Adhesive cryogel particles for bridging confined and irregular tissue defects.

BACKGROUND: Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging. Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies, making tissue bridging challenging. METHODS: This study proposes a tissue adhesive in the form of adhesive cryogel particles (ACPs) made from chitosan, acrylic acid, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart, intestine, liver, muscle, and stomach. Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells (LO2) and human intestinal epithelial cells (Caco-2). The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models. The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart, liver, and kidney as the ex vivo models. Furthermore, a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness, biocompatibility, and applicability in clinical surgery. RESULTS: ACPs are applicable to confined and irregular tissue defects, such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs. ACPs formed tough adhesion between tissues [(670.9 ± 50.1) J/m2 for the heart, (607.6 ± 30.0) J/m2 for the intestine, (473.7 ± 37.0) J/m2 for the liver, (186.1 ± 13.3) J/m2 for muscle, and (579.3 ± 32.3) J/m2 for the stomach]. ACPs showed considerable cytocompatibility in vitro study, with a high level of cell viability for 3 d [(98.8 ± 1.2) % for LO2 and (98.3 ± 1.6) % for Caco-2]. It has comparable inflammation repair in a ruptured rat liver (P = 0.58 compared with suture closure), the same with intestinal anastomosis in rabbits (P = 0.40 compared with suture anastomosis). Additionally, ACPs-based intestinal anastomosis (less than 30 s) was remarkably faster than the conventional suturing process (more than 10 min). When ACPs degrade after surgery, the tissues heal across the adhesion interface. CONCLUSIONS: ACPs are promising as the adhesive for clinical operations and battlefield rescue, with the capability to bridge irregular tissue defects rapidly.

Comparison of 3D printing model to 3D virtual reconstruction and 2D imaging for the clinical education of interns in hepatocellular carcinoma: a randomized controlled study.

Background: The clinical education of interns on hepatocellular carcinoma (HCC) is both crucial and difficult in China, even if the education reform has advanced constantly over the years. The value of specific 3D printing model (3DPM) in clinical education of HCC is uncertain, and relevant literatures are very few. This study aimed to explore the effects of a patient-specific 3D printing liver model on the clinical education of HCC. Methods: Three laparoscopic hepatectomies were collected. For each case, a 3D virtual reconstruction (3DVR) and 3DPM were created using multi-detector computed tomography (MDCT) data, respectively. A total of 62 interns were randomly assigned to each group (3DPM, 3DVR, and MDCT groups) through a table of random numbers for random grouping. Following lecture-based HCC education, interns in each group selected a corresponding model of HCC. All interns were tested on the hepatic tumor locations, the vessels adjacent to them, surgical planning, and test time using the centesimal system score within 90 min. A questionnaire investigation on the degree of satisfaction, interest, and helpfulness for improving the comprehension ability of liver anatomy and 3D spatial structures was also recorded. The 3DPM group were compared with both 3DVR and MDCT group by theoretical examination scores and questionnaire survey satisfaction to evaluate the effects of 3DPM on the interns' clinical education in HCC. Results: All the interns completed the test and questionnaire. The 3DPM group gained significantly higher scores on the following test contents: indicating the correct tumor location (3DPM vs. 3DVR, MDCT: 36.7±4.8 vs. 33.2±5.8, 26.8±10.0, P=0.03, P<0.01, respectively), accurately identifying the relationship between the tumor and vessels (3DPM vs. 3DVR, MDCT: 37.1±4.6 vs. 31.6±3.7, 30.0±5.8, P<0.01, P<0.01, respectively), and designing appropriate surgical plans (3DPM vs. 3DVR, MDCT: 8±2.7 vs. 4.9±2.7, 5.9±3.8, P<0.01, P=0.04, respectively). The 3DPM group showed a higher degree of satisfaction (86.2%), interest (92.1%), and helpfulness (80.5%) for improving the comprehension ability of liver anatomy and 3D spatial structures. Conclusions: The clinical teaching by utilizing 3DPM can significantly improve the professional theoretical level, strengthen clinical thinking and comprehensive ability, and improve the teaching effects of HCC for medical interns.

Current status of laparoscopic hepatectomy for the treatment of hepatocellular carcinoma: A systematic literature review.

BACKGROUND: Laparoscopic hepatectomy (LH) was first introduced in the 1990s and has now become widely accepted for the treatment of hepatocellular carcinoma (HCC). Laparoscopic liver resection (LLR) is considered a safe and effective approach for liver disease. However, the role of laparoscopic hepatectomy in HCC with cirrhosis remains controversial and needs to be further assessed, and the present literature review aimed to review the surgical and oncological outcomes of Laparoscopic hepatectomy (LH). According to Hong and colleagues laparoscopic resection for liver cirrhosis is a very safe and feasible procedure for both ideal cases and select patients with high risk factors [29]. The presence of only 1 of these factors does not represent an absolute contraindication for LH. METHODS AND RESULTS: We selected 23 studies involving about 1363 HCC patients treated with LH. 364 (27%) patients experienced major resections. The mean operative time was 244.9 minutes, the mean blood loss was 308.1 mL and blood transfusions were required in only 4.9% of patients. There were only 2 (0.21%) postoperative deaths and overall morbidity was 9.9%. Tumor recurrence ranged from 6 to 25 months. The 1-year, 3-year, and 5-year disease free Survival (DFS) rates ranged from 71.9% to 99%, 50.3% to 91.2%, and 19% to 82% respectively. Overall survival rates ranged from 88% to 100%, 73.4% to 94.5%, and 52.6% to 94.5% respectively. CONCLUSIONS: In our summery LH is lower risk and safer than conventional open liver surgery and is just as efficacious. Also, the LH approach decreased blood-loss, operation time, postoperative morbidity and had a lower conversion rate compared to other procedures whether open or robotic. Finally, LH may serve as a promising alternative to open procedures.

Comparison of laparoscopic proximal gastrectomy with double-tract reconstruction and laparoscopic total gastrectomy for proximal gastric cancer with stage cT1-2.

ABSTRACT: This study aimed to evaluate the feasibility and nutritional benefits of laparoscopic proximal gastrectomy (LPG) with double-tract reconstruction (DTR) in comparison with laparoscopic total gastrectomy (LTG).The demographic, clinical, and pathological data and postoperative nutritional status of patients undergoing LPG with DTR (n = 21) or LTG (n = 26) at Sir Run Run Shaw Hospital between January 2016 and January 2019 were retrospectively reviewed and compared.The operative time in the LPG group was slightly longer than that in the LTG group; however, the difference was not statistically significant. Blood loss was not significantly different between groups. The mean number of retrieved lymph nodes was higher in the LTG group than in the LPG group (P = .02). The time to first flatus, postoperative hospital stay, and postoperative complications were comparable between the groups. During the 3-year postoperative follow-up, a statistically significant decrease in hemoglobin level was observed in the LTG group. There were no differences between the two groups of patients before and after the operation regarding albumin levels. The mean vitamin B12 level was higher in the LPG group than in the LTG group from 12 to 18 months postoperatively.LPG with DTR is an acceptable procedure for patients with upper gastric cancer. LPG with DTR has numerous potential advantages in preserving the physiological and nutritional functions of the remnant stomach and the conservation of the gastric reservoir.

Development of an Aerobic Glycolysis Index for Predicting the Sorafenib Sensitivity and Prognosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a deadly tumor with high heterogeneity. Aerobic glycolysis is a common indicator of tumor growth and plays a key role in tumorigenesis. Heterogeneity in distinct metabolic pathways can be used to stratify HCC into clinically relevant subgroups, but these have not yet been well-established. In this study, we constructed a model called aerobic glycolysis index (AGI) as a marker of aerobic glycolysis using genomic data of hepatocellular carcinoma from The Cancer Genome Atlas (TCGA) project. Our results showed that this parameter inferred enhanced aerobic glycolysis activity in tumor tissues. Furthermore, high AGI is associated with poor tumor differentiation and advanced stages and could predict poor prognosis including reduced overall survival and disease-free survival. More importantly, the AGI could accurately predict tumor sensitivity to Sorafenib therapy. Therefore, the AGI may be a promising biomarker that can accurately stratify patients and improve their treatment efficacy.

Artificial intelligence in gastroenterology and hepatology: Status and challenges.

Originally proposed by John McCarthy in 1955, artificial intelligence (AI) has achieved a breakthrough and revolutionized the processing methods of clinical medicine with the increasing workloads of medical records and digital images. Doctors are paying attention to AI technologies for various diseases in the fields of gastroenterology and hepatology. This review will illustrate AI technology procedures for medical image analysis, including data processing, model establishment, and model validation. Furthermore, we will summarize AI applications in endoscopy, radiology, and pathology, such as detecting and evaluating lesions, facilitating treatment, and predicting treatment response and prognosis with excellent model performance. The current challenges for AI in clinical application include potential inherent bias in retrospective studies that requires larger samples for validation, ethics and legal concerns, and the incomprehensibility of the output results. Therefore, doctors and researchers should cooperate to address the current challenges and carry out further investigations to develop more accurate AI tools for improved clinical applications.

Endoscopic Versus Surgical Therapy for Early Esophagogastric Junction Adenocarcinoma Based on Lymph Node Metastasis Risk: A Population-Based Analysis.

BACKGROUND: In this study, we aimed to compare the prognosis and lymph node metastasis (LNM) risk in patients with early-stage esophagogastric junction (EGJ) adenocarcinoma after endoscopic treatment (ET) or radical surgery. METHODS: We collected data from eligible patients based on the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016. Logistic regression analysis was used to determine independent predictors of LNM (examination of at least 16 lymph nodes). Cox regression analysis and propensity score-matched (PSM) analysis were subsequently utilized to compare the overall survival (OS) and cancer-specific survival (CSS) of patients treated with ET or radical surgery. RESULTS: In total, 3708 patients were identified. Among them, 856 patients had greater than or equal to 16 examined lymph nodes (LNs) (LNE≥16). The LNM rates were 18.8% in all patients 8.3% in T1a patients and 24.6% in T1b patients. Independent predictors of LNM were submucosal invasion, tumor size ≥3cm and decreasing differentiation (P<0.05). The LNM rate decreased to approximately 5.3% in T1b tumors with well differentiation and tumor size <3cm. However, the LNM incidence increased to 17.9% or 33.3% in T1a tumors with poor differentiation or with both tumor size≥3cm and poor differentiation. Cox regression analysis demonstrated CSS was not significantly different in early-stage EGJ adenocarcinoma patients undergoing ET and those treated with radical surgery (HR= 1.004, P=0.974), which were robustly validated after PSM analysis. Moreover, subgroup analysis stratified by T1a and T1b showed similar results. CONCLUSIONS: The findings of this study indicated ET as an alternative to radical surgery in early EGJ adenocarcinoma.

Deep Learning for Accurate Diagnosis of Liver Tumor Based on Magnetic Resonance Imaging and Clinical Data.

Background: Early-stage diagnosis and treatment can improve survival rates of liver cancer patients. Dynamic contrast-enhanced MRI provides the most comprehensive information for differential diagnosis of liver tumors. However, MRI diagnosis is affected by subjective experience, so deep learning may supply a new diagnostic strategy. We used convolutional neural networks (CNNs) to develop a deep learning system (DLS) to classify liver tumors based on enhanced MR images, unenhanced MR images, and clinical data including text and laboratory test results. Methods: Using data from 1,210 patients with liver tumors (N = 31,608 images), we trained CNNs to get seven-way classifiers, binary classifiers, and three-way malignancy-classifiers (Model A-Model G). Models were validated in an external independent extended cohort of 201 patients (N = 6,816 images). The area under receiver operating characteristic (ROC) curve (AUC) were compared across different models. We also compared the sensitivity and specificity of models with the performance of three experienced radiologists. Results: Deep learning achieves a performance on par with three experienced radiologists on classifying liver tumors in seven categories. Using only unenhanced images, CNN performs well in distinguishing malignant from benign liver tumors (AUC, 0.946; 95% CI 0.914-0.979 vs. 0.951; 0.919-0.982, P = 0.664). New CNN combining unenhanced images with clinical data greatly improved the performance of classifying malignancies as hepatocellular carcinoma (AUC, 0.985; 95% CI 0.960-1.000), metastatic tumors (0.998; 0.989-1.000), and other primary malignancies (0.963; 0.896-1.000), and the agreement with pathology was 91.9%.These models mined diagnostic information in unenhanced images and clinical data by deep-neural-network, which were different to previous methods that utilized enhanced images. The sensitivity and specificity of almost every category in these models reached the same high level compared to three experienced radiologists. Conclusion: Trained with data in various acquisition conditions, DLS that integrated these models could be used as an accurate and time-saving assisted-diagnostic strategy for liver tumors in clinical settings, even in the absence of contrast agents. DLS therefore has the potential to avoid contrast-related side effects and reduce economic costs associated with current standard MRI inspection practices for liver tumor patients.

A retrospective pilot study to examine the feasibility of real-time navigation for laparoscopic liver resections in intrahepatic cholangiocarcinoma using fusion indocyanine green fluorescence imaging.

BACKGROUND AND OBJECTIVES: Recently, PINPOINT, a novel laparoscopic fusion indocyanine green fluorescence imaging (IGFI) system has become available for laparoscopic liver resection. This study aims to characterize fluorescence patterns of intrahepatic cholangiocarcinoma (ICC) using the negative counterstaining method in laparoscopic anatomical hepatectomies of ICC. METHODS: Eleven consecutive patients, diagnosed with intrahepatic cholangiocarcinoma and underwent laparoscopic liver resection between April 2017 and December 2018, were retrospectively reviewed. A laparoscopic IGFI navigation system was used to characterize fluorescence patterns of ICC with intraoperative liver segment demarcation by means of negative counterstaining. RESULTS: Fusion IGFI of ICC was successfully obtained from all 11 patients from the surgical specimens. The fluorescence patterns of ICC can be categorized into rim-type fluorescence and segmental fluorescence, depending on tumor growth. In eight patients, indocyanine green fluorescence imaging was used to identify the hepatic lobes or segments by negative counterstaining. In six cases, a valid and persistent demarcation was achieved intraoperatively. CONCLUSION: Laparoscopic IGFI system could identify different types of ICC lesions and may facilitate real-time navigation for laparoscopic anatomic liver resection of ICC.

Laparoscopic surgery for early gallbladder carcinoma: A systematic review and meta-analysis.

BACKGROUND: There is a controversy as to whether laparoscopic surgery leads to a poor prognosis compared to the open approach for early gallbladder carcinoma (GBC). We hypothesized that the laparoscopic approach is an alternative for early GBC. AIM: To identify and evaluate the safety and feasibility of laparoscopic surgery in the treatment of early GBC. METHODS: A comprehensive search of online databases, including MEDLINE (PubMed), Cochrane libraries, and Web of Science, was performed to identify non-comparative studies reporting the outcomes of laparoscopic surgery and comparative studies involving laparoscopic surgery and open surgery in early GBC from January 2009 to October 2019. A fixed-effects meta-analysis was performed for 1- and 5-year overall survival and postoperative complications, while 3-year overall survival, operation time, blood loss, the number of lymph node dissected, and postoperative hospital stay were analyzed by random-effects models. RESULTS: The review identified 7 comparative studies and 8 non-comparative studies. 1068 patients (laparoscopic surgery: 613; open surgery: 455) were included in the meta-analysis of 1-, 3-, and 5-year overall survival with no significant differences observed [(HR = 0.54; 95%CI: 0.29-1.00; I 2 = 0.0%; P = 0.051), (HR = 0.75; 95%CI: 0.34-1.65; I 2 = 60.7%; P = 0.474), (HR = 0.71; 95%CI: 0.47-1.08; I 2 = 49.6%; P = 0.107), respectively]. There were no significant differences in operation time [weighted mean difference (WMD) = 18.69; 95%CI: -19.98-57.36; I 2 = 81.4%; P = 0.343], intraoperative blood loss (WMD = -169.14; 95%CI: -377.86-39.57; I 2 = 89.5%; P = 0.112), the number of lymph nodes resected (WMD = 0.12; 95%CI: -2.95-3.18; I 2 = 73.4%; P = 0.940), and the complication rate (OR = 0.69; 95%CI: 0.30-1.58; I 2 = 0.0%; P = 0.377 ) between the two groups, while patients who underwent laparoscopic surgery had a reduced length of hospital stay (WMD = -5.09; 95%CI: -8.74- -1.45; I 2 = 91.0%; P= 0.006). CONCLUSION: This systematic review and meta-analysis confirms that laparoscopic surgery is a safe and feasible alternative to open surgery with comparable survival and operation-related outcomes for early GBC.

Prognostic factors and predictors of postoperative adjuvant transcatheter arterial chemoembolization benefit in patients with resected hepatocellular carcinoma.

BACKGROUND: Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) has improved overall survival (OS) in patients with hepatocellular carcinoma (HCC). However, the prognostic and predictive factors remain unclear. AIM: To assess the prognostic factors and the predictors of PA-TACE benefit for OS in patients with resected HCC. METHODS: Univariate and multivariate analyses were performed to identify the potential prognostic factors for OS. In order to assess the predictive factors of PA-TACE benefit, the interaction variables between treatments for each subgroup were evaluated using the Cox proportional hazards regression model. RESULTS: A total of 378 patients (PA-TACE vs surgery alone, 189:189) from three centers were included after a propensity-score 1:1 matching analysis. Compared to the group receiving surgery alone, PA-TACE prolonged the OS rate in patients with resected HCC (P < 0.001). The Barcelona Clinic Liver Cancer system and ferritin-to-hemoglobin ratio (FHR) were used as the prognostic factors for OS in both groups. Age (P = 0.023) and microscopic vascular invasion (MVI) (P = 0.002) were also identified in the PA-TACE group, while gender (P = 0.027), hepatitis B virus (P = 0.034) and albumin-bilirubin grade (P = 0.027) were also selected in the surgery alone group. In addition, PA-TACE resulted in longer OS than surgery alone across subgroups [all hazard ratios (PA-TACE-to-surgery alone) < 1]. Notably, a significantly prolonged OS following PA-TACE was observed in patients with high FHR (P = 0.038) and without MVI (P = 0.048). CONCLUSION: FHR and Barcelona Clinic Liver Cancer stages were regarded as prognostic factors for OS. Moreover, high FHR and the absence of MVI were important predictive factors, which can be used to assist clinicians in selecting which patients could achieve a better OS with PA-TACE.

Promising key genes associated with tumor microenvironments and prognosis of hepatocellular carcinoma.

BACKGROUND: Despite significant advances in multimodality treatments, hepatocellular carcinoma (HCC) remains one of the most common malignant tumors. Identification of novel prognostic biomarkers and molecular targets is urgently needed. AIM: To identify potential key genes associated with tumor microenvironments and the prognosis of HCC. METHODS: The infiltration levels of immune cells and stromal cells were calculated and quantified based on the ESTIMATE algorithm. Differentially expressed genes (DEGs) between high and low groups according to immune or stromal scores were screened using the gene expression profile of HCC patients in The Cancer Genome Atlas and were further linked to the prognosis of HCC. These genes were validated in four independent HCC cohorts. Survival-related key genes were identified by a LASSO Cox regression model. RESULTS: HCC patients with a high immune/stromal score had better survival benefits than patients with a low score. A total of 899 DEGs were identified and found to be involved in immune responses and extracellular matrices, 147 of which were associated with overall survival. Subsequently, 52 of 147 survival-related DEGs were validated in additional cohorts. Finally, ten key genes (STSL2, TMC5, DOK5, RASGRP2, NLRC3, KLRB1, CD5L, CFHR3, ADH1C, and UGT2B15) were selected and used to construct a prognostic gene signature, which presented a good performance in predicting overall survival. CONCLUSION: This study extracted a list of genes associated with tumor microenvironments and the prognosis of HCC, thereby providing several valuable directions for the prognostic prediction and molecular targeted therapy of HCC in the future.

Primary hepatic leiomyosarcoma successfully treated by transcatheter arterial chemoembolization: A case report.

BACKGROUND: Primary hepatic leiomyosarcoma is rare and reported sporadically, with less than 40 such cases have been reported in the English-language literature. Although it is reported to be associated with acquired immune deficiency syndrome, Epstein-Barr virus infection, Hodgkin's lymphoma, immunosuppression after organ transplantation, and hepatitis C virus-related liver cirrhosis, the precise steps leading to leiomyosarcoma have not been fully identified. Therapeutic strategies include liver wedge resection or lobectomy, chemotherapy, radiotherapy and liver transplantation; however, the prognosis of primary hepatic leiomyosarcoma is dismal. CASE SUMMARY: We describe here the first case of primary hepatic leiomyosarcoma successfully treated by transcatheter arterial chemoembolization (TACE). The patient was a 68-year-old woman who presented with right upper quadrant pain and weight loss over the past 5 wk before admission. Abdominal computed tomography (commonly known as CT) and ultrasonography showed a mixed echoic mass measuring about 10 cm × 7 cm occupying the right lobe of the liver. Exploratory laparotomy was performed 1 wk after admission. The tumor was unresectable and biopsy was performed. Based on rapid frozen-section and histopathological examination, a final diagnosis of primary hepatic leiomyosarcoma was established. TACE was performed 2 wk later. The postoperative course was uneventful and the patient was discharged on day 7 after the operation. Contrast-enhanced CT showed that the tumor significantly shrunk with satisfactory lipiodol deposition. The patient has been followed up for 82 mo until now, and no progressive enlargement of the tumor or distal metastasis was observed. CONCLUSION: TACE is a safe and effective treatment for primary hepatic leiomyosarcoma. The therapeutic effect of TACE combined with surgical resection should be further assessed.

GSK923295 as a potential antihepatocellular carcinoma agent causing delay on liver regeneration after partial hepatectomy.

BACKGROUND: The clinical trials emerged centromere protein E inhibitor GSK923295 as a promising anticancer drug, but its function in hepatocellular carcinoma (HCC) remain needs to be fully elucidated, especially as chemotherapy after hepatectomy for liver tumors. We aimed to describe anti-HCC activities of GSK923295 and compare its antiproliferative effects on liver regeneration after partial hepatectomy (PH). METHODS: All subjects were randomized to treatment with either vehicle or GSK923295. Antitumor activity of GSK923295 was assessed by xenograft growth assays. The C57BL/6 mice were subjected to 70% PH and the proliferation was calculated by liver coefficient, further confirmed by immunohistochemistry. The proliferation and cell cycle analysis of liver cell AML12 and HCC cells LM3, HUH7, and HepG2 were investigated using the cell counting kit-8 assay and Flow Cytometry. The chromosome misalignment and segregation in AML12 cells were visualized by immunofluorescence. RESULTS: Treatment with GSK923295 induced antiproliferation in HCC cell lines. It also caused delay on HCC tumor growth instead of regression both in a HCC cell line xenograft model and patient-derived tumor xenograft model. With microarray analysis, CENtromere Protein E was gradually increased in mouse liver after PH. Exposure of liver cells to GSK923295 resulted in delay on a cell cycle in mitosis with a phenotype of misaligned chromosomes and chromosomes clustered. In 70% PH mouse model, GSK923295 treatment also remarkably reduced liver regeneration in later stage, in parallel with the mitotic marker phospho-histone H3 elevation. CONCLUSION: The anticancer drug GSK923295 causes a significant delay on HCC tumor growth and liver regeneration after PH in later stage.

Laparoscopic Right Hepatectomy for Hepatocellular Carcinoma: A Propensity Score Matching Analysis of Outcomes Compared with Conventional Open Surgery.

BACKGROUND: The application of laparoscopic hepatectomy is gaining momentum. However, the safety and efficacy of laparoscopic right hepatectomy (LRH) on hepatocellular carcinoma (HCC) are yet to be adequately evaluated. We aimed to assess the surgical and oncological outcomes of LRH for HCC by comparing it with open right hepatectomy (ORH). MATERIALS AND METHODS: Data of patients who underwent hepatectomy for HCC from May 2007 to January 2018 in our hospital were obtained. Baseline characteristics, postoperative recovery, and survival outcomes were compared. One-to-one propensity score matching (PSM) was used to minimize selection biases by balancing factors, including age, sex, preoperative therapy, tumor size, and pattern. RESULTS: The original cohort included 109 patients (LRH, 41 patients; ORH, 68 patients). Of the 41 patients who underwent LRH, 8 patients (19.5%) required conversion to laparotomy. The overall morbidity was 19.5%, and no mortality in LRH was noted. After PSM, LRH was associated with a tendency of prolonged operative time (255.5 ± 93.4 minutes versus 225.9 ± 39.8 minutes, P = .08) and less intraoperative blood loss [300 (100-1200) versus 500 (200-2000) mL, P < .01]. LRH showed up a trend of less overall morbidity without statistical significance (18.4% versus 26.3%, P = .41). Moreover, the 3-year overall and disease-free survival did not differ significantly between the groups during a median follow-up of 19 (3-58) months for the LRH group and 23 (3-97) months for the ORH group. CONCLUSIONS: LRH can be performed as safe and effective as ORH for HCC in regard to both surgical and oncological outcomes. LRH holds the benefit in less intraoperative blood loss and appears to achieve less postoperative morbidity, which could serve as a promising alternative to ORH in selected individuals.

Harnessing accurate non-homologous end joining for efficient precise deletion in CRISPR/Cas9-mediated genome editing.

BACKGROUND: Many applications of CRISPR/Cas9-mediated genome editing require Cas9-induced non-homologous end joining (NHEJ), which was thought to be error prone. However, with directly ligatable ends, Cas9-induced DNA double strand breaks may be repaired preferentially by accurate NHEJ. RESULTS: In the repair of two adjacent double strand breaks induced by paired Cas9-gRNAs at 71 genome sites, accurate NHEJ accounts for about 50% of NHEJ events. This paired Cas9-gRNA approach underestimates the level of accurate NHEJ due to frequent + 1 templated insertions, which can be avoided by the predefined Watson/Crick orientation of protospacer adjacent motifs (PAMs). The paired Cas9-gRNA strategy also provides a flexible, reporter-less approach for analyzing both accurate and mutagenic NHEJ in cells and in vivo, and it has been validated in cells deficient for XRCC4 and in mouse liver. Due to high frequencies of precise deletions of defined "3n"-, "3n + 1"-, or "3n + 2"-bp length, accurate NHEJ is used to improve the efficiency and homogeneity of gene knockouts and targeted in-frame deletions. Compared to "3n + 1"-bp, "3n + 2"-bp can overcome + 1 templated insertions to increase the frequency of out-of-frame mutations. By applying paired Cas9-gRNAs to edit MDC1 and key 53BP1 domains, we are able to generate predicted, precise deletions for functional analysis. Lastly, a Plk3 inhibitor promotes NHEJ with bias towards accurate NHEJ, providing a chemical approach to improve genome editing requiring precise deletions. CONCLUSIONS: NHEJ is inherently accurate in repair of Cas9-induced DNA double strand breaks and can be harnessed to improve CRISPR/Cas9 genome editing requiring precise deletion of a defined length.

Correction to "Maturity of associating liver partition and portal vein ligation for staged hepatectomy-derived liver regeneration in a rat model [World J Gastroenterol 2018 March 14; 24(10): 1107-1119]".

[This corrects the article on p. 1107 in vol. 21, PMID: 26640344.].

Preliminary screening and analysis of metastasis-related lncRNA and co-expressed papillary thyroid carcinoma mRNA.

The objective of the present study was to investigate the long non-coding RNA (lncRNA) and mRNA expression profiles that are associated with the invasion and metastasis of papillary thyroid carcinoma (PTC). Transwell invasion assays were used to screen three highly invasive sub-strains of the human PTC IHH4 cell line: IHH4-M1, IHH4-M2 and IHH4-M3. In addition, tumor-bearing nude mice were used to identify the invasive and metastatic capacity of the three sub-strains. Agilent lncRNA microarray chips were used to screen 795 differentially expressed lncRNAs and 788 differentially expressed mRNAs. A total of 10 lncRNAs and 10 mRNAs were randomly selected for RT-qPCR validation to confirm that the results were consistent with the microarray chips, suggesting that the results of the microarray chip analysis were relatively accurate. Gene ontology enrichment-based cluster analysis revealed that the differentially expressed genes were mainly associated with steroid biosynthesis, bioadhesion, intercellular adhesion and other metastasis-associated biological processes. The results of the pathway cluster analysis identified that the differentially expressed genes were associated with tumor metastasis-associated signaling pathways, including the cholesterol metabolic signaling pathway, the sterol regulatory element-binding protein signaling pathway and the integrin signaling pathway, suggesting that lncRNA may regulate PTC metastasis through various signaling pathways. The present study screened and constructed PTC metastasis-associated lncRNA and mRNA expression profiles, and it provides a molecular basis for the future study of high-risk molecular markers of PTC.

Maturity of associating liver partition and portal vein ligation for staged hepatectomy-derived liver regeneration in a rat model.

AIM: To establish a rat model for evaluating the maturity of liver regeneration derived from associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). METHODS: In the present study, ALPPS, partial hepatecotmy (PHx), and sham rat models were established initially, which were validated by significant increase of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1. In the setting of accelerated proliferation in volume at the second and fifth day after ALPPS, the characteristics of newborn hepatocytes, as well as specific markers of progenitor hepatic cell, were identified. Afterwards, the detection of liver function followed by cluster analysis of functional gene expression were performed to evaluate the maturity. RESULTS: Compared with PHx and sham groups, the proliferation of FLR was significantly higher in ALPPS group (P = 0.023 and 0.001 at second day, P = 0.034 and P < 0.001 at fifth day after stage I). Meanwhile, the increased expression of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1 verified the accelerated liver regeneration derived from ALPPS procedure. However, ALPPS-induced Sox9 positive hepatocytes significantly increased beyond the portal triad, which indicated the progenitor hepatic cell was potentially involved. And the characteristics of ALPPS-induced hepatocytes indicated the lower expression of hepatocyte nuclear factor 4 and anti-tryptase in early proliferative stage. Both suggested the immaturity of ALPPS-derived liver regeneration. Additionally, the detection of liver function and functional genes expression confirmed the immaturity of renascent hepatocytes derived in early stage of ALPPS-derived liver regeneration. CONCLUSION: Our study revealed the immaturity of ALPPS-derived proliferation in early regenerative response, which indicated that the volumetric assessment overestimated the functional proliferation. This could be convincing evidence that the stage II of ALPPS should be performed prudently in patients with marginally adequate FLR, as the ALPPS-derived proliferation in volume lags behind the functional regeneration.

Comparison of Intracorporeal and Extracorporeal Esophagojejunostomy after Laparoscopic Total Gastrectomy for Gastric Cancer: A Meta-Analysis Based on Short-Term Outcomes.

BACKGROUND:: Laparoscopic total gastrectomy (LTG) is increasingly performed in patients with gastric cancer. However, the usage of intracorporeal esophagojejunostomy (IEJ) following LTG is limited, as the safety and efficacy remain unclear. The present meta-analysis aimed to evaluate the feasibility and safety of IEJ following LTG. METHODS:: Studies published from January 1994 to January 2017 comparing the outcomes of IEJ and extracorporeal esophagojejunostomy (EEJ) following LTG were reviewed and collected from the PubMed, EBSCO, Cochrane Library, Embase, and China National Knowledge Internet (CNKI). Operative results, postoperative recovery, and postoperative complications were compared and analyzed. The weighted mean difference (WMD) and odds ratio (OR) with a 95% confidence interval (CI) were calculated using the Review Manager 5.3. RESULTS:: Seven nonrandomized studies with 785 patients were included. Compared with EEJ, IEJ has less blood loss (WMD: -13.52 ml; 95% CI: -24.82--2.22; P = 0.02), earlier time to first oral intake (WMD: -0.49 day; 95% CI: -0.83--0.14; P < 0.01), and shorter length of hospitalization (WMD: -0.62 day; 95% CI: -1.08--0.16; P < 0.01). There was no significant difference between IEJ and EEJ regarding the operation time, anastomotic time, number of retrieved lymph nodes, time to first flatus, anastomosis leakage rate, anastomosis stenosis rate, and proximal resections (all P > 0.05). CONCLUSIONS: Compared with EEJ, IEJ has better cosmesis, milder surgical trauma, and a faster postoperative recovery. IEJ can be performed as safely as EEJ. IEJ should be encouraged to surgeons with sufficient expertise.