Machine learning based peri-surgical risk calculator for abdominal related emergency general surgery: a multicenter retrospective study.

BACKGROUND: Currently, there is a lack of ideal risk prediction tools in the field of emergency general surgery (EGS). The American Association for the Surgery of Trauma recommends developing risk assessment tools specifically for EGS-related diseases. In this study, we sought to utilize machine learning (ML) algorithms to explore and develop a web-based calculator for predicting five perioperative risk events of eight common operations in EGS. METHOD: This study focused on patients with EGS and utilized electronic medical record systems to obtain data retrospectively from five centers in China. Five ML algorithms, including Random Forest (RF), Support Vector Machine, Naive Bayes, XGBoost, and Logistic Regression, were employed to construct predictive models for postoperative mortality, pneumonia, surgical site infection, thrombosis, and mechanical ventilation >48 h. The optimal models for each outcome event were determined based on metrics, including the value of the Area Under the Curve, F1 score, and sensitivity. A comparative analysis was conducted between the optimal models and Emergency Surgery Score (ESS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and American Society of Anesthesiologists (ASA) classification. A web-based calculator was developed to determine corresponding risk probabilities. RESULT: Based on 10 993 patients with EGS, we determined the optimal RF model. The RF model also exhibited strong predictive performance compared with the ESS, APACHE II score, and ASA classification. Using this optimal model, the authors developed an online calculator with a questionnaire-guided interactive interface, catering to both the preoperative and postoperative application scenarios. CONCLUSIONS: The authors successfully developed an ML-based calculator for predicting the risk of postoperative adverse events in patients with EGS. This calculator accurately predicted the occurrence risk of five outcome events, providing quantified risk probabilities for clinical diagnosis and treatment.

Neoadjuvant tislelizumab and tegafur/gimeracil/octeracil (S-1) plus oxaliplatin in patients with locally advanced gastric or gastroesophageal junction cancer: Early results of a phase 2, single-arm trial.

Background: Recently, the combination of immunotherapy with chemotherapy has been recommended as first-line treatment of metastatic gastric/gastroesophageal junction (G/GEJ) in the clinical guidelines of many countries; the therapeutic potential of this application needs to be further investigated for neoadjuvant therapy of advanced G/GEJ cancer patients. Methods: We performed a prospective, single-arm, open-label, phase 2 trial of the PD-1 inhibitor tislelizumab combined with S-1 plus oxaliplatin (SOX) in patients with advanced LAG/GEJ cancer. All patients underwent the three-cycle (21 days/cycle) treatment except for one patient who underwent two cycles. The primary endpoints were tumor major pathology response (MPR) and other events of tumor response assessed by the RECIST 1.1 and Becker criteria. Moreover, we constructed a few-shot learning model to predict the probability of MPR, which could screen those patients who might benefit from the neoadjuvant immunotherapy-chemotherapy scheme. This study was registered at https://clinicaltrials.gov/ct2/show/NCT0-4890392. Results: Thirty-two patients were enrolled; 17 patients (53.1%) achieved MPR (≤10% viable tumor cells) after treatment, and among them, 8 (25.0%) had a pathological complete response (pCR). The 1-year overall survival (OS) rate was 91.4% and the 1-year recurrence-free survival (RFS) rate was 90.0%. Adverse events occurred in 24 patients (65.6%) and grade III-IV adverse events were observed in 4 patients (12.5%) during the neoadjuvant period. Furthermore, we found commonly used preoperative assessment tools such as CT and EUS, which presented limited accuracy of tumor therapeutic response in this study; thus, we developed a therapeutic response predictive model that consisted of TNFα, IFNγ, IL-10, CD4, and age of patient, and the AUC of this FSL model was 0.856 (95% CI: 0.823-0.884). Discussion: Our study showed that the neoadjuvant PD-1 inhibitor tislelizumab combined with SOX had promising application potential and presented no increasing treatment-related adverse events in patients with advanced G/GEJ cancer. Moreover, the predictive model could help therapists to evaluate the therapeutic response of this scheme accurately. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT0-4890392, identifier [NCT04890392].

Circ_0000591 served as endogenous RNA for miR-326 to promote progression of cholangiocarcinoma via the TLR4/MyD88/IL6 axis.

BACKGROUND: Cholangiocarcinoma (CCA) is the second most common liver malignancy with poor prognosis after hepatocellular carcinoma (HCC). Emerging evidences have proved that circular RNAs (circRNAs) are involved in the progression of multiple cancers, while their roles in tumorigenesis of CCA remains largely unclear. In the present study, we found circ_0000591 was upregulated in CCA cells and tissues. The highly expressed circ_0000591 could promote the proliferation, migration, invasion and carcinogenesis of CCA cells in vitro and in vivo. Functionally, circ_0000591 induced the proliferation, migration and invasion of CCA cells through sponging miR-326. Moreover, silencing of circ_0000591 attenuated LPS-induced anti-apoptosis of CCA cells through the TLR4/MyD88/IL6 pathway. In conclusion, this study revealed a novel regulatory mechanism that circ_0000591 contributed to the progression of CCA via miR-326/TLR4/MyD88/IL6 axis. These findings enhanced our knowledge of potential molecular mechanism involved in the malignant progression of CCA.

Duodenal gastrointestinal stromal tumors: A retrospective study based on a 13 years experience of a single center in China.

AIM: Duodenal gastrointestinal stromal tumors (GISTs) constitute a small rare subset. This study aims to analyze the prognostic differences between duodenal and jejunoileal GISTs and evaluate the clinical treatment and prognostic characteristics of patients with duodenal GISTs. METHODS: Data of patients with primary duodenal or jejunoileal GISTs were collected. Patients were matched through propensity score matching (PSM). Perioperative and long-term outcomes of patients with duodenal GISTs were compared based on surgical approach. RESULTS: Altogether, 101 duodenal and 219 jejunoileal GISTs were identified. In patients with duodenal GISTs, 79 (78%) underwent local resection (LR) and 22 (22%) underwent pancreaticoduodenectomy (PD). Patients undergoing PD had a longer postoperation stay (18.5 vs 13 days, P = 0.001) and more complications (Clavien-Dindo I-II complications for PD vs LR, 31.8 vs 15.2%; Clavien-Dindo III-V complications for PD vs LR, 22.7 vs. 2.5%; P < 0.001). There was no difference in recurrence-free survival (RFS) (P = 0.8) or overall survival (OS) (P = 0.9) when comparing patients who underwent LR versus PD. Multivariable analysis showed that tumor size >5 cm was the only independent predictor of shorter RFS (P = 0.004) and OS (P = 0.012). After matching, there was no significant difference in RFS and OS between patients with duodenal versus jejunoileal GISTs (both P > 0.05). CONCLUSION: The prognosis of duodenal and jejunoileal GISTs are similar. Recurrence and OS of duodenal GISTs primarily depend on tumor size. For duodenal GISTs, LR is associated with comparable long-term survival when compared to PD, but with superior short-term outcomes.

Safety and feasibility of prolonged versus early laparoscopic cholecystectomy for acute cholecystitis: a single-center retrospective study.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the standard treatment for acute cholecystitis (AC), and it should be performed within 72 h of symptoms onset if possible. In many undesired situations, LC was performed beyond the golden 72 h. However, the safety and feasibility of prolonged LC (i.e., performed more than 72 h after symptoms onset) are largely unknown, and therefore were investigated in this study. METHODS: We retrospectively enrolled the adult patients who were diagnosed as AC and were treated with LC at the same admission between January 2015 and October 2018 in an emergency department of a tertiary academic medical center in China. The primary outcome was the rate and severity of adverse events, while the secondary outcomes were length of hospital stay and costs. RESULTS: Among the 104 qualified patients, 70 (67.3%) underwent prolonged LC and 34 (32.7%) underwent early LC (< 72 h of symptom onset). There were no differences between the two groups in mortality rate (none for both), conversion rates (prolonged LC 5.4%, and early LC 8.8%, P = 0.68), intraoperative and postoperative complications (prolonged LC 5.7% and early LC 2.9%, P ≥ 0.99), operation time (prolonged LC 193.5 min and early LC 198.0 min, P = 0.81), and operation costs (prolonged LC 8,700 Yuan, and early LC 8,500 Yuan, P = 0.86). However, the prolonged LC was associated with longer postoperative hospitalization (7.0 days versus 6.0 days, P = 0.03), longer total hospital stay (11.0 days versus 8.0 days, P < 0.01), and subsequently higher total costs (40,400 Yuan versus 31,100 Yuan, P < 0.01). CONCLUSIONS: Prolonged LC is safe and feasible for patients with AC for having similar rates and severity of adverse events as early LC, but it is also associated with longer hospital stay and subsequently higher total cost.

A reciprocal feedback of Myc and lncRNA MTSS1-AS contributes to extracellular acidity-promoted metastasis of pancreatic cancer.

Rationale: Previous studies have reported on the role of extracellular acidity in the metastasis of numerous cancers. However, the involvement of long noncoding RNA (lncRNA) in the extracellular acidity-induced cancer metastasis of pancreatic cancer (PC) remains unclear. Methods: Different expression levels of lncRNAs in PC cells under normal and acidic conditions were compared by RNA sequencing (RNA-seq). The effects of antisense lncRNA of metastasis suppressor 1 (MTSS1-AS) on acidic PC cells were assessed by gain- and loss-of-function experiments. Fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull-down, Western blot, luciferase reporter, and Chromatin immunoprecipitation assays were employed to determine the regulatory mechanisms of MTSS1-AS in the acidity-induced metastasis of PC cells. The expression of MTSS1-AS and associated pathways were compared in PC samples and peritumoral normal tissues. Results: RNA-seq demonstrated that MTSS1-AS was significantly downregulated in pancreatic cells cultured with the acidic medium. The overexpression of MTSS1-AS remarkably inhibited the acidity-promoted metastasis of PC cells by upregulating the expression of its sense gene metastasis suppressor 1 (MTSS1). Mechanistically, MTSS1-AS scaffolded the interaction between E3 ubiquitin-protein ligase STIP1 homology and U-box containing protein 1 (STUB1) and transcription regulator myeloid zinc finger 1 (MZF1), leading to ubiquitination-mediated degradation of MZF1. Further, MZF1 inhibited the expression of MTSS1 by binding to the MTSS1 promoter. Thus, the acidity-reduced MTSS1-AS facilitated the stability of MZF1 and its inhibitory effect on MTSS1 transcription, thereby promoting the metastasis of PC cells under acidic conditions. Moreover, MTSS1-AS was transcriptionally repressed by the binding of MYC proto-oncogene (Myc) with initiator (Inr) elements of the MTSS1-AS promoter. Meanwhile, MTSS1-AS mutually repressed the expression of Myc by impairing the MZF1-mediated transcription activation of Myc, thereby forming a negative feedback loop between MTSS1-AS and Myc in acidic PC cells. In accordance with the experimental results, MTSS1-AS and MTSS1 were downregulated in PC and correlated with poor overall survival. Conclusions: The results implicated that a reciprocal feedback loop between Myc and MTSS1-AS contributed to the extracellular acidity-promoted metastasis of PC, and indicated that MTSS1-AS was a valuable biomarker and therapeutic target for PC.

Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 cooperates with enhancer of zeste homolog 2 to promote hepatocellular carcinoma development by modulating the microRNA-22/Snail family transcriptional repressor 1 axis.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is an oncogenic long noncoding RNA that has been found to promote carcinogenesis and metastasis in many tumors. However, the underlying role of MALAT1 in the progression and metastasis of hepatocellular carcinoma (HCC) remains unclear. In this study, aberrantly elevated levels of MALAT1 were detected in both HCC specimens and cell lines. We found that knockdown of MALAT1 caused retardation in proliferation, migration, and invasion both in vivo and in vitro. Mechanistic investigations showed that Snail family transcriptional repressor 1 (SNAI1) is a direct target of microRNA (miR)-22 and that MALAT1 modulates SNAI1 expression by acting as a competing endogenous RNA for miR-22. Inhibition of miR-22 restored SNAI1 expression suppressed by MALAT1 knockdown. Furthermore, MALAT1 facilitated the enrichment of enhancer of zeste homolog 2 (EZH2) at the promoter region of miR-22 and E-cadherin, which was repressed by MALAT1 knockdown. Cooperating with EZH2, MALAT1 positively regulated SNAI1 by repressing miR-22 and inhibiting E-cadherin expression, playing a vital role in epithelial to mesenchymal transition. In conclusion, our results reveal a mechanism by which MALAT1 promotes HCC progression and provides a potential target for HCC therapy.

Comparative efficacy and tolerability of adjuvant systemic treatments against resectable colon cancer: a network meta-analysis.

BACKGROUND: Currently, 6-month oxaliplatin-based chemotherapy has been recommended as the preferred adjuvant treatment against high-risk stage 2 and stage 3 colon cancer patients. METHODS: Record retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, American Society of Clinical Oncology and European Society for Medical Oncology meeting libraries from inception to November 2019. Regarding survival and tolerability, randomized controlled trials comparing different adjuvant systemic regimens against high-risk stage 2 and stage 3 colon cancer were eligible. Disease-free survival was primary endpoint. Network calculation was based on a random-effects model, and relative ranking of each node was numerically indicated by p score. RESULTS: A total of 30 trials were included, corresponding to 54,109 patients. Regarding disease-free survival, none of the analyzed regimens displayed significant superiority against common comparator 6-month capecitabine plus oxaliplatin (XELOX), while 12-month [network hazard ratio (HR) 0.81 (0.60-1.10); 0.79 (0.57-1.10)] and 3-month XELOX [0.95 (0.86-1.04); 0.93 (0.83-1.05)] were top-ranking regimens showing non-inferiority among overall and stage 3 patients. Moreover, by pairwise meta-analysis, 3-month XELOX demonstrated significant superiority against 6-month XELOX among low-risk stage 3 patients [pairwise HR 0.78 (0.63-0.97)]. Concerning adverse events, 3-month oxaliplatin-based chemotherapy was significantly better than the 6-month counterpart with respect to peripheral sensory neuropathy, thrombocytopenia and fatigue. The 12-month capecitabine monotherapy failed to display non-inferiority among other major adverse events. CONCLUSIONS: The 3-month XELOX treatment could be an alternative option of the 6-month regimen among low-risk stage 3 patients. Among high-risk stage 3 patients, 6-month oxaliplatin-based regimens still seem more competitive. In addition, clinical application of 12-month capecitabine monotherapy should be cautious, despite its top rankings, especially among non-Asian countries.

Primary Gastrointestinal Stromal Tumor Mimicking as Gynecologic Mass: Characteristics, Management, and Prognosis.

BACKGROUND: Primary gastrointestinal stromal tumor (GIST)-mimicking gynecologic masses are easily misdiagnosed. This study aimed to investigate the clinicopathological features, management, and prognosis of primary GIST mimicking as gynecologic mass. METHODS: Clinicopathological and survival data of GIST mimicking as gynecologic mass admitted to our center from January 2005 to December 2017 were retrospectively analyzed. RESULTS: Thirty-eight patients were included. The most common primary tumor site was the jejunoileum (n = 33, 86.9%), and 33 patients (86.9%) were classified as high recurrence risk. The short-term outcomes of operative incision length (P = 0.004), time to gas passage (P = 0.002), and hospital stay (P = 0.012) with laparoscopy-assisted resection were significantly shorter than those with open resection, showing no significant differences of long-term outcomes. With a median follow-up of 56 mo for 31 patients (81.6%), 18 (58.1%) received adjuvant therapy with imatinib. The 5-year disease-free survival and disease-specific survival of pelvic high-risk GIST was 37.0% and 48.3%, respectively; both were significantly lower than those of the other female high-risk group (both P < 0.05). CONCLUSIONS: GIST mimicking as gynecologic mass is not uncommon, most originate from the jejunoileum and have a high risk of recurrence. Laparoscopy-assisted resection may be preferable for more favorable short-term outcomes. Compared with the other female high-risk GIST, pelvic high-risk GIST has a significantly worse prognosis; a longer duration of adjuvant therapy with imatinib than recommended may be beneficial.

First-line systemic therapy for advanced gastric cancer: a systematic review and network meta-analysis.

BACKGROUND: Systemic therapy is the standard treatment against advanced gastric cancer. Fluoropyrimidine plus platinum doublet has been recommended as the preferred first-line strategy. However, there is still a lack of a comprehensive and hierarchical evidence that compares all eligible literature simultaneously. METHODS: Record retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Embase, ASCO, and ESMO meeting library from inception to October 2018. Randomized controlled trials featuring comparisons between different first-line systemic treatments against advanced gastric cancer were eligible. Overall survival was utilized as the primary endpoint. Pairwise and network calculations were based on a random-effects model and the hierarchical ranking was numerically indicated by P-score. All procedures were conducted according to Cochrane Handbook 5.1 and PRISMA for Network Meta-analysis (Registration identifier: CRD42018084951). RESULTS: A total of 119 studies were eligible for our pooled analysis. Concerning general analysis, 'fluoropyrimidine plus platinum-based triplet' topped the overall survival hierarchy (HR 0.91 [0.83-0.99], P-score = 0.903, p = 0.04) while it ranked in second place for progression-free survival and objective response rate. However, it displayed worse tolerability against 'fluoropyrimidine plus platinum doublet'. More specifically, 'Capecitabine plus cisplatin-based triplet plus targeted medication' topped the ranking among all fluoropyrimidine plus platinum-based regimens in additional analysis. Nevertheless, it did not reach statistical advantage against fluoropyrimidine plus oxaliplatin doublet in terms of survival benefits, while still displaying significantly worse safety profile. CONCLUSIONS: Taken together, fluoropyrimidine plus oxaliplatin doublet (especially capecitabine or S-1) should still be considered as the preferred first-line regimen owing to its comparable survival benefits and lower toxicity.

Systemic therapy for previously treated advanced gastric cancer: A systematic review and network meta-analysis.

Although paclitaxel plus ramucirumab has been recommended as the preferred second-line strategy, other regimens also display potentially comparable efficacies. Record retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Embase, ASCO and ESMO meeting libraries. Randomized controlled trials featuring comparisons between different systemic treatments among previously treated patients with advanced gastric cancer were eligible for our systematic review. Network calculation were based on random-effects model and the relative ranking of each regimen was numerically indicated by P-score (CRD42018104672). Concerning second-line regimens, "paclitaxel plus olaparib" and "paclitaxel plus ramucirumab" dominated the overall survival ranking while "paclitaxel plus ramucirumab" additionally topped the hierarchy for progression-free survival. Among refractory or third-line only cases, apatinib reigned the hierarchy by significantly and insignificantly surpassing placebo and nivolumab respectively. In conclusion, paclitaxel plus ramucirumab is the optimal second-line regimen. Both apatinib and nivolumab could be potentially recommended as refractory regimens.

Multimodal treatments for resectable gastric cancer: A systematic review and network meta-analysis.

Different countries prefer particular types of multimodal treatments against resectable gastric cancer. Due to lacking of unified conclusions, we therefore conducted a network meta-analysis to rank all recommended strategies simultaneously and hierarchically. Record retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Embase, ASCO and ESMO meeting libraries from inception to September 2018. Randomized controlled trials featuring comparisons between different preferred multimodal treatments against resectable gastric cancer were eligible. The Cochrane Risk of Bias Tool was applied to assess methodological quality of included trials. Overall survival was primary endpoint. Network calculation was based on random-effects model and the relative ranking of each node was numerically indicated by P-score. All procedures were conducted according to Cochrane Handbook 5.1 and PRISMA for Network Meta-analysis (CRD42018109147). As a result, a total of 11 studies were included into our systematic review, corresponding to 7235 patients. Regarding overall survival, "PeriCT (FLOT)" (perioperative 5-FU plus leucovorin plus oxaliplatin plus docetaxel chemotherapy) topped the hierarchy (HR 1.00, P-score = 0.918), followed by "PostCT (XP)" (postoperative capecitabine plus platinum chemotherapy; HR 1.14, P-score = 0.759) and "PostCT (S-1)" (postoperative S-1 monotherapy; HR 1.16, P-score = 0.732). In subgroup analyses, "PostCT (XP)" became the top regimen for eastern population while "PeriCT (FLOT)" was the optimal node for western population. In conclusion, perioperative FLOT chemotherapy could potentially be the best multimodal treatment against resectable gastric cancer than other recommended strategies. Therefore, a global D2-lymphadenectomy randomized controlled trial comparing perioperative FLOT chemotherapy with postoperative XELOX chemotherapy should be carried out.

Multimodal treatments for resectable esophagogastric junction cancer: a systematic review and network meta-analysis.

BACKGROUND: Currently, preoperative chemoradiotherapy, perioperative chemotherapy and preoperative chemotherapy are recommended by NCCN, ESMO and Japanese guidelines respectively for resectable esophageal and junctional cancer. However, these recommendations are mainly based on esophageal cancer research. Therefore, specific for esophagogastric junction cancer, we conducted the first systematic review and network meta-analysis to rank all potential treatments simultaneously and hierarchically. METHODS: Record retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Embase, ASCO and ESMO Meeting Library from inception to September 2018. Regarding time-to-event survival data, randomized controlled trials featuring comparisons between different multimodal treatments against resectable esophagogastric junction cancer were eligible. Overall survival was the endpoint. Network calculation was based on a random-effects model and the relative ranking of each node was numerically indicated by P-score (CRD42018110369, registration identifier of the meta-analysis in PROSPERO.). RESULTS: Eight studies were included in our systematic review, corresponding to 1218 patients. Regarding overall survival, 'PreCRT' (preoperative chemoradiotherapy) topped the hierarchy (HR 1.00, P-score = 0.823), better than 'PeriCT' (perioperative chemotherapy; HR 1.32, P-score = 0.591) and 'PreCT' (preoperative chemotherapy; HR 1.54, P-score = 0.428). In sensitivity analyses, irrespective of interchanging to fixed-effects model or removing potentially heterogeneous studies, relative rankings remained stable and 'PreCRT' was still the optimal node. CONCLUSION: Preoperative chemoradiotherapy could potentially be the optimal multimodal treatment, which displayed more overall survival benefits than perioperative chemotherapy and preoperative chemotherapy among resectable esophagogastric junction cancer patients. To further verify our pooled results, more randomized trials will be needed to compare preoperative chemoradiotherapy with perioperative chemotherapy (especially FLOT-based regimens).

Identification of a 5­microRNA signature and hub miRNA­mRNA interactions associated with pancreatic cancer.

miRNA­gene axes have been reported to serve an important role in the carcinogenesis of pancreatic cancer (PC). The aim of the present study was to systematically identity the microRNA signature and hub molecules, as well as hub miRNA­gene axes, and to explore the potential biomarkers and mechanisms associated with the carcinogenesis of PC. Eleven microRNA profile datasets were obtained from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) and ArrayExpress databases, and a meta­analysis was performed to identify the differentially expressed miRNAs (DEMs) between tumor tissue and normal tissue. Subsequently, a diagnostic regression model was constructed to identify PC based on The Cancer Genome Atlas (TCGA) miRNA sequence data by using the least absolute shrinkage and selection operator (LASSO) method. In addition, GSE41368 was downloaded, and a weighted gene co­expression network analysis (WGCNA) was performed to obtain the gene module associated with carcinogenesis by using the TCGAbiolinks and WGCNA packages, respectively. Finally, miRNA­gene networks were constructed and visualized using Cytoscape software, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses based on the Database for Annotation, Visualization, and Integrated Discovery (DAVID). A total of 14 DEMs were identified, and a 5­microRNA­based score generated by the LASSO regression model provided a high accuracy for identifying PC [area under the curve (AUC)=0.918]. In addition, 44 miRNA­mRNA interactions were constructed, and 4 hub genes were screened on the basis of the above bioinformatic tools and databases. Furthermore, 14 biological process (BP) functions and 6 KEGG pathways were identified according to gene set enrichment analysis (GSEA). In summary, the present study applied integrated bioinformatics approaches to generate a holistic view of PC, thereby providing a basis for further clinical application of the 5­miRNA signature and the identified hub molecules, as well as the miRNA­gene axes, which could serve as diagnostic markers and potential treatment targets.

Oncological consequence of emergent resection of perforated colon cancer with complete obstruction after stent insertion as a bridge to surgery.

PURPOSE: Colonic perforation is a life-threatening complication after colonic stent insertion as a bridge to surgery for acute obstruction caused by colorectal cancer. The oncological consequence of colonic perforation after emergent surgical intervention was unknown. The aim of this short communication was to investigate whether or not the perforation and emergent surgery had obviously impact on the peritoneal recurrence and long-term survival of patients. METHODS: Data of the patients who underwent colorectal stenting as a bridge to surgery in 5 years from 2012 to 2017 was collected by the Endoscopical Surgery Group of Hubei. The perforated cases treated by emergent operation were retrospectively analyzed. RESULTS: During 5 years from 2012 to 2017, 116 cases of colorectal stenting as a bridge to surgery had been performed, and 7 patients had perforation after stent placement and treated by emergent surgery, including 1 case of synchronic liver metastasis treated by one-stage metastasectomy. One of the 7 patients died of septic shock after operation, and the remaining patients were followed up for 6-60 months. There was no evidence of abdominal implantation or extra-abdominal metastasis. CONCLUSION: This small case series implicated that colonic perforation after stent insertion for malignant colorectal obstruction treated by emergent surgery might not obviously increase the peritoneal implantation and metastasis.

Clinicopathological Characteristics and Prognosis of Hepatoid Adenocarcinoma of the Stomach: Evaluation of a Pooled Case Series.

Hepatoid adenocarcinoma of the stomach (HAS) is an extremely rare and unique gastric malignancy. The present study aimed to examine the relevance of the clinicopathological characteristics of HAS with patient prognosis. We retrospectively reviewed clinical data of 34 HAS patients treated at our institution between January 2010 and December 2016, as well as 294 cases reported prior to 2017 in research databases. Among these patients, 45.6% (115/252) had lesions in the gastric antrum and 77.0% (235/305) were male. Elevated levels of serum alpha-fetoprotein (AFP) were detected in most patients (75/93, 80.6%). Vascular invasion (199/286, 69.6%), lymph node metastasis (222/283, 78.4%), and preoperative distant metastasis (121/328, 36.9%) were commonly observed. The 5-year disease-free survival (DFS) and disease-specific survival (DSS) were 20.7% and 29.2%, respectively. DFS and DSS of patients receiving neoadjuvant therapy were significantly higher than those of patients receiving postoperative adjuvant therapy [DFS: P<0.001, hazard ratio (HR)=-1.831, 95% confidence interval (CI): 0.060-0.429; DSS: P<0.001, HR=-2.185, 95% CI: 0.032-0.401]. In conclusion, HAS exhibits distinct clinicopathological characteristics and a strikingly worse prognosis when compared with common gastric cancer. Complete surgery, early pTNM stage, and adjuvant therapy may predict a more favorable prognosis. Neoadjuvant therapy is strongly recommended for patients with lymph node metastasis or/and preoperative distant metastasis.

[Safety and feasibility of the combined medial and caudal approach in laparoscopic D3 lymphadenectomy plus complete mesocolic excision for right hemicolectomy in the treatment of right hemicolon cancer complicated with incomplete ileus].

OBJECTIVE: To explore the safety and feasibility of the combined medial and caudal approach in laparoscopic D3 lymphadenectomy plus complete mesocolic excision(CME) for right hemicolectomy in the treatment of right hemicolon cancer complicated with incomplete ileus. METHODS: Clinical data of 65 patients with incomplete obstructive right-sided colon cancer (T1 to 4M0) diagnosed by abdominal CT enhanced scan or MRI and/or electric colonscope undergoing laparoscopic right hemicolectomy (D3 lymphadenectomy + CME) at Department of Emergency Medicine and Department of Gastrointestinal Surgery from June 2014 to June 2017 were retrospectively analyzed. Among them, 33 patients received the combined medial and caudal approach (combined medial and caudal approach group) and the other 32 patients received the cephalo medial-to-lateral approach (cephalo medial-to-lateral approach group). The operation highlights of the combined medial and caudal approach group were as follows: (1) The superior mesenteric vein (SMV) was first identified and exposed using the combined medial and caudal approach, and lymph node dissection along the anterior and right of SMV was performed. (2) With horizontal part of duodenum as landmarks, the dorsal mesenteric membrane of terminal ileum was opened by caudal-to-cranial approach, and right retroperitoneal space along the Toldt's space was separated. The anterior of pancreatic head and the right Toldt's space were then exposed. (3) Finally using medial-to-lateral approach, the roots of ileocolic vessels, middle colic vessel and right colic vessel were disconnected and ligated along the left border of SMV. The right branch of gastrocolic trunk of Henle was ligated and lymph node dissection along SMV was performed again. Patients in cephalo medial-to-lateral approach group underwent conventional operation. Baseline information, intraoperative blood loss, operation time, number of harvested lymph nodes, proportion of no less than 12 harvested lymph nodes per case, postoperative hospital stay and postoperative morbidity in both groups were analyzed and compared. RESULTS: Thirty-eight males and 27 females with age of 31 to 72 (56.8±11.7) years were enrolled in this study. There was no significant difference in baseline information between combined medial and caudal approach group and cephalo medial-to-lateral approach group(all P>0.05). Intraoperative blood loss [(106.5±24.5) ml vs. (308.4±27.1) ml, t=-31.501, P=0.000] was significantly less, and operative time [(176.3 ± 18.0) minutes vs. (208.4 ± 47.3) minutes, t=-3.602, P=0.001] was significantly shorter in the combined medial and caudal approach group. The proportion of no less than 2 harvested lymph nodes per case [87.9%(29/33) vs. 84.4%(27/32)], the number of harvested lymph nodes (22.5±8.9 vs. 21.5± 7.6), postoperative morbidity of complication [6.1%(2/33) vs. 12.5%(4/32)] and postoperative hospital stay [(11.9±1.5) days vs. (13.4±4.4) days] were not significantly different between the two groups(all P>0.05). CONCLUSION: The combined medial and caudal approach in laparoscopic right hemicolectomy (D3+CME) in the treatment of incomplete obstructive right-sided colon cancer is safe and feasible, and has advantages of less intraoperative blood loss and shorter operation time compared to the cephalo medial-to-lateral approach.

Secreted AGR2 promotes invasion of colorectal cancer cells via Wnt11-mediated non-canonical Wnt signaling.

Human anterior gradient-2 (AGR2), a member of protein disulfide isomerase (PDI) family, is present in both intracellular and extracellular compartments. Although AGR2 is overexpressed in various human cancers and reported to promote aggressive tumor features, little is known regarding AGR2's extracellular functions during tumorigenesis. Here, we demonstrate that secreted AGR2 promotes cell migration and metastasis of colorectal cancer (CRC) in vitro and in vivo. Mechanistically, secreted AGR2 elevated Wnt11 expression, triggering non-canonical Wnt signaling: the Ca2+/Calmodulin-dependent protein kinase II (CaMKII) and c-jun amino-terminal kinase (JNK) pathways. Knockdown of Wnt11 or pretreatment with CaMKII and JNK inhibitors reversed the secreted AGR2's migration-promoting effect. Further studies revealed that AGR2 antagonized canonical Wnt/ß-catenin signaling via activating CaMKII. Collectively, our study uncovers a critical role of Wnt11-mediated non-canonical Wnt signaling (CaMKII and JNK pathways) in secreted AGR2's promoted migration of CRC cells. These results raise the possibility that secreted AGR2 may be a potential therapeutic target towards inhibiting CRC metastasis.

Clinicopathological features and prognosis of intestinal hepatoid adenocarcinoma: evaluation of a pooled case series.

BACKGROUD: Intestinal hepatoid adenocarcinoma (IHA) is a very rare and unique intestinal malignancy. Due to the lack of case series specifically pertaining to IHA, the clinicopathological features and prognosis of it remain unclear. RESULTS: Of the 42 patients enrolled in this study, 30 (71.4%) were male. Twenty-one cases (50.0%) were located in the colon. Eight cases (19.0%) had accompanying inflammatory bowel disease (IBD). Elevated serum alpha-fetoprotein (AFP) was detected for most patients (25/33, 84.8%). Twenty-five (59.5%) patients received complete resections. Vascular invasion (22/36, 61.1%), lymph node metastasis (28/36, 77.8%) and distant metastasis (21/42, 50.0%) were common. The 1-year progression-free survival (PFS) and disease-specific survival (DSS) of IHA were 26.9% and 30.6%, respectively. Multivariate analysis showed that only pTNM stage was an independent risk factor for PFS and DSS. PFS and DSS in patients with IHA were significantly lower than those with colorectal adenocarcinoma (CA) and hepatoid adenocarcinoma of the stomach (HAS). CONCLUSIONS: IHA most commonly occurred in the colon and accompanied by IBD in several cases. pTNM stage was an independent factor for prognosis. The prognosis of IHA was significantly worse than that of CA and HAS. PATIENTS AND METHODS: Clinical data of IHA from four patients managed at our institution between January 2010 and December 2016, and 38 cases from research databases prior to 2017 were retrospectively studied.