Comparative long-term outcomes of natural orifice specimen extraction surgery and conventional laparoscopic colectomy for left-sided colorectal cancer: a propensity score-matched analysis.

BACKGROUND: Natural orifice specimen extraction surgery (NOSES) is currently widely used in left-sided colorectal cancer. Some clinical comparative studies have been conducted, providing evidence of its safety and oncological benefits. However, these studies are typically characterized by small sample sizes and short postoperative follow-up periods. Consequently, in this research, the authors adopt the propensity score matching method to undertake a large-scale retrospective comparative study on NOSES colectomy for left-sided colorectal cancer, with the goal of further augmenting the body of evidence-based medical support for NOSES. METHODS: This retrospective study involved patients who underwent NOSES colectomy and conventional laparoscopic (CL) colectomy for left-sided colorectal cancer between January 2014 and April 2021. In the NOSES group, specimens were extracted through the anus with the help of a Cai tube (homemade invention: ZL201410168748.2). The patients were matched at a ratio of 1:1 according to age, sex, BMI, tumor diameter, tumor location (descending and splenic flexure colon/ sigmoid colon/ middle and upper rectum), tumor height from anal verge, ASA grade, previous abdominal surgery, clinical pathologic stage, preoperative CEA. After matching, 132 patients in the NOSES group and 132 patients in the CL group were eligible for analysis. RESULTS: Compared with CL group, NOSES group was associated with decreased postoperative maximum pain score (2.6±0.7 vs. 4.7±1.7, P=0.000), less additional analgesia required (6.8 vs. 34.8%, P=0.000), faster time to passage of flatus (2.3±0.6 days vs. 3.3±0.7 days, P=0.000), less wound infection (0.0 vs. 6.1%, P=0.007), and longer operative time (212.5±45.8 min vs. 178.0±43.4 min, P=0.000). No significant differences were observed in estimated blood loss, time to resume regular diet, postoperative hospital stay, conversion to open surgery or conventional minilaparotomy, total morbidity, readmission, mortality, pathologic outcomes, and Wexner incontinence score between groups. After a median follow-up of 63.0 months, the 5-year overall survival rates were 88.3 versus 85.0% (P=0.487), disease-free survival rates were 82.9 versus 83.6% (P=0.824), and the local recurrence rates were 4.4 versus 4.0% (P=0.667) in the NOSES and CL groups, respectively. CONCLUSIONS: This study suggests that NOSES colectomy using a Cai tube for left-sided colorectal cancer is a safe and feasible option with better cosmetic results, less pain, faster recovery of gastrointestinal function, and comparable long-term clinical and oncologic outcomes to CL colectomy.

Clinical outcomes of laparoscopic-assisted natural orifice specimen extraction colectomy using a Cai tube for left-sided colon cancer: a prospective randomized trial.

BACKGROUND: The role of laparoscopic-assisted natural orifice specimen extraction (LA-NOSE) colectomy in the treatment of left-sided colon cancer has not been well defined, and there remains confusion about how to conveniently exteriorize specimens through natural orifices. Therefore, we introduced a homemade invention, the Cai tube, to facilitate the extraction of specimens and compared the clinical outcomes of LA-NOSE with conventional laparoscopic (CL) colectomy for left-sided colon cancer. METHODS: From March 2015 to August 2017, patients with left-sided colon cancer were randomly divided into LA-NOSE and CL groups. Specimens were extracted through the anus with the help of a Cai tube (Patent Number: ZL201410168748.2) in the LA-NOSE group. The primary outcome measure was postoperative pain. Secondary outcomes were the duration of operation, postoperative recovery, surgical morbidity, pathological quality of the specimen, and long-term outcomes, including 3-year overall survival, disease-free survival, local recurrence, and overall recurrence. RESULTS: A total of 60 patients (30 per group) were recruited for this study. None of the patients required emergency conversion to conventional laparoscopic or open surgery during the operation. The postoperative maximum pain score was significantly lower in the LA-NOSE group (mean 2.5 vs. 5.1, P = 0.001), as was the additional analgesia requirement (mean 2/30 vs. 10/30, P = 0.021). Patients in the LA-NOSE group experienced a shorter first time to passage of flatus (mean 2.2 vs. 3.1 days, P = 0.026). All patients could control their defecation at 6 months after surgery. The comparison between the two groups showed no significant differences in the operative time, bleeding volume, postoperative hospital stay, surgical morbidity rates, number of lymph nodes harvested, or resection margin status. The mean follow-up was 48 months (range 7-59) and was similar in both groups. The results showed no differences in long-term outcomes between the two groups. CONCLUSION: In the treatment of left-sided colon cancer, compared with conventional laparoscopic colectomy, LA-NOSE colectomy using the Cai tube exhibited lower postoperative pain, shorter recovery of gastrointestinal function, and similar long-term outcomes. REGISTRATION NUMBER: ChiCTR-OOR-15007060 ( http://www.chictr.org.cn/ ).

MicroRNA-18 facilitates the stemness of gastric cancer by downregulating HMGB3 though targeting Meis2.

The recurrence and metastasis of gastric cancer are related to the stemness of gastric cancer cells. Researches have shown that miR-18 level is negatively correlated to the occurrence and development of certain cancer types. However, the effects of miR-18 on the stemness of gastric cancer remain uncertain. In this research, gastric cancer cell lines with stable overexpression of miR-18 were constructed through lentivirus infection. CCK-8 assay, RT-qPCR, Western blot, flow cytometry, and in vivo tumorigenesis assays were performed to evaluate the effects of miR-18 on the stemness of gastric cancer cells. Moreover, luciferase reporter assays found that Meis2 was the target of miR-18. Furthermore, we also found that the low-expressed oncogene HMGB3 is involved in this miR-18/Meis2 axis to further promote the stemness of gastric cancer cells. These findings suggest that the miR-18/Meis2/HMGB3 axis may be potential prognostic indicators for patients with gastric cancer.

Multi-Transcriptomic Analysis Reveals the Heterogeneity and Tumor-Promoting Role of SPP1/CD44-Mediated Intratumoral Crosstalk in Gastric Cancer.

GC is a fatal disease with high heterogeneity and invasiveness. Recently, SPP1 has been reported to be involved in the tumor progression of multiple human cancers; however, the role of SPP1 in GC heterogeneity and whether it is associated with the invasiveness and mortality of GC remain unclear. Here, we combined multiple RNA sequencing approaches to evaluate the impact of SPP1 on GC. Through bulk RNA sequencing (bulk RNA-seq) and immunohistochemistry (IHC), we found that SPP1 was highly expressed in GC, and high levels of SPP1 were associated with macrophage infiltration, an advanced tumor stage, and higher mortality for advanced GC patients. Furthermore, through simultaneous single-cell and spatial analysis, we demonstrated that SPP1+ macrophages are tumor-specific macrophages unique to cancer and enriched in the deep layer of GC tissue. Cell-cell communication analysis revealed that SPP1/CD44 interactions between SPP1+ macrophages and their localized tumor epithelial cells could activate downstream target genes in epithelial cells to promote dynamic changes in intratumor heterogeneity. Moreover, these activated genes were found to be closely associated with poor clinical GC outcomes and with cancer-related pathways that promote GC progression, as shown by survival analysis and enrichment analysis, respectively. Collectively, our study reveals that tumor-specific SPP1+ macrophages drive the architecture of intratumor heterogeneity to evolve with tumor progression and that SPP1 may serve as a prognostic marker for advanced GC patients, as well as a potential therapeutic target for GC.

MiR-873-5p targets THUMPD1 to inhibit gastric cancer cell behavior and chemoresistance.

BACKGROUND: Gastric cancer is one of the most common gastrointestinal tumors. Evidence has pointed to the fact that miRNAs play critical roles in the occurrence, development, and metastasis of gastric cancer by regulating cell proliferation, differentiation, apoptosis, and invasion. METHODS: In this study, first the relationship of miR-873-5p level and tissues types/LN(+/-)/metastasis(+/-)/tumor size was analysis, respectively. Second, the CCK8 and Transwell assay was used to determine the proliferation, invasion and migration of GC cells transfected with overexpression-/low expression-miR-873-5p. Third, the cell viability were analysis in the GC cells transfected with overexpression-/low expression-miR-873-5p treatment with different chemotherapy drugs. Fourth, the target gene of miR-873-5p was predicted using bioinformation methods. Fifth, the relationship of miR-873-5p with target gene-THUMPD1 were explored by using Wb and luciferase activity assay, et al. RESULTS: We confirmed that miR-873-5p was negatively correlated with GC including tumor size, LN metastasis, distant metastasis. The miR-873-5p enhanced the sensitivity of Doxorubicin/Fluorouracil and cisplatin. The THUMPD1 was the target gene of miR-873-5p. Moreover, miR-873-5p could target the THUMPD1 axis so as to inhibit gastric cancer cell behavior as well as chemoresistance. CONCLUSIONS: MiR-873-5p plays a role in regulating cell behavior as well as regulating chemoresistance in gastric cancer. In addition, THUMPD1, as a downstream molecule of miR-873-5p, plays an important role in the cell behavior and chemoresistance of gastric cancer. The research first confirmed that miR-873-5p could inhibit gastric cancer cell behavior and chemoresistance by targeting the THUMPD1.

[Feasibility analysis on membrane-based right-sided approach of laparoscopic suprapancreatic lymph node dissection for advanced distal gastric cancer].

OBJECTIVE: To investigate the feasibility and safety of membrane-based right-sided approach of laparoscopic suprapancreatic lymph node dissection for advanced distal gastric cancer. METHODS: The clinical data of 41 patients with advanced distal gastric cancer who underwent laparoscopic gastrectomy using membrane-based right-sided approach for laparoscopic suprapancreatic lymph node dissection at the Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University from January 2016 to January 2018 were retrospectively analyzed. There were 24 males and 17 females with a mean age of 56.8 years and a mean body mass index of 22.6 kg/m². Membrane-based right-sided approach of laparoscopic suprapancreatic lymph node dissection contained 4 steps briefly: (1) dissection of mesenteria above the head of pancreas: the tri-junction of pancreas-duodenum was cut to expose and identify the logo of Benz;clearance of the membrane of No.5a was performed towards the left, and then expanded to the posterior layer of No.12a. (2) dissection of the V shape dorsal mesogastrium: membrane bridge at splenic artery trunk root was cut; in suprapancreatic space, clearance was performed towards to the left to the middle of the splenic artery trunk and expanded to the posterior Tolds plane upwards to the posterior phrenic angle and retroperitoneal esophagus, then the surrounding tissue of anterior abdominal aorta. (3) dissection of the U shape mesenteria:membrane bridge at common hepatic artery root was cut; mesentery was separated; the left gastric vein was freed and ligated at its root; in posterior pancreatic space, the mesentery of No.7, No.9 and No.8 was dissected in turns; the left gastric artery was high ligated and cut; the portal vein and posterior dorsal mesogastrium Toldt plane was routinely exposed; clearance was performed to right for No.8a and upward to the hepatic portal meeting at posterior mesentery No.12 plane. (4) dissection of the upper triangular area of pylorus: the trigone mesentery was cut along the upper edge of the pylorus; No.12a was swept upward along the gastric ventral mesentery; the upper boundary(No.8a) on the right side of the U-shaped membrane was joined. Intraoperative and postoperative presentations were analyzed. RESULTS: Laparoscopic gastrectomy for advanced distal gastric cancer with membrane-based right-sided approach of laparoscopic suprapancreatic lymph node dissection was successfully carried out in all the 41 patients. Distal gastric mesenteria en bloc resection was successfully performed. The operation time was (145.2±25.4) minutes and intraoperative blood loss was (53.3±18.3) ml without massive bleeding and severe complication. Number of lymph nodes dissected was 41.1±6.4, and number of suprapancreatic lymph node dissected was 23.3±3.7 without residual cancer at cut margin by pathology. Postoperative drainage volume was (65.8±21.7) ml; time to withdraw of catheter was (7.0±1.7) days; time to fluid intake was (3.5±1.8) days; postoperative hospital stay was (10.4±2.8) days; time to postoperative anal exhaust was (3.3±1.1) days. No complications, such as chyle leakage, postoperative massive bleeding, anastomotic leakage, abdominal cavity infection or gastroplegia occurred within 30 days after surgery. CONCLUSION: Membrane-based right-sided approach of laparoscopic suprapancreatic lymph node dissection for advanced distal gastric cancer can achieve en bloc resection and conform to the radical principle of oncology, and is safe and feasible.

miR-181d and c-myc-mediated inhibition of CRY2 and FBXL3 reprograms metabolism in colorectal cancer.

Colorectal cancer (CRC) is the second major cause of tumor-related deaths. MicroRNAs (miRNAs) have pivotal roles in CRC progression. Here, we describe the effect of miR-181d on CRC cell metabolism and underlying molecular mechanism. Our data firmly demonstrated that knockdown of miR-181d suppressed CRC cell proliferation, migration, and invasion by impairing glycolysis. Mechanistically, miR-181d stabilized c-myc through directly targeting the 3'-UTRs of CRY2 and FBXL3, which subsequently increased the glucose consumption and the lactate production. Inhibition of c-myc via siRNA or small molecular inhibitor abolished the oncogenic effects of miR-181d on the growth and metastasis of CRC cells. Furthermore, c-myc/HDAC3 transcriptional suppressor complex was found to co-localize on the CRY2 and FBXL3 promoters, epigenetically inhibit their transcription, and finally induce their downregulation in CRC cells. In addition, miR-181d expression could be directly induced by an activation of c-myc signaling. Together, our data indicate an oncogenic role of miR-181d in CRC by promoting glycolysis, and miR-181d/CRY2/FBXL3/c-myc feedback loop might be a therapeutic target for patients with CRC.

Long-term trend of chemical composition of atmospheric precipitation at a regional background station in Northern China.

Understanding the trend of chemical composition of precipitation is of great importance for air pollution control strategies in Northern China. A comprehensive study on the long-term chemical compositions of precipitation was carried out from 2003 to 2014 at the Shangdianzi (SDZ) regional background station in northern China. All samples were analyzed for pH, electrical conductivity and major ions (F-, Cl-, NO3-, SO42-, NH4+, Mg2+, Ca2+, K+ and Na+). The average pH during this period was 4.53±0.35, which is considerably lower than those reported in other background stations in China (Linan, Waliguan and Longfengshan). NH4+, SO42-, Ca2+ and NO3- were the dominant ions in precipitation, with concentrations (volume-weighted mean) of 212.99µeqL-1, 200.20µeqL-1, 116.88µeqL-1 and 98.56µeqL-1, respectively. The ion concentrations at SDZ were much higher than those of other background stations and megacities in China. A significantly increasing trend was observed for NO3- (7.26%year-1), and a decreasing trend was observed for SO42-/NO3-, suggesting that the precipitation of SDZ evolved from a sulfuric acid type to a mixed type dominated by both sulfuric and nitric acid. The source identification indicated that SO42-, NO3-, NH4+ and F- were dominated by secondary sources, Mg2+, Ca2+ and Na+ mostly originated from natural sources, and K+ and Cl- probably associated with anthropogenic sources. Long-range transport of air masses could influence the acidity, electrical conductivity and ion concentrations of precipitation at SDZ. The higher acidity and ion concentrations mainly occurred in the southerly and westerly trajectory pathways and partially in northwest pathways. Anthropogenic pollutants and crustal sources along these pathways were significant contributors to the chemical composition of precipitation in SDZ.