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.

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.

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.

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.

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.

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.

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.

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.

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.

Anatomical characteristics and classifications of gastrocolic trunk of Henle in laparoscopic right colectomy: preliminary results of multicenter observational study.

BACKGROUND: As a key landmark during laparoscopic right colectomy, the classification and variation of the gastrocolic trunk of Henle (GTH) remains to be clarified. The aim of this nationwide multicenter study was to describe the characteristics of the GTH intra-operatively during laparoscopic right colectomies. METHODS: Three hundred seventy-one patients who underwent laparoscopic right colectomies from January 2018 to March 2019 in 25 hospitals across China were enrolled in the study. The length of the GTH, the classification with a precise description of confluent tributaries, and other variations were analyzed. RESULTS: Of the 371 patients, 363 had a GTH. The proportion of type-0, type-I, type-II, and type-III was 15.2% (n = 55), 54.8% (n = 199), 25.3% (n = 92), and 4.7% (n = 17), respectively. The average length of the GTH was 8.5 mm, ranging from 2 to 30 mm. CONCLUSIONS: This is the first multicenter study with a large sample by which the GTH was classified based on laparoscopic intraoperative observation. Variations in the GTH were classified into four types based on the number of colic drainage veins (right colic, superior right colic, middle colic, accessory middle colic, and ileocolic veins), among which the right colic vein was the most common. The length of the GTH was relatively short, and thus might carry a risk of bleeding. Further clinical data should be correlated with the characteristics of the GTH.

Effects of CO2 pneumoperitoneum on the expression of thymidine kinase 1 and Ki67 in colorectal carcinoma cells.

BACKGROUND: To investigate thymidine kinase 1(TK-1) and Ki67 expression levels of human colorectal carcinoma cells line SW480 after exposure to a simulated laparoscopic carbon dioxide (CO2) pneumoperitoneum environment at different pressures and lengths of exposure time. METHODS: The effects of the simulated laparoscopic CO2 pneumoperitoneum environment at different CO2 pressures (6, 9, 12, and 15 mmHg) and exposure times (2 and 4 h) on TK-1 and Ki67 of SW480 cells were assessed by flow cytometry and reverse transcription (RT-PCR). Cells cultured in a standard environment were used as the control group (at 37 °C, 5% CO2). RESULTS: In this study, TK-1 and Ki67 in SW480 cells tended to decrease with the increase of CO2 pressure and exposure time. Significantly lower expression levels were observed at 0 and 24 h of culture after exposure to both at 12 and 15 mmHg, as compared with the control group at 6 and 9 mmHg (p < 0.05). The expression of TK-1 and Ki67 levels increased up to a plateau of the control group after 48 and 72 h (p > 0.05). With the CO2 pneumoperitoneum exposure time prolonging, the expression of TK-1 and Ki67 levels in 12 or 15 mmHg was lower than in 2 h (p < 0.05). In the same exposure time, the transcription level of TK-1 and Ki67 decreased significantly in 12 and 15 mmHg CO2 pneumoperitoneum groups (p < 0.05) and returned to the basal level of control group after being cultivated for 48 h (p > 0.05). In the same pressure, the difference of TK-1 mRNA between the groups of 2 and 4 h was also significant. CONCLUSION: The expression levels of TK-1 and Ki67 were suppressed temporarily after the continuous CO2 insufflation in higher pressure (at 12 and 15 mmHg). The higher the pressure of CO2 insufflation, the more the inhibiting effects of TK-1 and Ki67 will be. The longer the time of CO2 insufflation, the more significantly their expression decreased.

Short-term outcomes of distal gastrectomy versus total gastrectomy for gastric cancer under enhanced recovery after surgery: a propensity score-matched analysis.

Enhanced recovery after surgery (ERAS) has been used safely and effectively in patients with gastric cancer. Our aim was to evaluate the short-term outcomes of total gastrectomy (TG) versus distal gastrectomy (DG) for gastric cancer under ERAS. A prospectively collected database of 1349 patients with gastric cancer who underwent TG or DG between January 2016 and September 2022 was retrospectively analyzed. Propensity score matching analysis was used at a ratio of 1:1 to reduce confounding effects, and perioperative clinical outcomes were compared between the two groups. The primary outcome was overall postoperative complications (POCs). Secondary outcomes comprised time to bowel function recovery, postoperative hospital stay, mortality, and 30-day readmission rate. Of 1349 identified patients, 296 (21.9%) experienced overall POCs. Before matching, multivariable analysis revealed that age, body mass index, diabetes, operation time, and extent of gastrectomy were independent risk factors for overall POCs. After matching, each group comprised 495 patients, and no significant differences were observed between the groups for all parameters except tumor location. Compared with TG, DG was associated with significantly earlier days to first flatus and to eating a soft diet, and shorter postoperative hospital stay (P < 0.05). The incidence of overall- and severe POCs (Clavien-Dindo grade ≥ IIIa) in the TG group was significantly higher vs. the DG group (P < 0.05). There was no significant difference in the number of days to eating a liquid diet, or mortality and 30-day readmission rates between the groups (P > 0.05). In the subgroup analysis for middle-third gastric cancer, the TG group experienced higher rates of overall- and severe POCs, with a longer postoperative hospital stay. Compared with DG, patients who underwent TG had higher POC rates, slower recovery of bowel function, and longer duration of hospitalization under ERAS. Therefore, caution is needed when initiating early feeding for patients who undergo TG.

HNF1ɑ promotes colorectal cancer progression via HKDC1-mediated activation of AKT/AMPK signaling pathway.

The hepatocyte nuclear factor-1 (HNF1ɑ) is a transcription factor that contributes to several kinds of cancer progression. However, very little is known regarding the mechanisms underlying the activity of HNF1ɑ. We aimed to explore the role of HNF1ɑ in the progress of colorectal cancer (CRC) and elucidate its molecular mechanism. HNF1ɑ expression was upregulated in CRC samples and high expression of HNF1ɑ was associated with poor prognosis of CRC patients. HNF1α knockdown and overexpression inhibited and promoted proliferation, migration and invasion of CRC cells both in vitro and in vivo respectively. Mechanistically, HNF1ɑ increased the transcriptional activity of hexokinase domain component 1（HKDC1）promoter, thus activated AKT/AMPK signaling. Meanwhile, HKDC1 upregulation was important for the proliferation, migration and invasion of CRC cells and knockdown of HKDC1 significantly reversed the proliferation, migration and invasion induced by HNF1α overexpression. Taken together, HNF1ɑ contributes to CRC progression and metastasis through binding to HKDC1 and activating AKT/AMPK signaling. Targeting HNF1ɑ could be a potential therapeutic strategy for CRC patients.

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.

Machine learning-based screening and validation of liver metastasis-specific genes in colorectal cancer.

Colorectal liver metastasis (CRLM) is challenging in the clinical treatment of colorectal cancer. Limited research has been conducted on how CRLM develops. RNA sequencing data were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Four machine learning algorithms were used to screen the hub CRLM-specific genes, including Least Absolute Shrinkage and Selection Operator (Lasso), Random forest, SVM-RFE, and XGboost. The model for identifying CRLM was developed using stepwise logistic regression and was validated using internal and independent datasets. The prognostic value of hub CRLM-specific genes was assessed using the Lasso-Cox method. The in vitro experiments were performed using SW620 cells. The CRLM identification model was developed based on four CRLM-specific genes (SPP1, ZG16, P2RY14, and PRKAR2B), and the model efficacy was validated using GSE41258 and three external cohorts. Five CRLM-specific prognostic hub genes, SPP1, ZG16, P2RY14, CYP2E1, and C5, were identified using the Lasso-Cox algorithm, and a risk score was constructed. The risk score was validated using the GSE39582 cohort. Three genes have both efficacy in identifying CRLM and prognostic value: ZG16, P2RY14, and SPP1. Immune infiltration and enrichment analyses demonstrated that SPP1 was associated with M2 macrophage polarization and extracellular matrix remodeling. In vitro experiments indicated that SPP1 may act as a cancer-promoting factor. The hub CRLM-specific gene SPP1 can help determine the diagnosis, prognosis, and immune infiltration of patients with CRLM.

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.

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.

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.

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.