Safety and benefit of modified mesohepatectomy in the treatment of bilobar involvement congenital biliary dilatation.

BACKGROUND: The diseased bile duct in bilobar congenital biliary dilatation is extensive and often requires major hepatectomy or liver transplantation associated with a higher risk. We aimed to evaluate the safety and benefit of modified mesohepatectomy, in comparison with trisectionectomy, to treat bilobar congenital biliary dilatation. METHODS: This study included 28 patients with type IV and V bilobar congenital biliary dilatation. An innovative mesohepatectomy comprising the hepatectomy technique beyond the P/U point and bile duct shaping was applied to 14 patients to address the extensively diseased bile duct and difficulty in hepaticojejunostomy. Another 14 patients received trisectionectomy. The perioperative and long-term outcomes of these patients were compared. RESULTS: The ratio of residual liver volume to standard liver volume in the mesohepatectomy group was higher (78.68% vs. 40.90%, p = 0.005), while the resection rate of the liver parenchyma was lower (28.25% vs. 63.97%, p = 0.000), than that in trisectionectomy group. The mesohepatectomy group had a lower severe complication (>Clavein III, 0% vs. 57.70%, p = 0.019) and incidence of posthepatectomy liver failure (7.14% vs. 42.86%, p = 0.038). No significant difference was observed in blood loss and bile leakage (p > 0.05). All the patients in the mesohepatectomy group achieved optimal results in the long-term follow-up. CONCLUSIONS: mesohepatectomy provides an efficient treatment option for bilobar congenital biliary dilatation and can achieve radical resection, retain more liver parenchyma, and reduce the difficulty of hepaticojejunostomy, especially for patients that are not eligible for major hepatectomy and liver transplantation.

Efficacy of radiotherapy in combined treatment of hepatocellular carcinoma patients with portal vein tumor thrombus: a real-world study.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) has an extremely poor prognosis. A previous study proved that low-dose radiotherapy (RT) could prolong the prognosis of HCC patients with PVTT. This study aims to explore the sensitivity of PVTT to RT treatment. METHODS: Patients were selected based on imaging diagnosis of HCC accompanied by PVTT and received combined treatment of radiotherapy, antiangiogenic drugs and immune checkpoint inhibitors, followed by hepatectomy or liver transplantation from January 2019 to August 2022. The efficacy was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines and pathological assessment. The sensitivity of tumor cells to the treatment was compared between the primary tumor (PT)and PVTT by analyzing their residual tumor and pathologic complete remission (PCR) incidence. RESULTS: Data from 14 patients were collected in the study. After combined treatment, the size of PVTT decreased more significantly than that of the primary tumor in the imaging study (p < 0.05). The residual cancer was significantly more restrictive than that of primary tumor in paired patients based on pathological measurement (p = 0.008). The PCR incidence of the primary tumor (21.42%) was significantly lower (p = 0.008) than that of PVTT in the pathologic study (78.57%). CONCLUSION: PVTT is more sensitive to radiotherapy treatment than the primary tumor in patients with HCC. This combination therapy might be an effective option as a downstaging therapy for patients with HCC with PVTT.

Comparing the distal pancreatectomy fistula risk score (D-FRS) and DISPAIR-FRS for predicting pancreatic fistula after distal pancreatectomy.

BACKGROUNDS: Distal pancreatectomy fistula risk score (D-FRS) and DISPAIR-FRS has not been widely validated for predicting postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP). METHODS: We retrospectively analysed 104 patients undergoing DP. The predictive value of the D-FRS and DISPAIR-FRS were compared. Risk factors associated with POPF were investigated by multivariate analysis. RESULTS: Of the 104 patients, 23 (22.1%) were categorized into the POPF group (all grade B). The areas under the ROC (AUCs) of the D-FRS (preoperative), D-FRS (intraoperative), and DISPAIR-FRS were 0.737, 0.809, and 0.688, respectively. Stratified by the D-FRS (preoperative), the POPF rates in low-risk, intermediate-risk, and high-risk groups were 5%, 22.6%, and 36.4%, respectively. By the D-FRS (intraoperative), the POPF rates in low-risk, intermediate-risk, and high-risk groups were 8.8%, 47.1%, and 47.4%, respectively. By the DISPAIR-FRS, the POPF rates in low-risk, intermediate-risk, and extreme-high-risk groups were 14.8%, 23.8% and 62.5%, respectively. Body mass index and main pancreatic duct diameter were independent risk factors of POPF both in preoperative (P = 0.014 and P = 0.033, respectively) and intraoperative (P = 0.015 and P = 0.039) multivariate analyses. CONCLUSION: Both the D-FRS (preoperative), D-FRS (intraoperative), and DISPAIR-FRS has good performance in POPF prediction after DP. The risk stratification was not satisfactory in current Asian cohort.

Structural and compositional diversity of biosurfactants produced by a novel strain of Sporosarcina luteola ME44 from oil reservoir.

The urealytically active microorganism Sporosarcina luteola induces the precipitation of metals, which has attracted attention in biomineralization, bioremediation, and industrial waste recycling. Herein, we report a novel biosurfactant-producing strain of S. luteola ME44 isolated from Chinese Oilfield. The structure, composition, and surface activity of the biosurfactants produced by S. luteola ME44 were investigated by using a combination of the high-performance liquid chromatography, time-of-flight mass spectrometry, and surface tensiometer. The biosurfactant extracted by strain ME44 was identified as surfactin with five variants and the yield was 1010 ± 60 mg⋅L-1 . This is the first report on the structural composition and surface activity of biosurfactants isolated from the S. luteola. It extended our knowledge about the role of the species S. luteola in the ecosystem of extreme natural environments such as oil reservoir. In addition, S. luteola ME44 showed bioprecipitation properties for metal ions Cd(II), Cu(II), Zn(II), and Ag(I), which indicated the application potential of S. luteola in the field of bioremediation.

Effectiveness and Safety of the PD-1 Inhibitor Lenvatinib Plus Radiotherapy in Patients with HCC with Main PVTT: Real-World Data from a Tertiary Centre.

Background: Patients with hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT), especially type Vp-4, usually have a poor prognosis. However, the vast majority of Phase III clinical trials exclude this population based on the inclusion criteria. Lenvatinib plus a PD-1 inhibitor has shown promising antitumour activity and tolerable safety in patients with unresectable HCC in Asian populations. Radiotherapy has also demonstrated high response rates and favourable survival for HCC patients with PVTT. This study aimed to explore the preliminary clinical efficacy and safety of lenvatinib plus the PD-1 inhibitor combined with radiotherapy for HCC patients with main portal vein tumour thrombus. Methods: Between 1 March 2018 and 31 October 2020, HCC patients with main PVTT who received lenvatinib plus a PD-1 inhibitor (pembrolizumab, nivolumab or sintilimab) combined with radiotherapy from Beijing Tsinghua Changgung Hospital in China were reviewed for eligibility. The efficacy was evaluated by the survival and PVTT response rate, and the safety was evaluated by the frequency of key adverse events (AEs). Results: In total, 39 eligible HCC patients with type Vp-4 PVTT who received triple therapy were included in this study. The 2-year OS rate was 15.4%, which was the primary end-point of our study. The median overall survival (OS) and progression-free survival (PFS) were 9.4 months (range 2.3 to 57.1) and 4.9 months (range 1.4 to 36.1), respectively. The objective response rate (ORR) of PVTT based on mRECIST was 61.5%. AFP dropped to normal 3 months after radiotherapy and was an independent risk factor associated with OS. All AEs were controlled, and no treatment-related deaths occurred. Conclusion: Lenvatinib plus PD-1 inhibitor combined with radiotherapy had a significant therapeutic effect and manageable AEs in HCC patients with type Vp-4 PVTT and may be a potential treatment option for advanced HCC.

A new biosurfactant-producing strain, Fictibacillus nanhaiensis ME46, isolated from an oil field in China.

The genus Fictibacillus contains twelve species significant in the synthesis of cellulose-degrading enzymes and phenylalanine dehydrogenase, isolated mainly from marine sedimentary environments. Here, we report a new biosurfactant-producing strain, Fictibacillus nanhaiensis ME46, isolated from Daqing oil field in China. The biosurfactant extracted from Strain ME46 was determined as surfactin, one of the representative families of lipopeptide biosurfactants. The yield of the surfactin produced by strain ME46 was 0.62 g·L-1 as determined by high-performance liquid chromatography, and the critical micelle concentration (CMC) of the surfactin was estimated to be about 68 mg·L-1 and the surface tension at CMC was 35.1 mN·m-1. This study extended our knowledge about the role of the species Fictibacillus nanhaiensis in the ecosystem of natural environments such as the oil field.

Clinical characteristics of solitary intrahepatic biliary cyst.

Solitary intrahepatic biliary cyst (SIBC) is a rare disease, and due to the lack of adequate understanding of it, SIBC is often misdiagnosed as simple liver cyst (SLC), which in turn affects the therapeutic effect. In order to arouse more attention to SIBC, combined with clinical experience in our center, this study specifically screened 3 representative cases of SIBC, and conducted a comprehensive retrospective analysis of their clinical characteristics, diagnosis and treatment process. Combined with the relevant literature, the diagnosis and treatment process of SIBC is widely discussed.

A pyroptosis-related gene signature for prognosis prediction in hepatocellular carcinoma.

Introduction: Hepatocellular carcinoma (HCC) is one of the most invasive cancers with a low 5-year survival rate. Pyroptosis, a specialized form of cell death, has shown its association with cancer progression. However, its role in the prognosis of HCC has not been fully understood. Methods: In our study, clinical information and mRNA expression for 1076 patients with HCC were obtained from the five public cohorts. Pyroptotic clusters were generated by unsupervised clustering based on 40 pyroptosis-related genes (PRGs) in the TCGA and ICGC cohort. A pyroptosis-related signature was constructed using least absolute shrinkage and selection operator (LASSO) regression according to differentially expressed genes (DEGs) of pyroptotic clusters. The signature was then tested in the validation cohorts (GES10142 and GSE14520) and subsequently validated in the CPTAC cohort (n=159) at both mRNA and protein levels. Response to sorafenib was explored in GSE109211. Results: Three clusters were identified based on the 40 PRGs in the TCGA cohort. A total of 24 genes were selected based on DEGs of the above three pyroptotic clusters to construct the pyroptotic risk score. Patients with the high-risk score showed shorter overall survival (OS) compared to those with the low-risk score in the training set (P<0.001; HR, 3.06; 95% CI, 2.22-4.24) and the test set (P=0.008; HR, 1.61; 95% CI, 1.13-2.28). The predictive ability of the risk score was further confirmed in the CPTAC cohort at both mRNAs (P<0.001; HR, 2.99; 95% CI, 1.67-5.36) and protein levels (P<0.001; HR, 2.97; 95% CI 1.66-5.31). The expression of the model genes was correlated with immune cell infiltration, angiogenesis-related genes, and sensitivity to antiangiogenic therapy (P<0.05). Discussion: In conclusion, we established a prognostic signature of 24 genes based on pyroptosis clusters for HCC patients, providing insight into the risk stratification of HCC.

Hotspots and difficulties of biliary surgery in older patients.

ABSTRACT: With the accelerated aging society in China, the incidence of biliary surgical diseases in the elderly has increased significantly. The clinical characteristics of these patients indicate that improving treatment outcomes and realizing healthy aging are worthy of attention. How to effectively improve the treatment effect of geriatric biliary surgical diseases has attracted widespread attention. This paper reviews and comments on the hotspots and difficulties of biliary surgery in older patients from six aspects: (1) higher morbidity associated with an aging society, (2) prevention and control of pre-operative risks, (3) extending the indications of laparoscopic surgery, (4) urgent standardization of minimally invasive surgery, (5) precise technological progress in hepatobiliary surgery, and (6) guarantee of peri-operative safety. It is of great significance to fully understand the focus of controversy, actively make use of its favorable factors, and effectively avoid its unfavorable factors, for further improving the therapeutic effects of geriatric biliary surgical diseases, and thus benefits the vast older patients with biliary surgical diseases. Accordingly, a historical record with the highest age of 93 years for laparoscopic transcystic common bile duct exploration has been created by us recently.

Data-Driven Assisted Decision Making for Surgical Procedure of Hepatocellular Carcinoma Resection and Prognostic Prediction: Development and Validation of Machine Learning Models.

Background: Currently, surgical decisions for hepatocellular carcinoma (HCC) resection are difficult and not sufficiently personalized. We aimed to develop and validate data driven prediction models to assist surgeons in selecting the optimal surgical procedure for patients. Methods: Retrospective data from 361 HCC patients who underwent radical resection in two institutions were included. End-to-end deep learning models were built to automatically segment lesions from the arterial phase (AP) of preoperative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Clinical baseline characteristics and radiomic features were rigorously screened. The effectiveness of radiomic features and radiomic-clinical features was also compared. Three ensemble learning models were proposed to perform the surgical procedure decision and the overall survival (OS) and recurrence-free survival (RFS) predictions after taking different solutions, respectively. Results: SegFormer performed best in terms of automatic segmentation, achieving a Mean Intersection over Union (mIoU) of 0.8860. The five-fold cross-validation results showed that inputting radiomic-clinical features outperformed using only radiomic features. The proposed models all outperformed the other mainstream ensemble models. On the external test set, the area under the receiver operating characteristic curve (AUC) of the proposed decision model was 0.7731, and the performance of the prognostic prediction models was also relatively excellent. The application web server based on automatic lesion segmentation was deployed and is available online. Conclusions: In this study, we developed and externally validated the surgical decision-making procedures and prognostic prediction models for HCC for the first time, and the results demonstrated relatively accurate predictions and strong generalizations, which are expected to help clinicians optimize surgical procedures.

Safety and efficacy of radiotherapy combined with lenvatinib plus PD-1 inhibitors as neo-adjuvant therapy in hepatocellular carcinoma with portal vein thrombus: protocol of an open-label, single-arm, prospective, multi-center phase I trial.

Background: Surgical resection is a mainstay to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in east Asia. However, the postoperative recurrence rate is high. It is necessary to explore neo-adjuvant therapy to increase the surgical resection rate and improve overall survival. Evidence has shown that lenvatinib combined with PD-1 inhibitors is safe and effective in the treatment of advanced unresectable HCC. Radiotherapy is also an effective treatment method for PVTT and has a synergistic effect in combination with PD-1 inhibitors. Surgical resection after Lenvatinib and sintilimab combined with radiotherapy as a neoadjuvant treatment regimen may be a new exploration of HCC with PVTT, but there were not any reported. Methods: This open-label, single-arm, prospective, multi-center Phase I trial will enroll 20 HCC patients with PVTT who have a resectable primary tumor and no extra-hepatic metastasis. Eligible patients will be given radiotherapy, 3Gy*10 fraction, and will receive lenvatinib 8-12mg once daily and sintilimab 200mg once every three weeks. Surgical resection will be performed 6-8 weeks after radiotherapy. The primary endpoint is safety (number of patients ≥3G TRAE) and the number of patients who complete pre-op treatment and proceed to surgery. The secondary study endpoints include Major Pathological Response (MPR), 1-year tumor recurrence-free rate, Objective Response Rate (ORR), Imaging-Pathology Concordance Rate (IPCR), PVTT regression rate, Median Overall Survival (OS) and Recurrence Free Survival (RFS). Discussion: This trial may confirm that surgical resection following intensive neoadjuvant therapy can provide a safe and efficient regimen for BCLC stage C patients with PVTT. Clinical trial registration: https://clinicaltrials.gov/, identifier (NCT05225116).

Ensemble learning based on efficient features combination can predict the outcome of recurrence-free survival in patients with hepatocellular carcinoma within three years after surgery.

Preoperative prediction of recurrence outcome in hepatocellular carcinoma (HCC) facilitates physicians' clinical decision-making. Preoperative imaging and related clinical baseline data of patients are valuable for evaluating prognosis. With the widespread application of machine learning techniques, the present study proposed the ensemble learning method based on efficient feature representations to predict recurrence outcomes within three years after surgery. Radiomics features during arterial phase (AP) and clinical data were selected for training the ensemble models. In order to improve the efficiency of the process, the lesion area was automatically segmented by 3D U-Net. It was found that the mIoU of the segmentation model was 0.8874, and the Light Gradient Boosting Machine (LightGBM) was the most superior, with an average accuracy of 0.7600, a recall of 0.7673, a F1 score of 0.7553, and an AUC of 0.8338 when inputting radiomics features during AP and clinical baseline indicators. Studies have shown that the proposed strategy can relatively accurately predict the recurrence outcome within three years, which is helpful for physicians to evaluate individual patients before surgery.

Trans-arterial positive ICG staining-guided laparoscopic liver watershed resection for hepatocellular carcinoma.

Introduction: Anatomical liver resection is the optimal treatment for patients with resectable hepatocellular carcinoma (HCC). Laparoscopic Couinaud liver segment resection could be performed easily as liver segments could be stained by ultrasound-guided indocyanine green (ICG) injection into the corresponding segment portal vein. Several smaller liver anatomical units (liver watersheds) have been identified (such as S8v, S8d, S4a, and S4b). However, since portal veins of liver watersheds are too thin to be identified under ultrasound, the boundaries of these liver watersheds could not be stained intraoperatively, making laparoscopic resection of these liver watersheds demanding. Digital subtraction angiography (DSA) could identify arteries of liver watersheds with a diameter of less than 2 mm. Yet, its usage for liver watershed staining has not been explored so far. Purpose: The aim of this study is to explore the possibility of positive liver watershed staining via trans-arterial ICG injection under DSA examination for navigating laparoscopic watershed-oriented hepatic resection. Methods: We describe, in a step-by-step approach, the application of trans-arterial ICG injection to stain aimed liver watershed during laparoscopic anatomical hepatectomy. The efficiency and safety of the technique are illustrated and discussed in comparison with the laparoscopic anatomical liver resection via ultrasound-guided liver segment staining. Results: Eight of 10 HCC patients received successful trans-arterial liver watershed staining. The success rate of the trans-artery staining approach was 80%, higher than that of the ultrasound-guided portal vein staining approach (60%). Longer surgical duration was found in patients who underwent the trans-artery staining approach (305.3 ± 23.2 min vs. 268.4 ± 34.7 min in patients who underwent the ultrasound-guided portal vein staining approach, p = 0.004). No significant difference was found in major morbidity, reoperation rate, hospital stay duration, and 30-day and 90-day mortality between the 2 groups. Conclusions: Trans-arterial ICG staining is safe and feasible for staining the aimed liver watershed, navigating watershed-oriented hepatic resection under fluorescence laparoscopy for surgeons.

Augmented reality navigation with ultrasound-assisted point cloud registration for percutaneous ablation of liver tumors.

PURPOSE: We present a novel augmented reality (AR) surgical navigation method with ultrasound-assisted point cloud registration for percutaneous ablation of liver tumors. A preliminary study is carried out to verify its feasibility. METHODS: Two three-dimensional (3D) point clouds of the liver surface are derived from the preoperative images and intraoperative tracked US images, respectively. To compensate for the soft tissue deformation, the point cloud registration between the preoperative images and the liver is performed using the non-rigid iterative closest point (ICP) algorithm. A 3D AR device based on integral videography technology is designed to accurately display naked-eye 3D images for surgical navigation. Based on the above registration, naked-eye 3D images of the liver surface, planning path, entry points, and tumor can be overlaid in situ through our 3D AR device. Finally, the AR-guided targeting accuracy is evaluated through entry point positioning. RESULTS: Experiments on both the liver phantom and in vitro pork liver were conducted. Several entry points on the liver surface were used to evaluate the targeting accuracy. The preliminary validation on the liver phantom showed average entry-point errors (EPEs) of 2.34 ± 0.45 mm, 2.25 ± 0.72 mm, 2.71 ± 0.82 mm, and 2.50 ± 1.11 mm at distinct US point cloud coverage rates of 100%, 75%, 50%, and 25%, respectively. The average EPEs of the deformed pork liver were 4.49 ± 1.88 mm and 5.02 ± 2.03 mm at the coverage rates of 100% and 75%, and the average covered-entry-point errors (CEPEs) were 4.96 ± 2.05 mm and 2.97 ± 1.37 mm at 50% and 25%, respectively. CONCLUSION: Experimental outcomes demonstrate that the proposed AR navigation method based on US-assisted point cloud registration has achieved an acceptable targeting accuracy on the liver surface even in the case of liver deformation.

Combining Preoperative and Postoperative Inflammatory Indicators Can Better Predict the Recurrence of Hepatocellular Carcinoma After Partial Hepatectomy.

PURPOSE: Previous studies have shown that various preoperative inflammatory indicators can predict the prognosis of hepatocellular carcinoma (HCC), but the role of postoperative inflammatory indicators remains unclear. This study aimed to explore the prognostic value of postoperative inflammatory indicators and whether combining preoperative and postoperative inflammatory indicators can improve the predictive performance of the prognostic model. PATIENTS AND METHODS: Eighty-eight patients with primary HCC were included in this study. A preoperative model, postoperative model, and combined model that integrated preoperative and postoperative inflammatory indicators were established. The prognostic value of the models was evaluated by the area under the curve of time-dependent receiver operating characteristic curves (td-AUC). RESULTS: Multivariate analysis of preoperative and postoperative inflammatory indicators and clinicopathological indicators found that tumor number, alpha-fetoprotein (AFP) level, and the preoperative platelet-lymphocyte ratio (prePLR), preoperative prognostic nutritional index (prePNI), and postoperative neutrophil-lymphocyte ratio (postNLR) were independent prognostic factors for the disease-free survival. The prognostic efficacy of the postNLR at 2 years and 3 years was better than that of tumor number, AFP level, and the prePLR, and prePNI. The combined model had higher td-AUC values than the preoperative model, postoperative model, American Joint Committee on Cancer 8th edition stage, and Barcelona Clinic Liver Cancer stage at 2 years (0.814 vs 0.754, 0.765, 0.513 and 0.527, respectively), and 3 years (0.786 vs 0.749, 0.753, 0.509 and 0.529, respectively). The predictive performance of the combined model was better than that of the preoperative model, postoperative model, and traditional clinical stage. CONCLUSION: Postoperative inflammatory indicators were valuable prognostic indicators. The combination of preoperative and postoperative inflammatory indicators improved the predictive performance of the prognostic model. We should pay more attention to postoperative inflammatory indicators.

Clinical Activity and Safety of Penpulimab (Anti-PD-1) With Anlotinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: An Open-Label, Multicenter, Phase Ib/II Trial (AK105-203).

OBJECTIVE: This study aims to assess the efficacy and safety of penpulimab (a humanized anti-PD-1 IgG1 antibody) with anlotinib in the first-line treatment of Chinese patients with uHCC. METHODS: In this open-label multicenter phase Ib/II trial, patients with histologically or cytologically confirmed uHCC, without previous systemic treatment, aged 18-75 years old, classified as BCLC stage B (not amenable for locoregional therapy) or C, with Child-Pugh score ≤7 and ECOG performance status ≤1 were enrolled. Patients received penpulimab [200 mg intravenous (i.v.) Q3W] and oral anlotinib (8 mg/day, 2 weeks on/1 week off). The primary endpoint was objective response rate (ORR). Secondary endpoints included safety, disease control rate (DCR), progression-free survival (PFS), time to progression (TTP), duration of response (DoR), and overall survival (OS). This trial is registered with ClinicalTrials.gov (NCT04172571). RESULTS: At the data cutoff (December 30, 2020), 31 eligible patients had been enrolled and treated with a median follow-up of 14.7 months (range, 1.4-22.1). The ORR was 31.0% (95% CI, 15.3-50.8%), and the DCR was 82.8% (95% CI, 64.2-94.2%). The median PFS and TTP for 31 patients were 8.8 months (95% CI, 4.0-12.3) and 8.8 months (95% CI, 4.0-12.9) respectively. The median OS was not reached; the 12-month OS rate was 69.0% (95% CI, 48.9-82.5%). Only 19.4% (6/31) of patients had grade 3/4 treatment-related adverse events (TRAEs). CONCLUSION: Penpulimab plus anlotinib showed promising anti-tumor activity and a favorable safety profile as first-line treatment of patients with uHCC.

Prognostic value of the postoperative neutrophil-lymphocyte ratio in solid tumors: A meta-analysis.

PURPOSE: Numerous studies have demonstrated that a variety of systemic inflammatory markers were associated with the survival of different tumors. However, the association between elevated postoperative neutrophil-lymphocyte ratio (postNLR) and long-term outcomes, including overall survival (OS), disease-free survival (DFS), in patients with solid tumors remains controversial. A systematic review was conducted to explore the association between the postNLR and long-term outcomes in solid tumors. MATERIALS AND METHODS: Relevant literature was identified using PubMed, Embase, Web of Science, and the Cochrane Library from the initiation of the databases to October 2020. Data were extracted from included studies reporting hazard ratio (HR) and 95% confidence intervals (CI), and were pooled using generic inverse-variance and random-effects modeling. 25 studies reporting on7539 patients were included in the analysis. RESULTS: Elevated postNLR was associated with poor OS (HR 1.87, 95% CI = 1.53-2.28; P < 0.00001), and worse DFS (HR 1.69, 95% CI = 1.28-2.22; P = 0.0002). Subgroup analyses showed that the trend of the pooled HR for most of the subgroups was not changed, and the heterogeneity of the same tumor type was not obvious. However, there was no correlation between high postNLR obtained within 7days and poor DFS (n = 3, HR 1.25, 95CI% = 0.54-2.88; P = 0.60). CONCLUSIONS: Elevated postNLR might be a readily available and inexpensive biomarker for long-term outcomes in solid tumors. Multicenter and prospective studies are needed to explore the impact of the postNLR on the prognosis of solid tumors.

New evidence for a hydroxylation pathway for anaerobic alkane degradation supported by analyses of functional genes and signature metabolites in oil reservoirs.

Microbial degradation of recalcitrant alkanes under anaerobic conditions results in the accumulation of heavy oil fraction in oil reservoirs. Hydroxylation of alkanes is an important activation mechanism under anaerobic conditions, but the diversity and distribution of the responsible microorganisms in the subsurface environment are still unclear. The lack of functional gene polymerase chain reaction (PCR) primers and commercially available intermediate degradation chemical compounds are the major obstacles for this research. In this investigation, PCR primers for the ahyA gene (encoding alkane hydroxylase) were designed, evaluated, and improved based on the nucleotide sequences available. Using microbial genomic DNA extracted from oil-contaminated soil and production water samples of oil reservoirs, ahyA gene nucleotide sequences were amplified and retrieved successfully from production water sample Z3-25 of Shengli oilfield. Additionally, the signature biomarker of 2-acetylalkanoic acid was detected in both Shengli and Jiangsu oilfields. These results demonstrate that anaerobic hydroxylation is an active mechanism used by microorganisms to degrade alkanes in oxygen-depleted oil reservoirs. This finding expands the current knowledge of biochemical reactions about alkane degradation in subsurface ecosystems. In addition, the PCR primers designed and tested in this study serve as an effective molecular tool for detecting the microorganisms responsible for anaerobic hydroxylation of alkanes in this and other ecosystems.

HBx acts as an oncogene and promotes the invasion and metastasis of hepatocellular carcinoma both in vivo and vitro.

BACKGROUND AND AIMS: Hepatitis B virus X (HBx) has been reported to be closely related to hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study aimed to detect the expression pattern of HBx and explore whether HBx protein can promote HCC invasion and metastasis both in vivo and vitro. METHODS: HBx expression was detected in HCC tissues via immunochemistry. A recombinant adenovirus vector containing the HBx gene was constructed and transfected into the HCC cell line SMMC-7721. Wound healing, transwell migration, and invasion assays were performed to evaluate migration and invasion potentials. A splenic implant tumor nude mice model was established to confirm its invasion and metastatic abilities in vivo. RESULTS: The positive rate of HBx in HCC tissues was 67.89%. HBx overexpression significantly promoted the migration and invasion abilities of SMMC-7721 cells in vitro. The tumor model showed that splenic implant tumor volume and number of liver metastatic tumor nodes were significantly larger and higher in the HBx overexpression group than in the control group. CONCLUSIONS: HBx is highly expressed in HCC tissues and promotes HCC invasion and metastasis both in vivo and vitro with oncogene activity, thereby suggesting that HBx can serve as a novel therapeutic target in HCC.

Preoperative Remnant Liver Function Evaluation Using a Routine Clinical Dynamic Gd-EOB-DTPA-Enhanced MRI Protocol in Patients with Hepatocellular Carcinoma.

BACKGROUND: To investigate the clinical feasibility of preoperative routine clinical dynamic Gd-EOB-DTPA-enhanced MRI alone to predict post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC). METHODS: 116 patients with HCC who underwent liver resection in Southwest Hospital from 2014 through 2017 were selected in this retrospective cohort study. The remnant function (RF) of the liver RFUR and RFRE15 were calculated by the sum of the uptake rate (UR) or relative enhancement at 15 min (RE15) from dynamic Gd-EOB-DTPA-enhanced MR images in the remnant liver regions, and standardized by standard liver volume (SLV) to generate sRFUR (standardized RFUR) and sRFRE15 (standardized RFRE15). Student's t test or Mann-Whitney U test, logistic regression, and ROC analyses were used to test the associations of preoperative RFUR, sRFUR, RFRE15, sRFRE15, the remnant liver volume (RLV)/SLV, ICG retention rate at 15 min (ICG R15) and sRFICG-K [ICG clearance rate (ICG-K) × RLV/SLV] with PHLF. RESULTS: 28 patients were found to have PHLF, who showed lower RFUR, sRFUR, RFRE15, sRFRE15, RLV/SLV, sRFICG-K, and higher ICG R15 than patients without PHLF (p < 0.001 for all). After adjusting for clinical parameters, RFUR (p = 0.001), sRFUR (p = 0.001), RFRE15 (p = 0.002), or sRFRE15 (p = 0.003) was found to be independently significant indicator in multivariable logistic regression, respectively. RFUR (0.882) and sRFUR (0.882) had larger AUCs than RLV/SLV (0.731, p = 0.008; p = 0.005), ICG R15 (0.765, p = 0.039; p = 0.044) and sRFICG-K (0.767, p = 0.031; p = 0.023). RFRE15 (0.845) and sRFRE15 (0.839) had larger AUCs than RLV/SLV (0.731, p = 0.027; p = 0.025). CONCLUSIONS: The remnant liver function parameters preoperatively estimated from a routine clinical dynamic Gd-EOB-DTPA-enhanced MRI protocol can predict PHLF in patients with HCC, and may be better predictors than conventional methods.