecard datasets. Cellular senescence-related prognostic genes were identified by WGCNA, COX, and lasso regression analysis, and a cellular senescence-related risk score (CSRS) was calculated. We constructed a prognostic model based on CSRS. Validation was performed with an independent cohort that GSE53625. Three scoring systems for immuno-infiltration analysis were performed, namely ssGSEA analysis, ESTIMATE scores and TIDE scores. Result: Five cellular senescence-related genes, including H3C1, IGFBP1, MT1E, SOX5 and CDHR4 and used to calculate risk score. Multivariate regression analysis using cox regression model showed that cellular senescence-related risk scores (HR=2.440, 95% CI=1.154-5.159, p=0.019) and pathological stage (HR=2.423, 95% CI=1.119-5.249, p=0.025) were associated with overall survival (OS). The nomogram model predicts better clinical benefit than the American Joint Committee on Cancer (AJCC) staging for prognosis of patients with esophageal cancer with a five-year AUC of 0.946. Patients with high CSRS had a poor prognosis (HR=2.93, 95%CI=1.74-4.94, p<0.001). We observed differences in the distribution of CSRS in different pathological staging and therefore performed a subgroup survival analysis finding that assessment of prognosis by CSRS independent of pathological staging. Comprehensive immune infiltration analysis and functional enrichment analysis suggested that patients with high CSRS may develop immunotherapy resistance through mechanisms of deacetylation and methylation. Discussion: In summary, our study suggested that CSRS is a prognostic risk factor for esophageal cancer. Patients with high CSRS may have worse immunotherapy outcomes.

Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Initial Results of a Phase III Trial.

OBJECTIVE: To compare neoadjuvant chemotherapy (nCT) with CAPOX alone versus neoadjuvant chemoradiotherapy (nCRT) with capecitabine in locally advanced rectal cancer (LARC) with uninvolved mesorectal fascia (MRF). BACKGROUND DATA: nCRT is associated with higher surgical complications, worse long-term functional outcomes, and questionable survival benefits. Comparatively, nCT alone seems a promising alternative treatment in lower-risk LARC patients with uninvolved MRF. METHODS: Patients between June 2014 and October 2020 with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to nCT group with 4 cycles of CAPOX (Oxaliplatin 130 mg/m2 IV day 1 and Capecitabine 1000 mg/m2 twice daily for 14 d. Repeat every 3 wk) or nCRT group with Capecitabine 825 mg/m² twice daily administered orally and concurrently with radiation therapy (50 Gy/25 fractions) for 5 days per week. The primary end point is local-regional recurrence-free survival. Here we reported the results of secondary end points: histopathologic response, surgical events, and toxicity. RESULTS: Of the 663 initially enrolled patients, 589 received the allocated treatment (nCT, n=300; nCRT, n=289). Pathologic complete response rate was 11.0% (95% CI, 7.8-15.3%) in the nCT arm and 13.8% (95% CI, 10.1-18.5%) in the nCRT arm ( P =0.33). The downstaging (ypStage 0 to 1) rate was 40.8% (95% CI, 35.1-46.7%) in the nCT arm and 45.6% (95% CI, 39.7-51.7%) in the nCRT arm ( P =0.27). nCT was associated with lower perioperative distant metastases rate (0.7% vs. 3.1%, P =0.03) and preventive ileostomy rate (52.2% vs. 63.6%, P =0.008) compared with nCRT. Four patients in the nCT arm received salvage nCRT because of local disease progression after nCT. Two patients in the nCT arm and 5 in the nCRT arm achieved complete clinical response and were treated with a nonsurgical approach. Similar results were observed in subgroup analysis. CONCLUSIONS: nCT achieved similar pCR and downstaging rates with lower incidence of perioperative distant metastasis and preventive ileostomy compared with nCRT. CAPOX could be an effective alternative to neoadjuvant therapy in LARC with uninvolved MRF. Long-term follow-up is needed to confirm these results.

Increasing rate of hospitalization for severe peptic ulcer in digestive disease emergencies after the pandemic.

Since December 2019, the novel coronavirus has spread worldwide, affecting more than 510 million people, with more than 6 million deaths. However, some of the potential effects of the pandemic have not been thoroughly studied. We collected data from 2 regional emergency centers from May to November for the years 2015 to 2019, before the pandemic, and from May to November 2020, after the pandemic. We evaluated the incidence of each major type of digestive disease before and after the pandemic in adults at the 2 hospitals, which experienced coronavirus disease 2019 outbreaks with varying severity. A total of 11,394 patients were enrolled in the study Affiliated Hospital of Putian University (PUTIAN, n = 5503) Union Hospital, Tongji Medical college, Huazhong University of Science and Technology (UNION, n = 5891), and the proportion of male patients was approximately the same at both hospitals, with 3360 (61.1%) and 3680 (62.5%), respectively. The average ages of the patients were 55.8 ±â€…18.4 years PUTIAN and 54.3 ±â€…15.8 years UNION. The numbers of patients at the 2 hospitals increased steadily, but in 2020, the number of patients at UNION declined. The baseline characteristics of the 2 groups at the 2 hospitals showed significant differences for age before and after the pandemic but not for sex. The constituent ratios of diseases in each year in the 2 hospitals differed. The number of patients with peptic ulcers in 2020 was significantly different from those in each year from 2015 to 2019 (PUTIAN 2015-2020, 15.0%, 18.2%, 14.9%, 16.9%, 19.5%, 34.9%; UNION 2015-2020, 29.2%, 32.5%, 29.3%, 29.4%, 29.7%, 41.3%, respectively). The rates of peptic ulcer increased dramatically in both hospitals in 2020. An increase in the incidence of severe peptic ulcer was observed after the pandemic compared to the same period before the pandemic. Therefore, these factors should be considered in the formulation of public health strategies and the allocation of medical resources in the post pandemic era.

Nomogram for prediction of prolonged postoperative ileus after colorectal resection.

BACKGROUND: Prolonged postoperative ileus (PPOI) is a major complication in patients undergoing colorectal resection. The aim of this study was to analyze the risk factors contributing to PPOI, and to develop an effective nomogram to determine the risks of this population. METHODS: A total of 1,254 patients with colorectal cancer who underwent radical colorectal resection at Fujian Cancer Hospital from March 2016 to August 2021 were enrolled as a training cohort in this study. Univariate analysis and multivariate logistic regressions were performed to determine the correlation between PPOI and clinicopathological characteristics. A nomogram predicting the incidence of PPOI was constructed. The cohort of 153 patients from Fujian Provincial Hospital were enrolled as a validation cohort. Internal and external validations were used to evaluate the prediction ability by area under the receiver operating characteristic curve (AUC) and a calibration plot. RESULTS: In the training cohort, 128 patients (10.2%) had PPOI after colorectal resection. The independent predictive factors of PPOI were identified, and included gender, age, surgical approach and intraoperative fluid overload. The AUC of nomogram were 0.779 (95% CI: 0.736-0.822) and 0.791 (95%CI: 0.677-0.905) in the training and validation cohort, respectively. The two cohorts of calibration plots showed a good consistency between nomogram prediction and actual observation. CONCLUSIONS: A highly accurate nomogram was developed and validated in this study, which can be used to provide individual prediction of PPOI in patients after colorectal resection, and this predictive power can potentially assist surgeons to make the optimal treatment decisions.

Short-term Outcomes of Laparoscopy-Assisted vs Open Surgery for Patients With Low Rectal Cancer: The LASRE Randomized Clinical Trial.

Importance: The efficacy of laparoscopic vs open surgery for patients with low rectal cancer has not been established. Objective: To compare the short-term efficacy of laparoscopic surgery vs open surgery for treatment of low rectal cancer. Design, Setting, and Participants: This multicenter, noninferiority randomized clinical trial was conducted in 22 tertiary hospitals across China. Patients scheduled for curative-intent resection of low rectal cancer were randomized at a 2:1 ratio to undergo laparoscopic or open surgery. Between November 2013 and June 2018, 1070 patients were randomized to laparoscopic (n = 712) or open (n = 358) surgery. The planned follow-up was 5 years. Data analysis was performed from April 2021 to March 2022. Interventions: Eligible patients were randomized to receive either laparoscopic or open surgery. Main Outcomes and Measures: The short-term outcomes included pathologic outcomes, surgical outcomes, postoperative recovery, and 30-day postoperative complications and mortality. Results: A total of 1039 patients (685 in laparoscopic and 354 in open surgery) were included in the modified intention-to-treat analysis (median [range] age, 57 [20-75] years; 620 men [59.7%]; clinical TNM stage II/III disease in 659 patients). The rate of complete mesorectal excision was 85.3% (521 of 685) in the laparoscopic group vs 85.8% (266 of 354) in the open group (difference, -0.5%; 95% CI, -5.1% to 4.5%; P = .78). The rate of negative circumferential and distal resection margins was 98.2% (673 of 685) vs 99.7% (353 of 354) (difference, -1.5%; 95% CI, -2.8% to 0.0%; P = .09) and 99.4% (681 of 685) vs 100% (354 of 354) (difference, -0.6%; 95% CI, -1.5% to 0.5%; P = .36), respectively. The median number of retrieved lymph nodes was 13.0 vs 12.0 (difference, 1.0; 95% CI, 0.1-1.9; P = .39). The laparoscopic group had a higher rate of sphincter preservation (491 of 685 [71.7%] vs 230 of 354 [65.0%]; difference, 6.7%; 95% CI, 0.8%-12.8%; P = .03) and shorter duration of hospitalization (8.0 vs 9.0 days; difference, -1.0; 95% CI, -1.7 to -0.3; P = .008). There was no significant difference in postoperative complications rate between the 2 groups (89 of 685 [13.0%] vs 61 of 354 [17.2%]; difference, -4.2%; 95% CI, -9.1% to -0.3%; P = .07). No patient died within 30 days. Conclusions and Relevance: In this randomized clinical trial of patients with low rectal cancer, laparoscopic surgery performed by experienced surgeons was shown to provide pathologic outcomes comparable to open surgery, with a higher sphincter preservation rate and favorable postoperative recovery. Trial Registration: ClinicalTrials.gov Identifier: NCT01899547.

Can an incomplete ERAS protocol reduce postoperative complications compared with conventional care in laparoscopic radical resection of colorectal cancer? A multicenter observational cohort and propensity score-matched analysis.

Background: The patients undergoing laparoscopic radical colorectomy in many Chinese hospitals do not achieve high compliance with the ERAS (enhanced recovery programs after surgery) protocol. Methods: The clinical data from 1,258 patients were collected and divided into the non-ERAS and incomplete ERAS groups. Results: A total of 1,169 patients were screened for inclusion. After propensity score-matched analysis (PSM), 464 pairs of well-matched patients were generated for comparative study. Incomplete ERAS reduced the incidence of postoperative complications (p = 0.002), both mild (6.7% vs. 10.8%, p = 0.008) and severe (3.2% vs. 6.0%, p = 0.008). Statistically, incomplete ERAS reduced indirect surgical complications (27,5.8% vs. 59, 12.7) but not local complications (19,4.1% vs. 19, 4.1%). The subgroup analysis of postoperative complications revealed that all patients benefited from the incomplete ERAS protocol regardless of sex (male, p = 0.037, 11.9% vs. 17.9%; female, p = 0.010, 5.9% vs. 14.8%) or whether neoadjuvant chemotherapy was administered (neoadjuvant chemotherapy, p = 0.015, 7.4% vs. 24.5%; no neoadjuvant chemotherapy, p = 0.018, 10.2% vs. 15.8%). Younger patients (<60 year, p = 0.002, 7.6% vs. 17.5%) with a low BMI (<22.84, 9.4% vs. 21.1%, p < 0.001), smaller tumor size (<4.0 cm, 8.1% vs. 18.1%, p = 0.004), no fundamental diseases (8.8% vs. 17.0%, p = 0.007), a low ASA score (1/2, 9.7% vs. 16.3%, p = 0.004), proximal colon tumors (ascending/transverse colon, 12.2% vs. 24.3%, p = 0.027), poor (6.1% vs. 23.7%, p = 0.012)/moderate (10.3% vs. 15.3%, p = 0.034) tumor differentiation and no preoperative neoadjuvant radiotherapy (10.3% vs. 16.9%, p = 0.004) received more benefit from the incomplete ERAS protocol. Conclusion: The incomplete ERAS protocol decreased the incidence of postoperative complications, especially among younger patients (<60 year) with a low BMI (<22.84), smaller tumor size (<4.0 cm), no fundamental diseases, low ASA score (1/2), proximal colon tumors (ascending/transverse colon), poor/moderate differentiation and no preoperative neoadjuvant radiotherapy. ERAS should be recommended to as many patients as possible, although some will not exhibit high compliance. In the future, the core elements of ERAS need to be identified to improve the protocol.

Anatomic patterns and clinical significance of gastrocolic trunk of Henlé in laparoscopic right colectomy for colon cancer: Results of the HeLaRC trial.

BACKGROUND: Recent interest in laparoscopic right colectomy with D3 lymphadenectomy for right colon cancer, has raised renewed attention to the anatomic variations of the gastrocolic trunk of Henlé (GTH). Understanding the vascular structure of the GTH region for individual patients should improve surgical outcomes. The goal of this nationwide multicenter study (Anatomical Classification of Henlé's Trunk in Laparoscopic Right Hemi-colectomy (HeLaRC) trial) was to study the anatomic patterns of the GTH region, to clarify the implications of GTH in laparoscopic right colectomy with D3 lymphadenectomy (D3-RC) and analyze their clinical significance. METHODS: We enrolled 583 patients from 26 centers across China who underwent D3-RC. The number of tributaries, length and types of GTH constitutions and their influence on intra-operative data were investigated. A nomogram score (based on the length of GTH, body mass index (BMI), tumor location, T stage and type of GTH (type I vs. non-type I) was established to assess the potential hazard of bleeding. RESULTS: The GTH was found in 567 patients (97.3%). The distribution of GTH types was 0 (14.1%, n = 80), I (53.3%, n = 302), II (27.0%, n = 153), III (5.6%, n = 32). Of note, the type I GTH, T1 stage and tumor location at ileocecal or ascending colon were correlated with shorter exposure time of the GTH region (P < 0.0001). Short length of GTH (P = 0.002) and tumor location (transverse colon vs. non transverse colon) (P = 0.003) were correlated with the amount of GTH bleeding during the surgery. Nomogram discrimination was good (C-index: 0.72 (95% CI: 0.64, 0.80)). The dissection plane was better in patients with type I GTH than with other types (P = 0.023). CONCLUSION: GTH pattern variations may affect surgical outcomes in patients undergoing D3-RC. Better recognition of GTH anatomy might lead to a safer operation with better oncologic quality.

The CD133+CXCR4+ Colorectal Tumor Cells Promote Colorectal Cancer Progression by PI3K/AKT Signaling.

Colorectal cancer (CRC) is one of the most common cancers in the world. Due to its preferential metastasis to the liver, CRC has become one of the leading causes of cancer-related deaths worldwide. There has evidence showing that a variety of subpopulations exist among cancer cells, which play an important role in liver metastasis. Growing evidence suggests that CD133 and C-X-C chemokine receptor type 4 (CXCR-4) are thought to contribute to cancer progression and metastasis. However, it has not been fully characterized in CRC. Here, we found that the expression of CD133 and CXCR4 in metastatic liver cancer tissues was higher than that of the primary tumor tissue and paratumor tissue. Furthermore, CD133+CXCR4+ cells were found to contribute to colorectal carcinogenesis and liver metastasis in vitro and in vivo. Moreover, CXCR4 blocked significantly inhibited the CD133+CXCR4+ cells metastatic to the liver in a mouse model. We also showed that CD133+CXCR4+ induced significant phosphorylation of PI3K/AKT. In conclusion, our data demonstrate that CD133+CXCR4+ cell subsets play an important role in the development and progression of colon cancer.

Comparison of prolonged postoperative ileus between laparoscopic right and left colectomy under enhanced recovery after surgery: a propensity score matching analysis.

BACKGROUND: There were differences in the recovery of bowel function and prolonged postoperative ileus (PPOI) between laparoscopic right colectomy (RC) and left colectomy (LC) under the guidance of enhanced recovery after surgery. METHODS: We selected 870 patients who underwent elective laparoscopic colectomy from June 2016 to December 2021, including 272 patients who had RC and 598 who had LC. According to 1:1 proportion for propensity score matching and correlation analysis, 247 patients who had RC and 247 who had LC were finally enrolled. RESULTS: The incidence of PPOI in all patients was 13.1%. Age, sex, smoking habit, preoperative serum albumin level, operation type, and operation time were the important independent risk factors based on multivariate logistic regression and correlation analysis for PPOI (p<0.05). Age, sex, body mass index, preoperative serum albumin level, operation time, and degree of differentiation between the two groups were significantly different before case matching (p<0.05). There were no statistically significant differences in baseline characteristics and preoperative biochemical parameters between the two groups after case matching (p>0.05). The incidence of PPOI in patients who had RC was 21.9%, while that in patients who had LC was 13.0%. The first flatus, first semi-liquid, and length of stay in LC patients were lower than those in RC patients (p<0.05). CONCLUSION: The return of bowel function in LC was faster than that in RC, and the incidence of PPOI was relatively lower. Therefore, caution should be taken during the early feeding of patients who had laparoscopic RC.

IGHG1 upregulation promoted gastric cancer malignancy via AKT/GSK-3ß/ß-Catenin pathway.

BACKGROUND: Despite current advances in gastric cancer treatment, disease metastasis and chemo-resistance remain as major hurdles against better overall prognosis. Previous studies indicated that IGHG1 as well as -Catenin serve as important regulators of tumor cellular malignancy. Therefore, understanding detailed molecular mechanism and identifying druggable target will be of great potentials in future therapeutic development. METHODS: Surgical tissues and gastric cancer cell lines were retrieved to evaluate IGHG1 expression for patients with or without lymph node/distal organ metastasis. Functional assays including CCK8 assay, Edu assay, sphere formation assay and transwell assay, wound healing assay, etc. were subsequently performed to evaluate the impact of IGHG1/-catenin axis on tumor cell proliferation, migration and chemo-resistance. RESULTS: Gastric cancer tissues and tumor cell lines demonstrated significantly higher level of IGHG1. Functional study further demonstrated that IGHG1 promoted proliferative and migration as well as chemo-resistance of gastric cancer tumor cells. Further experiments indicated that IGHG1 activated AKT/GSK-3/-Catenin axis, which played crucial role in regulation of proliferative and chemo-resistance of gastric cancer cells. CONCLUSION: This study provided novel evidences that IGHG1 acted as oncogene by promotion of gastric cancer cellular proliferation, migration and chemo-resistance. Our research further suggested that IGHG1/AKT/GSK-3ß/ß-Catenin axis acted as novel pathway which regulated gastric cancer cellular malignant behavior. Our research might inspire future therapy development to promote overall prognosis of gastric cancer patients.

Development and external validation of a novel nomogram for screening Chinese Lynch syndrome: based on a multicenter, population study.

BACKGROUND: This multicenter study aimed to reveal the genetic spectrum of colorectal cancer (CRC) with deficient mismatch repair (dMMR) and build a screening model for Lynch syndrome (LS). METHODS: Through the immunohistochemical (IHC) screening of mismatch repair protein results in postoperative CRC patients, 311 dMMR cases, whose germline and somatic variants were detected using the ColonCore panel, were collected. Univariate and multivariate logistic regression analysis was performed on the clinical characteristics of these dMMR individuals, and a clinical nomogram, incorporating statistically significant factors identified using multivariate logistic regression analysis, was constructed to predict the probability of LS. The model was validated externally by an independent cohort. RESULTS: In total, 311 CRC patients with IHC dMMR included 95 identified MMR germline variant (LS) cases and 216 cases without pathogenic or likely pathogenic variants in MMR genes (non-Lynch-associated dMMR). Of the 95 individuals, approximately 51.6%, 28.4%, 14.7%, and 5.3% cases carried germline MLH1, MSH2, MSH6, and PMS2 pathogenic or likely pathogenic variants, respectively. A novel nomogram was then built to predict the probability of LS for CRC patients with dMMR intuitively. The receiver operating characteristic (ROC) curve informed that this nomogram-based screening model could identify LS with a higher specificity and sensitivity with an area under curve (AUC) of 0.87 than current screening criteria based on family history. In the external validation cohort, the AUC of the ROC curve reached 0.804, inferring the screening model's universal applicability. We recommend that dMMR-CRC patients with a probability of LS greater than 0.435 should receive a further germline sequencing. CONCLUSION: This novel screening model based on the clinical characteristic differences between LS and non-Lynch-associated dMMR may assist clinicians to preliminarily screen LS and refer susceptible patients to experienced specialists.

Predictive value of computed tomography with coronal reconstruction in right hemicolectomy with complete mesocolic excision for right colon cancers: a retrospective study.

BACKGROUND: Understanding the vascular anatomy is critical for performing central vascular ligation (CVL) in right hemicolectomy with complete mesocolic excision (CME). This study aimed to investigate the predictive value of multi-slice spiral computed tomography (MSCT) with coronal reconstruction in right hemicolectomy with CME. METHODS: This is a retrospective descriptive study. Eighty patients with right colon cancer who underwent right hemicolectomy from December 2015 to January 2020 were included. The intraoperative reports (including imaging data) and MSCT images with coronal reconstruction were analysed and compared. The detection rates of the ileocolic vein (ICV) and ileocolic artery (ICA) roots and the accuracy in predicting their anatomical relationship were analysed. The detection rate and accuracy in predicting the location of the gastrocolic trunk of Henle (GTH), middle colic artery (MCA) and middle colic vein (MCV) were analysed. The distance from the ICV root to the GTH root (ICV-GTH distance) was measured and analysed. The maximum distance from the left side of the superior mesenteric artery (SMA) to the right side of the superior mesenteric vein (SMV), named the 'lsSMA-rsSMV distance', was also measured and analysed. RESULTS: In seventy-four (92.5%) patients, both the ICV and ICA roots were located; their anatomical relationship was determined by MSCT, and the accuracy of the prediction was 97.2% (72/74). The GTH was located by MSCT in 75 (93.7%) patients, and the accuracy of the prediction was 97.33% (73/75). The MCA was located by MSCT in 47 (58.75%) patients, and the accuracy was 78.72% (37/47). The MCV was located by MSCT in 51 (63.75%) patients, and the accuracy of the prediction was 84.31% (43/51). The ICV-GTH distance was measured in 73 (91.2%) patients, and the mean distance was 4.28 ± 2.5 cm. The lsSMA-rsSMV distance was measured in 76 (95%) patients, and the mean distance was 2.21 ± 0.6 cm. CONCLUSIONS: With its satisfactory accuracy in predicting and visualising the information of key anatomical sites, MSCT with coronary reconstruction has some predictive value in CME with CVL in right hemicolectomy.

Failure of enhanced recovery programs after laparoscopic radical gastrectomy: a single-center retrospective study.

BACKGROUND: Enhanced recovery programs (ERPs), as a rapid rehabilitation method, have been widely used in gastric cancer patients. Although many related studies have confirmed their effectiveness, some patients may still experience poor clinical outcomes. This study analyzed risk factors associated with ERP failure after laparoscopic radical gastrectomy. METHODS: We analyzed the outcomes of 212 patients who underwent ERP following laparoscopic radical gastrectomy between March 2017 and December 2019. The ERP included preoperative education, short periods of fasting, non-mechanical intestinal preparation, early ambulation and oral feeding. ERP failure was defined as more than 7 days of hospitalization due to postoperative complications, unplanned readmission within 30 days of surgery, or death. RESULTS: The mean patient age was 62 years (range 39-89 years). Surgical procedures included total gastrectomy (n = 161) and distal gastrectomy (n = 51). Overall, 38 (17.9%) patients failed to complete the program, with no mortality. Univariable analysis (P < 0.15) revealed that ERP failure was associated with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) grade, tumor location, preoperative education, combined operation, long operation time, and significant blood loss. Multivariable analysis (P < 0.05) showed that age, ASA grade III, combined operation and preoperative education were independent risk factors for ERP failure. CONCLUSIONS: We showed that an advanced age, a high ASA grade, lack of a preoperative education and combined surgery were independent risk factors associated with ERP failure after laparoscopic gastrectomy. Therefore, a preoperative patient evaluations and education are important for the success of ERPs.

Effect of hematopoietic progenitor cells on the biological characteristics of colon cancer tumor stem cells.

BACKGROUND: Cancer stem cells (CSCs) are a type of tumor cell that are self-sustaining and can differentiate into several different types of cells. The present study aims to investigate the effect of hematopoietic progenitor cells (HPCs) on the biological behavior of colon CSCs (CCSCs) and to determine the underlying molecular mechanisms of liver metastasis in colorectal cancer. METHODS: Subsets of CCSCs were isolated from stem-like HCT116 cells and cocultured with CD133+ HPCs in vitro. Colony formation assay, and CCK-8 were used to assess the effects of HPCs on CCSC subsets. Invasive and migration assay were done to study the effects of HPCs mediated metastatic capacity of CCSC subsets. Expression of MMP-9, VEGF, E-cadherin and ß-catenin was analyzed by qPCR and Western blotting. RESULTS: CCK-8 and colony formation assays showed that HPCs significantly promoted proliferation and colony formation of the CCSC subsets (P=0.031). HPCs also significantly enhanced the migration (P=0.011) and invasive capacity (P=0.001) of the CCSC subsets. Quantitative PCR showed that MMP-9 and VEGF expression in CCSC subsets were significantly upregulated (P=0.000 and P=0.005). Western blotting showed that MMP-9, VEGF and ß-catenin expression in CCSC subsets were significantly upregulated (P=0.000, P=0.005, P=0.000). The protein expression levels of E-cadherin in the CCSC subsets was significantly downregulated (P=0.002). CONCLUSIONS: CD133+ HPCs enhanced migration, invasion and proliferation of CCSC subsets in vitro.

Single-port endoscopic mastectomy via the lateral chest approach for the treatment of grade II gynecomastia.

To investigate the feasibility of single-port endoscopic mastectomy via the lateral chest approach in the treatment of Simon grade II gynecomastia.Data from 12 patients with grade II gynecomastia admitted from January 2017 to November 2018 were retrospectively analyzed, and related satisfaction surveys were conducted 6 months after the operation.All surgeries were successfully performed under single-port endoscopy, and no patients were converted to open surgery. There were no serious complications related to the surgery, and all the patients were satisfied with the postoperative appearance.The application of single-port endoscopy in the surgical treatment of grade II gynecomastia is safe and reliable.