Prognosis value of microscopic bile duct invasion in hepatocellular carcinoma: A multicenter study.

OBJECTIVE: To evaluate the prognostic significance of microscopic bile duct invasion (MiBDI) in hepatocellular carcinoma (HCC) following R0 resection. PATIENTS AND METHODS: Patients who underwent R0 resection for HCC at nine medical centers were stratified into five groups: neither bile duct nor vascular invasion (MiBDI-MVI-), microscopic bile duct invasion alone (MiBDI+MVI-), both microscopic bile duct and vascular invasion (MiBDI+MVI+), microscopic vascular invasion alone (MiBDI-MVI+), and macroscopic bile duct invasion (MaBDI). Overall survival (OS) was assessed using Kaplan-Meier analysis, and independent risk factors of OS were determined using Cox proportional hazards models. RESULTS: A total of 377 HCC cases were analyzed. The OS for MiBDI+MVI- was similar to that of MiBDI-MVI- (p > 0.05) but better than MiBDI+MVI+, MiBDI-MVI+, and MaBDI (all p < 0.05). Multivariate analysis indicated that MiBDI was not an independent risk factor for OS, while MVI and MaBDI were. CONCLUSIONS: Overall survival (OS) in patients with MiBDI was superior to those with MVI and MaBDI. Isolated MiBDI did not influence OS in patients with HCC after R0 resection.

Proposal for a new N-stage classification system for intrahepatic cholangiocarcinoma.

Background: The number of metastatic lymph nodes (MLNs) is not considered in the nodal status (N classification) of intrahepatic cholangiocarcinoma (ICC) in the current 8thEdition of the American Joint Committee on Cancer (AJCC) staging system. The aim of this study was to find out the optimal cut-off point based on the number of MLNs and establish a modified AJCC staging system for ICC according to the new N category. Methods: A total of 675 ICC patients diagnosed between 2004 and 2015 were retrieved from the Surveillance, Epidemiology and End Results (SEER) database. The optimal cut-off value of MLNs affecting survival was determined by X-tile software. The relative discriminative power was assessed by Harrell's concordance index (C-index) and Akaike information criterion (AIC). Results: The proposed new nodal category subdivided patients into three groups (N0, no MLN; N1, 1-3 MLNs; and N2, ≥ 4 MLNs) with significantly different overall survival (P < 0.001). Multivariable analysis revealed that the new nodal category was an independent prognostic factor (P < 0.001). Both the C-index and AIC for our modified staging system were better than those for the 8th AJCC edition (0.574 [95% confidence interval 0.533-0.615] versus 0.570 [95% confidence interval 0.527-0.613], and 853.30 versus 854.21, respectively). Conclusion: The modified AJCC staging system based on the number of MLNs may prove to be a useful alternative for predicting survival of ICC patients in clinical practice.

Antioxidant Activities of Natural Polysaccharides and Their Derivatives for Biomedical and Medicinal Applications.

Many chronic diseases such as Alzheimer's disease, diabetes, and cardiovascular diseases are closely related to in vivo oxidative stress caused by excessive reactive oxygen species (ROS). Natural polysaccharides, as a kind of biomacromolecule with good biocompatibility, have been widely used in biomedical and medicinal applications due to their superior antioxidant properties. In this review, scientometric analysis of the highly cited papers in the Web of Science (WOS) database finds that antioxidant activity is the most widely studied and popular among pharmacological effects of natural polysaccharides. The antioxidant mechanisms of natural polysaccharides mainly contain the regulation of signal transduction pathways, the activation of enzymes, and the scavenging of free radicals. We continuously discuss the antioxidant activities of natural polysaccharides and their derivatives. At the same time, we summarize their applications in the field of pharmaceutics/drug delivery, tissue engineering, and antimicrobial food additives/packaging materials. Overall, this review provides up-to-date information for the further development and application of natural polysaccharides with antioxidant activities.

Lenvatinib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Lenvatinib was approved in 2018 as a first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). This systematic review and meta-analysis aimed to provide the most updated evidence about the efficacy and safety of lenvatinib as a first-line treatment for unresectable HCC. An electronic search of the PubMed database, Web of Science, Embase, and Cochrane Library was undertaken to identify all relevant studies up to May 2022. The pooled effect sizes were calculated based on the random-effects model. One phase III randomized controlled trial and 23 retrospective studies of 2438 patients were eligible for analysis. For patients treated with lenvatinib as first-line treatment, the pooled median overall survival (OS), median progression-free survival (PFS), 1-year OS rate, 1-year PFS rate, objective response rate (ORR), and disease control rate (DCR) were 11.36 months, 6.68 months, 56.0%, 27.0%, 36.0% and 75.0%, respectively. Lenvatinib showed a significantly superior efficacy compared with sorafenib (HR for OS, 0.85 and HR for PFS, 0.72; OR for ORR, 4.25 and OR for DCR, 2.23). The current study demonstrates that lenvatinib can provide better tumor responses and survival benefits than sorafenib as a first-line treatment for unresectable HCC, with a comparable incidence of adverse events.

A Review of Non-Invasive Drug Delivery through Respiratory Routes.

With rapid and non-invasive characteristics, the respiratory route of administration has drawn significant attention compared with the limitations of conventional routes. Respiratory delivery can bypass the physiological barrier to achieve local and systemic disease treatment. A scientometric analysis and review were used to analyze how respiratory delivery can contribute to local and systemic therapy. The literature data obtained from the Web of Science Core Collection database showed an increasing worldwide tendency toward respiratory delivery from 1998 to 2020. Keywords analysis suggested that nasal and pulmonary drug delivery are the leading research topics in respiratory delivery. Based on the results of scientometric analysis, the research hotspots mainly included therapy for central nervous systems (CNS) disorders (Parkinson's disease, Alzheimer's disease, depression, glioblastoma, and epilepsy), tracheal and bronchial or lung diseases (chronic obstructive pulmonary disease, asthma, acute lung injury or respiratory distress syndrome, lung cancer, and idiopathic pulmonary fibrosis), and systemic diseases (diabetes and COVID-19). The study of advanced preparations contained nano drug delivery systems of the respiratory route, drug delivery barriers investigation (blood-brain barrier, BBB), and chitosan-based biomaterials for respiratory delivery. These results provided researchers with future research directions related to respiratory delivery.

ZNF750 facilitates carcinogenesis via promoting the expression of long non-coding RNA CYTOR and influences pharmacotherapy response in colon adenocarcinoma.

The epidermal cell differentiation regulator zinc finger protein 750 (ZNF750) is a transcription factor containing the Cys2His2 (C2H2) domain, the zinc finger structure of which is located at the N-terminal 25||-|46 amino acids of ZNF750. It can promote the expression of differentiation-related factors while inhibiting the expression of progenitor cell-related genes. ZNF750 is directly regulated by p63 (encoded by the TP63 gene, belonging to the TP53 superfamily). The Krüppel-like factor 4 (KLF4), repressor element-1 (RE-1)|-silencing transcription factor (REST) corepressor 1 (RCOR1), lysine demethylase 1A (KDM1A), and C-terminal-binding protein 1/2 (CTBP1/2) chromatin regulators cooperate with ZNF750 to repress epidermal progenitor genes and activate the expression of epidermal terminal differentiation genes (Sen et al., 2012; Boxer et al., 2014). Besides, ZNF750 and the regulatory network composed of bone morphogenetic protein (BMP) signaling pathway, long non-coding RNAs (lncRNAs) (anti-differentiation non-coding RNA (ANCR) and tissue differentiation-inducing non-protein coding RNA (TINCR)), musculoaponeurotic fibrosarcoma oncogene (MAF)/MAF family B (MAFB), grainy head-like 3 (GRHL3), and positive regulatory domain zinc finger protein 1 (PRDM1) jointly promote epidermal cell differentiation (Sen et al., 2012).

Conversion surgery for initially unresectable pancreatic ductal adenocarcinoma following induction therapy: a systematic review of the published literature.

Patients with unresectable pancreatic ductal adenocarcinoma (UR-PDAC) are traditionally treated with palliative chemotherapy. The aim of this study was to evaluate the safety and efficacy of conversion surgery for initially UR-PDAC following induction therapy. The PubMed and Embase databases were systematically searched for eligible studies published between January 2000 and October 2020. Thirty-two series involving 1270 patients with 1056 locally advanced (LA) disease and 214 distant metastases were reviewed. The median mortality and morbidity was 0% (range 0-10%) and 47.1% (range 8.6-93.3%), respectively. Lymph-node negativity, negative resection margin and pathological complete response were observed in a median of 62.9% (38.5-90.9%), 84.4% (32.8-100%) and 6.7% (0-45.8%) of the specimens. The median survival was 32 (16.4-63.9) months with a 3-year survival rate of 47% (22-80%). Meta-analysis demonstrated that conversion surgery of initially UR-PDAC was associated with a significantly improved survival (hazard ratio [HR] = 0.55; 95% confidence intervals (CI) 0.45-0.66, P < 0.001). There was no significant difference in survival between the group with LA disease and that with distant metastases after conversion surgery (HR = 0.96; 95% CI 0.72-1.28, P = 0.790). Conversion surgery improved long-term survival of patients with initially UR-PDAC who had favorable response to induction therapy.

Redefining Hepatocellular Carcinoma Staging Systems Based on the Bile Duct Invasion Status: A Multicenter Study.

BACKGROUND AND AIMS: The prognostic value of bile duct invasion (BDI) remains controversial. We aimed to investigate the prognostic value of BDI and the stage of BDI in different staging systems. METHODS: Patients with hepatocellular carcinoma (HCC) from nine hepatobiliary medical centers who underwent R0 resection were included. Overall survival (OS) was assessed using the Kaplan-Meier method and tested using the log-rank test. The prognostic effect of BDI was analyzed using univariate and multivariate Cox proportional hazard regression analyses. The predictive performance of these models was evaluated using the concordance index and time-dependent receiver operating characteristic curve (tdAUC). RESULTS: Of 1021 patients with HCC, 177 had BDI. OS was worse in the HCC with BDI group than in the HCC without BDI group (p<0.001); multivariate analysis identified BDI as an independent risk factor for OS. After adjustment for interference of confounding factors using the Cox proportional hazard regression model, HCC with BDI and without macrovascular invasion was classified as Barcelona Clinic Liver Cancer (BCLC) B, eighth edition American Joint Committee on Cancer (AJCC) IIIA, and China Liver Cancer (CNLC) IIb, respectively, whereas HCC with BDI and macrovascular was classified as BCLC C, AJCC IIIB, and CNLC IIIA, respectively. C-indexes and tdAUCs of the adjusted staging systems were superior to those of the corresponding current staging systems. CONCLUSION: We constructed adjusted staging systems with the BDI status, improved their predictive performance and facilitate clinical use.

Proposal of a new T-stage classification system for ampullary carcinoma based on Surveillance, Epidemiology and End Result (SEER) database.

BACKGROUND: Tumor size is still considered a useful prognostic factor in currently available tumor-node-metastasis (TNM) classification staging systems for most solid tumors, but the significance of tumor size on the prognosis of ampullary carcinoma remains controversial. The aim of the current study was to propose a new T-stage classification system for ampullary carcinoma to address the impact of tumor size on the prognostic outcome. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 1080 patients with ampullary carcinoma who underwent radical surgical resection between 2004 and 2015. Based on the results obtained from analysis of various clinicopathologic factors, a new T-stage classification system was proposed. RESULTS: Among the 1080 patients, 618 were men and 462 were women, with a median tumor size of 2.3 (range 0.1-12) cm. Using the 7th edition of the American Joint Committee on Cancer (AJCC) staging manual, we noticed significant differences in overall survival (OS) between T2 vs. T3 tumors (P < 0.001) and T3 vs. T4 tumors (P = 0.002), but failed to observe significant differences between T1 vs. T2 tumors (P = 0.498) in our pair-wise comparison. Using the newly developed T-stage classification system, we were able to differentiate significant differences in OS between T1 vs. T2 tumors (P = 0.032), T2 vs. T3 tumors (P < 0.001) and T3 vs. T4 tumor (P = 0.003) in all pair-wise comparisons. The c-index of the new staging system was 0.653 (95% CI: 0.629-0.677), showing a better discriminatory power than the 0.636 of the 7th AJCC staging system (95% CI: 0.612-0.660). CONCLUSIONS: The new T-stage classification system described herein can better differentiate prognostic outcomes after radical resection in patients with ampullary carcinoma by incorporating tumor size and depth of tumor infiltration.

Clinicopathological characteristics and prognosis of signet ring cell carcinoma of the gallbladder.

BACKGROUND: Signet ring cell carcinoma (SRC) is a rare histological subtype of gallbladder adenocarcinoma. The current study evaluates the clinicopathologic features and prognosis of SRC. METHODS: Patients with adenocarcinoma of the gallbladder were identified in the Surveillance, Epidemiology, and End Results database from 1973 to 2016. Overall survival (OS) and cancer-specific survival (CSS) of patients who had SRC were compared with those of patients who had non-SRC using Cox regression and propensity score methods. RESULTS: Of 22,781 gallbladder adenocarcinomas retrieved, 377 (1.7%) were SRC and the other 22,404 were non-SRC. SRC was more significantly associated with older age, female gender, poor differentiation, advanced tumor stage, lymph node metastasis, distant metastasis, and advanced AJCC stage. The 5-year OS and CSS in the SRC group were 7.2 and 6.5%, respectively, both of which were significantly worse than the 13.2 and 13.3% seen in the SRC group (P = 0.002 and P = 0.012, respectively). This survival disadvantage persisted in multivariable analyses [hazard ratio (HR) = 1.256, P = 0.021 and HR = 1.211, P = 0.036] and after propensity score matching (OS: HR = 1.341, P = 0.012 and CSS: HR = 1.625, P = 0.005). Surgery in combination with chemotherapy improved OS of gallbladder SRC patients compared with surgery alone (HR = 0.726, P = 0.036) or chemotherapy alone (HR = 0.433, P < 0.001). CONCLUSION: Patients with SRC of the gallbladder have distinct clinicopathological features with poor prognosis. Surgery in combination with chemotherapy can improve survival.

ZEB1 enhances Warburg effect to facilitate tumorigenesis and metastasis of HCC by transcriptionally activating PFKM.

Metabolic reprogramming, especially Warburg effect, is a key event in tumor initiation and progression. ZEB1 plays a vital role in metastasis of various cancers. We previously found that ZEB1 was excessively expressed in hepatocellular carcinoma (HCC) and its high expression was closely correlated with metastasis and recurrence of HCC. We want to know whether glycolytic enzymes are regulated by ZEB1 and contribute to carcinogenesis and metastasis of HCC. Methods: To explore whether ZEB1 could enhance glycolysis in HCC, we knocked down ZEB1 by short hairpin RNA (shRNA) in MHCC-97H and HCC-LM3 cells and performed glucose uptake, lactate production, ECAR and OCR assays. To investigate how ZEB1 enhances glycolysis, the protein levels of glycolytic enzymes were detected in the same cell lines using Western blot. The regulatory effect of ZEB1 on PFKM mRNA level was confirmed by RT-qPCR, luciferase report assay and ChIP assay. In order to assess the role of ZEB1-PFKM axis in cell proliferation, cell counting and CCK-8 assays were performed in MHCC-97H and HCC-LM3 cell lines knocked down for ZEB1 and further re-expressed for either ZEB1 or PFKM or not. To explored whether the ZEB1-PFKM axis also functions in HCC cell migration, invasion and metastasis, the same MHCC-97H and HCC-LM3 cell lines were performed for wound healing assays, transwell assays and colony formation assays, meanwhile, MHCC-97H cell lines were performed for orthotopic liver transplantation assays. Finally, the expression of ZEB1 and PFKM were examined in human liver cancer specimens and non-tumorous liver tissues using immunohistochemical and Western blot. Results: We found that ZEB1 transcriptionally upregulates the expression of the muscle isoform of phosphofructokinase-1 (PFKM), a rate-limiting enzyme in glycolysis. Intriguingly, a non-classic ZEB1-binding sequence in the promoter region of PFKM was identified through which ZEB1 directly activates the transcription of PFKM. Silencing of ZEB1 in MHCC-97H and HCC-LM3 cell leads to impaired PFKM expression, glycolysis, proliferation and invasion, and such impairments are rescued by exogenous expression of PFKM. Importantly, in-situ HCC xenograft assays and studies from TCGA database demonstrate that ZEB1-PFKM axis is crucial for carcinogenesis and metastasis of HCC. Conclusions: Our study reveals a novel mechanism of ZEB1 in promoting HCC by activating the transcription of PFKM, establishing the direct link of ZEB1 to the promotion of glycolysis and Warburg effect and suggesting that inhibition of ZEB1 transcriptional activity toward PFKM may be a potential therapeutic strategy for HCC.

c-Src facilitates tumorigenesis by phosphorylating and activating G6PD.

Glucose-6-phosphate dehydrogenase (G6PD) is the first and rate-limiting enzyme in pentose phosphate pathway (PPP), excessive activation of which has been considered to be involved in tumorigenesis. Here, we show that tyrosine kinase c-Src interacts with and phosphorylates G6PD at Tyr 112. This phosphorylation enhances catalytic activity of G6PD by dramatically decreasing its Km value and increasing its Kcat value for substrate glucose-6-phosphate. Activated G6PD therefore augments the PPP flux for NADPH and ribose-5-phosphate production which is required for detoxification of intracellular reactive oxygen species (ROS) and biosynthesis of cancer cells, and eventually contributes to tumorigenesis. Consistently, c-Src activation is closely correlated with tyrosine phosphorylation and activity of G6PD in clinical colorectal cancer samples. We thus uncover another aspect of c-Src in promoting cell proliferation and tumorigenesis, deepening our understanding of c-Src as a proto-oncogene.

Pathological complete response after neoadjuvant therapy for pancreatic ductal adenocarcinoma does not equal cure.

BACKGROUND: There is a scarcity of data about patients with pancreatic ductal adenocarcinoma (PDAC) who received neoadjuvant therapy before radical resection and achieved a pathological complete response (pCR). The aim of this study was to describe the recurrence and survival in this subset of patients. METHODS: The Embase, Web of Science and PubMed databases were systematically searched for eligible studies published between January 2000 and August 2020. Clinicopathological data of individual patients with pCR after neoadjuvant therapy for PDAC were extracted, pooled and analysed. RESULTS: A total of 87 patients were subject to analysis. The majority of patients were female (61.5%) with a median age of 64 (range 43-75) years. Among reported, 41.9% of patients received gemcitabine-based neoadjuvant chemotherapy, 33.7% received FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan and leucovorin)-based regimen and 24.4% received fluoropyrimidine drugs-based regimen. Preoperative radiation was administered to 78.8% of the patients. Twenty-nine (33.3%) patients developed disease recurrence during a median follow-up period of 22.4 (range 2-194) months. The median, 1-, 3- and 5-year overall survival rates were 105 months, 93.6%, 70.3% and 70.3%, respectively. CONCLUSION: Despite the excellent long-term outcomes, a pCR does not equal cure because this cohort of patients still has a significant risk of recurrence.

Impact of Surgical Modalities on Long-term Survival Outcomes of Patients with Duodenal Gastrointestinal Stromal Tumor.

BACKGROUND: The optimal surgical modality for duodenal gastrointestinal stromal tumor (GIST) remains undefined. The purpose of this study was to evaluate long-term survival outcomes of patients who underwent radical resection (RR) or limited resection (LR) of duodenal GIST. METHODS: A total of 325 patients identified from the Surveillance, Epidemiology and End Results (SEER) database who underwent surgery for duodenal GIST between 1986 and 2016 were classified into a LR group and a RR group based on the type of surgery received. Propensity score matching (PSM) was performed to minimize the selection bias in comparisons. Disease-specific survival (DSS) and overall survival (OS) were observed, and factors affecting the survival outcome were analyzed. RESULTS: In the entire cohort, 105 patients (32.3%) underwent RR and 220 (67.7%) received LR. Both the 5-year OS and DSS in RR group were significantly better than those in LR group (71.0% vs. 54.1%, P = 0.014; 66.6% vs. 49.1%, P = 0.025). PSM resulted in 95 pairs of patients, with long-term outcomes being comparable between the two groups. After adjusting covariates in the propensity matched cohort, the type of surgery still showed no significant impact on OS (hazard ratio [HR] 1.160; 95% confidence interval [CI] 0.662-2.033) and DSS (HR 1.208; 95% CI 0.686-2.128). CONCLUSIONS: Surgical modalities do not seem to have a significant impact on long-term survival outcomes of patients with duodenal GIST and should mainly depend on the tumor size and location.

Characteristics and survival prognosis of patients with pure squamous cell carcinoma of the gallbladder.

BACKGROUND: Pure squamous cell carcinoma (SCC) of the gallbladder is rare and often confused with the adenosquamous carcinoma (ASC) subtype in previous studies. The present study was attempted to differentiate SCC from ASC by resolving their characteristics and prognosis. METHODS: The Surveillance, Epidemiology, and End Results database was queried for SCC and ASC of gallbladder cases from 1988 to 2015. Patients' clinicopathological characteristics and survival were analysed between the groups. RESULTS: Of the 709 patients with primary gallbladder cancer included in this study, 249 (35.1%) had pure SCC and the remaining 460 (64.9%) had ASC. It was found that pure SCC was associated with a larger median tumour size (58.0 versus 41.0 mm, P < 0.001), while ASC presented with a worse histological grade (47.4% versus 37.8% for grades III-IV, P = 0.019) and more lymph node invasion (27.4% versus 18.9%, P = 0.041). The 3-year overall survival and disease-specific survival rates in pure SCC were lower than those in ASC (7.5% versus 11.5% for overall survival, P < 0.001; 6.2% versus 10.9% for disease-specific survival, P < 0.001). Multivariate analysis showed that early Surveillance, Epidemiology, and End Results historic stage, treatment with surgery and chemotherapy were significant favourable prognostic factors for pure SCC, while tumour size, late study period, treatment with surgery and radiotherapy were significant predictors for ASC. CONCLUSION: There were significant differences in the clinicopathological characteristics and survival prognosis between pure SCC and ASC. Surgery combined with chemotherapy is the preferred treatment option for pure SCC.

Distal pancreatectomy with en bloc celiac axis resection for pancreatic cancer: a pooled analysis of 109 cases.

The aim of this study was to define the clinical outcome and prognostic determinants of distal pancreatectomy with en bloc celiac axis resection (DP-CAR) for pancreatic body/tail cancer. A pooled data analysis was performed on individual data for patients who underwent DP-CAR for pancreatic body/tail cancer as identified by systematic literature search. A total of 32 articles involving 109 patients were eligible for inclusion. Postoperative morbidity and mortality were 53% and 4%, respectively. Preoperative abdominal and/or back pain was completely relieved immediately after surgery in 98% of patients. The 1, 3 and 5 years overall survival (OS) rates were 59%, 21% and 10%, and the median OS was 14 months. Patients who received neoadjuvant treatment had a median OS of 23 months. In conclusion, DP-CAR for locally advanced pancreatic body/tail cancer can be performed safely with low mortality and provides survival benefit when combined with neoadjuvant treatment.

Prognostic factors and benefits of adjuvant therapy for ampullary cancer following pancreatoduodenectomy: A systematic review and meta-analysis.

Ampullary cancer is a relatively rare gastrointestinal malignancy. The purpose of this study was to evaluate prognostic factors for survival and assess the benefits of adjuvant therapy following pancreaticoduodenectomy for this entity. Medline and EMBASE databases were searched to identify eligible studies from January 2000 to August 2019. Review Manager 5.3 statistical software was used for meta-analysis. 71 studies met the inclusion criteria and were included in the analysis for a total of 8280 patients. The median (range) 5-year overall survival and disease-free survival rates were 58% (32-82%) and 51% (28-73%) respectively. In meta-analysis, age >65 years at diagnosis, tumor size >20 mm, poor differentiation, pancreaticobiliary histotype, pT3-4 stage disease, presence of metastatic lymph node, number of metastatic nodes, perineural invasion, lymphovascular invasion, vascular invasion, pancreatic invasion, and positive surgical margins were independently associated with worse overall survival, whereas adjuvant therapy was associated with improved overall survival. In summary, in patients with ampullary cancer undergoing pancreaticoduodenectomy, tumor factors are the main predictors of worse survival and adjuvant treatment confers a survival benefit.

Long-term survival outcomes of undifferentiated embryonal sarcoma of the liver: a pooled analysis of 308 patients.

BACKGROUND: Treatment of undifferentiated embryonal sarcoma of the liver (UESL) is a great clinical challenge due to its rarity. This study aims to examine the long-term survival of UESL patients after treatment using different therapeutic modalities. METHODS: A pooled analysis of individual data was performed on all UESL patients obtained from literature search (n = 307) and our institution (n = 1). RESULTS: The 5-year overall survival rate of the 308 patients was 65.8%, 70% for partial hepatectomy group (n = 271), 78.9% for liver transplantation group (n = 14) and 6.6% for nonsurgical treatment group (n = 23). For patients receiving partial hepatectomy, paediatric patients, radical resection and combined chemotherapy were independent predictors for improved survival. CONCLUSION: Radical hepatectomy combined chemotherapy should be considered as the preferred treatment option for USEL. Liver transplantation appears to be a reasonable alternative for unresectable disease.

Surgery for duodenal gastrointestinal stromal tumor: A systematic review and meta-analysis of pancreaticoduodenectomy versus local resection.

The purpose of this study is to assess the clinical outcomes and prognostic factors for survival of patients with duodenal gastrointestinal stromal tumors (GIST) who underwent pancreaticoduodenectomy (PD) or local resection (LR). PubMed database was searched for relevant studies. A meta-analysis was performed with Review Manager 5.3 software. Twenty-seven observational studies involving 1103 patients were included in the review. The overall morbidity and 30-day mortality was 27% and 0.5% respectively. The median (range) 5-year overall survival (OS) and disease-free survival (DFS) rates were 87% (60-100%) and 71% (44-100%) respectively. In meta-analyses, factors associated with shorter DFS included male sex, mitotic index >5/50 high-power fields, high risk, tumor size >5 cm, and the PD procedure. Factors associated with shorter OS included mitotic index >5/50 high-power fields and tumor size >5 cm. Patients in PD group had a higher incidence of mitotic index >5/50 HPF, a higher incidence of high-risk classification, a higher incidence of tumors in the second portion of the duodenum, a larger tumor size, a longer duration of operation, more intraoperative blood loss, a greater blood transfusion requirement, a higher morbidity rate, a longer hospital stay, and an increased recurrence rate than those in LR group. In conclusion, the current literature review demonstrates that the postoperative prognosis of duodenal GIST is promising and mainly affected by tumor factors. The choice of the surgical approach should depend on the anatomical location and tumor size.