Hepatic artery restriction operation combined with ALPPS (HARO-ALPPS), a novel ALPPS procedure for the treatment of hepatocellular carcinoma with severe fibrosis: Retrospective clinical cohort study.

BACKGROUND: Associating liver partition with portal vein ligation for staged liver resection (ALPPS) has been used in the treatment of patients with advanced or massive liver cancer without sufficient future liver remnant, but concerns remain regarding tumor outcomes and surgical safety. This study aims to evaluate the efficacy and safety of a new procedure, Hepatic artery restriction operation combined with ALPPS (HARO-ALPPS), in the treatment of HCC patients especially with severe fibrosis. METHODS: This retrospective study analyzed 8 patients who underwent HARO-ALPPS for HCC and compared their outcomes with 64 patients who underwent conventional ALPPS. The primary outcomes assessed were liver regeneration ability (measured by relative and absolute kinetic growth rates), postoperative complications, and mortality. The secondary outcomes included overall survival and disease-free survival. RESULTS: HARO-ALPPS significantly restricted the blood supply of the hepatic artery. One week after surgery, the blood flow of the right hepatic artery dropped to 62.1%. At the same time, HARO-ALPPS shows superior liver regeneration ability, which is particularly prominent in the background of liver fibrosis. No serious complications occurred after HARO-ALPPS. The overall survival rate of HARO-ALPPS was 75%, which was higher than that of ALPPS (64%, P=0.816). CONCLUSION: Compared to conventional ALPPS, HARO-ALPPS exhibits a better liver regeneration ability, and favorable long-term outcomes. Further prospective studies are needed to validate these findings and evaluate the long-term oncologic outcomes of this novel procedure.

Left Hepatectomy Combined with Right Hepatic Artery Resection and Reconstruction for Hilar Cholangiocarcinoma.

BACKGROUND: Hepatectomy combined with hepatic artery reconstruction in the operation for hilar cholangiocarcinoma (Klatskin tumor) is a challenging procedure. We present a video of left hepatectomy combined with right hepatic artery reconstruction for hilar cholangiocarcinoma. PATIENT AND METHODS: The patient was a 60-year-old male who presented with obstructive jaundice. The imaging examination showed that the confluence of left and right hepatic ducts and the wall of common hepatic duct were thickened, the local lumen was narrowed, the intrahepatic bile duct was dilated, and the right hepatic artery was invaded by tumors nearly 2.3 centimeters. Left hepatectomy with total caudate lobectomy, resection with reconstruction of right hepatic artery, hilar lymphadenectomy, and Roux-en-Y hepaticojejunostomy were performed. RESULTS: The operation time was 345 min, and the amount of bleeding was about 400 ml. There was no blood transfusion. The pathology showed poorly differentiated adenocarcinoma, with negative margins of common bile duct and right hepatic duct, and negative results of all lymph nodes. The patient's recovery was uneventful and he was discharged on postoperative day 14. The patient was disease free at 12-month follow-up evaluation. CONCLUSIONS: Hepatic artery resection and reconstruction procedure is safe and feasible for hilar cholangiocarcinoma in a highly tertiary hepatobiliary center.

CD4+CD25+ regulatory T cells decreased future liver remnant after associating liver partition and portal vein ligation for staged hepatectomy.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is an innovative surgical approach for the treatment of massive hepatocellular carcinoma (HCC), the key to successful planned stage 2 ALPPS is future liver remnant (FLR) volume growth, but the exact mechanism has not been elucidated. The correlation between regulatory T cells (Tregs) and postoperative FLR regeneration has not been reported. AIM: To investigate the effect of CD4+CD25+ Tregs on FLR regeneration after ALPPS. METHODS: Clinical data and specimens were collected from 37 patients who developed massive HCC treated with ALPPS. Flow cytometry was performed to detect changes in the proportion of CD4+CD25+ Tregs to CD4+ T cells in peripheral blood before and after ALPPS. To analyze the relationship between peripheral blood CD4+CD25+ Treg proportion and clinicopathological information and liver volume. RESULTS: The postoperative CD4+CD25+ Treg proportion in stage 1 ALPPS was negatively correlated with the amount of proliferation volume, proliferation rate, and kinetic growth rate (KGR) of the FLR after stage 1 ALPPS. Patients with low Treg proportion had significantly higher KGR than those with high Treg proportion (P = 0.006); patients with high Treg proportion had more severe postoperative pathological liver fibrosis than those with low Treg proportion (P = 0.043). The area under the receiver operating characteristic curve between the percentage of Tregs and proliferation volume, proliferation rate, and KGR were all greater than 0.70. CONCLUSION: CD4+CD25+ Tregs in the peripheral blood of patients with massive HCC at stage 1 ALPPS were negatively correlated with indicators of FLR regeneration after stage 1 ALPPS and may influence the degree of fibrosis in patients' livers. Treg percentage was highly accurate in predicting the FLR regeneration after stage 1 ALPPS.

Multifunctional Nanoparticles-Mediated PTT/PDT Synergistic Immune Activation and Antitumor Activity Combined with Anti-PD-L1 Immunotherapy for Breast Cancer Treatment.

Introduction: Photoimmunotherapy is a breakthrough treatment for malignant tumors. Its uniqueness is that it uses antibody mediated targeted delivery to achieve high tumor specificity and uses laser-activated biophysical mechanism to accurately induce the rapid death of cancer cells and avoid damaging the surrounding normal tissues. Methods: In this paper, an iron-based micelle was designed to encapsulate the photothermal agent indocyanine green (ICG) and a cyclic tripeptide of arginine-glycine-aspartic acid (cRGD) as targeted multifunctional ICG@SANPs-cRGD nanoparticles for combined photothermal/photodynamic/immune therapy of breast cancer. Results: The experimental results show that ICG@SANPs-cRGD nanoparticles have good biocompatibility and photothermal conversion ability. Photothermal therapy (PTT) and photodynamic therapy (PDT) based on ICG@SANPs-cRGD can not only inhibit the proliferation, invasion and migration of tumor cells, but also directly kill tumor cells by inducing apoptosis or necrosis. Dual-mode fluorescence light (FL) and magnetic resonance imaging (MRI) imaging in mice confirmed the selective accumulation at tumor sites and imaging ability of ICG@SANPs-cRGD. PTT/PDT combined with Anti-PD-L1 immunotherapy based on ICG@SANPs-cRGD mediated the immunogenic cell death (ICD) of tumor cells by regulating the expression of immune-related indicators and activated the body's immune response mechanism, which enhanced the immunotherapy effect of immune checkpoint block (ICB). PTT/PDT combined with Anti-PD-L1 therapy not only prevented the progression of the primary tumor but also inhibited the distant metastasis of the tumor. Discussion: This study explores the biomedical application of PTT/PDT combined with Anti-PD-L1 based on ICG@SANPs-cRGD nanomaterials for breast cancer treatment and demonstrates the potential of ICG@SANPs-cRGD as a multifunctional therapeutic platform for future cancer therapy.

Construction of a 3-mRNA hypoxia prognostic model to evaluate immune microenvironment in hepatocellular carcinoma.

BACKGROUND: Hypoxia is a key factor in the development of hepatocellular carcinoma (HCC), which is the most common primary liver cancer with poor prognosis. The current study aimed to identify the potential prognostic biomarkers of the hypoxia-associated gene signature in patients with HCC, and to further explore the relationship between hypoxia and immune infiltration. METHODS: After the determination of differentially expressed genes (DEGs) using the HCC transcriptome data of The Cancer Genome Atlas database and hypoxia-related gene set, the prognosis-associated genes were identified using univariate Cox regression analysis. Then, the hypoxia prognosis model was established via multivariate Cox regression analysis, with functional annotation conducted using Gene Set Enrichment Analysis. CIBERSORT was utilized to analyze the degree of tumor immune invasion, and an International Cancer Genome Consortium cohort to verify the reliability of the prognosis model. Expression levels of hypoxia-associated genes were detected by real-time quantitative polymerase chain reaction in HCC samples. RESULTS: 3 genes (ENO1, SAP30, and STC2) constructed the hypoxia prognosis model. The patients were subdivided into 2 groups based on median risk score, with a high hypoxic score indicating poor prognosis of HCC. The hypoxia signature could be employed as an independent prognostic factor in HCC. In addition, the proportion of macrophages was higher in the high-risk group. CONCLUSION: The hypoxia-associated signature could be a potential prognostic marker of HCC and provides a different perspective for immunotherapy of HCC.

Change of tumor-infiltrating lymphocyte of associating liver partition and portal vein ligation for staged hepatectomy for hepatocellular carcinoma.

BACKGROUND: The role of tumor-infiltrating lymphocytes (TILs) in the growth and progression of hepatocellular carcinoma (HCC) has attracted widespread attention. AIM: To evaluate the feasibility of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for massive HCC by exploring the role of TIL in the tumor microenvironment. METHODS: Fifteen massive HCC patients who underwent ALPPS treatment and 46 who underwent hemi-hepatectomy were selected for this study. Propensity score matching was utilized to match patients in ALPPS and hemi-hepatectomy groups (1:1). Quantitative analysis of TILs in tumor and adjacent tissues between the two groups was performed by immunofluorescence staining and further analyses with oncological characteristics. In the meantime, trends of TILs in peripheral blood were compared between the two groups during the perioperative period. RESULTS: Continuous measurement of tumor volume and necrosis volume showed that the proportion of tumor necrosis volume on the seventh day after stage-I ALPPS was significantly higher than the pre-operative value (P = 0.024). In the preoperative period of stage-I ALPPS, the proportion of tumor necrosis volume in the high CD8+ T cell infiltration group was significantly higher than that in the low group (P = 0.048). CONCLUSION: TIL infiltration level maintained a dynamic balance during the preoperative period of ALPPS. Compared with right hemi-hepatectomy, the ALPPS procedure does not cause severe immunosuppression with the decrease in TIL infiltration and pathological changes in immune components of peripheral blood. Our results suggested that ALPPS is safe and feasible for treating massive HCC from the perspective of immunology. In addition, high CD8+ T cell infiltration is associated with increasing tumor necrosis in the perioperative period of ALPPS.

Case Report: Combining liver partition and portal vein ligation after thrombectomy for tumor isolation (CLAPT) to treat advanced hepatocellular carcinoma with portal vein tumor thrombosis.

Background: Primary liver cancer is the third leading cause of cancer-related deaths worldwide in 2020, and hepatocellular carcinoma (HCC) is the major pathological type. Patients with HCC complicated with portal vein tumor thrombosis (PVTT) have a poor prognosis, and controversies regarding treatment options exist among international scholars. Patients with VP4 or Cheng's type III classification are generally considered ineligible for surgical treatment. Methods: We retrospectively analyzed three cases of HCC with PVTT who underwent a novel modified surgical procedure. The procedure included portal vein thrombectomy and portal vein ligation with liver parenchymal separation for the resection of the tumor thrombus involving the main portal vein trunk and for the isolation of the giant tumor. The three cases were then treated with targeted drugs postoperatively. Results: One case developed acute renal failure in the perioperative period, and the renal function gradually recovered after the treatment. The two remaining cases recovered uneventfully postoperatively. The prognosis of the three patients was encouraging. Only one patient died of lung metastasis after 13 months, and the remaining patients were still alive after 41 and 21 months, respectively. Conclusions: We provide a new possible surgical option for patients with advanced HCC with PVTT. The surgical procedure was inspired by associating liver partition with portal vein ligation for staged hepatectomy and portal vein thrombectomy. The survival time was significantly prolonged after the patients underwent thrombectomy, tumor isolation, and postoperative nonsurgical treatment. Hence, the combination of liver partition and portal vein ligation after thrombectomy for tumor isolation has the potential for the treatment of advanced HCC with PVTT.

Hepatectomy and pneumectomy combined with targeted therapy for primary hepatic neuroendocrine carcinoma: Case report and review of the literature.

Primary hepatic neuroendocrine carcinoma (PHNEC) manifests as a rare type of liver tumor. PHNEC is not specifically clinical or radiographical and is often misdiagnosed and mistreated. Here, we present a case report of PHNEC in a 50-year-old woman who was admitted to our department with concealed pain in the right upper abdomen. The initial diagnosis was a probable hepatic space-occupying lesion with tumor bleeding. The patient was subjected to a partial right hemihepatectomy, cholecystectomy, partial resection of the lower lobe of the right lung, partial resection of the diaphragm, and resection of the right perirenal fat sac to alleviate her symptoms. After surgery, gene sequencing was performed to determine the possible cause of the condition. However, five months after discharge, the patient was hospitalized again because of retroperitoneal and peritoneal multiple metastases. Nine months after surgery, the patient died. This case is likely to aid in furthering our understanding of PHNEC to improve the future diagnosis and treatment of this disease.

First Robotic Hepatectomy With Middle Hepatic Vein Reconstruction Using ePTFE Graft for Hepatic Adenoma: A Case Report.

Surgical resection remains the best choice for the treatment of liver tumors. Hepatectomy combined with artificial vascular reconstruction has been proven as an alternative to treating tumors involving the main hepatic veins. As the cutting-edge surgical technique, robotic liver surgery is a novel procedure expanding the field of minimally invasive approaches, especially in complex reconstruction. This study reports, for the first time, on a robotic hepatectomy with middle hepatic vein (MHV) reconstruction using an expanded polytetrafluoroethylene (ePTFE) graft for a patient with hepatic adenoma. The tumor, which was located in segment 8, was adjacent to the MHV. Robot-assisted resection of segment 4 and partial segment 8, and MHV reconstruction using a ePTFE graft were performed. During the post-operative examination and follow-up, the blood flow of the ePTFE graft was patent, and liver function recovered well. Thus, robotic hepatectomy with MHV reconstruction is a safe, minimally invasive, and precise surgery that may provide a novel approach for patients with liver tumors that are invading or adjacent to the main hepatic veins.

Bioinformatics Analysis for Constructing a Six-Immune-Related Long Noncoding RNA Signature as a Prognostic Model of Hepatocellular Carcinoma.

The present study was aimed at identifying the potential prognostic biomarkers of the immune-related long noncoding RNA (IRL) signature for patients with hepatocellular carcinoma (HCC). RNA-sequencing data and clinical information about HCC were obtained from The Cancer Genome Atlas. The IRLs were determined with regard to the coexpression of immune-related genes and differentially expressed lncRNAs. The survival IRLs were obtained using the univariate Cox analysis. Subsequently, the prognosis model was constructed via the multivariate Cox analysis. Subsequently, functional annotation was conducted using Gene Set Enrichment Analysis (GSEA) and principal component analysis (PCA). In total, 341 IRLs were identified, and 6 IRLs were found to have a highly significant association with the prognosis of patients with HCC. The immune prognosis model was constructed with these 6 IRLs (AC099850.4, negative regulator of antiviral response, AL031985.3, PRRT3-antisense RNA1, AL365203.2, and long intergenic nonprotein coding RNA 1224) using the multivariate Cox regression analysis. In addition, immune-related prognosis signatures were confirmed as an independent prognostic factor. The association between prognostic signatures and immune infiltration indicated that the 6 lncRNAs could reflect the immune status of the tumor. Collectively, the present study demonstrates that six-lncRNA signatures may be potential biomarkers to predict the prognosis of patients with HCC.

Bioinformatics analysis and experimental verification of five metabolism-related lncRNAs as prognostic models for hepatocellular carcinoma.

BACKGROUND: The number of patients with hepatocellular carcinoma (HCC) is showing a growing trend all over the world. The metabolic microenvironment has been shown to play a key role in the pathogenesis of HCC in recent studies. The expression of metabolites and metabolic processes in tumor cells can be regulated by gene regulation mediated by long non-coding RNAs (lncRNAs), the abnormal expression of which is closely related to tumor occurrence and metastasis. However, the fundamental mechanism of applying metabolism-related lncRNAs to predicting HCC is still unclear. METHODS: With the complete RNA sequence data and clinical data obtained from The Cancer Genome Atlas database and metabolism-related genes downloaded from the Kyoto Encyclopedia of Genes and Genomes database, with false discovery rate < 0.001, log fold change > 1.5 selected as the screening criteria for lncRNA, the relationship between the expression level of metabolism-related LncRNAs (MRLs) and the overall survival rate was determined by the Univariate Cox regression analyses with the establishment of the metabolic prognosis model by the application of Multivariate Cox regression analyses, revealing the different biological processes and signaling pathways in both high-risk groups and low-risk groups by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and gene set enrichment analysis, leading the expression of lncRNA to be assessed by the reverse transcription-polymerase chain reaction results. RESULTS: The overall survival rate of HCC patients is significantly correlated with signature of 5-MRLs. The prognosis characteristics of lncRNA reveal the relatively high death rate of patients in the high-risk groups, with the predicted signals by functional and pathway enrichment analysis related to biosynthesis, metabolic process, and metabolic pathway, with the prognostic characteristics of 5-MRLs by the combined analysis showing that it is an independent factor of HCC superior to the traditional clinical indicators in predicting the prognosis. A trend of high-expression was shown in MRLs in tumors by reverse transcription-polymerase chain reaction. CONCLUSION: The new 5-MRLs as potential biomarkers provide more powerful prognostic information for HCC patients. In the future clinical treatment of HCC, it will provide doctors with more methods.

Generation of in situ CRISPR-mediated primary and metastatic cancer from monkey liver.

Non-human primates (NHPs) represent the most valuable animals for drug discovery. However, the current main challenge remains that the NHP has not yet been used to develop an efficient translational medicine platform simulating human diseases, such as cancer. This study generated an in situ gene-editing approach to induce efficient loss-of-function mutations of Pten and p53 genes for rapid modeling primary and metastatic liver tumors using the CRISPR/Cas9 in the adult cynomolgus monkey. Under ultrasound guidance, the CRISPR/Cas9 was injected into the cynomolgus monkey liver through the intrahepatic portal vein. The results showed that the ultrasound-guided CRISPR/Cas9 resulted in indels of the Pten and p53 genes in seven out of eight monkeys. The best mutation efficiencies for Pten and p53 were up to 74.71% and 74.68%, respectively. Furthermore, the morbidity of primary and extensively metastatic (lung, spleen, lymph nodes) hepatoma in CRISPR-treated monkeys was 87.5%. The ultrasound-guided CRISPR system could have great potential to successfully pursue the desired target genes, thereby reducing possible side effects associated with hitting non-specific off-target genes, and significantly increasing more efficiency as well as higher specificity of in situ gene editing in vivo, which holds promise as a powerful, yet feasible tool, to edit disease genes to build corresponding human disease models in adult NHPs and to greatly accelerate the discovery of new drugs and save economic costs.

Intraoperative Indocyanine Green Retention Test of Left Hemiliver in Decision-Making for Patients With Hepatocellular Carcinoma Undergoing Right Hepatectomy.

Introduction: The aim of this study was to select qualified patients with hepatocellular carcinoma (HCC) who underwent right hepatectomy (RH) via intraoperative indocyanine green retention test at 15 min (ICG-R15) of the left hemiliver, which prevents severe posthepatectomy liver failure (PHLF). Methods: Twenty HCC patients who were preoperatively planned to undergo RH were enrolled. Intraoperative ICG-R15 of left hemiliver was measured after the right Glissonean pedicle was completely blocked. Patients then underwent RH if intraoperative ICG-R15 was ≤ 10%. Otherwise, patients underwent staged RH (SRH), either associating liver partitioning and portal vein ligation for staged hepatectomy (ALPPS) or portal vein ligation (PVL), followed by stage-2 RH. The comparison group consisted of patients with a ratio of standard left liver volume (SLLV) of > 40% and preoperative ICG-R15 ≤ 10% who underwent RH. The clinical outcomes of these two groups were compared. Results: Of the 20 patients, six underwent stage-1 RH, six underwent ALPPS, five underwent PVL followed by stage-2 RH, and three failed to proceed to stage-2 RH after PVL. No significant differences were found among the 17 patients who underwent stage-1 or stage-2 RH in the study group, the 19 patients in the comparison group, the 11 patients in the stage-2 RH group, and the six patients in the stage-1 RH group in incidences of PHLF, postoperative complications, hospital stay, and HCC recurrence within 1 year after RH. Compared with the stage-1 ALPPS group, the mean operative time and blood loss of the stage-1 PVL group were significantly less (p <0.001 and p = 0.022, respectively). The stage-1 PVL group had a significantly longer waiting-time (43.4 vs. 14.0 days, p = 0.016) than the stage-1 ALPPS group to proceed to stage-2 RH. After stage-2 RH, tumor recurrence within 1 year was 20% (1/5) in patients after PVL and 50% (3/6) after stage-1 ALPPS. Conclusions: Intraoperative ICG-R15 ≤ 10% of left hemiliver was valuable in intraoperative decision-making for patients who were planned to undergo RH. There is a possibility that stage-1 PVL might help to select patients with more favorable biological behavior to undergo stage-2 RH.

Signature of prognostic epithelial-mesenchymal transition related long noncoding RNAs (ERLs) in hepatocellular carcinoma.

ABSTRACT: Reliable biomarkers are of great significance for the treatment and diagnosis of hepatocellular carcinoma (HCC). This study identified potential prognostic epithelial-mesenchymal transition related lncRNAs (ERLs) by the cancer genome atlas (TCGA) database and bioinformatics.The differential expression of long noncoding RNA (lncRNA) was obtained by analyzing the lncRNA data of 370 HCC samples in TCGA. Then, Pearson correlation analysis was carried out with EMT related genes (ERGs) from molecular signatures database. Combined with the univariate Cox expression analysis of the total survival rate of hepatocellular carcinoma (HCC) patients, the prognostic ERLs were obtained. Then use "step" function to select the optimal combination of constructing multivariate Cox expression model. The expression levels of ERLs in HCC samples were verified by real-time quantitative polymerase chain reaction.Finally, we identified 5 prognostic ERLs (AC023157.3, AC099850.3, AL031985.3, AL365203.2, CYTOR). The model showed that these prognostic markers were reliable independent predictors of risk factors (P value <.0001, hazard ratio [HR] = 2.400, 95% confidence interval [CI] = 1.667-3.454 for OS). In the time-dependent receiver operating characteristic analysis, this prognostic marker is a good predictor of HCC survival (area under the curve of 1 year, 2 years, 3 years, and 5 years are 0.754, 0.720, 0.704, and 0.662 respectively). We analyzed the correlation of clinical characteristics of these prognostic markers, and the results show that this prognostic marker is an independent factor that can predict the prognosis of HCC more accurately. In addition, by matching with the Molecular Signatures Database, we obtained 18 ERLs, and then constructed the HCC prognosis model and clinical feature correlation analysis using 5 prognostic ERLs. The results show that these prognostic markers have reliable independent predictive value. Bioinformatics analysis showed that these prognostic markers were involved in the regulation of EMT and related functions of tumor occurrence and migration.Five prognostic types of ERLs identified in this study can be used as potential biomarkers to predict the prognosis of HCC.

Hepatic Arterioportal Fistula Is Associated with Decreased Future Liver Remnant Regeneration after Stage-I ALPPS for Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) patients often developed hepatic arterioportal fistula (APF). The aim of this study is to evaluate the impact of APF on future liver remnant (FLR) regeneration and surgical outcomes after the first stage of associating liver partition and portal vein ligation for staged hepatectomy (stage-I ALPPS). METHODS: Consecutive HCC patients who underwent ALPPS at our center between March 2017 and May 2019 were retrospectively studied. Data for the association between APF and clinicopathological details, liver volume, and surgical outcomes were analyzed. RESULTS: The enrolled 35 HCC patients were divided into three groups: 15 patients with preoperative APF were classified as the APF I group, 10 patients developed APF after stage-I ALPPS as the APF II group, whereas the other 10 patients without APF before and after stage-I ALPPS as the control group. After stage-I ALPPS, patients in the APF I and APF II groups had lower kinetic growth rate (KGR) of FLR volume (6.1±3.2%, 11.4±8.4%, 25.0±8.8% per week, respectively, P<0.001) and took longer median time to reach the sufficient FLR volume for stage-II ALPPS (17.5 days, 12 days, 6 days, respectively, P<0.001) than those in the control group. Meanwhile, the incidence of posthepatectomy liver failure (PHLF) in the APF I and APF II groups was significantly higher than that of the control group (P=0.007). There are 27 (77.1%) patients who completed stage-II ALPPS. The overall survival (OS) rates at 1 and 3 years were 59.3% and 35.1%, whereas the disease-free survival (DFS) rates at 1 and 3 years were 44.4% and 22.9%, respectively. CONCLUSIONS: Hepatic APF is significantly associated with decreased FLR regeneration and a higher risk of PHLF after stage-I ALPPS. HCC patients who are to undergo ALPPS may benefit from the timely perioperative intervention of APF.

Efficacy of the association liver partition and portal vein ligation for staged hepatectomy for the treatment of solitary huge hepatocellular carcinoma: a retrospective single-center study.

BACKGROUND: The feasibility of association liver partition and portal vein ligation for staged hepatectomy (ALPPS) for solitary huge hepatocellular carcinoma (HCC, maximal diameter ≥ 10 cm) remains uncertain. This study aims to evaluate the safety and the efficacy of ALPPS for patients with solitary huge HCC. METHODS: Twenty patients with solitary huge HCC who received ALPPS during January 2017 and December 2019 were retrospectively analyzed. The oncological characteristics of contemporaneous patients who underwent one-stage resection and transcatheter arterial chemoembolization (TACE) were compared using propensity score matching (PSM). RESULTS: All patients underwent complete two-staged ALPPS. The median future liver remnant from the ALPPS-I stage to the ALPPS-II stage increased by 64.5% (range = 22.3-221.9%) with a median interval of 18 days (range = 10-54 days). The 90-day mortality rate after the ALPPS-II stage was 5%. The 1- and 3-year overall survival (OS) rates were 70.0% and 57.4%, respectively, whereas the 1- and 3-year progression-free survival (PFS) rates were 60.0% and 43.0%, respectively. In the one-to-one PSM analysis, the long-term survival of patients who received ALPPS was significantly better than those who received TACE (OS, P = 0.007; PFS, P = 0.011) but comparable with those who underwent one-stage resection (OS, P = 0.463; PFS, P = 0.786). CONCLUSION: The surgical outcomes of ALPPS were superior to those of TACE and similar to those of one-stage resection. ALPPS is a safe and effective treatment strategy for patients with unresectable solitary huge HCC.

[Clinical characteristics and epidemiological analysis of pathogenic bacteria of severe abdominal infection in surgical intensive care unit].

OBJECTIVE: To study the clinical characteristics of patients with severe abdominal infection and the epidemiological characteristics of pathogenic bacteria in a hospital, to provide a basis for rational use of antibiotics and reduce the drug resistance rate of pathogens. METHODS: A retrospective analysis was performed on 237 patients with abdominal disease as the primary disease admitted to the surgical intensive care unit (ICU) of the First Affiliated Hospital of Guangxi Medical University from January 1st, 2017 to December 31st, 2019. They were divided into two groups according to whether abdominal infection occurred or not. The clinical features of patients in both groups were analyzed, including gender, age, acute physiology and chronic health evaluation II (APACHE II) score, chronic underlying diseases, primary abdominal site, abdominal trauma or bleeding, multiple organ dysfunction syndrome (MODS) involving organs and surgical treatment. At the same time, the bacterial origin, bacterial distribution and antibiotics sensitivity test results of patients with abdominal infection were recorded. RESULTS: Abdominal infection occurred in 141 of the 237 patients and did not occur in the remaining 96 patients. There were no statistically significant differences between the abdominal infection group and the non-abdominal infection group in terms of gender, age, chronic underlying diseases, etiology and trauma. The APACHE II score in the abdominal infection group was obviously higher than that of the non-abdominal infection group (24.0±8.1 vs. 17.1±5.8, P < 0.01). Incidences of abdominal bleeding, MODS involving four or more organs, surgery and the times of surgery ≥ 3 in the abdominal infection group were significantly higher than those in the non-abdominal infection group (36.2% vs. 17.7%, 20.6% vs. 1.0%, 84.4% vs. 21.9%, 9.3% vs. 0%, all P < 0.05). Among the 141 patients with abdominal infection, 107 obtained positive microbial culture results, and a total of 133 pathogenic strains were detected, including 115 strains of bacteria (86.5%) and 18 strains of fungi (13.5%). The main source of bacteria was abdominal drainage (46.1% of non-bloody specimens and 13.9% of bloody specimens). Among the 115 bacteria, Gram-negative (G-) bacteria were the most common (72.2%) and Gram-positive (G+) bacteria accounted for 27.8%. Escherichia coli and Acinetobacter baumannii were the top two G- bacteria (40.9% and 13.9%, respectively), and enterococcus faecalis accounted for the largest proportion of G+ bacteria (7.8%). The pathogenic bacteria of abdominal infection were sensitive to tigacycline. CONCLUSIONS: The patients with abdominal infection in our hospital had high APACHE II score, more organs failure and were easily complicated with intraperitoneal hemorrhage and required surgical intervention and even repeated surgery. The pathogenic bacteria in patients with abdominal infection in ICU were mainly G- bacteria, and the rate of multi-drug resistance of Acinetobacter baumannii was high. Empirical anti-infective treatment should be started as soon as possible according to the microbial spectrum of the region until the pathogenic bacteria results are obtained. Broad-spectrum antimicrobial therapy and combined antimicrobial therapy are recommended for the healthcare acquired abdominal infection in hospital.

Identification of Prognostic Immune-Related Genes in Pancreatic Adenocarcinoma and Establishment of a Prognostic Nomogram: A Bioinformatic Study.

BACKGROUND: The prognosis of pancreatic adenocarcinoma (PAAD) is extremely poor and has not been improved. Thus, an effective method to assess the prognosis of patients must be established to improve their survival rate. METHOD: This study investigated immune-related genes that could be used as potential therapeutic targets for PAAD. Level 3 gene expression data from the PAAD cohort and the relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database. For validation, other PAAD datasets (DSE62452) were downloaded from the Gene Expression Omnibus (GEO) database. The PAAD datasets from TCGA and GEO were used to screen immune-related genes through the Molecular Signatures Database using gene set enrichment analysis. Then, the overlapping immune-related genes of the two datasets were identified. Coexpression networks of the immune-related genes were constructed. RESULTS: A signature of three immune-related genes (CKLF, ERAP2, and EREG) was identified in patients with PAAD. The signature could be used to divide the patients with PAAD into high- and low-risk groups based on their median risk score. Multivariate Cox regression analysis was performed to determine the independent prognostic factors of PAAD. Time-dependent receiver operating characteristic (ROC) curve analysis was conducted to assess the prediction accuracy of the prognostic signature. Last, a nomogram was established to assess the individualized prognosis prediction model based on the clinical characteristics and risk score of the TCGA PAAD dataset. The accuracy of the prognostic signature was further evaluated through functional evaluation and principal component analysis. CONCLUSIONS: The results indicated that the signature of three immune-related genes had excellent predictive value for PAAD. These findings might help improve personalized treatment and medical decisions.

Fibroblast activation protein α-positive pancreatic stellate cells promote the migration and invasion of pancreatic cancer by CXCL1-mediated Akt phosphorylation.

BACKGROUND: Pancreatic stellate cells (PSCs) is a highly heterogeneic stroma cell population in pancreatic cancer tissue. Interaction between PSCs and pancreatic cancer cells has not been well elucidated. This research was aimed to study the relationship between fibroblast activation protein α (FAPα)-positive (FAPα+) PSCs and the pathological features and prognosis of pancreatic cancer. The effects and mechanisms of FAPα + PSCs in pancreatic cancer were also explored. METHODS: Tissue microarray analysis was used to detect FAPα expression in tumor and adjacent tissues. The relationship between FAPα expression and pancreatic pathological features and prognosis were analyzed. The effects of FAPα+ PSCs on the proliferation, migration and invasion of pancreatic cancer were detected in vitro and in vivo. A cytokine chip was used to detect the differential expression of cytokines in FAPα-positive (FAPα+) and FAPα-negative (FAPα-) PSCs. Phosphorylated tyrosine kinase receptors were detected by a human phosphotyrosine kinase receptor protein chip. The interaction between differential cytokine and tyrosine kinase receptors was detected by immunoprecipitation. RESULTS: Compared with the adjacent tissues, pancreatic cancer stromal tissues showed high FAPα expression. FAPα was mainly expressed in the PSCs. FAPα+ PSCs were associated with lymph node metastasis. Higher numbers of FAPα+ PSCs predicted shorter survival. Pancreatic cancer cells released TGFß1 and induced PSCs to express FAPα. FAPα+ PSCs released the chemokine CXCL1 and promoted the phosphorylation of the tyrosine kinase receptors EphB1 and EphB3 in pancreatic cancer cells. CXCL1, EphrinB1, and EphrinB3 worked together to promote the migration and invasion of pancreatic cancer cells by Akt phosphorylation. Talabostat (PT100), an FAPα inhibitor, inhibited the roles of FAPα+ PSCs. CONCLUSIONS: FAPα+ PSCs can promote the migration, invasion, and metastasis of pancreatic cancer by the Akt signaling pathway. This interaction of FAPα+ PSCs with pancreatic cancer cells may become a new strategy for the comprehensive treatment of pancreatic cancer.