Effect of Pringle maneuver on prognosis of patients with colorectal cancer liver metastases after liver resection: a meta-analysis.

PURPOSE: Pringle maneuver (PM) is a double-edged sword in liver resection, which is beneficial in reducing blood loss but also causes ischemia-reperfusion injury which may stimulate the outgrowth of micrometastases. The impact of PM on tumor recurrence remains controversial. This study aimed to assess whether PM has effect on the prognosis of colorectal cancer liver metastases (CRLM) after hepatectomy. METHODS: PubMed and the Cochrane Library databases were searched. The PM is defined as the portal triad clamping for several minutes, followed by several minutes of reperfusion, repeated as needed. Prolonged PM was defined as continuous clamping ≥ 20 min or ≥ 3 cycles for maximally 15-min intermittent ischemia. RESULTS: Eleven studies encompassing 4054 patients were included in this meta-analysis. The pooled hazard ratio (HR) did not show significant differences between PM and non-PM groups for disease-free survival (DFS) (HR = 0.91, 95% confidence interval (CI) 0.76-1.11, P = 0.36) and overall survival (HR = 1.03, 95% CI 0.76-1.39, P = 0.87). Subgroup analysis revealed that prolonged PM has adverse impact on DFS (HR 1.75, 95% CI = 1.28-2.40, P = 0.0005). However, non-prolonged PM is a protective factor for DFS (HR 0.82, 95% CI = 0.73-0.92, P = 0.001). CONCLUSION: These findings suggested that prolonged PM may have an adverse impact on the DFS of patients with CRLM and non-prolonged PM is a protective factor for DFS. Further prospective multicenter studies are warranted.

Laparoscopic common bile duct exploration with primary closure could be safely performed among elderly patients with choledocholithiasis.

BACKGROUND: For patients with choledocholithiasis, laparoscopic common bile duct exploration (LCBDE) is preferred over open surgery. Whether primary closure of the common bile duct (CBD) should be performed upon completion of choledochotomy remains unclear, and the corresponding indications for primary closure of the common bile duct have yet to be fully identified. This study was performed to evaluate the safety and feasibility of primary closure of CBD among elderly patients (≥ 70 years) after LCBDE. METHODS: Patients with choledocholithiasis who had undergone LCBDE with primary closure of the CBD between July 2014 and December 2020 were retrospectively reviewed. Included patients were assigned into two groups (Group A: ≥70 years and Group B: <70 years) according to age. Group A was compared with Group B in terms of preoperative characteristics, intraoperative results and postoperative outcomes. RESULTS: The mean operative time for Group A was 176.59 min (± 68.950), while the mean operative time for Group B was 167.64 min (± 69.635) (P = 0.324). The mean hospital stay after surgery for Group A was 8.43 days (± 4.440), while that for Group B was 8.30 days (± 5.203) (P = 0.849). Three patients in Group A experienced bile leakage, while bile leakage occurred in 10 patients in Group B (3.8% vs. 4.5%, P = 0.781). Group A was not significantly different from Group B in terms of postoperative complications and 30-day mortality except pneumonia (P = 0.016), acute cardiovascular event (P = 0.005) and ICU observation (P = 0.037). After a median follow-up time of 60 months, 2 patients in Group A and 2 patients in Group B experienced stone recurrence (2.5% vs. 0.9%, P = 0.612). One patient in Group A experienced stenosis of the CBD, while stenosis of the CBD occurred in 5 patients in Group B (1.3% vs. 2.2%, P = 0.937). CONCLUSIONS: Primary closure of CBD upon completion of LCBDE could be safely performed among patients ≥ 70 years.

The impact of sarcopenia on the outcome of patients with left-sided colon and rectal cancer after curative surgery.

BACKGROUND: The impact of sarcopenia on the outcome of patients with left-sided colon and rectal cancer has not been exhaustively investigated. Thus, the present study was performed to evaluate the effect of sarcopenia on the outcome of patients with left-sided colon and rectal cancer. METHODS: Patients with pathologically diagnosed stage I, II and III left-sided colon or rectal cancer who had undergone curative surgery between January 2008 and December 2014 were retrospectively reviewed. The psoas muscle index (PMI) identified by 3D-image analysis of computed tomographic images was the criterion used to diagnose sarcopenia. The cut-off value recommended by Hamaguchi (PMI value < 6.36 cm2/m2 for men and < 3.92 cm2/m2 for women) was adopted to confirm the diagnosis of sarcopenia. According to the PMI, each patient was divided into the sarcopenia group (SG) or the nonsarcopenia group (NSG). Then, the SG was compared with the NSG in terms of postoperative outcomes. RESULTS: Among the 939 patients included, 574 (61.1%) were confirmed to have preoperative sarcopenia. Initially, it was demonstrated that the SG was not significantly different from the NSG in terms of most baseline characteristics except for a lower body mass index (BMI) (P < 0.001), a larger tumour size (P < 0.001) and more weight loss (more than 3 kg in the last three months) (P = 0.033). The SG had a longer hospital stay after surgery (P = 0.040), more intraoperative blood transfusions (P = 0.035), and higher incidence of anastomotic fistula (P = 0.027), surgical site infection (SSI) (P = 0.037) and hypoalbuminemia (P = 0.022), 30-day mortality (P = 0.042) and 90-day mortality (P = 0.041). The SG had significantly worse overall survival (OS) (P = 0.016) and recurrence-free survival (RFS) (P = 0.036) than the NSG. Subsequently, Cox regression analysis revealed that preoperative sarcopenia was an independent predictive factor for worse OS (P = 0.0211, HR = 1.367, 95% CI: 1.049-1.782) and RFS (P = 0.045, HR = 1.299, 95% CI: 1.006-1.677). CONCLUSION: Preoperative sarcopenia adversely affects the outcome of patients with left-sided colon and rectal cancer, and preoperative nutrition supplementation may help us improve their long-term and short-term outcomes.

Robotic versus laparoscopic major hepatectomy for hepatocellular carcinoma: short-term outcomes from a single institution.

BACKGROUND: Currently, an increasing number of robotic major hepatectomies for hepatocellular carcinoma (HCC) are being performed. Despite the advantages of robotic surgery over laparoscopic procedures, studies comparing robotic with laparoscopic major hepatectomy in terms of short-term results remain scarce. This study was performed to compare robotic major hepatectomy and laparoscopic major hepatectomy in terms of their intraoperative and postoperative results. METHODS: Data regarding demographics and intraoperative and postoperative results of 131 patients undergoing robotic or laparoscopic major hepatectomy between January 2017 and March 2022 were retrieved from their medical records and compared between the two types of surgery. RESULTS: Between January 2017 and March 2022, 44 robotic major hepatectomies and 87 laparoscopic major hepatectomies were performed at the Department of Hepatobiliary and Pancreatic Surgery, Shenzhen People's Hospital. Patients undergoing robotic major hepatectomy were not significantly different from those undergoing laparoscopic major hepatectomy in terms of age (P = 0.397), sex (P = 0.624), body mass index (BMI) (P = 0.118), alpha-fetoprotein (AFP) (P = 0.09), tumor size (P = 0.176), cirrhosis (P = 0.384), fatty liver (P = 0.162), preoperative antiviral treatment (P = 0.934), hepatitis B virus (HBV) DNA (P = 0.646) and operation type (P = 0.054). Robotic major hepatectomy was associated with a longer operation time (median: 255.5 versus 206.8 min; P < 0.001) and less estimated blood loss (median: 118.9 versus 197.0 ml; P = 0.002) than laparoscopic major hepatectomy. However, robotic major hepatectomy was not significantly different from laparoscopic major hepatectomy regarding length of postoperative hospital stay (P = 0.849), open conversion (P = 0.077), ICU stay (P = 0.866), postoperative massive abdominal bleeding (P = 1.00), portal vein thrombosis (P = 1.00), abdominal infection (P = 1.00), pulmonary infection (P = 1.00), pulmonary embolism (P = 1.00), cardiac complications (P = 1.00), liver failure (P = 1.00), kidney failure (P = 1.00), biliary leak (P = 1.00), positive resection margin (P = 1.00), 30-day mortality (P = 1.00) and 90-day mortality (P = 1.00). CONCLUSIONS: Robotic major hepatectomy was as effective as laparoscopic surgery in terms of intraoperative and postoperative results but took longer and could more efficiently control intraoperative blood loss.

Does the level of inferior mesenteric artery ligation affect short-term and long-term outcomes of patients with sigmoid colon cancer or rectal cancer? A single-center retrospective study.

BACKGROUND: For sigmoid colon or rectal cancer, a definite consensus regarding the optimal level ligating the inferior mesenteric artery (IMA) has not been reached. We performed this study to determine whether the ligation level significantly affected short-term and long-term outcomes of patients with sigmoid colon or rectal cancer after curative laparoscopic surgery. METHODS: Medical records of patients with sigmoid colon or rectal cancer who had undergone curative laparoscopic surgery between January 2008 and December 2014 at the Department of Gastrointestinal Surgery, Guangdong Provincial Hospital of Traditional Chinese Medicine were reviewed. Then, the high tie group (HTG) was compared with the low tie group (LTG) in terms of short-term and long-term outcomes. RESULTS: Five-hundred ninety patients were included. No significant differences between two groups regarding baseline characteristics existed. HTG had a significantly higher risk of anastomotic fistula than LTG (21/283 vs 11/307, P = 0.040). Additionally, high ligation was proven by multivariate logistic regression analysis to be an independent factor for anastomotic fistula (P = 0.038, OR = 2.232, 95% CI: 1.047-4.758). Furthermore, LT resulted in better preserved urinary function. However, LTG was not significantly different from HTG regarding operative time (P = 0.075), blood transfusion (P = 1.000), estimated blood loss (P = 0.239), 30-day mortality (P = 1.000), ICU stay (P = 0.674), postoperative hospital stay (days) (P = 0.636), bowel obstruction (P = 0.659), ileus (P = 0.637), surgical site infection (SSI) (P = 0.121), number of retrieved lymph nodes (P = 0.501), and number of metastatic lymph nodes (P = 0.131). Subsequently, it was revealed that level of IMA ligation did not significantly influence overall survival (OS) (P = 0.474) and relapse-free survival (RFS) (P = 0.722). Additionally, it was revealed that ligation level did not significantly affect OS (P = 0.460) and RFS (P = 0.979) of patients with stage 1 cancer, which was also observed among patients with stage 2 or stage 3 cancer. Ultimately, ligation level was not an independent predictive factor for either OS or RFS. CONCLUSIONS: HT resulted in a significantly higher incidence of anastomotic fistula and worse preservation of urinary function. Level of IMA ligation did not significantly affect long-term outcomes of patients with sigmoid colon or rectal cancer after curative laparoscopic surgery.

Down-regulation of SOCS6: an unfavorable prognostic factor for gastrointestinal stromal tumor proven by survival analysis.

BACKGROUND: Many studies reporting that down-regulation of SOCS6 plays vital roles in promoting progression of malignant tumors have been published. The present study was performed to evaluate whether SOCS6 was significantly associated with prognosis of GIST patients. METHODS: Immunohistochemical staining was accomplished to evaluate the expression levels of SOCS6 among GIST patients. The impacts of SOCS6 expression on overall survival (OS) and recurrence-free survival (RFS) of GIST patients were assessed by Cox proportional hazard regression model analysis and Kaplan-Meier curve analysis. RESULTS: It was demonstrated that the expression level of SOCS6 was significantly associated with tumor size (P=0.001). Then according to Kaplan-Meier curve analysis, low expression of SOCS6 was significantly correlated with worse OS and RFS of GIST patients. Ultimately, it was revealed by Cox proportional regression model analysis that low expression of SOCS6 was an independent predictive factor for OS and RFS. CONCLUSIONS: Low expression of SOCS6 was an independent prognostic factor for GIST, suggesting its potential as a novel biomarker predicting survival of GIST patients.

The prognostic impacts of PABPC1 expression on gastric cancer patients.

Aim: To assess the prognostic impacts of PABPC1 on gastric cancer (GC) patients. Methods: The expression levels of PABPC1 in GC tissues and normal gastric tissues were initially compared via bioinformatics analysis. Immunohistochemical staining was accomplished to assess the expression of PABPC1 in the included GC patients. Then the impacts of PABPC1 expression on survival of GC patients were evaluated by Cox regression and Kaplan-Meier analyses. Results: The expression levels of PABPC1 in gastric tissues were significantly higher than those in normal gastric tissues (paired, p = 0.002; unpaired, p = 3.60e-9). By Kaplan-Meier, it was demonstrated that high expression of PABPC1 was significantly associated with worse overall and disease-free survival. Furthermore, high PABPC1 expression was demonstrated to be an independent predictive factor for both overall (p = 0.013; hazard ratio = 2.058; 95% CI: 1.162-3.644) and disease-free (p = 0.018; hazard ratio = 2.284; 95% CI: 1.153-4.524) survival. Conclusion: PABPC1 is a potential prognostic biomarker for GC patients.

Lay abstract Previous studies have reported that PABPC1 is involved in a series of biological processes and participates in many cancers. However, the specific role of PABPC1 in different cancers varies significantly, and PABPC1 has not been fully investigated in gastric cancer (GC). In the present study, it was demonstrated that PABPC1 was significantly upregulated in GC and its high expression in GC was significantly associated with worse overall and disease-free survival, indicating the potential of PABPC1 as a novel prognostic biomarker for GC.

MRPS17 promotes invasion and metastasis through PI3K/AKT signal pathway and could be potential prognostic marker for gastric cancer.

In this study, the molecular mechanisms through which Mitochondrial Ribosomal Protein S17 (MRPS17) contributes to gastric cancer (GC) and its prognostic significance in GC have been explored. As a protein encoding gene, MRPS17 encodes a 28s proteins belonging the ribosomal protein S17P family. The specific roles and molecular mechanisms of MRPS17 in cancers remain ambiguous. It was revealed by analyzing data from TCGA and GEO that elevated expression of MRPS17 was significantly associated with invasion of GC and poor survival of GC patients. Then through univariate and multivariate Cox regression analyses it was demonstrated that MRPS17 an independent prognostic factor for GC patients (P<0.001). It was demonstrated by differentially expressed gene analysis and functional enrichment analysis that MPRS17 is related to PI3K/AKT pathway and Cell adhesion molecules (CAMs), while its function is mediated by collagen-containing extracellular matrix and receptor ligand/regulator activity. Then it was proven by in-vitro experiments that knocking down of MRPS17 gene in AGS and SGC7901 cells would significantly inhibit proliferation and invasion capability of these cells. Furthermore, it was revealed by cell immunofluorescence assay that as a ribosomalprotein, MRPS17 was mainly distributed in the cytoplasmic surface of cell membrane. Additionally, activation of PI3K/AKT pathway is responsible for malignant progression of glioma that was promoted by MRPS17. In conclusion, it was revealed in the present study that MRPS17 promoted invasion and metastasis of GC and potential molecular mechanisms through which it exerted its influences on GC were explored, suggesting its potential as a novel prognostic biomarker for GC.

RANK promotes colorectal cancer migration and invasion by activating the Ca2+-calcineurin/NFATC1-ACP5 axis.

The tumor necrosis factor (TNF) receptor superfamily member 11a (TNFRSF11a, also known as RANK) was demonstrated to play an important role in tumor metastasis. However, the specific function of RANK in colorectal cancer (CRC) metastasis and the underlying mechanism are unknown. In this study, we found that RANK expression was markedly upregulated in CRC tissues compared with that in matched noncancerous tissues. Increased RANK expression correlated positively with metastasis, higher TNM stage, and worse prognosis in patients with CRC. Overexpression of RANK promoted CRC cell metastasis in vitro and in vivo, while knockdown of RANK decreased cell migration and invasion. Mechanistically, RANK overexpression significantly upregulated the expression of tartrate-resistant acid phosphatase 5 (TRAP/ACP5) in CRC cells. Silencing of ACP5 in RANK-overexpressing CRC cells attenuated RANK-induced migration and invasion, whereas overexpression of ACP5 increased the migration and invasion of RANK-silencing cells. The ACP5 expression was transcriptionally regulated by calcineurin/nuclear factor of activated T cells c1 (NFATC1) axis. The inhibition of calcineurin/NFATC1 significantly decreased ACP5 expression, and attenuated RANK-induced cell migration and invasion. Furthermore, RANK induced phospholipase C-gamma (PLCγ)-mediated inositol-1,4,5-trisphosphate receptor (IP3R) axis and stromal interaction molecule 1 (STIM1) to evoke calcium (Ca2+) oscillation. The RANK-mediated intracellular Ca2+ mobilization stimulated calcineurin to dephosphorylate NFATC1 and induce NFATC1 nuclear translocation. Both blockage of PLCγ-IP3R axis and STIM1 rescued RANK-induced NFATC1 nuclear translocation, ACP5 expression, and cell metastasis. Our study revealed the functional expression of RANK in human CRC cells and demonstrated that RANK induced the Ca2+-calcineurin/NFATC1-ACP5 axis in the regulation of CRC metastasis, that might be amenable to therapeutic targeting.

Laparoscopic gastrectomy plus D2 lymphadenectomy is as effective as open surgery in terms of long-term survival: a single-institution study on gastric cancer.

BACKGROUND: Laparoscopic surgery has been widely accepted to treat early-stage gastric cancer. However, it is still controversial to perform laparoscopic gastrectomy plus D2 lymphadenectomy for locally advanced gastric cancer. We performed the present study to compare the long-term outcomes of patients after laparoscopic or open gastrectomy plus D2 lymphadenectomy. METHODS: The clinicopathological data of 182 gastric cancer patients receiving gastrectomy plus D2 lymphadenectomy between January 2011 and December 2015 at Shenzhen Traditional Chinese Medicine Hospital were retrospectively retrieved. The overall survival (OS) and disease-free survival (DFS) of these 182 patients were compared. Then, the prognostic significance of positive lymph node ratio (LNR) was assessed. RESULTS: As a whole, OS (P = 0.789) and DFS (P = 0.672) of patients receiving laparoscopic gastrectomy plus D2 lymphadenectomy were not significantly different from those of patients receiving open surgery. For stage I patients, laparoscopic gastrectomy plus D2 lymphadenectomy was not significantly different from open surgery in terms of OS (P = 0.573) and DFS (P = 0.157). Similarly, for stage II patients, laparoscopic gastrectomy plus D2 lymphadenectomy was not significantly different from open surgery in terms of OS (P = 0.567) and DFS (P = 0.830). For stage III patients, laparoscopic gastrectomy plus D2 lymphadenectomy was not significantly different from open surgery in terms of OS (P = 0.773) and DFS (P = 0.404). Laparoscopic or open gastrectomy plus D2 lymphadenectomy was not proven by Cox regression analysis to be an independent prognostic factor for OS and DFS. High LNR was significantly associated with worse OS (P < 0.001) and DFS (P < 0.001). Surgical type did not significantly affect prognosis of patients with low LNR or survival of patients with high LNR. CONCLUSIONS: For patients with gastric cancer, laparoscopic gastrectomy plus D2 lymphadenectomy was not inferior to open surgery in terms of long-term outcomes. LNR is a useful prognostic marker for GC patients.

Prognostic Value and Biological Functions of RNA Binding Proteins in Stomach Adenocarcinoma.

PURPOSE: To investigate the prognostic value and biological function of RNA binding proteins (RBPs) in stomach adenocarcinoma (STAD). MATERIALS AND METHODS: Datasets of the differentially expressed genes (DEGs) were downloaded from the TCGA-based (The Cancer Genome Atlas) GEPIA database, from which the differentially expressed RBPs were determined. Functions and prognostic values of these determined RBPs were systematically investigated by a series of methods in bioinformatics analysis. In addition, transwell assays were performed to explore the effect of PTBP1 in STAD cells. RESULTS: Three hundred and sixty-two differentially expressed RBPs were determined, with 331 up-regulated and 31 down-regulated. Seven RBPs (PTBP1, PPIH, SMAD5, MSI2, RBM15, MRPS17, and ADAT3) were identified to be prognosis-related and adopted to construct a prognostic model. Compared with low-risk patients in TCGA training cohort, TCGA testing cohort and GEO cohort, high-risk patients had poorer overall survival (OS). The area under the ROC curves of this prognostic model were 0.804, 0.644 and 0.581 for TCGA training cohort, TCGA testing cohort and GEO cohort, respectively, justifying itself as a good prognostic model with reliable predictive ability. Using the seven identified RBPs, we then constructed a nomogram to generate a clinical utility model. The regulatory networks and functions of the seven RBPs were then investigated, the results of which demonstrated that MRPS17 and PTBP1 reduced the number of infiltrated immune cells. In-vitro experiments showed that the downregulation of PTBP1 weakened the migration and invasion capability of AGS and HGC27 cells. CONCLUSION: The seven-gene signature can be used as a reliable STAD prognostic biomarker, and these findings help us better understand the prognostic roles and functions of RBPs in STAD.

Derivation and Validation of a Prognostic Model for Cancer Dependency Genes Based on CRISPR-Cas9 in Gastric Adenocarcinoma.

As a CRISPR-Cas9-based tool to help scientists to investigate gene functions, Cancer Dependency Map genes (CDMs) include an enormous series of loss-of-function screens based on genome-scale RNAi. These genes participate in regulating survival and growth of tumor cells, which suggests their potential as novel therapeutic targets for malignant tumors. By far, studies on the roles of CDMs in gastric adenocarcinoma (GA) are scarce and only a small fraction of CDMs have been investigated. In the present study, datasets of the differentially expressed genes (DEGs) were extracted from the TCGA-based (The Cancer Genome Atlas) GEPIA database, from which differentially expressed CDMs were determined. Functions and prognostic significance of these verified CDMs were evaluated using a series of bioinformatics methods. In all, 246 differentially expressed CDMs were determined, with 147 upregulated and 99 downregulated. Ten CDMs (ALG8, ATRIP, CCT6A, CFDP1, CINP, MED18, METTL1, ORC1, TANGO6, and PWP2) were identified to be prognosis-related and subsequently a prognosis model based on these ten CDMs was constructed. In comparison with that of patients with low risk in TCGA training, testing and GSE84437 cohort, overall survival (OS) of patients with high risk was significantly worse. It was then subsequently demonstrated that for this prognostic model, area under the ROC (receiver operating characteristic) curve was 0.771 and 0.697 for TCGA training and testing cohort respectively, justifying its reliability in predicting survival of GA patients. With the ten identified CDMs, we then constructed a nomogram to generate a clinically practical model. The regulatory networks and functions of the ten CDMs were then explored, the results of which demonstrated that as the gene significantly associated with survival of GA patients and Hazard ratio (HR), PWP2 promoted in-vitro invasion and migration of GA cell lines through the EMT signaling pathway. Therefore, in conclusion, the present study might help understand the prognostic significance and molecular functions of CDMs in GA.

Prognostic Significance of ACP5 in Human Gastric Cancer.

INTRODUCTION: Tartrate-resistant acid phosphatase (ACP5) plays crucial roles in multiple pathological processes, including the genesis and progression of malignant tumors. We performed this study with the purpose of determining whether ACP5 is a crucial biomarker significantly related to prognoses of gastric cancer (GC) patients. METHODS: The expression level of ACP5 level was assessed among 170 GC specimens using immunohistochemistry. The associations between ACP5 expression and clinicopathological variables were evaluated. Univariate and multivariate Cox regression analyses were performed to confirm independent prognostic factors for GC patients. RESULTS: It was revealed that ACP5 expression level in GC tissue was significantly associated with depth of invasion (p = 0.029) and TNM stage (p = 0.036). ACP5 was demonstrated by multivariate Cox regression analysis to be an independent prognostic factor for overall survival (OS) (p = 0.001) and recurrence-free survival (RFS) (p = 0.011) of GC patients. CONCLUSIONS: The expression of ACP5 in GC tissue was significantly higher than that in normal tissues, and its overexpression was associated with a poorer prognosis, suggesting its potential roles in preventing and treating GC.

A thioredoxin reductase inhibitor ethaselen induces growth inhibition and apoptosis in gastric cancer.

Gastric cancer (GC) is the third leading cause of cancer deaths worldwide. Conventional chemotherapy has been proven useful to only a portion of the patients. Previous developed targeted drugs are more effective and tolerable than conventional drugs. Thus the development of novel drugs targeting markers is an urgent task and the main direction for future research. Ethaselen, an inhibitor of thioredoxin reductase (TrxR), has been considered an important anticancer target drug. Previous studies show that it is effective on treating many kinds of cancers. In this paper, we examined that ethaselen effectively inhibited the growth of gastric cancer cells and promoted apoptosis. Organoids were cultured from patient-derived cells in a three-dimension form which are widely used in cancer research to help us understand cancer cells behavior at the sub-organ level and develop novel drugs. We established a drug testing and screening system using GC-derived organoids by recapitulating tumor microenvironment. We confirmed that the TrxR-targeting ethaselen could be a novel and effective drug for gastric cancer treatment.